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  • 1985-1989
  • 1975-1979  (2,615)
  • 1977  (2,615)
  • Polymer and Materials Science  (2,521)
  • Rat
  • pharmacokinetics
Material
Years
  • 1985-1989
  • 1975-1979  (2,615)
Year
  • 1
    ISSN: 1432-2013
    Keywords: Altitude ; Myocardium ; Regional blood flow ; Blood volume ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Circulating blood volume, cardiac output and relative organ perfusion changes were studied, using the Sapirstein method of86Rb tissue uptake, in male 75-day-old rats exposed to intermittent high altitude hypoxia (gradually up to 7000 m, 4 h daily, 5 days a week; the total number of exposures was 24). Intermittent hypobaric exposure caused a significant rise of the erythrocyte volume, whereas the plasma volume remained unchanged. The relative perfusion of the left and particularly of the right ventricular myocardium, as well as of the spleen, liver, lung, small intestine and skeletal muscle, was significantly higher. The cardiac output determined in other experimental animals similarly treated was significantly higher after 24 exposures to the intermittent high altitude hypoxia. We suggest that these changes are triggered by tissue hypoxia and a greater blood flow demand.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 368 (1977), S. 125-128 
    ISSN: 1432-2013
    Keywords: Endotoxin ; Rat ; Fever ; Anti-endotoxin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In conscious unrestrained rats, at an ambient temperature of 22°C, oesophageal temperature was measured and temperature effect of single and repeated intravenous injection ofE. coli endotoxin was examined. The first injection of endotoxin in a dose of 10.0 μg/rat did not change the rat body temperature. The second injection of this dose in the same animals repeated after 48 h produced fever. With following injections the fevers observed were less pronounced. The absence of fever after a single injection of endotoxin was accompanied by the rapid loss of pyretic activity of the rat plasma samples (bioassayed in rabbits). When fever was observed (48 h interval between endotoxin injections) the pyretic activity of the rat plasma remained unchanged for 90 min following endotoxin injection. It was concluded that after a single injection endotoxin is rapidly detoxified in the rat circulation while this process does not take place after the second endotoxin injection (48 h interval). The process of endotoxin detoxification can be depressed by the pretreatment with nitrogen mustard. Analysis of changes of skin temperature following endotoxin injections and the influence of aspirin on endotoxin-induced fever suggest that the fever observed was of central origin.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2013
    Keywords: Dibutyryl cyclic AMP ; Pancreas ; Rat ; Secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary DbcAMP≥0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-d-glucose andl-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neuro-transmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 205-216 
    ISSN: 1432-1912
    Keywords: Chronic ethanol treatment ; Rat ; Behaviour ; Central monoamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats weaned at 16 days of age were treated with various ethanol concentrations (8–24% w/v) for 270 days. The effect of the chronic ethanol treatment on the growth rate, the diurnal pattern of drinking, the open field activity, and the conditioned avoidance acquisition and retention of the rats were studied. Termination of the chronic ethanol administration caused two types of withdrawal syndromes. The first, an acute withdrawal syndrome was observed within 12 h after the discontinuation of the ethanol treatment and was characterized by extreme hyperexcitability. The second, a delayed withdrawal syndrome was characterized by a more coordinated behavioural stimulation and developed first after about 3 days after the discontinuation of the ethanol treatment. Biochemically, the latter withdrawal syndrome was accompanied by an increased rate of tyrosine hydroxylation (measured as the accumulation of dopa after inhibition of aromatic amino acid decarboxylase) in the striatum and dopamine-rich limbic structures. No differences in the accumulation of 5-hydroxytryptophan were observed. Furthermore, there was an increased level of dopamine concomitant with a decreased level of noradrenaline in the limbic areas during ongoing ethanol treatment. On the 4th day after withdrawal of ethanol the endogenous levels of dopamine and noradrenaline were statistically significantly reduced in the limbic structures. The data of the present study indicate that chronic ethanol administration induces various kinds of behavioural changes and that these changes at least partially are mediated via central catecholamine mechanisms.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Histidin ; Gehirn ; Skelettmuskel ; Leber ; Urämie ; Ratte ; Histidine ; Brain ; Striated muscle ; Liver ; Uremia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Intracellular histidine levels were determined in brain, striated muscle and liver of rats with chronic renal insufficiency (5/6-nephrectomy) and compared both with normal rats and food-restricted (pair-fed) animals. There was no difference in plasma histidine concentration of the three groups whereas in the brain of the uremic rats histidine was significantly increased. Since there existed no alteration of the cerebral histidine in the corresponding pair-fed group, the finding of a raised histidine level in the renal insufficient rats seems to be due to a specific uremic disorder caused by a cerebral disturbance in histidine metabolism.
    Notes: Zusammenfassung Bei chronisch niereninsuffizienten Ratten (5/6-Nephrektomie) wurden die intrazellulären Histidin-Konzentrationen verschiedener Organe (Gehirn, Skelettmuskel und Leber) bestimmt. Als Vergleichsgruppen dienten gesunde Kontroll-Ratten sowie sog. „pair-fed“ Ratten, die entsprechend den niereninsuffizienten Tieren eine verminderte Nahrungsmenge zu sich nahmen. Während sich in den untersuchten Gruppen die Plasma-Histidin-Konzentration nicht unterschied, war Histidin im Gehirn der chronisch niereninsuffizienten Tiere signifikant erhöht. Dieser Konzentrations-Anstieg dürfte als urämie-spezifisch anzusehen sein, da die entsprechend minderernährten Kontrolltiere keine Alteration zeigten. Als Ursache ist in erster Linie eine cerebrale Störung des Histidin-Metabolismus zu diskutieren.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 22 (1977), S. 77-84 
    ISSN: 1432-0827
    Keywords: Fluoride ; Blood plasma ; Enamel mineralization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract It is postulated that tissue fluid F concentrations are the primary determinants of fluoride effects on bones and developing teeth and that these concentrations are dependent on, or mirrored by, blood plasma F. It has earlier been shown that the plasma F levels are dependent on the dietary F supply as well as on skeletal F concentration. Fasting and post-ingestion or postinjection plasma F levels have been determined in rats on F doses that cause different degrees of enamel fluorosis. The results indicate that temporary peak values rather than elevated fasting values are responsible for the occurrence of enamel fluorosis and that the peak values must approach about 10 μM in order to block enamel formation by the ameloblasts. The diagnostic and prognostic importance of plasma F determinations is discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 23 (1977), S. 161-170 
    ISSN: 1432-0827
    Keywords: Bone ; Growth ; Rat ; Remodeling ; Tetracyclines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Cortical bone remodeling along the femur diaphysis was determined in normal female rats (Sprague-Dawley) with the tetracycline technique. Three segments on the cortical bone circumference (the anterolateral, the medial, and the posterior) were found to be most suitable for the study of the remodeling process. Oxytetracycline was administered at age 60 and 75 days, and groups of animals were killed at age 75, 85, 95, and 105 days. The accumulated endosteal growth during age 60 to 75 days in the anterolateral segment was found to increase uniformly in the distal direction along the femur diaphysis. A method is described where this accumulated endosteal growth is used. This method eliminates the use of calipers to determine the section level and makes it possible to study comparable sections even after varying periods of time. The proximal part of the diaphysis showed periosteal apposition in all three segments. The periosteal apposition turned into resorption in the distal part of the diaphysis in the anterolateral and medial segments, whereas the periosteal appsition increased in the posterior segment. The endosteal growth increased in the distal direction in the anterolateral and medial segments. Irregular OTC bands made measurements of endosteal remodeling in the posterior segment impossible. The cortical width decreased in the distal direction along the femoral shaft. Comparison between the different age groups is described and also the relation between the accumulated endosteal growth and the diameter of the medullary cavity.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 37 (1977), S. 319-325 
    ISSN: 1432-0738
    Keywords: Sulfhydryls ; Enzymes ; Brain ; Liver ; Testis ; Manganese ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Wirkung von Mangan auf Sulfhydrylgruppen und SH-enthaltende Enzyme in Gehirn, Leber und Hoden von Ratten wurde untersucht. Mangan verminderte den Gehalt an Nicht-Eiweiß-SH und hemmte die Glucose-6-phosphatdehydrogenase sowie die Glutathionreduktase in diesen Geweben. In Gehirn, Leber und Hoden der Mn-behandelten Tiere war der Mn-Gehalt signifikant erhöht.
    Notes: Abstract The effect of manganese on sulfhydryls and sulfhydryl-containing enzymes in brain, liver and testis of rats was investigated. Manganese produced lowering in the contents of non-protein sulfhydryl groups and inhibited the activity of glucose-6-phosphate dehydrogenase and glutathione reductase in these tissues. The contents of the metal increased significantly in brain, liver and testis of manganese administered rats. The significance of these findings is discussed.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 151 (1977), S. 53-62 
    ISSN: 1432-0568
    Keywords: Large intestine ; Intestinal absorption ; Postnatal development ; Rat ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The absorption of horseradish peroxidase in the rat large intestine during the postnatal developing period was investigated by cytochemical and ultrastructural methods. In the ceca and ascending colons from 4-, and 5-day-old rats, intraluminaly injected peroxidase became localised on microvilli, in the intracytoplasmic network of the apical tubules and small vacuoles (tubulo-vacuolar system), in the large supranuclear vacuole, in the Golgi apparatus, on the lateral and basal cell membranes of the surface principal cells, and also in the lumen of blood capillaries in the subjacent propria. On the other hand, the protein tracer was not seen in the large intestinal epithelial cells that lack tubulo-vacuolar systems and large supranuclear vacuoles within their cytoplasm. In the descending colons of rats of any postnatal age, the epithelial principal cells are devoid of these membrane systems, and exogenous peroxidase was not detected in the cytoplasm of the principal cells. It is assumed that at least the proximal portion of the large intestine in neonatal animals has the capacity to absorb macromolecular protein through those surface principal cells that have specialized intracellular membrane systems.
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  • 10
    ISSN: 1432-0568
    Keywords: Neurosecretion ; Adrenalectomy ; Diabetes insipidus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of adrenalectomy on the amount of “Gomori-positive” neurosecretory material in the outer layer of the median eminence and in the supraoptico-hypophysial system was studied in normal Long-Evans rats and in Long-Evans rats heterozygous and homozygous for hypothalamic diabetes insipidus. In all non-adrenalectomized rats very few “Gomori-positive” granules were found in the outer median eminence layer. After adrenalectomy the amount of the granules increased markedly in normal Long-Evans rats and only slightly in Long-Evans rats heterozygous for diabetes insipidus. However, no augmentation of the granules occurred in homozygous diabetes insipidus rats. The amount of “Gomori-positive” substances demonstrable in the supraoptic and paraventricular nuclei, in the inner layer of the median eminence, and in the neural lobe of the hypophysis was less in rats heterozygous for diabetes insipidus than in normal Long-Evans rats and the smallest in homozygous diabetes insipidus rats. No differences in the amounts of the substances were observed between adrenalectomized and non-adrenalectomized animals. The findings suggest that the “Gomori-positive” granules occurring in the outer layer of the median eminence of adrenalectomized rats are of similar origin as those of the supraoptico-hypophysial system and represent a vasopressin-neurophysin-complex. The results support the concept that vasopressin is involved in the regulation of ACTH release.
    Type of Medium: Electronic Resource
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 151 (1977), S. 29-34 
    ISSN: 1432-0568
    Keywords: Optic tectum ; Rat ; Cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The death of cells was studied by light microscopy in the optic tectum of normal, developing rats. Normal cell death in the tectum during development has previously been described in chickens but not in a mammal. The total period of cell death was from the 20th embryonic day through the 11th postnatal day. During this period the number of dying cells was comparatively small for the first 2 days, reached a peak at birth and then decreased over the next 11 days. In comparison to the number of surviving cells the number of dead cells in each section was small. The dead cells appeared to be randomly distributed in all layers of the optic tectum.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 151 (1977), S. 63-69 
    ISSN: 1432-0568
    Keywords: Rat ; Phrenic nerve ; Accessory phrenic nerve ; Diaphragmatic myotomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Reinnervation studies of the diaphragm led us to reinvestigate the normal anatomy of the phrenic nerve of the rat. The phrenic nerve originates from the cervical nerve roots C4 and C5. In 16 out of 19 normal rats an accessory phrenic nerve was observed receiving its segmental fibres from C6. The number of myelinated axons of the accessory phrenic nerve varied from 41 to 101 (mean: 64.3, i.e. about 15% of the average number of axons in the common phrenic nerve). The accessory phrenic nerve innervates the dorsal part of the costal and the lateral part of the crural region, whereas the remaining parts of the hemidiaphragm are supplied by the segments C4 and C5. There is no evidence for any additional contribution to the motor innervation of the diaphragm from intercostal nerves.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 151 (1977), S. 241-265 
    ISSN: 1432-0568
    Keywords: Scanning E.M. ; Third ventricle ; Neurohypophysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The surface of the recessus infundibularis of the third ventricle has been studied with the scanning and transmission technique in normal and experimental material. Surface specializations such as microvilli, craters and areas of discontinuous lining are described. Supraependymal cells and fibres have been found; some of these cells form wide-meshed networks. The supraependymal fibres may be regular or varicose; the former seem to perforate the ependyma. With the transmission electron microscope the supraependymal cells are divided into three categories: nerve cells, lymphocytes and “dense cells”. Two fibre populations are distinguished: thin profiles (nerve fibres) and thick profiles (nerve terminals). Axosomatic and axoaxonic synapses are described. Synapses between supraependymal fibres and ependyma cells have also been found.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 151 (1977), S. 335-339 
    ISSN: 1432-0568
    Keywords: Autoradiography ; Hippocampus ; Neurogenesis ; Rat ; Thyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The postnatal development of the dentate gyrus and the effect of 5 μg/day triiodothyronine treatment was examined by means of tritiated thymidine autoradiography. The polymorph layer of the dentate gyrus is a secondary germinal layer and forms cells for the granular layer. The cell formation in the dentate gyrus was found to be nearly completed on the 21st day, but development ended only in adulthood. Thyroid-hormone treatment did not affect significantly the postnatal cell formation of the dentate gyrus, but resulted in the appearance of a great number of pycnotic cells in the granular layer.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 152 (1977), S. 43-64 
    ISSN: 1432-0568
    Keywords: Habenula ; Ependyma ; Supraependymal cells ; Supraependymal axons ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The surface features of the ependymal lining of the habenular complex in rats, aged between three weeks and nine months, were studied by means of scanning and transmission electron microscopy. The ependyma of the medial habenular nucleus is heavily ciliated, the cilia obscuring underlying substructure in SEM — preparations. On the habenular commissure most cilia are arranged in tufts. Cilia are provided with segmental indentations and occasional apical thickenings. Vesicular protrusions of the ependymal cytoplasm into the ventricular lumen and the frequent occurrence of homogeneous supraependymal globules were interpreted as signs of ependymosecretory activity of nucl. hab. med. Supraependymal cells are most numerous on the anterior and superior surface of the habenular commissure. Cells presenting features identical to Kolmer (epiplexus) cells were identified on the ventricular surface of nucl. hab. med. in one specimen showing degenerative changes of undetermined aetiology in the habenular nuclei. It is therefore suggested that such cells need not necessarily be restricted to the choroid plexus. Supraependymal unmyelinated axons are particularly numerous on both nucl. hab. med. and commiss. hab. They make desmosome contacts (maculae adherentes) with the ependymal plasmalemma. Contacts presenting all features of typical synapses were not encountered. The vesicle population of the axonal profiles mainly comprises 35–50 nm translucent round vesicles besides small numbers of 60–100 nm dense-cored vesicles and large pleiomorphic vesicles. Most probably the axons belong to the well-established dense population of serotonergic axons in the dorsal part of the third ventricle.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 40 (1977), S. 253-257 
    ISSN: 1432-0533
    Keywords: Protein-calorie malnutrition ; Rat ; Spinal root ; Paranodal region ; OTAN method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the early postnatal development of spinal roots in rats paranodal regions were often found, containing OTAN-positive inclusions in the Schwann cell cytoplasm. The presence of OTAN-positive paranodal regions showed variations in time, which were synchronous for ventral and dorsal roots. Dorsal roots, however, showed a more marked presence during development than ventral roots. Spinal roots of animals submitted to a 50% food restriction, were shown to contain more OTAN-positive paranodal regions than controls. This was true for ventral as well as dorsal roots. It is suggested that crowding of internodal segments could be one factor, determining the presence of paranodal, OTAN-positive material.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 11 (1977), S. 283-286 
    ISSN: 1432-1041
    Keywords: Paracetamol ; Acetaminophen ; pharmacokinetics ; first-pass elimination ; intravenous administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352±40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63±0.02 after 500 mg, to 0.89±0.04 and 0.87±0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 11 (1977), S. 329-335 
    ISSN: 1432-1041
    Keywords: Digoxin ; pharmacokinetics ; two-compartment model ; radioimmunoassay ; neonates ; infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The distribution and elimination of intravenous digoxin were investigated in seven neonates and infants with heart failure. Serum digoxin concentrations during a 24 h period were determined by radioimmunoassay, using125I as tracer. The serum values declined biexponentially after the injection and could be fitted to a two-compartment open model by non-linear least-squares regression. The calculated mean half-lives of the distribution (alpha) phase in neonates and infants were 37 and 28 min, respectively. The mean half-life of the elimination (beta) phase in neonates was 44 h, as compared to 19 h in infants. The mean volume of the central compartment and the mean volume of distribution at steady-state were calculated to be 1.3 and 9.9 l/kg, respectively; no significant differences between neonates and infants were found. The relation between these volumes indicates that digoxin is extensively distributed in tissues. The steady-state distribution volumes of digoxin in neonates and infants exceed those reported in adults. The larger volume of distribution might explain in part why infants with cardiac insufficiency require larger doses of digoxin than adults (on a mg/kg body weight basis) to obtain the same serum concentrations. Elimination of digoxin from the body was slower in neonates than in infants.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 11 (1977), S. 351-358 
    ISSN: 1432-1041
    Keywords: Phenprocoumon ; protein binding ; pharmacokinetics ; pharmacodynamics ; drug therapy ; myocardial infarction ; chronic disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In nine patients, the synthesis rate Rsyn of the vitamin K-dependent clotting factors was calculated from changes in prothrombin-complex activity after intravenous administration of a synthesis-blocking dose of phenprocoumon (PPC). The biological half-life of PPC was between 2.70 and 7.01 days. No correlation was found between the level of the free fraction of this strongly protein-bound drug and its biological half-life. There was a positive correlation (p〈0.01) between the size of the free fraction of PPC and the apparent volume of distribution of the drug. Four of the patients had had an acute myocardial infarction and they showed increased sensitivity to PPC. In them the plasma level of PPC sufficient to reduce Rsyn to 50% of R°syn was significantly lower, and the depression of individual vitamin K-dependent coagulation factors was more pronounced and prolonged, than in five other patients with chronic disease. The degradation rate of coagulation factors was also found to be higher in the patients with acute myocardial infarction. In four patients with chronic disease, anticoagulant therapy with PPC was continued in the out-patient clinic. The calculated oral maintenance dose of PPC, assuming complete absorption, first-order elimination kinetics and a linear relationship between the pharmacological effect and the logarithm of the PPC-plasma concentration, showed good agreement with the dose actually found to produce the desired PP% level.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 11 (1977), S. 367-375 
    ISSN: 1432-1041
    Keywords: Acenocoumarol ; excretory balance man ; pharmacokinetics ; biotransformation ; plasma protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption, biotransformation and elimination of the anticoagulant acenocoumarol, 3-[α- (4′-nitrophenyl)-β-acetylethyl]-4-hydroxycoumarin, have been studied by oral administration of 12 mg of a14C-labelled preparation to two male volunteers. Absorption from the gastro-intestinal tract was rapid and the plasma concentration of unchanged drug reached a maximum of 169 and 412 ng/ml, respectively, after 3 hours. The elimination half-life in the two subjects, calculated from the decline between 6 and 24 h, was 8.7 and 8.2 hours. A constant proportion of 98.7% of the drug was bound in vitro to serum proteins over a concentration range of 0.021–8.34 µg/ml, with little interindividual variation. The major portion of the binding was to human serum albumin (97.5%) at two classes of binding sites: association constant K1=1.04×105 l/mole (n1=1) and K2=5.55×103 l/mole (n2=4). In addition to unchanged acenocoumarol, four metabolites were determined in plasma by isotope dilution techniques: the amino-, acetamido-, alcohol1- and alcohol2-metabolites. Of them, the amino-metabolite showed the highest concentration, namely 278 ng/ml, after 6 h in Subject A, and 163 ng/ml after 10 hours in Subject B. Judged from the integrated concentrations, the compounds analyzed accounted for 76 and 89%, respectively, of the total radioactivity in plasma. All the metabolites detected in plasma showed anticoagulant activity when tested in mice. The quantities of the metabolites excreted in urine from 0–120 hours were (Subject A/Subject B): acenocoumarol 0.3/0.2%, amino-metabolite 12.3/7.7%, acetamido-metabolite 19.0/11.1%, alcohol1-metabolite 4.6/9.0%, alcohol2-metabolite 1.7/4.4%, 6-hydroxy-metabolite 6.9/18.3% and 7-hydroxy-metabolite 14.0/22.2%.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 11 (1977), S. 51-56 
    ISSN: 1432-1041
    Keywords: Antidepressive agent ; protriptyline ; plasma concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of protriptyline have been determined in 30 depressed female patients undergoing antidepressant therapy. After 3 1/2 weeks treatment at dosage levels of 40 mg/day, protriptyline plasma levels ranged from 430 to 1430 nmol/l. During this period only two-thirds of the subjects had definitely achieved asymptotic concentrations. Single dose studies in 5 volunteers suggest that the volume of distribution of protriptyline shows little intersubject variation. The half life of the drug, however, may vary appreciably from subject to subject, ranging from 54 to 198 h. The effects of two sedatives on mean protriptyline plasma levels have been determined. Mean plasma levels for nitrazepam recipients are indistinguishable from those for patients receiving no night sedation. The mean plasma levels for a group of patients receiving sodium amylobarbitone were significantly reduced. The problem of choice and early adjustment of dosages in order to achieve satisfactory plasma levels is discussed. For practical purposes it is suggested that early values may be of predictive significance in allowing early dosage adjustments to be made.
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  • 22
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    European journal of clinical pharmacology 11 (1977), S. 473-477 
    ISSN: 1432-1041
    Keywords: Salicylate ; aspirin ; indomethacin ; pharmacokinetics ; coeliac disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentrations of salicylate and indomethacin were measured after a single oral dose of aspirin (600 mg) and indomethacin (50 mg) in twelve starved normal subjects and twelve adult patients with coeliac disease. The absorption of salicylate in the coeliac patients was faster than in the normal subjects. The plasma concentration/time curve of indomethacin in both groups was similar during the absorption phase, but there were significant differences between the groups in its elimination. The abnormal absorption pattern of salicylate in coeliac disease does not appear to be related to its pKa. Possible causes of the difference in salicylate absorption include changes in gastric emptying or altered small intestinal permeability.
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  • 23
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    European journal of clinical pharmacology 12 (1977), S. 297-303 
    ISSN: 1432-1041
    Keywords: Hydrochlorothiazide ; pharmacokinetics ; dose/response relationship ; natriuresis ; kaliuresis ; calciuresis ; magnesiuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Hydrochlorothiazide (hct) was administered orally in four different doses (12.5, 25, 50 and 75 mg), to eight healthy volunteers. Plasma and urine concentrations of hct were determined by GLC. Maximal plasma levels were found at 1.5–5 h, and averaged 70, 142, 260 and 376 ng × ml−1 respectively. The peak plasma levels and AUC0→9h of hct were highly correlated (p〈0.001) with the dose. The decline in the plasma curve was biphasic in those experiments in which the plasma levels of hct could be determined for at least 24 h. The half life of the slower phase lay between 5.6 and 14.8 h. The urinary recovery of hct, which represented the gastrointestinal absorption, averaged 65 to 72 per cent of the dose. The mean renal plasma clearance did not vary with the dose and averaged 319 to 345 ml × min−1. The diuresis during the 10 h after hct 12.5 mg exceeded that after placebo by a mean of 800 ml. The diureses was not increased further after higher doses of hct. The maximal natriuretic effect (+ 100 mmol), too, was found after the 12.5 mg dose. The excretion of potassium, however, rose with increasing doses; the maximal increment, after 75 mg hct, averaged 25 mmol. The excretion of calcium was significantly increased after 50 mg hct (+ 0.6 mmol). The maximal effect on magnesium excretion occurred after 25 mg hct (+ 0.5 mmol). In healthy volunteers there was no correlation between peak plasma level of hct or AUC0→9h and the renal excretion of water and electrolytes.
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  • 24
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    European journal of clinical pharmacology 12 (1977), S. 305-310 
    ISSN: 1432-1041
    Keywords: Phenobarbital ; pharmacokinetics ; neonates ; infancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 neonates 1–4 weeks old, 30 babies aged 1–12 months, and 7 infants of 1–5 years of age, the serum levels of phenobarbital were determined by a gas chromatographic micro-method after intravenous injection of phenobarbital 5–10 mg per kg body weight. It was possible to calculate the pharmacokinetic parameters using a two compartment open model. The distribution volumes within the individual age groups and the rate constants k12 and k21 showed no significant differences, but the elimination half-life was significantly longer in neonates (118.6±16.1 h) than in babies (62.9±5.2 h) or infants (68.5±3.2 h).
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  • 25
    ISSN: 1432-1041
    Keywords: Muzolimine ; pharmacodynamics ; pharmacokinetics ; furosemide ; saluresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first two hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.
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  • 26
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    European journal of clinical pharmacology 11 (1977), S. 19-25 
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; sulfonylurea ; glibenclamide ; pharmacokinetics ; repeated administration ; deep compartment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating “deep” compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.
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  • 27
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    European journal of clinical pharmacology 12 (1977), S. 117-123 
    ISSN: 1432-1041
    Keywords: Methyldopa ; radioactive label ; pharmacokinetics ; metabolism ; healthy volunteers ; intravenous and oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of 2-14C-L-α-methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined α-methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of α-methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.
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  • 28
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    European journal of clinical pharmacology 12 (1977), S. 355-357 
    ISSN: 1432-1041
    Keywords: Nitrazepam ; placental transfer ; pharmacokinetics ; plasma levels ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six women from 14 to 17 weeks pregnant, and 12 woman from 36 to 40 weeks pregnant, were given nitrazepam 5 mg orally about 12 h before legal abortion by hysterotomy in the former group and elective caesarean section in the latter group. The concentration of nitrazepam was determined by gas-liquid chromatography. Binding to plasma proteins was evaluated by separation of the protein-free fraction by ultracentrifugation. In the first group (early pregnancy) the level of nitrazepam was found to be lower in the fetal than in the maternal circulation. The concentration in amniotic fluid was still lower. In the latter group (late pregnancy) the concentration both of unbound and total nitrazepam in maternal and fetal plasma were in equilibrium, which indicated an increase in transplacental transfer in late pregnancy. The percentage of unbound nitrazepam in both cases was 12%.
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  • 29
    ISSN: 1432-1041
    Keywords: Tolmetin ; pharmacokinetics ; bioavailability ; antacid ; oral dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.
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  • 30
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    European journal of clinical pharmacology 11 (1977), S. 91-99 
    ISSN: 1432-1041
    Keywords: Disopyramide ; plasma concentration ; cardiodepressant drugs ; ventricular arrhythmia ; ventricular tachycardia ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with various heart diseases and ventricular arrhythmia received a single oral dose of disopyramide (DE) 200 mg. The ECG was recorded continuously for about 50 h from 2–4 h before drug administration. A statistically significant reduction in the number of ventricular ectopic beats (VEBs) was seen 1.0–3.5 h after drug intake; the average number of VEBs per 30 min decreased from 317 during the control period to 92 by 1.0–3.5 h after treatment and if one patient who did not respond is excluded, the corresponding figures were 272 and 14, respectively. Consecutive VEBs were seen in seven patients before DE was given and decreased significantly (p〈0.05) 1.5–5.5 h after drug administration. There was no change in the PQ interval, the QRS interval showed a slight increase, whereas the QT interval was prolonged 0.5–4 h after administration of DE. A specific gas chromatographic method was used for DE assay in plasma and urine. Absorption was rapid in all patients. Urinary excretion during the first 48 h after drug intake varied between 35 and 75%. The lowest effective antiarrhythmic concentration estimated in six patients ranged from 1.4 to 7.0 µg/ml. β-Phase half-life in five patients was between 10.3 and 22.1 h.
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  • 31
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    European journal of clinical pharmacology 11 (1977), S. 149-154 
    ISSN: 1432-1041
    Keywords: Hydroflumethiazide ; spectrofluorometry ; pharmacokinetics ; plasma half life ; renal excretion ; renal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A spectrofluorometric method for determination of hydroflumethiazide in human plasma and urine has been developed. The limit of detection was 10 ng/ml plasma and 100 ng/ml urine. The plasma concentration of hydroflumethiazide was determined for 9–11 hours and excretion in urine for 24–37 hrs after oral administration of about 1 mg/kg body weight to 7 subjects. Plasma half life in healthy subjects was 1.9–2.1 h, and 2.7–8.6 h in patients during the period 4–9 hrs after dosing. Cumulative excretion in urine was 67–79% of the dose during 31–37 hrs in 6 subjects; one patient with renal disease was found to excrete only 25.8% of dose during 24 hours. Renal clearance of hydroflumethiazide was higher in the healthy subjects (0.29–0.44 1 h−1 kg−1) than in the patients (0.040–0.15 l h−1 kg−1). Plasma half life of hydroflumethiazide was not closely correlated with renal clearance of the drug, which suggests that other factors may play a role in determining plasma half life.
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  • 32
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    European journal of clinical pharmacology 11 (1977), S. 57-64 
    ISSN: 1432-1041
    Keywords: General equation ; pharmacokinetics ; first pass effect ; extra-hepatic drug elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A general expression for the ratio of areas below the blood concentration-time curves after intravenous and oral drug administration is derived. This derivation does not require the assumption of a specific compartmental model to describe drug distribution within the body. Similarly an expression for the amount of drug metabolised in the liver is derived. The latter expression is used to estimate the extent of extra-hepatic drug elimination from the body.
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  • 33
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    European journal of clinical pharmacology 12 (1977), S. 73-76 
    ISSN: 1432-1041
    Keywords: Quinidine ; pharmacokinetics ; non-linearity ; dose-dependent pharmacokinetics ; steady state plasma level ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Quinidine was administrated orally to five healthy male volunteers. Doses of 0.2 g t. i. d., 0.3 g t. i. d. and 0.4 g t. i. d. were given for five days with at least four weeks between each test period. The plasma concentration of quinidine was measured before the morning dose on Days 2–5 of treatment, and 1, 2, 4 and 8 h after the morning dose on the 5th day. There was not a linear relationship between the increase in dose and the increase in plasma concentration of quinidine. A dose increase of 50% from 0.6 to 0.9 g quinidine sulphate per day resulted in an increase in steady state concentration of 94%. A further 33% increase in dose, from 0.9 to 1.2 g daily, resulted in a 55% increase in the steady stae concentration of quinidine. The results demonstrate dose-dependent pharmacokinetics for quinidine. Possible explanations for the nonlinear pharmacokinetics are discussed.
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  • 34
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    European journal of clinical pharmacology 12 (1977), S. 137-145 
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; pharmacokinetics ; metabolites ; oral administration ; young and elderly human subjects ; quantitative gas chromatographymass spectrometry ; whole blood distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration of chlormethiazole and two of its metabolites has been measured in three young and three aged human subjects following administration of a single oral dose of chlormethiazole. A sensitive analytical method based on gas chromatography-mass spectrometry using the selective ion monitoring mode of operation was developed to permit quantitation of the plasma levels. The time course of the plasma concentration of chlormethiazole and metabolites showed wide inter-subject variation, particularly between the young and elderly subjects. Absorption of chlormethiazole was rapid in the subjects of both groups as assessed by the time taken to reach the peak plasma concentration. The mean peak plasma level of chlormethiazole was more than five times greater in the elderly (2.90±1.56 µg/ml) than in the young (0.55±0.58 µg/ml) subjects. The plasma level of chlormethiazole was consistently higher in the aged subjects and this was reflected by the larger area under the plasma curve in aged (7.62±5.37 µg.h/ml) than in young (0.94±0.66 µg.h/ml) individuals. Decreased pre-systemic elimination by the liver has been suggested as an important factor contributing to the higher plasma level in the elderly. Estimates of absolute systemic availability, calculated by reference to previous intravenous studies, were greater for the elderly subjects. The distribution of chlormethiazole in whole blood from six young and six elderly human subjects was investigated in vitro. The unbound fraction of chlormethiazole in plasma increased significantly from 0.308±0.035 in young subjects to 0.403±0.067 in the elderly. Distribution of the drug in whole blood was different for the two age groups; the fraction of drug distributed to plasma water was significantly greater and the fraction in blood cells was significantly less in the aged.
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  • 35
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    European journal of clinical pharmacology 12 (1977), S. 171-174 
    ISSN: 1432-1041
    Keywords: Tolamolol ; hypertension ; pharmacokinetics ; mean steady-state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tolamolol was administered in a “double-blind” study to fifteen hypertensive patients by dose-titration against arterial blood pressure. Mean steady-state plasma tolamolol concentrations (Css) were determined for each patient from the area under the plasma concentration — time curve during a dosage interval whilst patients were receiving optimal tolamolol doses. No significant correlation was observed between daily tolamolol dose and Css; the relationship between fall in lying mean arterial pressure and Css also failed to reach conventional levels of statistical significance, but Css was observed to be correlated with the fall in standing pressure. The results suggest that plasma concentrations in excess of 200 ng/ml may be required to achieve an effective hypotensive response with the drug.
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  • 36
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    European journal of clinical pharmacology 12 (1977), S. 205-208 
    ISSN: 1432-1041
    Keywords: Cetiedil ; vasodilator ; anticholinergic drug ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cetiedil, a new vasodilating drug with anticholinergic properties, was shown to be metabolised very rapidly in man after intravenous and oral administration of the14C-compound. Higher concentrations of labelled compound after oral than after intravenous administration at the same sampling time, and proportional differences in urinary excretion, suggest that metabolic handling of the drug differs depending on the route of administration. Experiments in which inhibition of saliva secretion was measured indicated that (an) active metabolite(s) probably was (were) responsible for the action of the drug. As an anticholinergic drug, cetiedil is at least 400 times weaker than atropine.
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  • 37
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    European journal of clinical pharmacology 12 (1977), S. 221-227 
    ISSN: 1432-1041
    Keywords: Cefuroxime ; cephalosporin antibiotics ; intravenous injection ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cefuroxime, a new cephalosporin antibiotic which is stable to most β-lactamases produced by Gram-negative bacteria, was given by bolus intravenous injection to six volunteers in doses of 500 mg and 750 mg. The concentrations of cefuroxime in serum and urine were measured at pre-determined times after injection and the data analysed by a two-compartment open system model. A serum concentration of 8 µg/ml was exceeded for 100.3 min (±18.3) after a 500 mg dose and for 144.5 min (±19.8) after 750 mg. The ultimate serum half-life was 1.1 h. Excretion of cefuroxime in the urine was almost complete in 24 h, the clearance being 150 ml/min/1.73 m2. About 45% was excreted through the renal tubules. The injections were well tolerated and no changes in haematological or biochemical values were seen. The resulting data are compared with those published for some other cephalosporins. It is concluded that the favourable pharmacokinetics, especially the high concentrations of unbound cefuroxime in the serum, are likely to aid effective therapy of human infection caused by sensitive bacteria.
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  • 38
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    European journal of clinical pharmacology 12 (1977), S. 383-386 
    ISSN: 1432-1041
    Keywords: Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
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  • 39
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    European journal of clinical pharmacology 12 (1977), S. 125-132 
    ISSN: 1432-1041
    Keywords: Valproic acid ; pharmacokinetics ; saliva concentration ; urinary excretion ; serum protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of valproic acid (VPA) have been studied in 6 healthy subjects following a single 600 mg dose, and after multiple doses over 12 days (1200 mg daily) of enteric-coated sodium valproate. A time lag before absorption of 1 to 2 h was observed in each subject, and then absorption was rapid, peak concentrations being recorded 3 to 4 h after administration of the dose. The plasma level decline was biphasic with a terminal half-life of 15.9±2.6 h in the single dose and 17.3±3.0 h in the multiple dose experiments. There was no evidence of dose dependent kinetics or autoinduction. Total plasma clearance was 0.0064±0.0011 l/kg×h. The apparent volume of distribution was small at 0.15±0.2 l/kg. The mean steady state plasma concentration (Css) reached after 4 days was 81.3±13.0 µg/ml. Css observed was lower than Css predicted (99.2±14.7 µg/ml) from single dose kinetics (p〈0.001). The difference was probably due to a reduction in plasma protein binding at higher concentrations. VPA concentration in saliva was between 0.4 and 4.5% of the total plasma concentration and was not equal to the concentration of unbound drug in plasma (6.7±0.8% unbound). 3.2% of the dose was excreted in urine as the parent drug and 21.2% as conjugated metabolites.
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  • 40
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    European journal of clinical pharmacology 12 (1977), S. 387-392 
    ISSN: 1432-1041
    Keywords: Digoxin ; β-methyldigoxin ; prolonged administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy volunteers received digoxin 0.4 mg or β-methyldigoxin 0.4 mg i. v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and β-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54±0.31 days was significantly shorter than the half life of 2.29±0.34 days for β-methyldigoxin. The distribution volume of 807±187 liters for digoxin was not significantly larger than the 735±227 liters for β-methyldigoxin. Renal digoxin clearance of 191±25 ml/min was significantly higher than both the renal clearance of β-methyldigoxin of 111±23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of β-methyldigoxin injected once a day, which was significantly higher than the 1.8-fold accumulation of digoxin.
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  • 41
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    European journal of clinical pharmacology 12 (1977), S. 451-456 
    ISSN: 1432-1041
    Keywords: Bioavailability ; carbamazepine ; elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following values were obtained for various pharmacokinetic parameters:k abs =0.176±0.209 h−1;k=0.0203±0.0055 h−1; T1/2=37.5±13.1 h; VD=0.825±0.1041 · kg−1; Clearance=0.0163±0.0061 l · kg−1. The elimination rate constant showed a statistically significant increase with increasing drug dose. This may help explain the clinical observation that the rate of rise of steady state plasma carbamazepine concentrations tends to decrease with dose increase in patients taking carbamazepine alone.
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  • 42
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    European journal of clinical pharmacology 12 (1977), S. 367-373 
    ISSN: 1432-1041
    Keywords: Sulphamethizole ; tetracycline ; doxycycline ; rest ; exercise ; pharmacokinetics ; excretion ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The serum level and urinary excretion of sulphamethizole, tetracycline and doxycycline were studied in healthy volunteers subjected to intensive exercise and bed rest in a cross-over trial. Each group consisted of 7–8 subjects. The exercise or bed rest began 15 min before oral administration of the drug and was continued for the following 4 hours. During exercise serum drug concentration and the area under the serum concentration-time curve for each agent was significantly higher (p〈0.05) than the corresponding values at rest. Exercise greatly suppressed the renal excretion of tetracycline and doxycycline, but the decrease alone appeared insufficient to account for the pronounced increase in serum drug concentration. Total drug excretion in urine was unchanged. Thus, it seemed most unlikely that overall absorption from the gastrointestinal tract had been altered by exercise. However, the rate of absorption appeared to be more rapid in the exercise than in the rest period. Marked haemoconcentration was not produced by the exercise. In addition to changes in absorption and elimination rates, alteration in the volume of distribution might contribute to the higher serum drug concentration during exercise. Therefore, the level of physical activity should be considered in the interpretation of pharmacokinetic data both in clinical practice and in pharmacokinetic studies.
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  • 43
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    Archives of toxicology 37 (1977), S. 219-225 
    ISSN: 1432-0738
    Keywords: Inorganic mercury ; Renal enzyme excretion ; Chelating agents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Wirkung von intravenös verabreichtem HgCl2 auf die renale Ausscheidung von alkalischer Phosphatase (AP) und Leucinaminopeptidase (LAP) wurde an Ratten untersucht. Am ersten Tag nach Hg-Injektion erfolgte ein Anstieg der Enzymausscheidung, der von einem Schwellenwert von 0.44 mg Hg/kg ausgehend eine lineare Abhängigkeit von der Hg-Dosis aufwies. Am zweiten Tag wurde ein statistisch signifikanter Effekt bereits nach 0.25 mg Hg/kg beobachtet. Nach Dosen von 0.75 mg Hg/kg oder mehr fand ein Abfall der Enzymaktivität unter die Kontrollwerte statt, der mehr als 4 Tage anhielt. Behandlung mit 2,3-Dimercaptopropansulfonat (DMPS) bewirkte eine Normalisierung der AP-Ausscheidung. Eine Wirkung auf die LAP-Exkretion wurde nur bei baldiger Verabreichung von DMPS beobachtet. Das gleiche gilt für den Effekt von DMPS auf die Hg-induzierte Letalität. Die Nützlichkeit einer LAP-Bestimmung im Urin zur Abschätzung einer Hg-Inkorporation wird diskutiert.
    Notes: Abstract The effect of intravenous injections of HgCl2 on the renal excretion of alkaline phosphatase (AP) and leucine aminopeptidase (LAP) was investigated in rats. On the first day after Hg enzyme excretion showed a linear rise with the Hg dose from a threshold value of 0.44 mg Hg/kg. On the second day a statistically significant effect was seen already after 0.25 mg Hg/kg. After doses of 0.75 mg/kg or more a decrease of enzyme activity below control values occurred which persisted for more than 4 days. Treatment with 2,3-dimercaptopropansulfonate (DMPS) brought about a normalization of AP excretion. An effect on LAP excretion was observed only with early treatment. The same holds for the effect of DMPS on Hg-induced lethality. The usefulness of a measurement of LAP excretion for estimating the exposure to inorganic mercury is discussed.
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  • 44
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    Archives of toxicology 37 (1977), S. 247-263 
    ISSN: 1432-0738
    Keywords: Lead in blood ; Longterm exposure ; Learning deficit ; Overreaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zur Erfassung neuropsychologischer Störungen nach ontogenetisch früher Bleiexposition wurde bei männlichen Wistar-Ratten pränatal über deren Mütter, neonatal über die Muttermilch und postnatal über Bleiazetathaltiges Futter (745 mg Pb/kg Futter) chronisch ein erhöhter Blutbleispiegel (PbB) eingestellt. In der Trächtigkeits-und Säugezeit stieg der PbB-Spiegel der Mütter von 24.2 auf 31.2 μg-% an, während derjenige der Nachkommen im Alter von ca. 16 Tagen 26.6 μg-% und im Alter von ca. 190 Tagen 28.5 μg-% betrug. PbB altersgleicher Kontrollen war stets 〈 6 μg-%. Im Alter zwischen 100 und 200 Tagen wurden 20 Bleitiere und 20 Kontrollen blind verschiedenen Verhaltensprüfungen unterzogen, und zwar einem Open Field-Test und einer visuellen Unterscheidungs-Lernaufgabe. Zwei Lernprobleme unterschiedlicher Schwierigkeit, Richtungs- und Größenunterscheidung, wurden benutzt. Im Open Field-Test waren die Bleitiere im Vergleich mit den Kontrollen signifikant unruhiger: Lokomotorische Aktivität, Aufrichten und Putzverhalten waren gesteigert. Die schwierige Größenunterscheidung erlernten nur die Kontrollen, während das leichte Problem, nämlich die Richtungsunterscheidung, von Kontroll- und Bleitieren gleich schnell erlernt wurde. Die beobachteten Bleiwirkungen, gesteigerte motorische Unruhe und Lernleistungshemmung, lassen sich als Indikatoren einer funktionellen Hirnschädigung deuten. Sie legen den Schluß nahe, daß die „Wirkschwelle” für neuropsychologische Störungen nach ontogenetisch frühzeitiger Bleieinwirkung bei der Ratte als unterhalb 35 μg/100 ml liegend angenommen werden muß.
    Notes: Abstract In order to assess neurobehavioral deficit subsequent to early low-level lead-exposure, Wistar-rats were prenatally Pb-exposed via their mothers, neonatally via their dams' milk, and later on via their diet containing lead acetate (745 mg Pb/kg diet). Blood-lead levels (PbB) of dams increased from 24.2–31.2 μg-% during pregnancy and suckling-periods, those of offsprings were 26.6 μg-% at about 16 days of age and 28.5 μg-% at about 190 days of age. Between 100 and 200 days of age 40 male offsprings were subjected to behavioral testing, namely an open field-test and a visual discrimination-learning task. Two learning-tasks of different complexity, i.e. orientation-and size-discrimination, were used. Data of 20 lead-treated animals were compared with those of 20 age-matched controls. In the open-field test lead-fed animals were significantly more restless than controls; an increase of ambulation, rearing and grooming was observed. In the difficult learning-task, i.e. size discrimination, only the controls did learn the problem, whereas only one of the lead-group did; there was, however, no difference between lead-and control-animals for the easy task, i.e. orientation-discrimination. The observed effects, namely overreaction in the open field and a deficit of visual discrimination learning, may be interpreted in terms of lead-induced CNS-dysfunction. They clearly suggest that the “no-response level” for neurobehavioral damage in the rat, subsequent to early lead-exposure, must be assumed to be lower than 35 μg/100ml.
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  • 45
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    Archives of toxicology 37 (1977), S. 275-288 
    ISSN: 1432-0738
    Keywords: Carbromal ; Bromoethylbutyramide ; Ethylbutyrylurea ; Rat ; Pharmacokinetics ; Smooth muscle ; Carbromal ; Carbromid ; Äthylbutyrylharnstoff ; Ratte ; Pharmakokinetik ; glatter Muskel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Oral verabreichtes Carbromal und Carbromid wurden bei Ratten in Dosen unter 20 mg/kg rasch aus dem Magen-Darmtrakt aufgenommen, aus dem Dünndarm 5–8mal rascher als aus dem Magen. Die enterale Resorption von Carbromaldosen größer als 20 mg/kg verlief wesentlich langsamer. Dies ist hauptsächlich auf eine verzögerte Magenentleerung zurückzuführen. Sowohl Carbromal als auch Carbromid hemmten in vitro den Tonus und die durch Acetylcholin induzierte Kontraktion glatter Muskeln des Magenfundus. Carbromal und Carbromid fanden sich im Organismus in gleicher Konzentration in Serum, Gehirn und Skelettmuskulatur. Im Fettgewebe wurden dreimal höhere Werte gemessen. Die Konzentrationen beider Stoffe fallen in den untersuchten vier Organen mit der gleichen Geschwindigkeit wieder ab. Es lassen sich daher mit Hilfe der leicht zu messenden Serumkonzentrationen rasch die im Organismus verteilten Mengen beider Substanzen ermitteln. Intraperitoneal injizieŕtes Carbromal und Carbromid verlassen Serum und Gehirn mit einer Halbwertzeit von 3–4 h, Äthylbutyrylharnstoff mit einer Halbwertzeit von 5–7 h. Carbromal, Carbromid und Äthylbutyrylharnstoff werden von der Ratte rasch und nahezu vollständig metabolisiert. In Urin und Kot erschienen nur Spuren dieser Substanzen. Für eine Sekretion von Carbromal und seinen beiden Metaboliten in den Magen ergab sich kein Anhalt. Die Ergebnisse werden im Hinblick auf die akute Carbromalvergiftung beim Menschen diskutiert.
    Notes: Abstract Oral doses up to 20 mg/kg of carbromal and of bromoethylbutyramide were rapidly absorbed in the rat. Absorption from the stomach ligated at the pyloric end was 5–8-fold less than absorption of carbromal injected directly into the small intestine. Oral doses greater than 20 mg/kg of carbromal disappeared more slowly from the gastro-intestinal tract because gastric emptying was delayed. Both carbromal and bromoethylbutyramide were able to reduce the basal tone and the acetylcholine-induced contraction of isolated rat fundus strips. Carbromal and bromoethylbutyramide distributed evenly between serum, brain and skeletal muscle. Concentrations in adipose tissue were three times those in the other three tissues. Concentrations of both carbromal and of bromoethylbutyramide in all four tissues declined at the same rate. Thus, serum concentration of either compound may be used to estimate the total body content. Intraperitoneally injected carbromal, bromoethylbutyramide and ethylbutyrylurea disappeared from the brain and from the serum with a half-life of 3–4 h and 5–7 h, respectively. Traces only of unchanged carbromal, bromoethylbutyramide, or ethylbutyrylurea were excreted with urine or feces indicating rapid and extensive biotransformation of the three compounds in this species. No evidence was obtained of secretion of either carbromal or its two metabolites into the lumen of the stomach. The findings are discussed as to their relevance for acute carbromal poisoning in humans.
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  • 46
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    Archives of toxicology 37 (1977), S. 159-164 
    ISSN: 1432-0738
    Keywords: Nickel ; Rat ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zu verschiedenen Zeiten nach täglicher Zufuhr von Nickelsulfat an Ratten wurden Leber, Niere, Hoden und Herzmuskel auf biochemische und histologische Änderungen untersucht. Während sich in der Initialphase noch keine signifikanten Veränderungen nachweisen ließen, traten nach längerer Exposition deutliche enzymatische und histopathologische Veränderungen in allen vier untersuchten Organen auf. Das Ausmaß der Organläsionen zeigte einen direkten Zusammenhang mit der Behandlungsdauer.
    Notes: Abstract Biochemical and histological alterations in liver, kidney, testis and myocardium of albino rats were investigated at various intervals after daily administration of nickel sulphate. No significant changes were observed during the initial periods of the treatment, but longer exposures produced marked enzymatic and histopathological alterations in all the four organs examined. The severity of the histological lesions was found to be directly related to the duration of the treatment.
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  • 47
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    Acta neuropathologica 40 (1977), S. 249-252 
    ISSN: 1432-0533
    Keywords: Low-protein diet ; Rat ; Peripheral nerve ; Paranodal area ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Young rats, submitted to severe protein restriction were studied concerning the width of intermyelin gaps at the nodes of Ranvier in peripheral nerve fibres. The results gave no proof of increased paranodal myelin retraction in lumbar spinal roots or the sciatic nerves of low-protein rats. Malnourished rats as well as controls showed great interindividual differences as to the presence of nodes with wide inter-myelin gaps.
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  • 48
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    Psychopharmacology 51 (1977), S. 279-283 
    ISSN: 1432-2072
    Keywords: Morphine ; Naloxone ; Abstinence signs ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphine pellets (75 mg) were implanted subcutaneously in albino rats. Three days later, following 24 h without water, these rats (Group MSN) were given access to a saccharin solution for 30 min, then injected with naloxone hydrochloride. The classical abstinence signs, including “wet dog shakes” and weight loss, were noted in these subjects, but not in controls given placebo pellets and/or saline injections. In addition, when given an opportunity to drink either saccharine solution or water 24 h later, Group MSN rats drank significantly less saccharin than any of the control groups. Similar drinking patterns were found even when naloxone injection was delayed as long as 3 weeks after pellet implantation, when none of the classical abstinence signs were seen and serum levels of morphine and its metabolites were 100 times lower according to radioimmunoassay. This simple and objective technique is thus more sensitive as a measure of prior morphine exposure than any of the commonly used indices. The continued utility of a dependent-nondependent dichotomy is also examined in light of these and other findings.
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  • 49
    ISSN: 1432-2072
    Keywords: Rat ; Exploratory behaviour ; Stereotyped behaviour ; Hole-board ; dl-Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A technique is described for studying exploratory as well as stereotyped behaviour in rats using an automated hole-board. Both visual and automated recordings can be employed using the technique. Hole dipping is monitored automatically using an infra-red detector system. Repetitive patterns of hole-dipping are used as parameters of stereotyped behaviour while the more random patterns of hole-dipping are used as parameters of exploration. There was a high significant correlation between the records of hole-dipping behaviour as recorded visually and automatically. There was also a high significant correlation between the measures of repetitiveness/randomness of hole-dipping behaviour from automatic and visual recordings. The pattern and levels of hole-dipping conformed with expectations both as regards changes with time and with increasing doses of dl-amphetamine.
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  • 50
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    Psychopharmacology 54 (1977), S. 139-143 
    ISSN: 1432-2072
    Keywords: Atropine ; Cholinergic mechanisms ; Learning ; Ontogeny ; Passive avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The maturation of cholinergic inhibitory mechanisms that may be involved in passive-avoidance learning was studied in rats 14, 17, 21, 25, 28, and 34 days of age. Acquisition and extinction of the conditioned response were examined under saline and atropine sulfate (5 mg/kg). Learning was also tested following scopolamine hydrobromide injections (1, 4, 8 mg/kg) in rats 17 days of age and following α-methylatropine (5 mg/kg) in 17-and 34-day-old groups. In normal animals the rate of acquisition increased during ontogenesis, with a significant improvement between postnatal days 17 and 21, whereas the rate of extinction did not vary with age. Acquisition was impaired by atropine sulfate at all ages and even totally prevented in younger groups (14 and 17 days of age). It was also completely disrupted by scopolamine in 17-day-old rats. Extinction following acquisition under atropine was more rapid than after normal acquisition. Methyl-atropine was without effect. These results support the hypothesis of central cholinergic mechanisms involved in response suppression, already functioning in the rat 14 days of age and maturing mainly between the 17th and the 21st postnatal days.
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  • 51
    ISSN: 1432-2072
    Keywords: Rat ; Exploratory behaviour ; Stereotyped behaviour ; Hole-board ; dl-Amphetamine ; Haloperidol ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exploratory and stereotyped behaviour of Male Wistar rats was studied on a hole-board. The two forms of behaviour were differentiated according to the pattern of hole-dipping activity. Increasing doses of dl-amphetamine stimulated both forms of behaviour with stereotyped behaviour becoming predominant particularly at the higher dose levels. At the highest dose of amphetamine used (16 mg/kg) a gradual transition from exploratory to stereotyped behaviour was observed with time. As the drug wore off this transition was reversed. Haloperidol at a dosage of 0.1 and 0.05 mg/kg blocked the response to a high dose of amphetamine whereas a lower dose (0.02 mg/kg) blocked the stereotyped response to amphetamine while some exploratory behaviour still took place. Apomorphine inhibited hole-dipping but at lower doses another form of exploratory behaviour was induced, this behaviour becoming stereotyped as the dose was increased. It is concluded that there is a close relationship between exploratory and stereotyped behaviours. Monoamine systems appear to play a significant role in the regulation of both forms of behaviour.
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  • 52
    ISSN: 1432-2072
    Keywords: Abstinence syndrome ; Tolerance ; Physical dependence ; Rat ; THC ; Morphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ten rats were injected s.c. with THC twice daily for 5 weeks in increasing doses. In the last 3 weeks they received 40 mg/kg THC in each administration. Ten control rats received the same amount of vehicle by the same route for the same period. The comparison of rectal temperatures of the first and fifteenth days showed that a very pronounced tolerance developed to the hypothermic effect of THC. The administration of naloxone on the 22nd and 31st days precipitated an opiatelike abstinence syndrome. The termination of the drug administration on the 35th day also produced a similar withdrawal syndrome. The most common signs of abstinence syndrome in THC-treated animals were teeth chattering, defecation, urination, dyspnea, and complete palpebral closure. Although the frequency of the incidence of the following signs were not high, they have been observed only in THC-treated animals: chewing, tremors on the face, escape behavior, jumping, eating of objects, biting of fingers, and sniffing. During abstinence, an increased locomotor activity was recorded by an activity-meter. Similarly, the total amount of excreted feces and urine was higher in the THC group than in the controls. Both abstinence scores and increased motility exhibited the peak in the 48th h of withdrawal. Some similarities between the effects of THC and morphine have been reviewed.
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  • 53
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    Naunyn-Schmiedeberg's archives of pharmacology 296 (1977), S. 187-190 
    ISSN: 1432-1912
    Keywords: Cyclic nucleotide phosphodiesterase ; Gastric mucosa ; Human ; Rat ; Inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cyclic adenosine-3′,5′-monophosphate (cAMP) phosphodiesterases (PDE) were partially purified from human and rat gastric mucosa. Drugs known to affect the cyclic nucleotide system and/or gastric secretion were tested for effects on the PDE-activities from both species. In rat gastric mucosa PDE-activity can be detected in the 100 000×g sediment (K m =8.3 μM; V max=3.2 nmoles cAMP hydrolyzed/mg protein x min) and the cytoplasma (K m =5.6 μM; V max=2.6 nmoles cAMP hydrolyzed/mg protein x min). The most effective inhibitors of the particle-bound activity are papaverine (K i =4 μM, non-competitive) and 3-isobutyl-1-methylxanthine (K i=14 μM, competitive). There was only a modest competitive inhibition by theophylline (K i =495 μM). PDE-activity in the cytoplasma was inhibited competitively by these three drugs (papaverine: K i =6.5 μM; 3-isobutyl-1-methylxanthine: K i =37 μM; theophylline: K i =152 μM. In human gastric mucosa PDE-activity can be detected in the particular fraction (K m =23.9 μM; V max=1.2 nmoles cAMP hydrolyzed/mg protein x min), and the soluble fraction (K m =12.1 μM; V max=2.4 nmoles cAMP hydrolyzed/mg protein x min). PDE-activity in the 100 000×g sediment was inhibited by papaverine (K i =5.6 μM, non-competitive), 3-isobutyl-1-methylxanthine (K i =16 μM, non-competitive), theophylline (K i =165 μM, non-competitive), and N6-2′-O-dibutyryl-cAMP (K i =746 μM, competitive). Inhibition in the 100 000×g supernatant was noncompetitive with 3-isobutyl-1-methylxanthine (K i =7.1 μM and papaverine (K i =8.5 μM), but competitive with N6-2′-O-dibutyryl-cAMP (K i =170 μM), and theophylline (K i =225 μM). This study indicates that PDE-activities of the two species are qualitatively similar, but quantitative differences exist.
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  • 54
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    European archives of oto-rhino-laryngology and head & neck 215 (1977), S. 1-9 
    ISSN: 1434-4726
    Keywords: Respiratory epithelium ; Larynx ; Microridge cells ; Rat ; Scanning electron microscopy ; Respiratorisches Epithel ; Kehlkopf ; Mikroleistenzelle ; Ratte ; Rasterelektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Kehlkopfepithel ausgewachsener männlicher Albinoratten wird rasterelektronenmikroskopisch untersucht. Zusätzlich zu den zilientragenden und zu den Mikrovillizellen, zu den Bürsten- und Becherzellen, welche insgesamt für das respiratorische Epithel charakteristisch sind, werden in bestimmten Abschnitten des Larynx die Mikroleisten- oder Labyrinthzellen beschrieben. Die freie Oberfläche typischer Labyrinthzellen ist durch ein System von sich verzweigenden Mikroleisten gekennzeichnet, die miteinander durch Querbrücken verbunden sind und in der Zellperipherie eine bevorzugte Parallelausrichtung zur Zellgrenze zeigen können. Der Durchmesser der Mikroleisten beträgt ca. 0,05–0,15 μm. Die Querverbindungen zwischen den Mikroleisten haben einen Durchmesser von ca. 0,01 μm. Der Raum zwischen zwei benachbarten Querbrücken variiert. Labyrinthzellen können außer Mikroleisten auch Mikrovilli zeigen und es gibt Übergänge zwischen den Mikroridge- und den Mikrovillizellen. Die bevorzugte Lokalisation der Mikroleistenzellen im Bereich der Glottis und des Aditus laryngis wird belegt. Die mögliche Funktion dieser Zellen und ihre Bedeutung für die Diagnostik pathologischer Schleimhautveränderungen wird diskutiert.
    Notes: Summary The laryngeal epithelium of male white rats is studied by reflection scanning electron microscopy (SEM). In addition to ciliated cells, microvilli cells, brush cells and goblet cells that are characteristic for normal respiratory epithelium the microridge or labyrinth cell can be seen in particular regions of the larynx. The apical surface of a typical labyrinth cell is characterized by a system of narrow standing microridges of about 0.05–0.15 μm in diameter and interconnecting microridges with a diameter of about 0.01 μm. The microridge system of a labyrinth cell originates from the fusion of densely standing microvilli. Between microridge cells and microvilli cells all transition forms can be observed. The preferable localiziation of the microridge cell in the larynx and its possible function is discussed.
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  • 55
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    European archives of oto-rhino-laryngology and head & neck 217 (1977), S. 41-51 
    ISSN: 1434-4726
    Keywords: Respiratory epithelium ; Epiglottis ; Rat ; Scanning electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The epithelial surface of the epiglottis in adult male and female albino rats is studied by scanning electron microscopy. Prominent differences exist between the surface morphology as observed in the males and that observed in the females sacrificed in the estrus phase of the ovarial cycle. The differences are most pronounced in respect to the amount of secretory vesicles, microvilli- and microridge-cells and in respect to the observable number of desquamating cells. The existence and the importance of the microridge-cells are discussed. Special attention is also paid to the results indicating that at least some parts of the extrapulmonary airway epithelia act as possible target organs for sex hormones. Finally the importance of the observed differences is discussed for the correct interpretation of pathomorphological alterations in the extrapulmonary airway epithelia that have been observed under experimental conditions and during infections.
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  • 56
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 335-358 
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; perfusion models ; sampling ; parameter estimation ; computer program ; Org GB 94 ; mianserin ; Org GC 94
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A mathematical treatment of the influence of sampling on drug kinetics in liver perfusion is presented. Based on the derived equations, a Fortran IV computer program (PERFUS) is given, by which the time course of drug concentrations can be simulated for any sampling scheme. The simulations show that the withdrawal of large samples from the reservoir, i.e., larger than 5% of the reservoir volume, results in substantially biased parameters for drugs that are rapidly distributed and/or metabolized. For the fitting of empirical data, a Fortran IV computer program is given, based on BMDX85 nonlinear least squares by Gauss-Newton iterations. This program (PERFIT) estimates model parameters corrected as if no sampling had occurred, no matter how distorted the drug disappearance curve mày be as a result of sampling or due to degeneration of the two-compartment model into a one-compartment model. The conditions under which this degeneration occurs are discussed.
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  • 57
    ISSN: 1573-8744
    Keywords: chlordiazepoxide ; benzodiazepine ; two-compartment model, biopharmaceutics ; pharmacokinetics ; single dose ; routes of administration ; intravenous ; intramuscular ; oral
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Single 30- mg doses of chlordiazepoxide HCl were administered to six healthy human subjects by the intravenous, oral, and intramuscular routes. Plasma concentration- time curves following intravenous administration were satisfactorily described by a biexponential equation consistent with a two-compartment open model system. Mean values of half-lives for the so-called distribution and elimination phases were 0.252 and 9.39 hr, respectively. The mean values for the volume of the central compartment (V 1) and volume of distribution $$(V_{d_\beta } )$$ were 18.0 and 30.9% of body weight, respectively. Following oral administration, the drug was rapidly and completely absorbed. Absorption was first order (t1/2≈27 min), and three of the six subjects showed a discernible lag time of approximately 20 min. Drug absorption following intramuscular administration was comparatively slow. A two- compartment “muscle model” comprised of precipitated and solubilized drug in the muscle was found to satisfactorily characterize the absorption process following administration by this route.
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  • 58
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    Journal of pharmacokinetics and pharmacodynamics 5 (1977), S. 421-433 
    ISSN: 1573-8744
    Keywords: methotrexate ; pharmacokinetics ; model ; computer ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The infusion of high doses of methotrexate followed by folinic acid rescue is clinically useful against a variety of tumors. We studied the plasma pharmacokinetics of high-dose methotrexate infusions in patients with advanced cancer and devised a compartmental, kinetic model. our model is based on an earlier, mathematical model which describes the pharmacokinetics of moderate- to- high-dose methotrexate given as a single, intravenous injection. Mathematical equations for our model were solved on a UNIVAC1108 computer with the SAAM program. Seven compartments represent the distribution spaces for methotrexate and its metabolites. The transport of drug into and out of compartments is described by first-order differential equations. A nonlinear, concentration-dependent function is used for renal excretion with saturation of secretory and reabsorption mechanisms by methotrexate. Our model accurately depicts the pharmacokinetics of nine courses of therapy in five patients. The model can also be used to simulate the kinetics of methotrexate for patients with impaired renal function.
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  • 59
    ISSN: 1432-1106
    Keywords: Spinal cord ; Dorsal horn interneurones ; Pain mechanisms ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological properties of neurones in the spinal cord dorsal horn were studied in decerebrated, immobilized spinal rats. Extracellular recordings were performed at the thoraco-lumbar junction level. Each track was systematically located by extracellular injection of pontamine sky blue. According to their responses to mechanical peripheral stimuli, cells were classified in four classes: Class 1 cells: Cells activated only by nonnoxious stimuli. They were divided into — 1A: hair movement and/or touch and 1B: hair movement and/or touch and pressure or pressure only. Class 2 cells: Cells driven by both nonnoxious and noxious stimuli, divided into — 2A: hair movement and/or touch, pressure, pinch and/or pin-prick, and 2B: pressure, pinch and/or pin-prick. Class 3 cells: Cells only activated by noxious stimuli (pinch and/or pin-prick). Class 4 cells: Cells responding to joint movement or pressure on deep tissues. Peripheral transcutaneous or sural nerve stimulation clearly showed that class 1 cells were activated only by A fiber input while 68% of classes 2 and 3 cells received A and C input. Histological examination indicated that cells driven only by noxious input were located either in the deepest part or in the marginal zone (lamina I) of the dorsal horn. Nevertheless, some lamina I cells were also driven by both nonnoxious and noxious stimuli. In addition, there is a great deal of overlap between class 1 and class 2 cells. This fact was confirmed by considering the wide distribution in the dorsal horn of cells receiving A and C input. However, spinal organization of the different classes of cells consists of a preferential distribution rather than a strict lamination. This study indicates that properties of dorsal horn interneurones in the rat have a high degree of similarity with those previously described in other species (cat and monkey).
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  • 60
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    Experimental brain research 29 (1977), S. 249-263 
    ISSN: 1432-1106
    Keywords: Preoptic area ; Basal septum ; Amygdala ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular microelectrode recordings were made from single neurones in the medial preoptic area and basal septum of normal female rats anaesthetised with urethane and the effects of stimulation of the ipsilateral amygdala (AMY) was tested. 1. Quiescent cells were excited with latencies between 4 and 〉 40 msec with the majority being between 10 and 27 msec. Variable latency, changing latency and recruitment were observed and suggest that many pathways are oligo- or polysynaptic. 2. A minority of spontaneously active units (20.6%) were excited with latencies between 5 and 36 msec. The predominant initial response was inhibition (67.1%). The remaining 12.3% of neurones did not respond. 3. A predominantly positive complex field potential was associated with excitation, particularly of quiescent neurones. 4. Inhibitory responses were classified according to duration (short: 20–60 msec; long: 100–400 msec). All responses contained an inhibitory component. Responses were further described on the basis of presence and rhythmicity of post-inhibitory excitation. 5. The majority of action potentials evoked from quiescent neurones were of small amplitude (80–150 μV) and occurred in small groups. These characteristics and their occurrence at the onset of inhibition are consistent with the view that all or a proportion of them may be generated by inhibitory interneurones. 6. Only minor differences were observed between response characteristics evoked by stimulation of the corticomedial or basolateral AMY indicating that differential effects of these regions on adenohypophysial hormone secretion are determined at the septopreoptic level.
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    Experimental brain research 30 (1977), S. 149-154 
    ISSN: 1432-1106
    Keywords: Dentate and interpositus nuclei ; Pontine gray ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following removal of a significant part of the dentate nucleus and most of the interpositus nucleus in the rat cerebellum degenerated cerebellopontine fibres are shown to end in three fairly restricted regions in the contralateral pontine gray: in the paramedian position, in the middle and in the lateral third. The three regions are arranged in rostro-caudal longitudinal columns in the caudal three-quarters of the pons and these columns are continuous with one another by regions of scattered degeneration. The fibres appear to end in relation to distal dendrites of the pontine cells.
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    Experimental brain research 30 (1977), S. 313-321 
    ISSN: 1432-1106
    Keywords: Rat ; Hypoglossal nucleus ; Botulinum toxin ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural effects of local injection of botulinum toxin into the left half of the tongue of the rat, were studied quantitatively 35 days postoperatively in the left hypoglossal nucleus. The results showed (1) a decrease in somatic and neuropil bouton numbers because of loss of boutons with symmetrical synapses and clear spherical synaptic vesicles, (2) a decrease in the numbers of dendrite profiles in the neuropil, (3) an increase in the proportion of dendrites and boutons with unusual inclusions, suggestive of profile retraction, (4) an increase in the proportion of profiles which were unusually electron-dense, (5) an increase in the amount of astrocyte, and a growth of astrocyte sheaths around bouton-free neurone surfaces, (6) the presence of occasional microglia, and (7) subastrocytic subsurface cisterns. Control rats injected with boiled toxin had no responses except (3) and (4) above, and then only to a modest extent, possibly due to mechanical damage of a few axons or terminals at the time of injection, or to insufficient inactivation of the toxin by boiling. The results were compared with those at 35 days after axotomy, and it was concluded that botulinum toxin, which interrupts neuromuscular transmission, elicits the same responses in the hypoglossal neurones, as does transection of the hypoglossal nerve, even though earlier studies had discovered no glial replication after botulinum toxin, in contrast to axotomy.
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    Experimental brain research 27 (1977), S. 211-219 
    ISSN: 1432-1106
    Keywords: Visual system ; Degeneration ; AChE ; Choline acetyltransferase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of unilateral enucleation, ablation of the visual cortex or coagulation of the lateral geniculate nucleus (LGN) upon the activity of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) in different structures of the visual system of albino rats was studied. The localization and extent of the degeneration pattern were followed up by histological silver degeneration methods. Afferents from the retina project mainly contralaterally to the dorsal and ventral LGN, the pretectal region and the superior colliculus. Afferent fibres from the dorsal LGN enter the visual cortex in area 17 only. Neurons of this area project back ipsilaterally to the LGN and the superior colliculus (SC). No significant decrease in the activity of the cholinergic marker enzyme choline acetyltransferase could be observed under any of the experimental conditions; there was rather a tendency to increased activity in the subcortical centres. AChE as a less specific marker also exhibited no gross changes in activity in the lesioned animals. The results add more direct proof to pharmacological and physiological evidence that ACh is not involved in the synaptic transmission of the direct optic projections in rats, either at the subcortical or at the cortical level.
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    Experimental brain research 29 (1977), S. 219-231 
    ISSN: 1432-1106
    Keywords: Rat ; Hypoglossal nucleus ; Delayed regeneration ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron micrographs of the left hypoglossal nucleus of adult male albino rats were quantitatively analyzed from 9–70 days after allowing the transected left hypoglossal nerve to regenerate after an 84 day delay. Delay was achieved by implanting the proximal stump into already innervated sternomastoid muscle, where no regeneration occurred. Regeneration was then allowed by denervating the sternomastoid. During the regenerative period the initially high number of abnormally electron dense perikarya and dendrites decreased to almost normal values, but no cell removal was seen. This suggested that the degenerate appearance of many profiles after prolonged prevention of regeneration, was reversible. The neuropil bouton and dendrite counts, and the numbers of synapsing boutons per dendrite, increased steadily to normal values from the low values of suppressed regeneration. Somatic bouton frequencies, even though already low, decreased further at 32 days, and later increased but not to normal values. The decrease at 32 days coincided with the loss of many subsurface cisterns, and dispersion of Nissl substance, all suggestive of chromatolysis. Later the subsurface cisterns and Nissl substance returned. It was suggested that the delay of complete recovery of somatic bouton frequencies might be because of lack of sensory information from the denervated muscle into which the hypoglossal nerve was regenerating, or because of abnormally low starting values for the recovery phase. Astrocyte (or, occasionally microglial) sheaths persisted along boutonfree perikaryal surfaces.
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    Experimental brain research 28 (1977), S. 335-344 
    ISSN: 1432-1106
    Keywords: Hippocampus ; Rat ; Lamellae
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A series of experiments was conducted in the urethane anaesthetised rat to determine the organisation of some hippocampal pathways in this species, using stimulating and recording microelectrodes to elicit and record population spikes. It was found that the mossy fibres, alvear fibres and perforant path were clearly arranged in a lamellar fashion. Lamellar organisation could not be demonstrated for the afferents in the stratum radiatum which include the Schaffer collaterals. It was concluded that hippocampal organisation in this species essentially resembles that in the rabbit and cat.
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    Langenbeck's archives of surgery 344 (1977), S. 71-82 
    ISSN: 1435-2451
    Keywords: Cancer risk ; Resected stomach ; Rat ; Duodenogastric reflux ; N-methyl-N′-nitro-N-nitrosoguanidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurde die Frage geprüft, ob obligater duodenogastrischer Reflux unter Langzeitbedingungen das Wachstum von Carcinomen oder Sarkomen im resezierten Magen beeinflußt. 72 männliche Wistarratten wurden einer Magenresektion unterworfen. Die erforderliche Gastroenteroanastomose wurde bei 39 Tieren als short loop GE (Billroth II) mit obligatem Reflux von Galle und Duodenalsekret in den Restmagen angelegt. Die restlichen 33 Tiere erhielten eine Y-förmige GE (nach Roux) mit seitlicher Einmündung des Duodenum in den Dünndarm; Reflux von Galle in den resezierten Magen war dadurch unmöglich. Die Carcinominduktion erfolgte durch kontinuierliche Gabe von N-Methyl-N'-Nitro-N-Nitrosoguanidin im Trinkwasser. Bei der Sektion der Tiere mit Reflux 33 Wochen nach Carcinogengabe fand sich die Mehrzahl der malignen Tumore von Magenstumpf, Anastomose (GE) und angrenzendem Dünndarm in der Tiergruppe mit obligatem Reflux (13 von 22). Die Tiergruppe ohne Reflux (Y-Roux GE) wies demgegenüber signifikant weniger Carcinome auf (7 von 21); die Tumorincidenz dieser Gruppe entsprach derjenigen eines nicht operierten Kontrollkollektives (5 von 22). - Die Ergebnisse unserer Untersuchungen zeigen, daß die in der Technik des short loop durchgeführte Gastroenteroanastomose des Billroth 11-Magens das Krebswachstum im Anastomosengebiet in besonders ausgeprägtem Maße fördert. Ausschlaggebend für die gesteigerte Carcinominduktion ist der chronische Reflux von Galle und Duodenalsekret, der bei der short loop-GE obligat über den Magnrest fließt.
    Notes: Summary The purpose of this study was to find whether the reflux of bile and pancreatic juices following stomach resection (duodenogastric reflux) enhances the incidence of carcinomas near the gastroenteric anastomosis. 72 male Wistar rats were subjected to stomach resection. The gastroenteric anastomosis (GE) was performed either as short loop anastomosis (Billroth II;n = 39), thus providing a continuous duodenogastric reflux, or as Y-shaped GE (according to Roux;n = 33). By the latter technique, bile and pancreatic juices are derived quantitatively into the jejunum without coming into contact with the remaining part of the stomach. During a period of 33 weeks, operated rats as well as intact animals were given the carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (NG; 120 mg/1) in the drinking water. At autopsy, 33 to 36 weeks after daily oral administration of NG, most of the tumours were found in operated rats undergoing continuous ref lux (Billroth II group). In contrast to these findings, the incidence of carcinomas was significantly lower in animals without reflux (Roux group or intact control rats).-The results of our experiments demonstrate that, in rats, the duodenogastric reflux contributes substantially to the development of carcinomas of the resected stomach.
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    Langenbeck's archives of surgery 344 (1977), S. 109-114 
    ISSN: 1435-2451
    Keywords: Gastric carcinoma ; Gastroenterostomy ; Bacterial flora ; Nitrit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Anlage einer Gastroenterostomie ohne Enteroanastomose führt zu einer Veränderung der bakteriellen Magenbesiedlung, wobei besonders der Anteil nitritspaltender Bakterien erhöht ist. Dies hat ein Ansteigen der Nitrit-Konzentration im Magensaft zur Folge. Die hierdurch mögliche vermehrte Bildung carcinogener Nitrosamine wird im Hinblick auf das Entstehen eines Carcinoms im operierten Magen diskutiert. Da die beschriebenen Veränderungen durch eine Gastroenterostomie nach Roux weitgehend verhindert werden, soll dies bei der Passagewiederherstellung nach Operation am Magen berücksichtigt werden.
    Notes: Summary A gastroenterostomy without enteroanastomosis leads to a change in the bacterial flora of the stomach, where-by in particular the proportion of nitrite-decomposing bacteria, is enhanced. This results in an increase of nitrite concentration in the gastric fluid, which may possibly be accompanied by an augmented production of carcinogenic nitrosoamine. This latter aspect is considered with respect to the origin of carcinoma in the operated stomach. Since the reported changes will be largely prevented by a Roux-Y-gastroenterostomy, this should be taken into consideration for reconstruction of the alimentary tract after gastric surgery.
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    Langenbeck's archives of surgery 344 (1977), S. 207-217 
    ISSN: 1435-2451
    Keywords: Gastroenterostomy ; Duodenal reflux ; Epithelial lesions ; Nitrosoguanidine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Einfluß des chronischen duodenogastrischen Refluxes auf die Magenschleimhaut des nicht resezierten Magens wurde im Hinblick auf die Disposition der gastroenteralen Anastomose für die Krebsentstehung tierexperimentell an männlichen Wistarratten untersucht. Hierzu wurden Tiere mit einer Gastroenterostomie ohne Enteroanastomose und Tiere, bei denen ein Reflux durch eine Y-Gastroenterostomie nach Roux ausgeschlossen war, mit einer zeitlich unterschwelligen Cancerogendosis (Nitrosoguanidin) exponiert. Es wird gezeigt, daß auch unabhängig von der Cancerogenexposition ein chronischer duodenogastrischer Reflux zu adenomartigen Drüsenproliferationen mit z. T. atypischen Epithelregeneraten an der Anastomose führt, die durch eine Gastroenterostomie nach Roux verhindert werden können. Anastomosencarcinome, wie in früheren Untersuchungen am resezierten Magen bei sonst gleichen Versuchsbedingungen beschrieben, konnten nicht induziert werden. Somit spielen für die Krebsentstehung an der gastroenteralen Anastomose neben dem Reflux auch die durch die Magenresektion selbst hervorgerufenen Veränderungen eine nicht unwesentlilche Rolle.
    Notes: Summary The cancerogenic effect of continous duodenal reflux on the gastric mucosa has been investigated in male Wistar-rats after gastrointestinal anastomosis. Groups of animals with gastroenterostomy without enteroenteral anastomosis and with Roux-en-y-anastomosis preventing duodenal reflux were treated with lower dosages of the cancerogenic Nitrosoguanidine. Proliferative mucosal alterations near the gastroenteral anastomosis were observed. In addition the gastric mucosa was characterized by adenomatous lesions caused by duodenal reflux. The changes detected were not influenced by Nitrosoguanidine and did not appear in cases of Roux-en-y-anastomosis.
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    Langenbeck's archives of surgery 343 (1977), S. 133-151 
    ISSN: 1435-2451
    Keywords: Peptic ulcer ; Anastomosis ; Duodenogastric reflux ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die vorliegende Studie gilt dem Anastomosengeschwür am operierten Magen. Diese schwerwiegende Komplikation entsteht nahezu ausschließlich nach Resektionsverfahren mit duodenaler Exklusion (Billroth II; Verlegung des Duodenum in den Nebenschluß). - An 54 männlichen Wistarratten wurden verschiedene Formen der duodenalen Exklusion mit und ohne duodenogastrischen Reflux durchgeführt. Die Ergebnisse unserer Untersuchungen zeigen, daß nach duodenaler Exklusionmit Reflux gesetzmäßig peptische Anastomosengeschwüre entstehen. Der kontinuierliche Reflux von Galle und Pankreassekret ist der ausschlaggebende ätiologische Faktor für die Ulcusentstehung im Grenzgebiet der Anastomose von Magen und Dünndarm. Stase im ausgeschalteten Zwölffingerdarm (Syndrom der zuführenden Schlinge) fördert die lcerogene Refluxwirkung. Fehlt der Pylorus, so potenzieren sich Reflux und Stase zur größten Ulcusfrequenz (〉 90%). Bei erhaltenem Pylorus ist die Geschwürsincidenz wesentlich geringer. Der duodenogastrische Reflux hemmt die meßbare Salzsäuresekretion signifikant (P 〈 0,01); Salzsäure spielt demnach für die Entstehung des experimentellen Anastomosengeschwürs der Ratte keine wesentliche Rolle. - Im Hinblick auf die Prophylaxe des Anastomosengeschwürs führen diese Erkenntnisse zu der Forderung, auf Operationsverfahren mit duodenaler Exklusion und Reflux (Billroth II) zu verzichten und das Operationsziel bei der Magenresektion auf die Wiederherstellung der orthograden MagenDarm-Passage zu richten.
    Notes: Summary Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of ref lux and stasis potentiate, resulting in a high frequency of ulcer (〉 90 %). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (P 〈 0.01); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. - In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis.
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    Cell & tissue research 176 (1977), S. 431-443 
    ISSN: 1432-0878
    Keywords: Cornea ; Rat ; NaK-ATPase ; K-NPPase ; Histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The sodium-potassium activated adenosine triphosphatase (NaKATPase) activity of the rat cornea was investigated histochemically using a Pb2+-precipitation technique in which adenosine triphosphate (ATP) is used as substrate and two methods for potassium-dependent para-nitrophenyl-phosphatase (K-NPPase) activity. With all the three techniques used it was demonstrated that the sodium-potassium-activated adenosine triphosphatase (NaK-ATPase) activity is localized in the cell membranes of the endothelium whereas a much weaker activity was observed in the epithelium. When the Pb2+-technique was used, the epithelial cell membranes showed a weaker reaction in the presence of ouabain. This activity was only Mg2+-dependent and was presumably due to an Mg2+-dependent ATPase. The validity of the histochemical techniques for NaK-ATPase activity is discussed. The results emphasize the importance of the endothelium as the main site of Na+ transport in the cornea. Small amounts of the enzyme are also present in the epithelium, which seems to be rich in Mg2+-ATPase. Provided that careful controls are performed, all the methods give consistent results in the cornea.
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    Cell & tissue research 181 (1977), S. 423-426 
    ISSN: 1432-0878
    Keywords: Heart muscle cells ; Rat ; Anabolic steroid hormone ; Lesion ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Early changes in the composition of heart muscle cells of the rat caused by an anabolic hormone were investigated by electron microscopy. Mitochondria and myofibrils showed changes similar to those observed in early heart failure: The mitochondria were swollen and elongated. Their matrix was sparse and the cristae were few in number. The myofibrils showed either disintegration and widened and twisted Z-bands or a complete dissolution of the sarcomeric units.
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    Cell & tissue research 184 (1977), S. 133-137 
    ISSN: 1432-0878
    Keywords: Pineal ; Rat ; Unusual organelle ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An electron microscopic survey of pinealocytes from normal rats revealed a highly organized arrangement of cytoplasmic tubules. Such tubules had been previously observed in normal rats (Lin, 1967) and in rats after melatonin administration or two weeks exposure to darkness (Freire and Cardinali, 1975). In a later publication the presence of the tubules was attributed to experimental manipulation resulting in infertility (Gusek, 1976). The present study resolves the discrepancy in the literature by establishing that the tubular organelle does indeed occur in untreated male rats, but rather rarely.
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 6-16 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Investigations on Long Term Behaviour of Lead and Lead-AlloysIn a team work of several laboratories on long term behaviour of non-iron metals sponsored by the Dechema Specialist Committee “Materials and design in chemical engineering”, lead and some lead alloys have been tested to obtain creep values for 50 000 hrs. Results are given in creep diagrams and in tables for 1% and 5% creep limit and for creep strength as well, showing their dependence on temperature (between 20 and 140 °C) at 1000 hrs., 10 000 hrs. and 50 000 hrs.
    Notes: In einem Gemeinschaftsprogramm über das Zeitstandverhalten von Nichteisen-Metallen, das im Dechema-Fachausschuß „Werkstoffe und Konstruktion im Chemie-Apparatebau“ bearbeitet wird, wurden auch 22 Bleiwerkstoffe untersucht, um Zeitstandwerte über 50000 h für den Temperaturbereich zwischen 20 und 140 °C zu ermitteln. Die hier vorgelegten Ergebnisse zeigen den Verlauf der Zeitstandfestigkeit und der 1%-Zeitdehngrenze und geben für die konstruktive Anwendung Zahlenwerte für die 1%- und 5%-Zeitdehngrenze und die Zeitstandfestigkeit bei 1000 h, 10 000 h und 50 000 h Belastungsdauer. Sie ermöglichen einen Vergleich der untersuchten Werkstoffe und können damit eine Einschränkung der Legierungspalette anregen.
    Additional Material: 20 Ill.
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 36-36 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. A18 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 76
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Precipitation and embrittlement behaviour of nickel containing SuperferritesDuring the last years high chromium ferritic stainless steels socalled Superferrites have become of general interest since the mean disadvantages of these steel grades, namely cold brittleness and susceptibility to intergranular corrosion, can be avoided by means of new melting techniques. This group of steels show remarkable strength properties and excellent corrosion behaviour especially in chloride containing solutions. Because of the high content of alloying elements the ferritic solid solution is supersaturated, so that precipitation and embrittlement can occur. From 950° to 550 °C the brittle Chi- and/or Sigmaphase can be precipitated, at temperatures below 550 °C the material can fail by the socalled 475°-embrittlement. Additions of nickel and stabilising by titanium enhance the precipitation process well as the 475°-embrittlement, while a columbium stabilisation of the present carbon and nitrogen contents up to 150 ppm shows no influence. Within the investigated alloying range with 20 to 28% Cr, up to 5% Mo and up to 4% Ni the columbium stabilised steel with 28% Cr, 2% Mo and 4% Ni results as the optimal combination referring to its technological properties as well as to its precipitation and embrittlement behaviour.
    Notes: Die hochchromhaltigen, ferritischen nichtrostenden Stähle, sog. Superferrite, sind in letzter Zeit stark in den Vordergrund getreten, nachdem die Kardinalfehler dieser Werkstoffgruppe, nämlich die Kaltsprödigkeit und Anfälligkeit gegen interkristalline Korrosion mit Hilfe neuer Schmelztechnologien vermieden werden können. Diese Stähle zeichnen sich durch hohe Festigkeit und hervorragende Korrosionseigenschaften besonders in chloridhaltigen Medien aus. Der hohe Legierungsanteil dieser Stähle führt jedoch zu einer Übersättigung des ferritischen Mischkristalls, die nach einem Wärmeeinbringen Ausscheidungs- und Vesprödungserscheinungen verursachen kann. Zwischen 950 ° und 550 °C können dabei die spröde Chiund/oder Sigmaphase auftreten, unterhalb 550 °C setzt die sog. 475°-Versprödung ein. Nickelzusätze sowie eine Stabilisierung mit Titan beschleunigen sowohl die Ausscheidung der intermetallischen Phasen als auch die 475°-Versprödung, während eine Niobstabilisierung bei Gehalten an Kohlenstoff und Stickstoff bis 150 ppm keinen Einfluß ausübt. Im untersuchten Legierungsbereich von 20 bis 28% Cr, bis zu 5% Mo und bis zu 4% Ni ergibt sich der niobstabilisierte Stahl mit 28% Cr, 2% Mo und 4% Ni sowohl hinsichtlich seiner technologischen Eigenschaften als auch seines Ausscheidungs- und Versprödungsverhaltens als optimale Kombination.
    Additional Material: 12 Ill.
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Fundamental aspects of the fatigue processes in metallic materialsThe present situation in fatigue research is characterized by a great number of scientific as well as of applied work. However, despite of extensive activities no unified theoretical approach of fatigue is to be seen. This paper gives a survey of the well-established fundamentals of fatigue of metallic materials. The research work of the last two decades led to the development of criteria to classify the multi-layered experiences and the detailed assessments of many facts in this field. Considering the fatigue stages, initial-deformation, crack-initiation, crack-propagation and fracture some characteristic experimental and theoretical results are presented and discussed. Cyclic plastic deformation is a prerequisit for fatigue of metals. It changes the mechanical behavior of the whole samples in the crack-free fatigue stage. It also develops surface structures, which act as sites of micro cracks. Crack growth also is a consequence of plastic deformation and needs a tensile component of the applied stress system. Structure-sensitive factors influence the fatigue behavior of metals mainly in the initial stage of fatigue.
    Notes: Der gegenwärtige Stand der Ermüdungsforschung ist durch eine Fülle sowohl grundlagen- als auch anwendungsorientierter Einzelarbeiten gekennzeichnet. Trotzdem erscheint es zur Zeit nicht möglich, eine geschlossene Theorie des Ermüdungsverhaltens metallischer Werkstoffe in nächster Zukunft zu entwickeln. Die vorliegende Arbeit soll einen Überblick geben über die hinreichend gesicherten Erkenntnisse auf dem Gebiet der Metallermüdung. Die Forschungstätigkeit der letzten zwei Jahrzehnte führte zur Entwicklung einiger Ordnungskriterien für die vielfältigen experimentellen Ergebnisse sowie zu einigen quantitativen Abschätzungsverfahren. Für die einzelnen Ermüdungsstadien, den Anfangsbereich, den Rißbildungsbereich, die Rißausbreitung und den Restbruch werden einige wichtige Ergebnisse vorgestellt und diskutiert. Plastische Verformung ist die Voraussetzung für das Auftreten eines Ermüdungsbruchs bei metallischen Werkstoffen. Sie führt in der anrißfreien Phase der Ermüdung zu einer Veränderung der mechanischen Eigenschaften des Werkstoffs sowie zur Bildung besonderer Oberflächenverformungsstrukturen, die bevorzugt Ausgangspunkte für Ermüdungsrisse sind. Auch die Rißausbreitungsphase ist durch das Auftreten von plastischen Deformationen charakterisiert und erfordert eine hinreichend große Zugspannungskomponente. Strukturabhängige Werkstoffkenngrößen wirken sich insbesondere in der anrißfreien Phase des Ermüdungsvorgangs aus.
    Additional Material: 28 Ill.
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  • 78
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    Materialwissenschaft und Werkstofftechnik 8 (1977) 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 79
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 2-5 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: The creep properties of hard leadThe exact dimensioning of structural elements which are susceptible to creep deformation is acquiring increasing technical importance. A search through the literature (1, 2, 3, 4) for the mechanical properties of hard lead alloys reveals hardly any data on the creep behaviour of these materials. Genuine creep tests extending over prolonged periods are required in order to obtain definitive data on the strength properties of lead and its common engineering alloys. The following discussion reports on the results of creep tests lasting up to 80 000 hours on five types of hard lead.
    Notes: Die genaue Dimensionierung von Bauteilen, die einer Verformung durch Kriechen unterliegen, gewinnt in der Technik immer größere Bedeutung. Bei der Durchsicht des Schrifttums (1, 2, 3, 4) nach den mechanischen Eigenschaften von Hartbleilegierungen findet man kaum Angaben über das Zeitstandverhalten dieser Werkstoffe. Um eindeutige Aussagen über das Festigkeitsverfahren von Blei und seinen technisch gebräuchlichen Legierungen machen zu können, sind echte Zeitstandversuche über lange Zeiträume notwendig. Im folgenden wird über Ergebnisse aus Zeitstandversuchen bis zu 80 000 h an fünf Hartbleisorten berichtet.
    Additional Material: 4 Ill.
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  • 80
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 16-21 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Investigations on the Strength of Galvanic DepositsPure nickel, nickel alloys, austenitic steel, copper and aluminium alloys were coated with adhesive and heat resisting layers of nickel or copper by electroplating. Production and examination of these metal connections was performed by specially developed methods. The investigations demonstrated, that high quality metal connections can be produced by electroplating. These connections will be of great interest for construction and fabrication.
    Notes: Reinnickel, Nickellegierungen, austenitischer Stahl sowie Kupfer- und Aluminiumlegierungen wurden auf galvanischem Wege mit haftfesten und temperaturbeständigen Nickel- bzw. Kupferüberzügen beschichtet. Zur Herstellung und Untersuchung dieser Metallverbindungen wurden geeignete Verfahren und Prüfmethoden ausgearbeitet. Die Arbeiten konnten zeigen, daß auf galvanischem Wege hochwertige Metallverbindungen hergestellt werden können, die zum Einsatz in Konstruktion und Fertigung geeignet sind.
    Additional Material: 10 Ill.
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  • 81
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    Materialwissenschaft und Werkstofftechnik 8 (1977) 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 82
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 83
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 37-55 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Pitting corrosion on alloy systems of the elements iron, chromium and nickelPitting corrosion on stainless steels and nickel alloys is a serious problem in commercial operation, especially in the chemical industry, because its widespread occurrence and the usually fast rate of growth of such pits may substantially restrict the life of components and production facilities and possibly also give rise to environmental hazards. In this respect the nearly unlimited occurrence of chlorides which cause pitting, often even in very low concentrations, is a special disadvantage. As a result of this there have been many studies to determine the mechanisms, time regularities and parameters of pitting and to utilize them in commercial practice, i.e. to derive from them efficient protection against pitting. Since the research and study results described in literature do not give a uniform illustration of pitting and hardly permit a useful survey of the effect of the various parameters the series of publications starting with this contribution attempts to give a clear synopsis of the state of knowledge on pitting, to describe the customary test methods for determining potential pitting and to discuss their significance, and finally from our own extensive studies to show the regularities of pitting and to quantify as far as possible the parameters.Accordingly the subject has been divided into three main parts:Part 1. Pitting parameters - an analysis of literature. Fundamentals - attacking reagents - material influences.Part 2. Test methods to determine resistance to pitting - chemical tests - electrochemical investigations.Part 3. Electrochemical measurements to determine the parameters of pitting on homogenized materials. Based on the results of studies this part deals with systematic dependences of pitting on the nature of the attacking reagent (chloride concentration, hydrogen ion concentration, temperature) and the composition of the materials under study (effect of alloy components).
    Notes: Die Lochkorrosion an nichtrostenden Stählen und Nickellegierungen stellt ein ernsthaftes Problem für die Praxis dar, insbesondere für die chemische Industrie, weil durch die Häufigkeit des Auftretens und die meist hohe Wachstumsgeschwindigkeit der entstehenden Löcher eine erhebliche Beschränkung der Lebensdauer von Bauteilen und Produktionsanlagen und u. U. auch eine Gefährdung der Umwelt eintreten kann. Von besonderem Nachteil ist hierbei die beinahe uneingeschränkte Verbreitung der lochfraßauslösenden Chloride, die oft schon bei Vorliegen nur sehr geringer Konzentrationen wirksam werden. Es hat daher nicht an Untersuchungen gefehlt. Mechanismen, Zeitgesetze und Einflußgrößen der Lochkorrosion zu ermitteln und sie für die Praxis auszuwerten, d. h. einen gezielten Schutz vor Lochkorrosion nutzbar zu machen. Da die in der Literatur beschriebenen Forschungs- und Untersuchungsergebnisse kein einheitliches Bild der Lochkorrosion ergeben und kaum einen brauchbaren Überblick über die Abhängigkeit von den verschiedenen Einflußgrößen gestatten, wird mit dieser hir beginnenden Veröffentlichungsreihe der Versuch unternommen, den Stand des Wissens über die Lochkorrosion übersichtlich darzustellen, die gebräuchlichen Prüfverfahren zur Ermittlung der Lochfraßanfälligkeit zu beschreiben und ihre Aussagefähigkeit zu diskutieren sowie anhand eigener umfangreicher Untersuchungen die Gesetzmäßigkeiten der Lochkorrosion aufzuzeigen und die Einflußgrößen so weit wie möglich zu quantifizieren. Der Stoff ist aus diesem Grunde in drei Hauptteile gegliedert worden:Teil 1. Einflußgrößen der Lochkorrosion - eine Literaturauswertung. Grundlagen - Angriffsmittel - Werkstoffeinflüsse.Teil 2. Prüfverfahren zur Ermittlung der Lochkorrosionsbeständigkeit Chemische Prüfungen - Elektrochemische Untersuchungen.Teil 3. Elektrochemische Messungen zur Ermittlung von Einflußgrößen der Lochkorrosion an diffusionsgeglühten Werkstoffen. Dieser Teil behandelt - anhand von Untersuchungsergebnissen - systematische Abhängigkeiten der Lochkorrosionspotentiale von der Art des angreifenden Mediums (Chloridkonzentration, Wasserstoffionenkonzentration, Temperatur) und der Zusammensetzung der untersuchten Werkstoffe (Einfluß der Legierungselemente).
    Additional Material: 23 Ill.
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  • 84
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 68-68 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 85
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 68-68 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 86
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. A20 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 87
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 82-88 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Fatigue behaviour of High Temperature Brazed Joints tested at elevated temperaturesFatigue testing, on a systematic and statistical basis, was carried our on high temperature brazed joints produced in the base metal NiCr20TiAl joined with BNi-5 and BAu-4 filler metals. The single-stage tests were conducted with various temperatures of 500 and 700 °C. Microscopic examination of the fracture surfaces (SEM) yielded information about crack initiation and propagation and the fracture behaviour of the joints.
    Notes: Es wurden systematische und statistisch abgesicherte Schwingfestigkeitsuntersuchungen an Hochtemperaturlöt-Verbindungen, NiCr20TiAl gelötet mit BNi-5 und BAu-4, im Einstufenversuch vorgenommen. Als Versuchsparameter kamen unterschiedliche Grenzspannungsverhältnisse sowie erhöhte Prüftemperaturen von 500 bzw. 700 °C zur Anwendung. Mikrofraktografische Untersuchungen gaben Hinweise über den Rißbeginn und den Rißfortschritt sowie über das Bruchverhalten der Proben.
    Additional Material: 17 Ill.
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  • 88
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    Materialwissenschaft und Werkstofftechnik 8 (1977) 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 89
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 105-108 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: A Concept to Calculate Notch- and Size-Effect for Fatigue Life PredictionThe fatigue behaviour of a specimen depends on its size and shape. To describe this, the following assumptions are made: There are flaws statistically distributed in the specimen. The largest of these flaws propagates during fatigue loading and forms the final crack. These two assumptions formulate a method for the calculation of the influence of specimen size and shape on fatigue life.This method is applied to own fatigue test results and to those presented in literature.
    Notes: Das Schwingverhalten eines Bauteiles ist abhängig von seiner Form und Größe. Zur Beschreibung dieses Einflusses wird der Ermüdungsvorgang im Zeitfestigkeitsgebiet wie folgt erklärt: In einem Bauteil befinden sich  -  statistisch verteilt  -  Fehlstellen bestimmter Größe. Die größte dieser Fehlstellen breitet sich durch die Schwingbelastung aus und führt zum Dauerbruch.Die mathematische Formulierung dieser beiden Annahmen führt auf ein Berechnungsverfahren, das es gestattet, die Lebensdauer eines Bauteiles im Zeitfestigkeitsgebiet in Abhängigkeit von seiner Form und Größe vorherzusagen.Die Gültigkeit dieses Verfahrens wird an Hand eigener und in der Literatur angegebener Versuchsergebnisse nachgewiesen.
    Additional Material: 4 Ill.
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  • 90
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Microanalytical Investigations of the Precipitation Behaviour of Commercial Aluminized and Chromium-Aluminized Coatings on Ni-Base Alloys and Austenitic SteelsThe precipitation and diffusion behaviour of commercial aluminized and chromiumaluminized coatings on nickel-base alloys and austenitic steels was studied by aid of an electron probe microanalyzer. It is shown, that the protected nickel-base alloys all have a similar layer structure: an external NiAl-layer, which is delimited by an intermediate CrNi-(Mo)-layer to a small Al- containing mixed crystal zone. In the case of aluminized austenitic steels only a very small NiAl-layer can be detected, followed by an extended Al-containing mixed crystal. These layers on Fe-base alloys are predamaged by a perforated zone, due to the Kirkendall-effect. A previous chromium diffusion prevents this effect, but the diffusion behavior was not influenced during an extended heat treatment. The protected nickel-base alloys showed the best durability during long time oxidation tests.
    Notes: Mit Hilfe eines Elektronenstrahlmikroanalysators wurde das Ausscheidungs- und Diffusionsverhalten von kommerziell hergestellten Alitier- und Chromalitierschichten auf Nickelbasislegierungen und austenitischen Stählen untersucht. Dabei zeigte es sich, daß die geschützten Nickelbasislegierungen alle einen ähnlichen Schichtaufbau aufweisen: eine NiAl-Außenschicht, die durch eine chromhaltige Zwischenschicht gegen den schmalen Al-haltigen Mischkristall abgegrenzt ist. Bei den austenitischen Stählen tritt nur eine sehr schmale NiAl-Zone auf, auf die ein ausgedehnter Al-haltiger Mischkristallbereich folgt. Diese Schichten auf Eisenbasislegierungen sind durch eine Kirkendall-Lochbildung vorgeschädigt. Eine der Alitierung vorangegangene Chromierung verhindert die Lochbildung, allerdings beeinflußt sie das Diffusionsverhalten der Schicht bei längerem Wärmebehandeln kaum. Bei den orientierenden Langzeitoxidationstests zeigt sich die überlegene Beständigkeit der alitierten- und chromalitierten Nickelbasislegierungen.
    Additional Material: 6 Ill.
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  • 91
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 139-139 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 92
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 93
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 94
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 95
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. A29 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 96
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    Materialwissenschaft und Werkstofftechnik 8 (1977) 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 97
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 149-157 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Distortion of Steels Due to Heat TreatmentDistortion comprises size and shape distortion. Size distortion is brought about by thermal stresses and structural changes, mainly by hardening and tempering. Thermal stresses cause size-dependant, structural changes size-in dependent distortion. Size-distortion is a system property. Tempering at room temperature over a long period of time influences the size stability. Material anisotropy leads to directional distortion. Shape distortion or warpage originates in residual stresses and differences within the material. Further a nonsymmetrical temperature distribution or geometry of the part have to be considered.
    Notes: Verzug umfaßt Maß- und Formänderungen. Maßänderungen entstehen durch Wärmespannungen und Gefügeumwandlungen, insbesondere beim Härten und Anlassen. Wärmespannungen bewirken abmessungsabhängige, Gefügeumwandlungen abmessungsunabhängige Maßänderungen. Das Maßänderungsverhalten ist eine Systemeigenschaft. Anlaßvorgänge durch langzeitige Auslagerung bei Raumtemperatur beeinträchtigen die Maßstabilität. Werkstoffanisotropie führt zu richtungsabhängiger Maßänderung. Formänderungen haben ihre Ursache in Reststpannungen und Unterschieden im Werkstoff. Weiter Kommen unsymmetrische Temperaturführung oderunsymmetrische Werkstückgeometrie in Betracht.
    Additional Material: 6 Ill.
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  • 98
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. A37 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 99
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 177-181 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Lösung von Werkstoffproblemen in der Kerntechnik durch konstruktive MaßnahmenWerkstoffprobleme in Kernenergie-Anlagen können nur im Zusammenhang mit der Konstruktion, der Fertigung, Betriebsführung, der Wartung und Überwachung gesehen und gelöst werden. Eine enge Zusammenarbeit zwischen Konstrukteur und erkstofffachmann ist daher dringend erforderlich. Dies wird in der vorliegenden Arbeit am Beispiel einiger Entwicklungen im Zusammenhang mit Leichtwasser-Reaktoren diskutiert. Von besondere Bedeutung bei der Entwicklung neuer Werkstoffe und neuer Fertigungstechnologien sind die Begriffe Zuverlässigkeit und Sicherheit der Anlagen durch Qualitätssicherung.
    Notes: Materials problems in nuclear power stations can rarely be dealt with independently of design, maintenance, including operation, inspection and control as well as environmental factors. Therefore they require combined efforts of designers and materials, specialists. The paper illustrates this by examples of some current developments of light-water reactors: tubing in condensers and steam generators in PWR, primary piping in BWR, pressure vessels and fuel elements. Keywords in the development of materials engineering and technology in this field are reliability and safety through quality assurance, rather than increased efficiency and performance data.
    Additional Material: 8 Ill.
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  • 100
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    Materialwissenschaft und Werkstofftechnik 8 (1977), S. 204-208 
    ISSN: 0933-5137
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Description / Table of Contents: Designing with new high-strength low-expansion steelsThe potential of high-strength low-expansion steels has been illustrated by a series of specific design examples through comparing performance against that of alternative materials. The new products have advantages where large temperature excursions are encountered in piping and pressure vessel applications. The benefits to be gained through using the alloys in the design of labyrinth seals are also demonstrated. Finally the position with respect to diesel engine combustion chamber components is examined, and the alloys are shown to be better than alternatives. Apart from the different design requirements in the above applications, other possible applications are suggested, based on this work which has shown one of their main design merits to be low expansivity coupled with low moduls resulting in very low thermal stresses.
    Notes: Die Eignung neuer hochfester Stähle mit niedrigem Ausdehnungskoeffizienten wird an verschiedenen Konstruktionsbeispielen durch Vergleich mit anderen Werkstoffen dargestellt. Die neuen Stähle eignen sich vor allem für Rohrleitungen und Druckbehälter, bei denen große Temperaturbereiche auftreten. Die Vorteile der Legierungen bei der Konstruktion von Labyrinthdichtungen werden ebenfalls aufgezeigt. Untersucht wird das Verhalten der Stähle im Brennkammerbereich von Dieselmotoren. Außer den unterschiedlichen konstruktionsmäßigen Anforderungen werden aufgrund der vorliegenden Arbeit weitere mögliche Einsatzgebiete erörtert. Der für die Konstruktion wesentliche Vorteil der neuen Legierungen besteht in ihrem niedrigen Ausdehnungskoeffizienten in Verbindung mit geringem E-Modul und den daraus resultierenden sehr geringen Wärmespannungen.
    Additional Material: 3 Ill.
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