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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 247-255 
    ISSN: 1432-1041
    Keywords: Aldosterone antagonists ; aldosterone infusion ; evaluation in man ; spironolactone ; potassium canrenoate ; spironolactone metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method of assessing the qualitative and quantitative activity of competitive aldosterone antagonists in healthy man is described. It requires intravenous infusion of aldosterone (0.5 mg/6 h), iv and oral water loading for six hours and fractionated collection of urine over eight hours. Aldosterone antagonists were administered orally 1.5 h before the start of the infusion (spironolactone 50, 200 or 800 mg) or added to the infused solution (potassium canrenoate 300, 600 or 1000–1200 mg). The effect was assessed by changes in urinary sodium and potassium excretion and in urinary Na+/K+ ratio. The plasma levels and urinary excretion of canrenone, canrenoate and canrenoate ester glucuronide, respectively, were determined after administration of spironolactone and potassium canrenoate. Between 4–8 h (spironolactone) or 2–8 h (potassium canrenoate) after commencement of the infusion there was linear, dose-dependent reversal of the mineralocorticoid-induced sodium retention and/or decrease in the Na+/K+ ratio. The plasma levels and urinary excretion of the metabolites measured were also dose-dependent. The method appears suitable for comparison of the potency of aldosterone antagonists and for defining the time course of drug action within the observation period employed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    BBA - Protein Structure 263 (1972), S. 658-665 
    ISSN: 0005-2795
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Chaos 9 (1999), S. 682-690 
    ISSN: 1089-7682
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We present an experimental study of velocity statistics for a partial layer of inelastic colliding beads driven by a vertically oscillating boundary. Over a wide range of parameters (accelerations 3–8 times the gravitational acceleration), the probability distribution P(v) deviates measurably from a Gaussian for the two horizontal velocity components. It can be described by P(v)∼exp(−|v/vc|1.5), in agreement with a recent theory. The characteristic velocity vc is proportional to the peak velocity of the boundary. The granular temperature, defined as the mean square particle velocity, varies with particle density and exhibits a maximum at intermediate densities. On the other hand, for free cooling in the absence of excitation, we find an exponential velocity distribution. Finally, we examine the sharing of energy between particles of different mass. The more massive particles are found to have greater kinetic energy. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 33 (1977), S. 1076-1077 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary N-methanesulfonyl 16-phenoxy-ω-tetranor PGE2 is a prostaglandin analog which is markedly more tissue selective than PGE2. This compound is 10–30 times more potent than PGE2 in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE2.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 160 (1973), S. 307-316 
    ISSN: 1433-8580
    Keywords: Insulin secretion ; Cyclic AMP ; Analogs of cyclic AMP ; Insulinsekretion ; 3′,5′-AMP ; 3′,5′-AMP-Analoga
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Außer Adenosin-3′,5′-monophosphat (3′,5′-AMP) wurde Guanosin-3′,5′-monophosphat (3′,5′-GMP) als zweites cyclisches Nucleotid-3′,5′-monophosphat im Organismus verschiedener Tierarten nachgewiesen. An Ratten wurde untersucht, ob diese Substanz ebenso wie 3′,5′-AMP an der Steuerung der Insulinsekretion beteiligt sein könnte. Die vorliegenden Resultate sprechen nicht für diese Möglichkeit. Während bei adrenalektomierten, mit einem Glucocorticoid substituierten Ratten nach i.v. Injektion von 20 mg/kg Dibutyryl-3′,5′-AMP oder Monobutyryl-3′,5′-AMP eine deutliche Steigerung der Insulinkonzentration im Serum des Pfortaderblutes nachweisbar war, wurde ein derartiger Effekt weder unter dem Einfluß von 20 mg/kg Dibutyryl-3′,5′-GMP noch gleicher Dosen der Monobutyrylderivate von bisher in der Natur nicht nachgewiesenen Cyclophosphaten (Inosin-3′,5′-monophosphat, Uridin-3′,5′-monophosphat) beobachtet.
    Notes: Summary Besides cyclic AMP (cAMP), a second cyclic nucleotide, cyclic GMP (cGMP), has been identified in tissues of several animal species. In rats it was investigated whether this nucleotide might be involved in the regulation of insulin secretion. The results obtained do not support this possibility. Whereas i.v. injection of 20 mg/kg body weight dibutyryl-cAMP or monobutyryl-cAMP was followed by an increase of serum insulin concentration in the portal vein blood of adrenalectomized, glucocorticoid treated rats, no similar effects could be measured under the influence of same doses of either dibutyryl-cGMP, or monobutyryl derivatives of cyclic IMP and cyclic UMP the natural occurance of which has not yet been shown.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-8580
    Keywords: Spontaneous diabetes mellitus in laboratory animals ; Chinese hamsters ; Insulin secretion ; Adenosine-3′,5′-monophosphate ; Sulfonylureas ; Spontandiabetes bei Versuchstieren ; Chinesische Streifenhamster ; Insulinsekretion ; Adenosin-3′,5′-monophosphat ; Sulfonylharnstoffe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei spontandiabetischen chinesischen Streifenhamstern besteht ein auf einerβ-Zelldegeneration beruhender Insulinmangel mit den sich daraus für den Kohlenhydrat- und Fettstoffwechsel ergebenden Konsequenzen (Hyperglykämie, pathologische Glucosetoleranz, Erhöhung der Gluconeogenese — u. a. erkennbar an einem Anstieg der Glucose-6-phosphatase-Aktivität in der Leber —, Anstieg der Konzentration freier Fettsäuren im Serum). Die stark herabgesetzte Ansprechbarkeit derβ-Zellen auf Glucose konnte durch eine hohe Dosis Glymidin-Natrium (250 mg/kg, p.o.) nicht verbessert werden, während nach i.p. Applikation von Glucagon (0,3 mg/kg), Isopropylnoradrenalin (0,5 mg/kg) oder Theophyllin (100 mg/kg) ein z. T. noch stärkerer Anstieg der Insulinkonzentration im Serum auftrat als bei gesunden Tieren. Der insulinfreisetzende Effekt geringerer Dosen von Glucagon (0,003 mg/kg) oder Isopropylnoradrenalin (0,03 mg/kg) war bei spontandiabetischen Tieren abgeschwächt oder aufgehoben. Bei streptozotocin-diabetischen Hamstern führten selbst 100 mg/kg Theophyllin nur zu einer geringen Erhöhung des Seruminsulins. Diese Befunde erlauben folgende Schlußfolgerungen: 1. Derβ-cytotrope Effekt von Glymidin-Natrium und anderen Sulfonylaminoverbindungen wird offensichtlich nicht durch Adenosin-3′,5′-monophosphat vermittelt. 2. Es bestehen grundsätzliche Unterschiede zwischen der erblichen und experimentell erzeugtenβ-Zelldegeneration dieser Tiere. 3. Bei spontandiabetischen Tieren scheint das Adenylatcyclasesystem derβ-Zellen vermindert erregbar zu sein.
    Notes: Summary Spontaneously diabetic Chinese hamsters are characterized by a lack of insulin caused by a degeneration of the pancreaticβ-cells resulting in disturbances of carbohydrate and lipid metabolism (hyperglycemia, abnormal glucose tolerance, increase of gluconeogenesis as demonstrated by an increase of liver glucose-6-phosphatase activity, increase of serum free fatty acid concentration). The reduced sensitivity of theβ-cells of spontaneously diabetic hamsters to stimulation by glucose could not be improved by a high dose of sodium glymidine (250 mg/kg, orally), whereas i.p. application of glucagon (0.3 mg/kg), isopropylnorepinephrine (0.5 mg/kg), or theophylline (100 mg/kg) resulted in a partially higher increase of serum insulin than in normal animals. The effect of lower doses of glucagon (0.003 mg/kg) or isopropylnorepinephrine (0.03 mg/kg) was reduced or abolished. In hamsters with streptozotocin-induced diabetes i.p. injection of 100 mg/kg theophylline only provoked a small increase of serum insulin. These results allow the following conclusions: 1. The insulin releasing effect of antidiabetic sulfonylurea and sulfonylpyrimidine compounds does not seem to be mediated by adenosine-3′,5′-monophosphate. 2. There are principle differences between the hereditary and experimentally inducedβ-cell lesion in Chinese hamsters. 3. There is some evidence for a reduced sensitivity of theβ-cell adenylate cyclase system to hormonal stimuli in spontaneously diabetic animals.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 247 (1964), S. 353-354 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 372-382 
    ISSN: 1432-1912
    Keywords: 1) d-aldosterone — enzyme synthesis and activation of cellular sodium transport, diminution of renal proximal transit time prolonged in adrenalectomized rats ; 2) actinomycin D — prevention of renal and extrarenal aldosterone action ; 1. d-Aldosteron — Enzym-Induktion und Aktivierung des cellulären Na+-Transports, Verkürzung der verlängerten proximalen tubulären Passagezeit adrenalektomierter Ratten ; 2. Actonomycin D — Verhinderung der renalen und extrarenalen Aldosteron-Wirkung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments are described in which the distribution of sodium and potassium ions between the intra- und extracellular fluid of liver has been studied in nephrectomized adrenalectomized rats and in nephrectomized adrenalectomized rats given d-aldosterone (1 μg/150 g b.w., subcutaneously, single dose). d-Aldosterone has been found to decrease intracellular sodium concentration in liver and to increase the concentration quotient $$\frac{{{\text{Na}}^{\text{ + }} _e }}{{{\text{Na}}^{\text{ + }} _i }}$$ after a delay time of 90 min. Pretreatment with actinomycin D (300 μg/150 g b.w., i.p., single dose) prevents the aldosterone induced acceleration of cellular net sodium transport as well as the aldosterone induced increase in tubular sodium transport. Our findings indicate the aldosterone dependent increase in extrarenal cellular sodium transport being mediated by an induction of enzyme proteins as has been assumed by Edelman et al. as well as by Leaf et al. for the urinary bladder of Bufo marinus and the rat kidney. The results are discussed with respect to whether the enzyme system induced by aldosterone may function by increasing the permeability of the mucosal (luminal) cell membrane for sodium and a consequent increase in the availability of sodium to be transported through the serosal (peritubular) cell membrane, or by a channelling of metabolism to provide more energy for the active transport of sodium. It is difficult to apply the “permease” theory to explain the aldosterone dependent increase in hepatic cellular sodium transport resulting in a decrease in intracellular sodium concentration. Renal proximal transit time measured with lissamin green in adrenalectomized rats has been found to diminish with chronic treatment with d-aldosterone (1 μg/300 g b.w., s.c., daily for 4 days). This finding may explain why the effect of aldosterone decreases with chronic administration of the hormone. Although tubular reabsorptive capacity remains increased shortening of the contact of tubular fluid with the epithelial cells results in a reduction of the amount of sodium ions reabsorbed by the tubules under the influence of aldosterone.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 391-408 
    ISSN: 1432-1912
    Keywords: Glucose Basal Transport and Insulin Secretion ; Glucocorticoids and Insulin Secretion ; Corticosterone and Gluconeogenesis ; Glycogenolysis and Intracellular Sodium Concentration ; Negative Potassium Balance and Tissue Electrolyte Content ; Glucosebasaltransport und Insulininkretion ; Glucocorticoide und Insulininkretion ; Corticosteron und Gluconeogenese ; Glykogenolyse und intracelluläre Natriumkonzentration ; Negative Kaliumbilanz und Elektrolytverteilung zwischen dem intra- und extracellulären Raum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Feeding rats a low potassium diet over a period of 2–3 weeks produces a negative potassium balance the mean of which is 1445±125 μeq/animal. Blood glucose concentration has been found increased under this condition. Following intravenous loading with glucose there is a decrease in the elimination constant k 2 of glucose. Cellular glucose uptake has also been found to be impaired in alloxan diabetic animals fed a low potassium diet. From this it is concluded that there is a reduction in basal glucose transport in potassium deficiency. L-arabinose distribution volume is also decreased, indicating that the impairment in cellular glucose uptake is not caused by a reduction in intracellular utilisation of glucose. Endogenous insulin has been found to accelerate impaired basal glucose transport to a smaller degree than the unimpaired glucose transport in normal rats. Insulin plasma concentration is elevated. The same applies to the pancreatic function to secrete insulin in response to an increase in blood glucose concentration. The increase in insulin secretion is considered to be the consequence of the diminished action of insulin. The same relation holds for experiments in which glucocorticoids were given to rats at a pharmacological dose level: as glucocorticoids diminish basal glucose uptake, insulin secretion increases, apparently to compensate for the impaired peripheral action of endogenous insulin. The reduction in basal glucose transport as well as its consequences on insulin secretion in potassium deficient rats may partly be caused by an increase in glucocorticoid secretion. This has been concluded from an increase in suprarenal corticosterone concentration. An enhanced rate of corticosterone synthesis and output may be responsible for the increase in hepatic and renal glucose-6-phosphatase activity of potassium depleted rats. Lowering intracellular pH values has also been found to lead to an increase in hepatic glucose-6-phosphatase activity. Therefore, an intracellular acidosis in liver could contribute to the increase in glucose-6-phosphatase activity measured in the liver of potassium deficient rats. Cellular acidosis has been found to occur in skeletal muscles of potassium deficient animals, and this was explained by hydrogen ions partially replacing the decrease in intracellular potassium concentration (Cooke, Segar, Cheek, Coville, and Darrow, 1952; Irvine, Saunders, Milne, and Crawford, 1960). Cellular sodium and potassium concentration are, however, unaltered in the liver of potassium deficient rats. Thus, there is no indication for a compensatory increase in intracellular hydrogen concentration in this tissue. In contrast to liver, besides the glucocorticoid induced effect a pH dependent increase in glucose-6-phosphatase activity may contribute to the increase in enzymic hydrolysis of glucose-6-phosphate observed in the kidneys of potassium depleted rats. In addition to the replacement of cellular potassium by hydrogen ions there is also a compensatory increase in intracellular sodium concentration of skeletal muscles. Sodium ions inhibit glycogen phosphorylase phosphatase thereby reducing the rate of conversion of active glycogen phosphorylase a into the inactive glycogen phosphorylase b. Consequently, the glycogenolytic action of epinephrine is increased in potassium deficiency.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 418-429 
    ISSN: 1432-1912
    Keywords: Intracellular Potassium Deficiency Caused by Adrenalectomy, Aminonucleoside Nephrosis, Low Potassium Diet ; Cellular Li+ Transport in Skeletal Muscle and Liver — Li+ Distribution Volume ; Intracelluläres Kaliumdefizit bei adrenalektomierten, aminonucleosidnephrotischen und kaliumarm ernährten Ratten — Cellulärer Li+-Transport in der Skeletmuskulatur und Leber ; Li+-Verteilungsvolumen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of Li+ between the intracellular and extracellular fluid of liver and skeletal muscle has been measured in rats following intravenous injection of LiCl. In the liver intracellular Li+ concentration has been found lower than the extracellular Li+ concentration. This is in contrast to skeletal muscle in which intracellular Li+ concentration has been found to be higher than extracellular Li+ concentration. In the liver, the direction of Li+ net transport corresponds to the direction of Na+ net transport. The same holds for erythrocytes (Lode, 1966) and for the tubular net transport of both ions (Maibauer, Pröhl, Senft, 1963). In skeletal muscle Li+ net transport, like K+ net transport, is directed from the extracellular to the intracellular space. The distribution volume has been measured in different types of intracellular K+ deficiency occuring in skeletal muscle. A decrease in cellular potassium concentration has been produced by adrenalectomy, injection of aminonucleoside leading to a nephrotic syndrome with generalized edema and by feeding rats a low potassium diet. Li+ distribution volume has been found to decrease in adrenalectomized and nephrotic rats. This can be explained by a simultaneous decrease in cellular K+ and Li+ net transport in skeletal muscle. On the other hand, intracellular K+ deficiency caused by feeding the animals a low potassium diet is accompanied by an increase in Li+ distribution volume. This can be explained by an increse in cellular Li+ transport in skeletal muscle. In spite of the decrease in intracellular K+ concentration cellular K+ transport is increased. There is a simultaneous increase in K+(ICF)/K+(ECF) and Li+(ICF)/Li+(ECF) under this experimental condition. The results indicate that an increase in Li+ distribution volume may reflect an increase in cellular K+ transport compensating for cellular K+ loss caused by a negative potassium balance. A decrease in Li+ distribution volume may reflect a decrease in cellular K+ transport caused by metabolic and hormonal disturbances.
    Type of Medium: Electronic Resource
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