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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 258 (1967), S. 297-308 
    ISSN: 1432-1912
    Keywords: Atria of guinea pigs ; 3H-digoxin ; Digoxin-binding ; Vorhof des Meerschweinchens ; 3H-Digoxin ; Digoxin-Bindung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An isolierten Meerschweinchenvorhöfen wird die Austauschgeschwindigkeit von 3H-Digoxin bei bestehendem chemischen Digoxin-Gleichgewicht zwischen Gewebe und extracellulärer Flüssigkeit gemessen. Für drei Konzentrationen (1·10−7, 5·10−7 und 2,5·10−6 g/ml) bestimmten wir jeweils den Austauschvorgang Extracellulärraum → Zelle und Zelle → Extracellulärraum und verglichen ihn mit dem einfachen Aufnahme- bzw. Abgabeprozeß. Zur Messung der 3H-Aktivität wurde das Vorhofgewebe durch Hyamin-Hydroxid verflüssigt und die Radioaktivität mittels der Flüssigkeitsszintillationszählung bestimmt. Da auf Grund chromatographischer Analysen ein Abbau von Digoxin in der Herzmuskulatur ausgeschlossen werden konnte, ist die gemessene 3H-Aktivität ein Maß für die im Muskel vorhandene 3H-Digoxin-Konzentration. Die Geschwindigkeiten der Austauschvorgänge in beiden Richtungen entsprechen sich, sind aber deutlich geringer als die Aufnahmegeschwindigkeit. Sie gleichen aber der einfachen Abgabegeschwindigkeit. Wir stellen folgende Hypothese zur Diskussion: 1. Der Aufnahmeprozeß ist ein Maß für die Membranpermeabilität für Digoxin. 2. Der Abgabe- und die Austauschprozesse spiegeln die Bindung von Digoxin an celluläre Strukturen wider und sind durch die Dissoziationskonstanten der Digoxin-Zellstruktur-Komplexe bestimmt.
    Notes: Summary The exchange of 3H-digoxin between extracellular fluid and the tissues was investigated in guinea pig isolated atria. Throughout the experiments there existed a chemical equilibrium between the digoxin in the bath and that in the tissues. The exchange processes extracellular space → cell and cell → extracellular space were determined for three different digoxin concentrations in the bath, i.e. 1×10−7, 5×10−7 and 2.5×10−6 g digoxin/ml. For each bath concentration the exchange was compared with the corresponding uptake and release processes of 3H-digoxin, which had been established previously. For the determination of the tritium concentration the organs were digested in Hyaminehydroxide. In the solution thus obtained radioactivity was determined by means of liquid scintillation spectrometry. Chromatographic studies have demonstrated that in atrial tissue the cardiac glycoside is not metabolized to a measurable extent. Accordingly, the total radioactivity determined is a measure for the 3H-digoxin content of the organs. The exchange rates in both directions are approximately the same. These rates, however, proved considerably lower than the uptake rate. Nevertheless, there is no difference between the rate of exchange and the release of 3H-digoxin. In order to explain these experimental findings, we have proposed the following hypothesis: 1. The uptake process is probably determined by the membrane's permeability for digoxin; 2. for the release, but also for the exchange processes (in both directions) the binding of digoxin to so far unknown cellular structures seems to be decisive. Accordingly, the rates of these processes may be considered as a measure for the dissociation constants of the complexes formed between digoxin and the cellular structures.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 327 (1984), S. 14-17 
    ISSN: 1432-1912
    Keywords: Bethanechol ; Electromyogram ; Substantia nigra pars reticulata ; Morphine ; Muscular rigidity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bethanechol chloride (5–25 μg), when injected into the substantia nigra pars reticulata (SNR) of rats, produced muscular rigidity in a dose-dependent way, and in addition, catalepsy and ipsilateral posture. The effects of bethanechol in the dose of 25 μg were prevented by coadministration of 10 μg scopolamine hydrochloride. Injections of 25 μg betanechol or 10 μg scopolamine into the reticulata only slightly affected the muscular rigiditiy produced by 15 mg/kg i.p. morphine hydrochloride. The results suggest that muscarinic cholinergic mechanisms in the substantia nigra pars reticulata, although effective by themselves, affect by expression of at least one striatal functional alteration, the muscular rigidity, in a less effective way than GABAergic or endogenous opioid mechanisms do.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Key words Nicotine ; Hydroxyl radicals ; PBN ; MPTP ; Neuroprotection ; Parkinson’s disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Parkinson’s disease (PD) is one of the most frequent disorders of the basal ganglia. From epidemiological studies there is a controversial discussion on the question whether tobacco smoking is correlated with a decreased incidence of PD. The present study aimed to elucidate the role of nicotine and its potential neuroprotective effects in a rodent model of PD. These effects may be related to an altered hydroxyl radical formation; this possibility was studied in vitro. Nicotine and α-phenyl-N-tert-butyl nitrone (PBN) were examined in a cell-free in vitro Fenton system (Fe3+/EDTA + H2O2) for their radical scavenging properties using the salicylate trapping method. Salicylic acid (0.5 mM) was incubated in the presence and absence of nicotine or PBN and the main products of the reaction of hydroxyl radicals with salicylic acid, namely 2,3- and 2,5-dihydroxybenzoic acid, were immediately determined using HPLC in combination with electrochemical detection. Nicotine and PBN were both able to significantly reduce hydroxyl radical levels at concentrations of 1, 2.5 and 5 mM. Interestingly, at 5 mM nicotine was able to reduce hydroxyl radical levels significantly more than the radical scavenger PBN (5 mM). To investigate the in vivo effects of nicotine, male C57BL/6 mice were used in the MPTP mouse model of PD. Nicotine (0.1 or 0.4 mg/kg s.c.) was administered twice daily for a period of 14 days. On day 8 a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg s.c.) was given as well as an enhanced protocol of nicotine treatment (0.1 or 0.4 mg/kg s.c., 30 min before MPTP and 30, 90, 210, 330, 450, 570 min after MPTP) for a total of seven injections of nicotine. High dosage nicotine treatment significantly increased the MPTP-induced loss of body weight and resulted in a significantly decreased striatal dopamine content and an increased dopamine turnover in comparison with the MPTP-treated controls at day 15. However, the lower dosage of nicotine did not significantly alleviate the MPTP-induced effects, although some parameters showed a slight tendency in this direction. These results demonstrate that in vitro nicotine has radical scavenging properties which might suggest neuroprotective effects. In vivo experiments with nicotine, however, showed that a low dosage of nicotine did not alleviate the MPTP-induced dopamine depletion, but a large dosage even enhanced it.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 208-213 
    ISSN: 1432-1912
    Keywords: Nicotine ; Behavioural signs of nicotine ; Conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nicotine produces behavioural signs which are, in part, characteristic of dopaminergic activation. In the present study, it was investigated, to which degree these signs can be conditioned. The drug produced dose-dependent (0.15–0.60 mg/kg s.c.) increases in locomotor activity, hyperkinesia and stereotyped sniffing. The effects produced by 0.6 mg/kg nicotine were significantly inhibited by mecamylamine (1 mg/kg i. p.), but only in part by haloperidol (0.2 mg/kg i. p.). In a subsequent series, the administration of nicotine (0.6 mg/kg s.c.) was repeatedly associated with well-defined environmental (conditioned) stimuli: a wire cage associated with an auditory and an olfactory stimulus. Another group was pseudoconditioned, a third group remained drug-naive. When the animals were given saline in presence of the conditioned stimuli 24 h after the last conditioning session, locomotor activity, hyperkinesia and stereotyped sniffing were significantly higher in conditioned than in pseudoconditioned and drug-naive rats. Similarly, when the rats were injected with nicotine (0.6 mg/kg s. c.) in presence of the conditioned stimuli 24 h after the last conditioning session, locomotor activity and stereotyped sniffing were most pronounced in the conditioned animals. These results demonstrated that behavioural effects of nicotine can be conditioned. Phenomena of this kind might contribute to the addictive behaviour to nicotine.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 259 (1968), S. 394-399 
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Protein Binding ; Sephadex Gelfiltration ; Herzglykoside ; Eiweißbindung ; Sephadex-Gelfiltration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of tritium labelled cardiac glycosides to plasma proteins was investigated by means of the Sephadex gel-filtration method. After pre-saturation with water, Sephadex G 25 was incubated with an excess of guinea pig plasma which contained 3H-labelled heart glycosides. In this procedure, the Sephadex G 25 could not disturb the equilibrium between the free and protein-bound glycoside to a noticeable extent. The uptake of 3H-glycosides by Sephadex from serum was compared with that from a TRIS-buffered 0.9% NaCl-solution containing the drug in the same concentration as the serum or plasma. From the ratio of both values the amount of protein-bound glycoside could be calculated. Approximately 90% of the 3H-digitoxin incubated with guinea pig plasma or with human serum became bound to protein; for 3H-digoxin, this figure was about 55%. No significant protein binding could be established for 3H-ouabain, neither in guinea pig plasma nor in human serum. In contrast to previous investigators, who used toxic concentrations of the glycosides, the present studies have been carried out with glycoside concentrations within the therapeutic range. The results have been compared with those of previous authors.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 262 (1969), S. 463-473 
    ISSN: 1432-1912
    Keywords: Cardiac Glycosides ; Reserpine ; Tissue Uptake ; Herzglykoside ; Reserpin ; Aufnahme im Gewebe ; Eiweißbindung ; Positiv inotrope Wirkung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die positiv-inotrope Wirkung, die Aufnahme in isolierte Vorhöfe und die Eiweißbindung im Plasma wurden für Digoxin, Digitoxin und Digitoxigenin an normalen und mit Reserpin vorbehandelten Meerschweinchen untersucht. Die Versuche wurden zum Teil mit Tritium-markierten Cardenoliden durchgeführt. 1. Die drei Pharmaka wirkten an elektrisch gereizten Vorhöfen von reserpinisierten oder unbehandelten Meerschweinchen gleich stark positiv inotrop. 2. Die Aufnahme von 3H-Digoxin in isolierte Vorhöfe wurde von einer Reserpin-Vorbehandlung der Spendertiere nicht beeinflußt. Nach einer Reserpin-Vorbehandlung nahmen die Vorhöfe jedoch etwa 20% mehr 3H-Digitoxin oder 3H-Digitoxigenin auf. 3. Die Eiweißbindung von 3H-Digoxin im Plasma wurde von einer Reserpin-Vorbehandlung der Meerschweinchen nicht beeinflußt. 3H-Digitoxin und 3H-Digitoxigenin wurden dagegen von Plasma-Eiweißen reserpinisierter Meerschweinchen stärker gebunden als von denen unbehandelter Kontrolltiere. 4. Das Plasma von mit Reserpin vorbehandelten Meerschweinchen zeigte dieselbe Osmolalität, Refraktion und Gesamteiweißkonzentration wie das Plasma unbehandelter Kontrolltiere. Auch das Elektropherogramm des Plasmas und der Hämatokrit des Blutes wurden durch die Reserpin-Vorbehandlung nicht verändert. 5. Wahrscheinlich erhöht die Vorbehandlung mit Reserpin durch einen bisher unbekannten Mechanismus die Bindungsfähigkeit des Albumin für Cardenolide. Ein ähnlicher Mechanismus könnte die verstärkte Aufnahme der Substanzen durch den Herzmuskel erklären.
    Notes: Summary The positive inotropic effect, the tissue uptake and the binding to plasma proteins were determined in isolated atria and in plasma of normal and reserpinized guinea pigs for digoxin, digitoxin and digitoxigenin. Some of the experiments were carried out with tritium-labelled cardenolides. 1. The three cardenolides caused the same positive inotropic effect in electrically driven isolated atria from either reserpinized or normal guinea pigs. 2. Pretreatment of the animals with reserpine did not influence the uptake of 3H-digoxin in isolated atria. After pretreatment with reserpine, however, approximately 20% more 3H-digitoxin and 3H-digitoxigenin were taken up. 3. Pretreatment of the guinea pigs with reserpine did not influence the binding of 3H-digoxin to plasma proteins. The binding of 3H-digitoxin and 3H-digitoxigenin to proteins, however, was increased in plasma of reserpinized guinea pigs in comparison with that of untreated control animals. 4. The plasma of reserpinized guinea pigs showed the same osmolality, refraction and total protein content as the plasma of untreated control animals. The plasma electropherogram and also the haemotacrit value of the blood proved to be unaltered in reserpinized guinea pigs. 5. Probably, the pretreatment with reserpine increase the binding capacity of plasma albumin for cardenolides by a mechanism so far unknown. A similar mechanism might cause the increased accumulation by heart muscle tissue.
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