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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    CNS drug reviews 4 (1998), S. 0 
    ISSN: 1527-3458
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1997), S. 39-48 
    ISSN: 1432-1912
    Keywords: Key words Antinociception ; Toxicity ; Sodium ; channel ; Aconitum spec. ; Aconitine ; 3-Acetylaconitine ; Hypaconitine ; Lappaconitine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extracts of the plant Aconitum spec. are used in traditional Chinese medicine predominantly as anti-inflammatory and analgesic agents, the latter allegedly equally potent as morphine but without any habit-forming potential. As the only pharmacologically active compounds, the C19 diterpenoid alkaloid aconitine, and some of its derivatives, have been proven to be antinociceptive in different analgesic assays, but the mode of action is unknown. To elucidate the mode of action, ten aconitine-like derivatives were investigated with respect to their affinity for voltage-dependent Na+ channels, the action on synaptosomal Na+ and Ca2+ homoeostasis and their antinociceptive, arrhythmogenic and acute toxic properties. Since aconitine is known to bind to site II of Na+ channels, we determined the affinity of the aconitine-like derivatives in vitro to synaptosomal membranes by the [3H]-batrachotoxinin-binding assay and their properties on intrasynaptosomal concentrations of free Na+ and Ca2+ ([Na+]i and [Ca2+]i), both the latter determined fluorometrically with SBFI and Fura-2 respectively. Furthermore, the alkaloids’ arrhythmogenic potential was investigated in guinea-pig isolated atria and the antinociceptive action on formalin-induced hyperalgesia and the acute toxic action estimated in mice. The results show that the alkaloids could be divided into at least three groups. The first is characterized by a high affinity to the site II of Na+ channels (K i about 1.2 μM), the ability to enhance [Na+]i and [Ca2+]i (EC50 about 3 μM), a strong arrhythmogenic action that starts at about 30 nM, an antinociceptive effect (ED50 about 0.06 mg/kg) and high acute toxicity (LD50 values about 0.15 mg/kg). To this group belong aconitine, 3-acetylaconitine and hypaconitine. The second group, with lappaconitine as the only member, has an affinity to Na+ channels an order of magnitude lower (K i = 11.5 μM), less acute toxicity (LD50 about 5 mg/kg), and a two orders of magnitude lower antinociceptive action (ED50 about 2.8 mg/kg) and lower cardiotoxicity (bradycardia observed at 3 μM). Additionally, lappaconitine suppresses the increase in [Ca2+]i of aconitine-stimulated synaptosomes and increases the excitation threshold of left atria, indicating an inhibition of Na+ channels. The other derivatives, i.e. delcorine, desoxydelcorine, karakoline, lappaconidine, lappaconine and lycoctonine, belong to the third group, which has hardly any effects. They have a low affinity to Na+ channels with K i values in the millimolar range, show no effect on synaptosomal [Na+]i and [Ca2+]i, no arrhythmogenic potential up to 100 μM, no antinociceptive activity and low toxicity with LD50 values greater than 50 mg/kg. For the investigated alkaloids we suggest two different antinociceptive-like modes of action. Aconitine, hypaconitine and 3-acetylaconitine may induce a block of neuronal conduction by a permanent cell depolarisation, whereas lappaconitine might act like local anaesthetics. However, because of the low LD50/ED30 quotients of 2–6, the antinociceptive-like action of the Aconitum alkaloids seems to reflect severe intoxication rather than a specific antinociceptive action. The structure/activity relationship shows that alkaloids that activate or block Na+ channels have a benzoyl ester side chain in the C-14 or C-4 positions respectively, whereas the other compounds lack this group.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 65 (1985), S. 285-292 
    ISSN: 1432-0533
    Keywords: Thalidomide ; Neuropathy ; Conduction velocity ; Myelin sheath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphological studies of experimental thalidomide neuropathy have thus far failed to show any significant structural changes. The present investigation was performed on sural nerves of female New Zealand white rabbits showing a reduction of sensory conduction velocity after oral treatment with thalidomide (100 mg/kg b.wt. per day) for a period of 33 weeks. Rabbits of the same strain and equal sex, weight, and number served as controls. Very few nerve fibers were undergoing Wallerian degeneration in both groups, experimental animals and controls. Morphometry, however, revealed a statistically significant reduction of the mean myelin thickness of sural nerve fibers in the thalidomide group of rabbits as compared to controls. The mean myelin thickness of the largest nerve fibers was also significantly smaller than in the control group. On the other hand, axonal diameters were not significantly altered. The association between the decrease of the sensory conduction velocity, the reduction of the myelin sheath thickness, and the chronic thalidomide application is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-119X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Saruplase — a recombinant single-chain urokinase-type plasminogen activator was identified immunohistochemically in normal rat tissue after intravenous administration by means of a polyclonal antibody. For this purpose, rat tissues were fixed in various ways (liquid nitrogen, ethanol, formaldehyd solution). Saruplase could be detected by the PAP method, streptavidinbiotin system and indirect immunofluorescence in the kidney (proximal tubule), liver (hepatocytes, Kupffer cells) and spleen (reticular cells). Saruplase was not localized in the rat endothelium. It is discussed that the ratspecific receptors for urokinase-type plasminogen activator on endothelial cells cannot bind Saruplase due to the extreme species specificity.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2021-05-11
    Description: Summary The continental margins of southern Italy are located along converging plate boundaries, which are affected by intense seismicity and volcanic activity. Most of the coastal areas experienced severe earthquakes, landslides, and tsunamis in historical and/or modern times. The most prominent example is the Messina earthquake of Dec. 28, 1908 (Ms=7.3; 80,000 casualties), which was characterized by the worst tsunami Italy experienced in the historical time (~2000 casualties). It is, however, still unclear, whether this tsunami was triggered by a sudden vertical movement along a major fault during the earthquake or as a result of a giant marine slide initiated by the earthquake. The recurrence rates of major landslides and therefore the risk associated with landslides is also unknown. Based on detailed bathymetric data sets collected by Italian colleagues in the frame of the MaGIC Project (Marine Geohazards along the Italian Coast), we collected seismic data (2D and 3D) and gravity cores in three working areas (The Messina Straits, off Eastern Sicily, the Gioia Basin). A dense grid of new 2D-seismic data in the Messina Straits will allow to map fault patterns in great detail. One interesting outcome in this context is the identification of a set of normal faults striking in an EW-direction, which is almost perpendicular to the previously postulated faults. This EW-striking faults seem to be active. The area off eastern Sicily is characterized by numerous landslides and a complex deformation pattern. A 3D-seismic data set has been collected during the cruise using the so called P-cable in order to investigate these deformation patterns in detail. The new data will be the basis for a risk assessment in the working areas.
    Type: Report , NonPeerReviewed
    Format: text
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  • 6
    Publication Date: 2016-12-29
    Description: Energy & Fuels DOI: 10.1021/acs.energyfuels.6b00627
    Print ISSN: 0887-0624
    Electronic ISSN: 1520-5029
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering , Process Engineering, Biotechnology, Nutrition Technology
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