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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 339-348 
    ISSN: 1432-0428
    Keywords: Autoradiography ; 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; mouse ; pancreatic islets ; reserpine ; ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé En appliquant la technique autoradiographique, on a étudié la distribution cellulaire et subcellulaire de la radioactivité dans les îlots pancréatiques de la souris après une injection intra-veineuse de3H-5-hydroxytryptophane. Des grains d'argent autoradiographiques dont la plupart représentent probablement de la 5-hydroxytryptamine qui s'est formée à partir du précurseur marqué, sont apparus sur les cellules A2 et B, tandis que très peu de grains ont été trouvés sur les cellules A1 à chacun des examens (entre 20 min et 16 h) et de même après l'inhibition de la monoamine-oxidase. L'analyse quantitative des coupes autoradiographiques a révélé que la concentration de grains d'argent sur les granules spécifiques des cellules A2 et B était 5 à 10 fois plus élevée que sur les parties restantes de ces cellules. Sur les cellules A2 le nombre le plus élevé de grains a été noté 20 min après l'injection du marqueur et sur les cellules B une heure après cette injection. Au bout de 8 h, il n'apparaissait que très peu de grains d'argent sur les cellules des îlots, et plus aucun au bout de 16 h. L'inhibition de la monoamine-oxidase a provoqué une augmentation de la rétention de marqueur sur les cellules des îlots, plus prononcée sur les cellules A2. Un traitement préalable à la réserpine a supprimé cette réaction autoradiographique.
    Abstract: Zusammenfassung Mit Hilfe der Technik der Autoradiographie wurde die zelluläre und subzelluläre Verteilung der Radioaktivität nach intravenöser Applikation von3H-5-Hydroxytryptophan in den Pankreasinseln der Maus untersucht. Die autoradiographischen Silberkörner, welche zumeist 5-Hydroxytryptamin darstellen, das aus der radioaktiven Ausgangssubstanz gebildet worden war, erschienen über den A2 und B-Zellen, während nach jedem untersuchten Zeitintervall (20 min–16 Std) auch wenn die Monoamino-Oxidase gehemmt wurde, nur sehr wenige Körner über den A1-Zellen erschienen. Quantitative Untersuchungen der Autoradiographieschnitte zeigten, daß die Konzentration der Silberkörner über den spezifischen Granula der A2-Zellen und der B-Zellen etwa 5–10 mal höher als über den restlichen Teilen der Zellen war. In den A2-Zellen wurde die höchste Körnerkonzentration nach 20 min, in den B-Zellen 1 Std nach Injektion der markierten Substanz festgestellt. Nach 8 Std zeigten sich nur wenige, nach 16 Std keine Silberkörner mehr über den Inselzellen. Die Hemmung der Monoamino-Oxidase verursachte eine vermehrte Anreicherung von Radioaktivität über den Inselzellen, am meisten über den A2-Zellen. Eine Vorbehandlung mit Reserpin verhinderte die autoradiographische Darstellung.
    Notes: Summary By application of autoradiographic technique the cellular and subcellular distribution of radio-activity in mouse pancreatic islets was investigated following intravenous administration of3H-5-hydroxytryptophan. Autoradiographic silver grains, most of which probably represent 5-hydroxytryptamine formed from the labelled precursor, appeared over A2 and B cells, whereas very few grains were recorded over A1 cells at any time investigated (20 min–16 hours) and also when monoamine oxidase was inhibited. Quantitative analysis of autoradiographic sections revealed that the concentration of silver grains over the specific granules of A2 and B cells was 5–10 times higher than over the remaining parts of these cells. In A2 cells the highest grain count was recorded at 20 minutes, in B cells at 1 hour after the injection of label. After 8 hours very few, and after 16 hours no silver grains appeared over islet cells. Inhibition of monoamine oxidase caused an increased retention of label over islet cells, most pronounced over A2 cells. Pretreatment with reserpine abolished the autoradiographic reaction.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 414-422 
    ISSN: 1432-0428
    Keywords: 5-hydroxytryptamine ; 5-hydroxytryptophan ; monoamine oxidase inhibition ; decarboxylase inhibition ; glucose ; glibenclamide ; isopropylnoradrenaline ; alloxan diabetes ; mouse ; blood glucose ; immunoreactive insulin ; tissue glycogen ; hypoglycaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez la souris normale a été étudiéein vivo la signification fonctionnelle du stockage de 5-hydroxytryptamine (5-HT) dans les cellules β du pancréas pour les mécanismes de la sécrétion d'insuline. Un traitement préalable des animaux avec leL-5-hydroxytryptophane (L-5-HTP) a nettement réduit la capacité de sécrétion d'insuline après stimulation par sulfonylurée. Cette inhibition de la sécrétion d'insuline pouvait être évitée par l'administration préalable d'un inhibiteur de décarboxylation d'acide aminé aromatique. D'un autre côté, le traitement préalable avec la nialamide, inhibiteur de la monoamine oxydase, réduisait la sécrétion d'insuline provoquée par sulfonylurée. Le traitement combiné avec la nialamide et leL-5-HTP n'a pas réduit davantage la réponse de l'insuline. Il a été trouvé que la sécrétion d'insuline provoquée par laL-isopropylnoradrénaline (L-IPNA) se réduisait également aprés l'administration préalable deL-5-HTP ou de nialamide, mais, contrairement à la réponse de l'insuline après sulfonylurée, la sécrétion d'insuline provoquée par l'IPNA pouvait être totalement supprimée par le traitement combiné avec la nialamide ou la pargyline et leL-5-HTP. La sécrétion d'insuline provoquée par le glucose n'était influencée de façon significative par aucun des traitements ci-dessus. Le taux basal d'insuline du plasma n'était pas affecté par l'injection deL-5-HTP et n'était pas réduit de façon certaine par le traitement combiné avec l'inhibiteur de la monamine oxydase et leL-5-HTP. Il a été trouvé que le traitement combiné avec l'inhibiteur de la monoamine oxydase et leL-5-HTP provoquait une hypoglycémie profonde à la fois chez la souris normale et chez la souris diabétique par l'alloxane. L'hypoglycémie était accompagnée d'un épuisement du contenu du glycogène du foie et des muscles. Il était possible d'éviter l'hypoglycémie par un traitement préalable avec un inhibiteur de décarboxylation d'acide aminé aromatique. Un traitement combiné avec la pargyline et la 5-HT a provoqué une nette hyperglycémie. — En conclusion: 1. Le taux intracellulaire de la 5-HT dans les cellulesβ du pancréas a la capacité de modifier les mécanismes de la sécrétion d'insuline. 2. L'action hypoglycémique des inhibiteurs de la monoamine oxydase est provoquée par l'accroissement du taux intracellulaire de 5-HT qui s'accompagne d'une nette augmentation de l'utilisation du glucose par les tissus.
    Abstract: Zusammenfassung Es wurde bei normalen Mäusenin vivo die funktionelle Bedeutung der Speicherung von 5-Hydroxytryptamin (5-HT) in den B-Zellen des Pankreas für die Mechanismen der Insulinsekretion untersucht. Eine Vorbehandlung der Tiere mitL-5 Hydroxytryptophan (L-5-HTP) verminderte deutlich die Insulinsekretion nach Stimulation mit Sulfonylharnstoff. Diese Hemmung der Insulinsekretion konnte durch vorherige Behandlung mit einem Hemmer der aromatischen Aminosäurendekarboxylase verhindert werden. Andererseits wurde die durch Sulfonylharnstoff bewirkte Insulinsekretion nach alleiniger Vorbehandlung mit dem Monoamino-oxidasehemmer Nialamid vermindert. Die kombinierte Behandlung mit Nialamid undL-5-HTP hat die Insulinantwort nicht weiter gemindert. Die durchL- Isopropylnoradrenalin (L-IPNA) bewirkte Insulinausschüttung wurde ebenfalls nach einer vorherigen Behandlung mitL-5-HTP oder Nialamid reduziert. Aber im Gegensatz zu der Insulinantwort nach Sulfonylharnstoff konnte die durch IPNA induzierte Insulinausschüttung völlig durch die kombinierte Behandlung mit Nialamid oder Pargylin plusL-5-HTP unterdrückt werden. Die durch Glucose herbeigeführte Insulinausschüttung wurde nicht wesentanimals lich durch eine der oben erwähnten Behandlungen verändert. Die basale Plasmainsulinkonzentration wurde durch dieL-5-HTP-Injektion nicht beeinflußt und war auch nicht wesentlich durch die kombinierte Behandlung mit dem Monoaminooxidasehemmer undL-5-HTP vermindert worden. — Die kombinierte Behandlung mit Monoaminooxidase-Inhibitoren undL-5-HTP erzeugte eine tiefe Hypoglykämie in normalen und alloxandiabetischen Mäusen. Der hypoglykämische Zustand wurde von einem Verschwinden des Leber- und Muskelglykogens begleitet. Die Hypoglykämie konnte durch eine Vorbehandlung mit einem Inhibitor der aromatischen Aminosäuredekarboxilation verhindert werden. Die kombinierte Behandlung mit Pargylin und 5-HT führte zu einer starken Hyperglykämie. — Daraus wurde geschlossen, 1. daß die intrazelluläre Konzentration von 5-HT in den B-Zellen des Pankreas die Fähigkeit besitzt, den Mechanismus der Insulinsekretion zu beeinflussen, 2. daß die hypoglykämische Wirkung der Monoaminooxidase-Inhibitoren durch eine erhöhte intrazelluläre 5-HT-Konzentration erzeugt wird, welche von einer stark erhöhten Glucoseutilisation der Gewebe begleitet wird.
    Notes: Summary The functional significance of 5-hydroxytryptamine (5-HT) storage in the pancreatic B cells for insulin secreting mechanisms was studied in normal micein vivo. Pretreatment of the animals withL-5-hydroxytryptophan (L-5-HTP) markedly decreased the insulin releasing capacity after sulphonylurea stimulation. This inhibition of insulin release could be abolished by previous administration of an inhibitor of aromatic amino acid decarboxylation. On the other hand, pretreatment with the monoamine oxidase inhibitor nialamide alone, decreased sulphonylurea-induced insulin release. The combined treatment with nialamide andL-5-HTP did not further decrease the insulin response. Insulin release induced byL-isopropylnoradrenaline (L-IPNA) was also found to diminish after previous administration ofL-5-HTP or nialamide; but, unlike the insulin response to sulphonylurea, insulin release induced by IPNA could be totally suppressed by the combined treatment of nialamide or pargyline andL-5-HTP. Insulin release induced by glucose was not significantly influenced with any of the above treatments. Basal levels of plasma insulin were not affected byL-5-HTP injection, and were not consistently diminished by the combined treatment with monoamine oxidase inhibitor andL-5-HTP. The combined treatment with monoamine oxidase inhibitors andL-5-HTP was found to elicit a profound hypoglycaemia in both normal and alloxan-diabetic mice. The hypoglycaemic condition was accompanied by exhaustion of liver and muscle glycogen. The hypoglycaemia could be abolished by previous treatment with an inhibitor of aromatic amino acid decarboxylation. Combined treatment with pargyline and 5-HT brought about a marked hyperglycaemia. It is concluded that: 1. intracellular levels of 5-HT in the pancreatic B cells possess the ability to modify insulin secreting mechanisms; and 2. the hypoglycaemic action of monoamine oxidase inhibitors is brought about by raised intracellular levels of 5-HT, which is accompanied by a markedly increased glucose utilization by the tissues.
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  • 3
    ISSN: 1432-0428
    Keywords: Blood glucose ; glibenclamide ; immunoreactive insulin ; isopropylnoradrenaline ; mouse ; pancreatic islets ; ultrastructure ; vinblastine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of vinblastine in vivo on ultrastructure and insulin releasing capacity of the B-cell was studied in mice. Treatment with vinblastine (1.1 μmole/mouse) resulted in a 75% decrease of the amount of normal microtubules and the appearance of characteristic paracrystals. Basal plasma immunoreactive insulin levels were depressed to about 60% of the control level. The dose-response pattern for insulin release (first phase) following two chemically unrelated insulin secretagogues, the potent sulphonylurea derivative, glibenclamide, and the β-adrenergic agonist L-isopropylnoradrenaline, (L-IPNA), was tested with and without vinblastine pretreatment. The dose-response curves for L-IPNA-induced insulin release in vinblastine-treated and control animals did not deviate significantly from each other, whereas insulin release following glibenclamide was almost totally suppressed by vinblastine except at the lowest dose level. Injection of maximal doses of glibenclamide or L-IPNA did not alter the ultrastructural changes induced by vinblastine in the B-cells. It is suggested that the microtubular system of the B-cell might play a minor role for certain insulin-releasing processes and/or that vinblastine might have other important effects on the insulin secretory machinery.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: B-cell ; B-cell granules ; DOPA ; dopamine ; electron microscopic autoradiography ; glibenclamide ; glucose ; insulin secretion ; isopropylnoradrenaline ; mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation and subcellular localization of dopamine (DA) in pancreatic B-cells and its effects on insulin secretion were investigated in mice following a single injection of L-3,4-dihydroxyphenyl-alanine (L-DOPA). Electron microscopic autoradiography showed that3H-DA formed from administered3H-DOPA was present over B-cells as well as over other types of islet cells. Pretreatment of the animals with a decarboxylase inhibitor greatly reduced the number of autoradiographic grains. In the B-cells the3H-DA-grains were associated with the secretory granules. The location of the label may suggest an incorporation in the periphery of the β-granule, rather than in the dense core, supposed to contain insulin. Accumulation of DA in the B-cells following L-DOPA administration was found to inhibit partially the insulin secretory response to different insulin secretagogues (glucose, glibenclamide and L-isopropylnoradrenaline (L-IPNA)). Treatment with monoamine oxidase inhibitor + L-DOPA induced an almost total suppression of L-IPNA-stimulated insulin secretion, whereas glucose-induced insulin release was still only partially inhibited. Pretreatment with a decarboxylase inhibitor abolished the effects of L-DOPA. It is suggested that intracellularly accumulated DA in the B-cell exerts an inhibitory action on insulin releasing mechanisms induced by different secretagogues and that this action might involve interference with a calcium translocation process at the level of the secretory granule.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage (SAH) ; intracranial aneurysm ; vasospasm ; cerebral metabolism ; cerebral circulation time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A retrospective study of cerebral angiographies from 173 patients with subarachnoid haemorrhage (SAH) were investigated and divided into three groups. The diameters of the middle cerebral artery and the internal carotid artery were measured and correlated with time elapsing between the onset of SAH and the angiographic study. A significant (p〈0.001) reduction in vascular diameter was found at all levels of intraas well as extradural parts of the internal carotid artery in patients with aneurysms (group I). Also, bilateral angiographic investigation from 70 patients showed a significant (p〈0.001) reduction at all levels on both sides, regardless of whether aneurysms were present (group II) or not (group III). Moreover, the reduction in vascular diameter was more pronounced in patients with than in patients without aneurysms. The most pronounced reduction in vascular diameter was found in one of the extradural parts of the internal carotid artery in both group II and III. However, reduction in vascular diamter did not correlate significantly with the cerebral circulation time despite a tendency towards it. On the other hand, layering of the contrast medium along the posterior wall of the internal carotid artery was more often found in patients with prolongation in cerebral circulation time suggesting a reduced cerebral blood flow in these patients. It is suggested that the significant reduction in vascular diameter of intra-as well as extradural parts of the internal carotid artery, might reflect an adaptation to altered cerebral metabolism after SAH.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neurochirurgica 97 (1989), S. 146-149 
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage (SAH) ; blood brain barrier (BBB) ; positron emission tomography (PET)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 26 patients with subarachnoid haemorrhage (SAH) were investigated with 68-Ga-EDTA and positron emission tomography (PET) in order to evaluate the presence of a blood brain barrier (BBB) disturbance. Only one patient showed a BBB disruption. It is suggested that increased levels of substances with higher molecular weight than 68-Ga-EDTA in the cerebrospinal fluid (CSF) are the result of a change in the metabolism of the CSF and the brain tissue caused by a SAH.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta neurochirurgica 98 (1989), S. 164-166 
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage (SAH) ; glycosaminoglycans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixteen patients dying after subarachnoid haemorrhage (SAH) were investigated with regard to the presence of angiographic vasoconstriction and of glycosaminoglycans in samples from the main cerebral arteries. All patients had a statistically significant (p 〈 0.001) vasoconstriction at angiography performed before death. At morphological examination, the vessels of all patients showed signs of intimai thickening, necrosis of the media and leucocyte infiltration of the adventitia. The presence of glycosaminoglycans was determined semiquantitatively and did not differ from the values obtained from presumably normal controls. It is suggested that the angiographically verified vasoconstriction found after SAH as well as the morphological changes of the cerebral arteries are not related to a concentration increase of glycosaminoglycans.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 102 (1990), S. 171-174 
    ISSN: 1432-2072
    Keywords: Discrimination ; Avoidance ; PCP ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to performed an aversely motivated discriminative task in a shuttle-box. The administration of phencyclidine (PCP), 2 mg kg−1 SC at −20 min, produced disruption of discriminative performance and an increase in intertrial crosses. There were no changes in avoidance performance or in avoidance latency. Pretreatment with haloperidol, 0.1 or 0.2 mg kg−1 SC at −40 min, or remoxipride 8 mg kg−1 IP at −30 min, did not antagonize the PCP-induced disruption of discriminative performance, nor was the PCP-induced increase in number of intertrial crosses antagonized. In fact, there appeared to be a further increase in intertrial crosses, above PCP levels, by haloperidol treatment and this effect was statistically significant after remoxipride treatment. The present results, together with previous observations that alsod-amphetamine disrupts discriminative conditioned avoidance behavior, suggest the possibility that this model could be used in the search for new, non-dopaminergic, antipsychotic drugs.
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  • 9
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Sensorimotor gating ; Schizophrenia ; Medial geniculate body ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition of acoustic startle is the normal reduction in startle response to an intense auditory stimulus when this stimulus is immediately preceded by a weaker prestimulus. Previous studies have shown that several neuroanatomical structures and pathways in the brain are involved in the modulation of prepulse inhibition. In the present study, the functional importance of the medial geniculate body (MG) in the modulation of prepulse inhibition was investigated. To this end, in vivo brain microdialysis probes were used to infuse drugs locally into the MG of awake, freely moving rats simultaneously with startle response and prepulse inhibition measurements in the same animals. Intrageniculate infusion of the sodium channel blocker, tetrodotoxin, significantly reduced prepulse inhibition without affecting baseline startle amplitude. A similar effect was obtained after intrageniculate infusion of the GABAB receptor agonist, baclofen. In addition, intrageniculate infusion of muscimol, an agonist at the GABAA receptor complex, reduced prepulse inhibition, although this effect was obtained at a higher concentration of the drug compared to that of baclofen. These studies suggest that the MG is involved in the modulation of prepulse inhibition and that auditory signals relayed via the MG may be subjected to inhibitory control at this level, involving GABA neurotransmission.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 128 (1972), S. 406-425 
    ISSN: 1432-0878
    Keywords: Parafollicular Cells ; Rat ; Normalcalcemia ; Vitamin D2 ; Electronmicroscopy ; Histochemical fluorescence method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Thyroid parafollicular cells of normocalcemic and vitamin D2-treated rats were investigated by electron microscopy and with the histochemical fluorescence technique of Hillarp and Falck. Administration of high doses of vitamin D2 caused hypercalcemia and an extensive degranulation of the parafollicular cells. The formation and storage of monoamines in granulated and degranulated parafollicular cells was investigated by fluorescence microscopy after injection of monoamine precursors (DOPA, 5-HTP), alone or in combination with Ro 4-4602, nialamide or reserpine. No fluorescence was observed in parafollicular cells of untreated rats. l-DOPA and l-5-HTP (but not the corresponding D-amino acids) were taken up by a process closely linked to the decarboxylation of the amino acids to the corresponding amines (dopamine and 5-hydroxytryptamine). Treatment with vitamin D2 did not seem to affect the formation of amines in the parafollicular cells or the formation and storage of amines in other cell systems investigated. The amine itself (dopamine) was not taken up by the parafollicular cells. In normocalcemic rats, the amine formed was retained in the cytoplasm of the parafollicular cells by a partially reserpine-resistant mechanism. The storage of amines is concluded to occur in association with the calcitonin-containing granules. In parafollicular cells of vitamin D2-treated rats, a certain amount of amine was bound in the cytoplasm in the absence of typical granules. As a considerable amount of calcitonin is known to remain in the thyroid of vitamin D2-treated rats, the present observations may indicate an association between the amine and the polypeptide hormone calcitonin, whether the latter is confined to typical granules or not.
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