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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Portacaval anastomosis (PCA) in the rat is used as a model for portal systemic encephalopathy. Changes in the serotonergic, histaminergic, and catecholaminergic neurotransmitter systems are often found shortly after PCA. We have examined the long-term effects of PCA on the aminergic systems in brains of male Wistar rats, which 8 months previously had been subjected to PCA. Precursors, amines, and metabolites were assayed by HPLC. Eight months after PCA, the catecholamine levels were unchanged in all brain regions. In contrast, tryptophan was evenly increased throughout the brain. The accumulation of 5-hydroxytryptophan after decarboxylase inhibition (NSD-1015; 100 mg/kg i.p.) and the endogenous levels of 5-hydroxyindoleacetic acid were significantly higher in PCA rats, particularly in the hypothalamus and midbrain, whereas 5-hydroxytryptamine concentrations were unchanged. Histamine levels were elevated throughout the brain with the greatest increase found in the hypothalamus and in the striatum. tele-Methylhistamine levels were significantly elevated in cortex and hypothalamus. We conclude that 8 months after PCA, catecholaminergic systems had reestablished their homeostasis, whereas serotonergic and histaminergic systems still show profound disturbances in their function. With histamine, this is reflected as an increase in the amounts of both transmitter and metabolite; serotonergic neurons respond by increasing only the level of the metabolite.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 358 (1998), S. 574-581 
    ISSN: 1432-1912
    Keywords: Key words Portacaval anastomosis ; Brain histamine ; Histamine release ; Histamine H3 receptors ; Autoradiography ; [3H]-R-α-methylhistamine binding ; Thioperamide ; Microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The long-term effects of portacaval anastomosis (PCA) on histamine H3 receptors in rat brain were studied by in vitro and in vivo methods. The overflow of histamine from the anterior hypothalamus and from cortex after long-term PCA was determined by in vivo microdialysis. The binding properties of [3H]-R-α-methylhistamine in membranes from cortex, cerebellum, and rest of brain (ROB) were examined with saturation binding experiments. The regional distribution of [3H]-R-α-methylhistamine binding sites in the brain of sham- and PCA-operated rats was assessed also with autoradiography. The tissue levels of histamine were significantly elevated in cortex and ROB of PCA-operated rats. In addition, the spontaneous and K+-evoked overflow of histamine from anterior hypothalamus, and the thioperamide-induced overflow from both anterior hypothalamus and cortex were increased after chronic PCA. In spite of the significantly elevated tissue concentrations and the moderate increase in histamine release, the binding properties of [3H]-R-α-methylhistamine to cortical membranes were not significantly changed. However, the autoradiography study did reveal a decrease in [3H]-R-α-methylhistamine binding density, particularly in striatum and cortex, where H3 receptors are located mainly at non-histaminergic neurons. In conclusion, we suggest that there is a region-selective increase in the histaminergic activity in chronic PCA, which leads to the down-regulation of somadendritic and pre-synaptic H3 receptors located at non-histaminergic neurons. At the same time, the autoreceptor mediated control of histamine neuronal activity via pre-synaptic H3 receptors located at histaminergic neurons is preserved after long-term PCA.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Keywords: Key words Mitotic index ; Chemotherapy ; Sensitivity ; SRCA ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The subrenal capsule assay (SRCA) is used in clinical oncology to assess the sensitivity of individual malignant tumors to various anticancer agents and their combinations. Mitotic indices reflect cancer cell proliferation and have prognostic value in epithelial neoplasms, including ovarian carcinoma. We combined the two tests (SRCA, mitotic index) by evaluating the numbers of mitotic figures per square millimeter of neoplastic epithelium (M/V) in paraffin-embedded tumor samples after SRCA. The M/V index was compared with the tumor size measurement (dTS), which is used in conventional SRCA to predict the drug response. Histology examination showed insignificant changes in the size of tumor transplants due to host reaction but disclosed a number of potential errors in the use of dTS to evaluate transplant growth and drug effects. In our series of 62 patients with advanced ovarian carcinoma the M/V value was superior to the dTS in explaining the clinical response after 6 months as assessed at second-look laparotomy. Patients showing no response had significantly higher M/V values than did those displaying complete or partial responses (P 〈 0.033). The use of 6 mitotic figures/mm2 as a limit differentiating responders from nonresponders resulted in an overall predictive accuracy of 79% in the logistic regression analysis. In comparison to the FIGO stage, residual tumor size, and the dTS, the M/V value obtained for the cytostatic combination given to the patient was the single most significant factor predicting the 6-month clinical response. The results indicate that the combined use of the M/V index and SRCA is a promising new approach to prediction of the drug response in ovarian adenocarcinoma.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 44 (1995), S. S52 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1420-908X
    Keywords: Key words: Brain histamine — Growth hormone-blood — Growth rate — Portacaval anastomosis — Prolactin-blood
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Histamine can modulate feeding behaviour and hormone release; therefore we examined the hypothalamic histamine system, the growth pattern and the serum levels of prolactin and growth hormone in rats with portacaval anastomosis (PCA).¶Material: The growth rate of 30 PCA- and 30 sham-operated male Han:Wistar rats was monitored for 6 months. Thirteen sham and 9 PCA rats were used for biochemical studies.¶Methods: Histamine was assayed by HPLC, tele-methylhistamine by GC-MS, prolactin and growth hormone by RIA. Student's t-test was used to compare the groups.¶Results: Six months after surgery, the PCA rats exhibited marked growth retardation (weight gain of 20 g vs. 140 g for the sham rats; p 〈 0.001), increased plasma levels of prolactin (9.7 ± 2.4 vs. 3.6 ± 0.6; p 〈 0.01) and unaltered growth hormone levels (6.2 ± 0.5 vs. 8.1 ± 1.0). A six-fold elevation of histamine concentration (29.5 ± 3.9 vs. 4.8 ± 0.4; p 〈 0.001) and a two-fold increase of tele-methylhistamine levels (1.8 ± 0.1 vs. 0.8 ± 0.02; p 〈 0.001) were found in hypothalamus.¶Conclusion: We suggest that increased histaminergic activity in the hypothalamus may be involved in the development of growth retardation and in the enhanced basal secretion of prolactin in male rats with long-term PCA.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1463
    Keywords: Thioperamide ; H3 autoreceptors ; histamine ; portocaval anastomosis ; EEG ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histaminergic H3 receptor antagonists stimulate neuronal histamine release and could consequently have a number of physiological effects in the brain. The effects of H3 receptor blockade, induced by systemically administered thioperamide, were assessed on the frontal cortex electroencephalographic (EEG) properties in freely behaving rats. The relationship of EEG activity variables to endogenous brain histaminergic markers was also examined, both in controls and in portocaval anastomosis (PCA)-operated rats (which show increased levels of brain histamine and t-methylhistamine). Thioperamide reduced the incidence of thalamusregulated EEG spindles, while it slightly increased their amplitude. It furthermore reduced the spectral power of low-frequency (1.5–5 Hz) EEG, which effect was equally distributed over the spindle and non-spindle EEG states. These EEG effects were accompanied by increased motor activity of the animals. Both the low-frequency EEG activity and spindle incidence correlated inversely with the histamine level of the brain (hypothalamus and cerebellum excluded) while t-methylhistamine level correlated with the degree of thioperamide-induced reduction of slow-wave EEG activity. The present results provide evidence for the involvement of endogenous brain histamine level, histamine release (as assessed by t-methylhistamine level) and H3 receptors in the histaminergic regulation of neocortical synchronization patterns assumed to be linked to arousal control.
    Type of Medium: Electronic Resource
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