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  • 1995-1999  (4)
  • Autoreceptors  (2)
  • toxicity  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Effect of chronic administration of the selective serotonin (5-HT) uptake inhibitor citalopram on extracellular 5-HT and apparent autoreceptor sensitivity in rat forebrain in vivo (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 597-606 
    Details
    ISSN: 1432-1912
    Keywords: Key words Microdialysis ; 5-HT release ; Chronic antidepressant ; Citalopram ; 5-HT reuptake inhibitor ; Tolerance ; Autoreceptors ; Frontal cortex ; Dorsal hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats were administered the selective serotonin (5-HT) uptake blocker citalopram or saline for 14 days to determine if prolonged treatment would lead to changes in extracellular 5-HT or autoreceptor sensitivity. One day after drug withdrawal, dialysis probes were implanted in the frontal cortex and dorsal hippocampus. Dialysis experiments were carried out using chloral hydrate anesthetized rats. The experimental protocol comprised the administration of three consecutive drug challenges: (1) After stable baseline levels were obtained, citalopram was infused through the dialysis probes to locally block uptake in the forebrain. (2) Subsequently, a 5-HT1B receptor agonist (RU24969 or CP93,129) was infused through the probe to test for changes in terminal autoreceptor sensitivity. (3) Last, citalopram was administered systemically to test the effect of indirect activation of somatodendritic autoreceptors. Under these conditions, with uptake already blocked locally in the forebrain, systemic citalopram produces a decrease in extracellular 5-HT, an effect that can be inhibited by pretreatment with antagonists of 5-HT1A receptors. The results indicate that during local infusion of citalopram extracellular 5-HT was significantly higher in the dorsal hippocampus of the chronic citalopram as compared to saline treatment group. This difference persisted throughout the full time course of the experiment. However, the decreases in 5-HT levels produced by local infusion of a 5-HT1B receptor agonist or after systemic citalopram administration were not significantly different between the chronic citalopram and saline treated groups. There were no significant differences between chronic citalopram and saline treated animals in frontal cortex. These results suggest that prolonged inhibition of 5-HT uptake may produce a selective change in the regulation of release from median raphe 5-HT neurons, but this change could not be clearly linked to a change in nerve terminal or somatodendritic autoreceptor sensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171317
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Effect of chronic administration of the selective serotonin (5-HT) uptake inhibitor citalopram on extracellular 5-HT and apparent autoreceptor sensitivity in rat forebrain in vivo (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 597-606 
    Details
    ISSN: 1432-1912
    Keywords: Microdialysis ; 5-HT release ; Chronic antidepressant ; Citalopram ; 5-HT reuptake inhibitor ; Tolerance ; Autoreceptors ; Frontal cortex Dorsal hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were administered the selective serotonin (5-HT) uptake blocker citalopram or saline for 14 days to determine if prolonged treatment would lead to changes in extracellular 5-HT or autoreceptor sensitivity. One day after drug withdrawal, dialysis probes were implanted in the frontal cortex and dorsal hippocampus. Dialysis experiments were carried out using chloral hydrate anesthetized rats. The experimental protocol comprised the administration of three consecutive drug challenges: (1) After stable baseline levels were obtained, citalopram was infused through the dialysis probes to locally block uptake in the forebrain. (2) Subsequently, a 5-HT1B receptor agonist (RU24969 or CP93,129) was infused through the probe to test for changes in terminal autoreceptor sensitivity. (3) Last, citalopram was administered systemically to test the effect of indirect activation of somatodendritic autoreceptors. Under these conditions, with uptake already blocked locally in the forebrain, systemic citalopram produces a decrease in extracellular 5-HT, an effect that can be inhibited by pretreatment with antagonists of 5-HT1A receptors. The results indicate that during local infusion of citalopram extracellular 5-HT was significantly higher in the dorsal hippocampus of the chronic citalopram as compared to saline treatment group. This difference persisted throughout the full time course of the experiment. However, the decreases in 5-HT levels produced by local infusion of a 5-HT1B receptor agonist or after systemic citalopram administration were not significantly different between the chronic citalopram and saline treated groups. There were no significant differences between chronic citalopram and saline treated animals in frontal cortex. These results suggest that prolonged inhibition of 5-HT uptake may produce a selective change in the regulation of release from median raphe 5-HT neurons, but this change could not be clearly linked to a change in nerve terminal or somatodendritic autoreceptor sensitivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171317
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Treatment of advanced pancreatic carcinoma with a combination of protracted infusional 5-fluorouracil and weekly carboplatin: A Mid-Atlantic Oncology Program study (1997)
    Springer
    Annals of oncology 8 (1997), S. 439-444 
    Details
    ISSN: 1569-8041
    Keywords: carboplatin ; fluorouracil ; pancreatic carcinoma ; response ; survival ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Advanced pancreatic cancer is a rapidly fatal disease whosecourse has been little influenced by chemotherapy. Earlier studies have shownsome modest promise for the combination of protracted infusional5-fluorouracil (PIF)and cisplatin. We sought to evaluate a regimen of possibly lesser toxicity,PIF plus weekly carboplatin. Patients and methods: Fifty-four patients with advanced adenocarcinoma ofthe pancreas were treated with a regimen of protracted infusional fluorouracil300 mg/m2/day for 70 days and carboplatin 100mg/m2/weekly on weeks 1 through 10 of a 12-week cycle. Aftera two-week rest, cycles were repeated until progression. Results: Median duration on treatment was 82 days (range 4–490 days).Toxicity was mild. Grade 3–4 toxicities were anemia 11%,leukopenia 6%, thrombocytopenia 2%, nausea/vomiting 7%,diarrhea 9%, mucositis 9%, and renal 2%. Response wasevaluable in 47 patients. There were two complete and seven partial responses(17% overall objective response rate among all patients). Stabledisease for greater than 12 weeks was seen in 19 patients (40%) andprogression in 19 (40%). The median overall survival was 22 weeks(1–99), with 61 weeks median survival in responders (22–99).One-year survival was 13%. Conclusions: Response and survival results with this regimen are at leastequal to the best combination regimens reported, and were obtained with a lowoverall rate of serious toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008299429294
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Impacts of ocean CO2 disposal on marine life: I. A toxicological assessment integrating constant‐concentration laboratory assay data with variable‐concentration field exposure (1997)
    Springer
    Environmental modeling and assessment 2 (1997), S. 333-343 
    Details
    ISSN: 1573-2967
    Keywords: carbon dioxide ; sequestration ; plume ; pH ; toxicity ; zooplankton
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Feasibility studies suggest that the concept of capturing CO2 from fossil fuel power plants and discharging it to the deep ocean could help reduce atmospheric CO2 concentrations. However, the local reduction in seawater pH near the point of injection is a potential environmental impact. Data from the literature reporting on toxicity of reduced pH to marine organisms potentially affected by such a plume were combined into a model expressing mortality as a function of pH and exposure time. Since organisms exposed to real plumes would experience a time‐varying pH, methods to account for a variable exposure were reviewed and a new method developed based on the concept of isomortality. In part II of this paper, the method is combined with a random‐walk model describing the transport of passive organisms through a low pH plume leading to a Monte‐Carlo‐like risk assessment which is applied to several candidate CO2 injection scenarios.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019029931755
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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