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S. Hjorth A. Carlsson P. Lindberg D. Sanchez H. Wikström L. -E. Arvidsson U. Hacksell J. L. G. Nilsson 《Journal of neural transmission (Vienna, Austria : 1996)》1982,55(3):169-188
Summary It was demonstrated that the simplified ergot congener 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, is able to elicit pronounced biochemical and behavioural alterations indicative of central serotoninomimetic activity. Since these effects are resistant to prior monoamine depletion and/or synthesis inhibition by means of reserpine and-propyldopacetamide (H22/54), respectively, they are most likely to be attributable to direct serotonin-receptor agonism by 8-OH-DPAT. With regard to central 5-HT neurotransmission the effects of 8-OH-DPAT-increased 5-HT levels, decreased 5-HIAA levels, 5-HT-synthesis rate and 5-HT utilization and inhibited 5-HT neuronal firing-are virtually identical, and comparable in potency, to those reported to result from the administration of lisuride or LSD. In contrast, however, to lisuride and LSD (included for comparative purposes in this study) as well as to several differently N-substituted, 5,6-dihydroxy, 6,7-dihydroxy and 5-, 6- and 7-monohydroxy 2-aminotetralins, 8-OH-DPAT lacks appreciable effects on central catecholamine receptors. The compound may thus be regarded the most potent, selective centrally acting 5-HT agonist described to date. accordance with this it was shown that the full-blown 5-HT-like behaviour syndrome induced by 8-OH-DPAT cannot be antagonized by reserpin phenoxybenzamine, propranolol and haloperidol. In addition, of the truputative 5-HT-receptor blockers cyproheptadine, methergoline and methrothepin only the latter was able to counteract the 8-OH-DPAT-induce syndrome. The results are discussed in relation to the recent subclassification of central 5-HT receptor sites.A comparison between the chemical structures and biological activities for different fragments of the ergot nucleus was also made. The data suggest, in that while the role of the A ring in the ergot structure for dopaminer activity at present is unclear, this ring may be important for the 5-HT-receptor activity like in e.g. lisuride and LSD.Moreover, based on the present results and literature reports, it is speculated that a selective 5-HT-receptor agonist such as 8-OH-DPAT would be liable to induce hallucinations in man.Presented in part at the 19th ACNP meeting, San Juan, December 15–19,1980. [Psychoph. Bull.17, 180–183 (1981).] 相似文献
63.
Executive function and verbal working memory in adolescents with closed head injury (CHI) 总被引:3,自引:0,他引:3
The relationship between executive function (EF) and working memory (WM) was studied in eight adolescents with closed head injury (CHI) and eight controls, matched for age, gender and socioeconomic status (SES). A cognitive-linguistic test (Scales of Cognitive Ability for Traumatic Brain Injury, SCATBI) was used to group CHI participants by severity. EF was tested with a measure of daily functioning (Pro-Ex) and WM was tested with a recognition memory task (RMT). When all subject test data were grouped, a positive linear correlation was found for the Pro-Ex and the RMT. A strongto-moderate positive correlation was found for components of the EF measure and the RMT. Severity of injury influenced test performance for both the EF and WM measures, with a significance between group effects found on the RMT task. Results indicate a relationship between executive function and working memory, severity of injury and test performance and the need to assess EF of CHI adolescents with a measure of daily functioning. 相似文献
64.
The purpose of this study was to examine absorption of basic drugs as a function of the composite solubility curve and intestinally relevant pH by using a gastrointestinal tract (GIT) absorption simulation based on the advanced compartmental absorption and transit model. Absorption simulations were carried out for virtual monobasic drugs having a range of pKa, log D, and dose values as a function of presumed solubility and permeability. Results were normally expressed as the combination that resulted in 25% absorption. Absorption of basic drugs was found to be a function of the whole solubility/pH relationship rather than a single solubility value at pH 7. In addition, the parameter spaces of greatest sensitivity were identified. We compared 3 theoretical scenarios: the GIT pH range overlapping (1) only the salt solubility curve, (2) the salt and base solubility curves, or (3) only the base curve. Experimental solubilities of 32 compounds were determined at pHs of 2.2 and 7.4, and they nearly all fitted into 2 of the postulated scenarios. Typically, base solubilities can be simulated in silico, but salt solubilities at low pH can only be measured. We concluded that quality absorption simulations of candidate drugs in most cases require experimental solubility determination at 2 pHs, to permit calculation of the whole solubility/pH profile. 相似文献
65.
Tavernier B Sanchez R Pattou F Mallat J Sperandio M Proye C 《Annales fran?aises d'anesthèsie et de rèanimation》2000,19(1):54-61
OBJECTIVES: To evaluate the incidence of cardiac deaths following noncardiac nonvascular surgery. STUDY DESIGN: Retrospective survey. PATIENTS: All patients undergoing mainly endocrinous and digestive surgery in a University department of general surgery between 1991 and 1996. METHODS: Analysis of all deaths occurring intra- and postoperatively, until discharge of the patients. Demographic and medical data, including patent myocardial ischaemia and risk factors for coronary artery disease, were recorded and compared with a control group including all patients undergoing surgery from January to September 1996. RESULTS: In the 8,700 patients who underwent mainly endocrine neck surgery (66%), or intra-abdominal surgery (31%), the mortality rate (n = 96) was 1.1% (95% confidence interval [95% CI] = 0.9-1.3%). Patent myocardial ischaemia or high risk factors for coronary artery disease were existing in 24% of patients with neck surgery, 31% of those with intra-abdominal surgery, and in 60% of the deceased patients (P < 0.01 vs control group). Those who died were older, were in a higher ASA physical class, and had undergone an emergency procedure more often than patients of the control group (P < 0.002 for each parameter). Two cardiac deaths, in patients with a patent cardiopathy, were recorded (cardiac mortality: 0.02%; 95% CI = 0.003-0.08%). The main cause of death was infection (n = 46), followed by haemorrhage (n = 12). Seven deaths remained unexplained. CONCLUSION: This study suggests that cardiac morbidity is a rare cause of death after noncardiac nonvascular surgery. 相似文献
66.
V Alberola C Camps M Provencio D Isla R Rosell C Vadell I Bover A Ruiz-Casado P Azagra U Jiménez J L González-Larriba P Diz F Cardenal A Artal A Carrato S Morales J J Sanchez R de las Pe?as E Felip G López-Vivanco 《Journal of clinical oncology》2003,21(17):3207-3213
PURPOSE: To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). RESULTS: Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). CONCLUSION: On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC. 相似文献
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69.
Forte L Migliaccio G Sanchez M Migliaccio AR Passarelli AM Amadori S 《Annali dell'Istituto superiore di sanità》2000,36(3):333-342
The small volume of placental/umbilical cord blood (PUCB) collectable restricts the use of these stem cells to pediatric transplantation. To extend the use of PUCB to adult recipients, many laboratories are investigating the feasibility of ex vivo PUCB expansion. The present study analyses the effects that PUCB banking cell manipulations (cell sedimentation, cryopreservation and thawing, mononuclear and CD34+ cell isolation) have on the number, viability and ex vivo expansion potential of PUCB cells. The results presented indicate the necessity of an open discussion on whether procedures used for handling the cells in PUCB banks can be extrapolated or not as such to the clinical use of ex vivo expanded PUCB. 相似文献
70.