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51.
Theo F. Meert Carlos J. E. Niemegeers Frans Awouters Paul A. J. Janssen 《Drug development research》1988,13(4):237-244
A series of test compounds were studied for their ability to inhibit and block the head-twitch response to either intraperitoneal (i.p.) 5-hydroxytryptophan (5-HTP) or intravenous (i.v.) mescaline in rats. Both responses were found to be sensitive to serotonin S2 antagonists, and there was very good agreement between the inhibitory doses in both tests, particularly for the selective serotonin S2 antagonists ritanserin and seganserin. However, these two compounds did not block the 5-HTP response, although they completely abolished the mescaline response. In contrast, the mixed serotonin-dopamine-norepinephrine antagonist risperidone was a potent blocker of both responses. The use of various antagonists and the combination treatments of ritanserin with haloperidol or prazosin indicated that the 5-HTP response is abolished when potent serotonin S2 antagonism is associated with antagonistic activity on either dopamine D2 or α1 receptors. 相似文献
52.
Hydroxypropyl-beta-cyclodextrin increased the effectiveness of sufentanil after epidural and intrathecal administration in rats, both in terms of a longer duration of analgesia after a fixed dose of sufentanil, and in a reduction of the lowest ED50s to produce analgesia. There was also an increase in specificity, as indicated by the greater dissociation between the ED50s for analgesia and for supra-spinal side-effects. Maximal activity was measured after inclusion complexation of sufentanil in 10% hydroxypropyl-beta-cyclodextrin. At higher concentrations of hydroxypropyl-beta-cyclodextrin, both the activity and the specificity were attenuated. The increased safety of sufentanil in 10% hydroxypropyl-beta-cyclodextrin after spinal administration was also confirmed in terms of opioid-induced deviations in arterial PO2, PCO2 and oxygen saturation. At a dose of twice the ED50 for deep surgical analgesia, the sufentanil/hydroxypropyl-beta-cyclodextrin complex produced no changes in these parameters. With sufentanil alone at comparable analgesic doses, significant shifts in all three parameters were present immediately after drug administration. At higher concentrations of sufentanil in hydroxypropyl-beta-cyclodextrin changes in the three blood gases were present but the deviations were always smaller than those observed with comparable doses of plain sufentanil. These results support the notion that after complexation sufentanil is present longer at the spinal level after spinal administration. As a consequence, there is less free sufentanil available for redistribution into lipid tissue and into the circulatory system, producing less systemic side-effects. 相似文献
53.
T. F. Meert 《Pharmacy World & Science》1996,18(1):1-15
The clinically available opiolds have different physicochemical properties, resulting in differences in clinical profile with regard to potency, onset, and duration of activity. However, they all have comparable side-effects after acute systemic application. Several approaches can be used to overcome these side-effects. The following approaches, with special emphasis on the perioperative use of the opioids, are discussed: (1) the use of alternative routes of administration, such as via the spine (epidurally and intrathecally); (2) optimization of opioid delivery by means of slow-release preparations, chronic infusions with indwelling catheters, and transdermal delivery systems; (3) use of additional agents to potentiate the analgesic properties of the oploids so that the dose of oploid can be reduced; and (4) searching for new analgesics on the basis of knowledge of the pain-transmission system and the different opioid receptors with their functional interactions. 相似文献
54.
Rats given a 10% (v/v) alcohol liquid diet over two weeks reached high blood alcohol levels of around 200mg/dl. Discontinuation of the alcohol intake resulted within 6h in several withdrawal reactions including a tremorogenic activity and a reduction in exploratory behaviour in novel environments. The tremorogenic activity of the alcohol withdrawal could be quantified, using a piezo-film technique, in terms of a supersensitivity to both an inactive and a moderately active dose of the tremorogenic compound harmine. As compared to controls, the rats in alcohol withdrawal revealed more frequent tremor after both 5 and 10mg/kg harmine. The supersensitivity to harmine-induced tremor started within 6h after alcohol withdrawal and remained present with 10mg/kg harmine for up to 48h. The supersensitivity was independent of the length of the tremor bursts used to quantify harmine-induced tremor. Alcohol withdrawal also resulted in an inhibition of exploratory behaviour in a neutral two-chamber box. Both in terms of the number of transits into the open field as well as the time spent in the open area, rats in alcohol withdrawal were significantly less active than control animals. The reduced exploration started within 6h after withdrawal and remained present for up to 24h after the last alcohol intake. These results indicate that both alcohol withdrawal-induced sensitivity to tremorogenic agents and inhibition of exploratory behaviour can be quantified over time, allowing the pharmacological mechanisms involved to be studied. 相似文献
55.
Meert TF 《Behavioural pharmacology》1992,3(2):149-154
Rats given a subchronic cocaine treatment for 10 days display an inhibition of exploratory behaviour 24h after the last cocaine treatment in the open field test. As compared to the vehicle controls, the exploratory inhibition could be measured in terms of a longer latency to enter the open area, a reduction in the time spent in the open field and a decrease in the number of transits from the small dark compartment into the open area. The serotonin (5-HT(2/1C)) antagonist ritanserin, given subcutaneously 1h prior to testing, overcame this behavioural inhibition. At doses between 0.04mg/kg and 10.0mg/kg ritanserin, a complete normalization of exploratory activity was obtained. In chronic vehicle treated rats, ritanserin did not increase exploration. Therefore the effects of ritanserin cannot be attributed to a general activation. The results are discussed with regard to withdrawal anxiety and a possible therapeutic role of ritanserin in drug addicts. 相似文献
56.
Lin Alexander J. Campian Jian L. Hui Caressa Rudra Soumon Rao Yuan J. Thotala Dinesh Hallahan Dennis Huang Jiayi 《Journal of neuro-oncology》2018,136(2):403-411
Journal of Neuro-Oncology - Prolonged severe lymphopenia has been shown to persist beyond a year in glioma patients after radiation therapy (RT) with concurrent and adjuvant chemotherapy. This... 相似文献
57.
58.
J P Sculier J J Lafitte M Paesmans J Lecomte C G Alexopoulos O Van Cutsem V Giner A Efremidis M C Berchier T Collon A P Meert A Scherpereel V Ninane G Koumakis M M Vaslamatzis N Leclercq T Berghmans 《The European respiratory journal》2007,30(6):1186-1192
The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60-70 on the Karnofsky scale. Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy. Of the patients, 80% had good PS (Karnofsky 80-100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2 versus 2.1%). In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status. 相似文献
59.
Comette P D'Hoore W Malhomme B Van Pee D Meert P Swine C 《Aging clinical and experimental research》2005,17(4):322-328
BACKGROUND AND AIMS: This study aimed at analyzing rates and factors associated with early and later readmission (0-1 month and 2-3 months after discharge, respectively) of older people after index hospitalization. METHODS: This prospective observational study was conducted in two teaching hospitals. People 70 years and over were interviewed within 48 h of emergency admission. Socio-demographic and medical factors were collected, together with functional factors including Activities of Daily Living (basis and instrumental), cognitive state, and geriatric syndromes. Medical diagnosis, length of stay, and destination were collected at discharge, and patients were followed up by phone 1 and 3 months after discharge. During these interviews, outcomes on readmission, institutionalization, need for help, and death were evaluated. RESULTS: The population of 625 patients had a mean age of 80.0 years. The rate of early readmission (01 month) was 10. 7% and the overall rate within 3 months was 23.1%. Logistic regression analysis showed that variables predicting early readmission were previous hospitalization within 3 months, a longer length of stay, and a discharge diagnosis in chapter 8 (respiratory system) and chapter 10 (genito-urinary system) of the ICD-9-CM. Variables predicting later readmission were previous hospitalization within 3 months, a discharge diagnosis in chapter 7 (circulatory system) of the ICD-9-CM, and a poor pre-admission IADL score. CONCLUSIONS: In a medicalized population of older people, several risk factors may be identified for 0-1 month and 2-3 month readmission. Besides severe morbidities at discharge, diagnoses and previous hospitalization, pre-admission IADL was an independent risk factor for 2-3 month readmission. 相似文献
60.
Jun-Jie Li Caressa N. Spychala Fupin Hu Ji-Fang Sheng Yohei Doi 《Antimicrobial agents and chemotherapy》2015,59(6):3002-3007
Community-associated infections due to Escherichia coli producing CTX-M-type extended-spectrum β-lactamases are increasingly recognized in the United States. The blaCTX-M genes are frequently carried on IncF group plasmids. In this study, blaCTX-M-15-harboring plasmids pCA14 (sequence type 131 [ST131]) and pCA28 (ST44) and blaCTX-M-14-harboring plasmid pCA08 (ST131) were sequenced and characterized. The three plasmids were closely related to other IncFII plasmids from continents outside the United States in the conserved backbone region and multiresistance regions (MRRs). Each of the blaCTX-M-15-carrying plasmids pCA14 and pCA28 belonged to F31:A4:B1 (FAB [FII, FIA, FIB] formula) and showed a high level of similarity (92% coverage of pCA14 and 99% to 100% nucleotide identity), suggesting a possible common origin. The blaCTX-M-14-carrying plasmid pCA08 belonged to F2:A2:B20 and was highly similar to pKF3-140 from China (88% coverage of pCA08 and 99% to 100% nucleotide identity). All three plasmids carried multiple antimicrobial resistance genes and modules associated with virulence and biochemical pathways, which likely confer selective advantages for their host strains. The blaCTX-M-carrying IncFII-IA-IB plasmids implicated in community-associated infections in the United States shared key structural features with those identified from other continents, underscoring the global nature of this plasmid epidemic. 相似文献