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101.
102.
Purpose. Ketamine is known to interact with opioid receptors. However, because this agent does not produce opioid-like respiratory
depression, it might not interact with μ2 opioid receptors. Therefore, we have studied the interaction of ketamine with μ2 opioid receptors expressed in SH-SY5Y cells.
Methods. SH-SY5Y cells (passage 70–80) were used to obtain ketamine dose-response curves for inhibition of 0.4 nM [3H][d-Ala2,MePhe4,Gly(ol)5] enkephalin (DAMGO) binding to μ2 opioid receptors and of forskolin (1 μM)-stimulated cyclic AMP (cAMP) formation.
Results. Ketamine displaced [3H]DAMGO binding in SH-SY5Y cells with a K
i of 12.1 μM. However, this concentrations did not inhibit forskolin-stimulated cAMP formation, although at supraclinical concentrations,
significant inhibition was observed with an estimated IC50 of 700 μM.
Conclusion. The present study indicates that a clinically relevant concentration of ketamine interacts with μ2 opioid receptors. However, no agonist activity was observed.
Received for publication on September 10, 1998; accepted on January 5, 1999 相似文献
103.
104.
The objective of this study was to investigate whether nitric oxide (NO) inhalation might be an alternative strategy as a chemical assist for the circulation in patients showing a deterioration in oxygen delivery. Twelve adult patients whose oxygen delivery indices (DO2I) were less than 400 ml/min/m2 after cardiovascular surgery were included in this study. NO was administered via a premixing system or a side stream system at doses between 1 and 10 (5.1+/-2.4) ppm. Data obtained before and during a 120 min NO inhalation were compared using the paired Student's t-test. The increase in PaO2/FiO2 resulting from NO inhalation was significant (from 162 to 251 mm Hg). DO2I increased significantly from 326 to 417 ml/min/m2 concomitantly with significant increases in both arterial oxygen content (CaO2) and cardiac index (CI) (from 14.1 to 15.4 vol% and from 2.31 to 2.71 L/min/m2 , respectively). The increase in SvO2 during NO inhalation was significant (from 55.2 to 62.6%). Among the other hemodynamic parameters, both total pulmonary resistance and systolic pulmonary arterial pressure (SPAP) showed significant decreases during NO inhalation, but right atrial pressure did not change significantly. There was a close relationship between the baseline SPAP level (bSPAP) and the decrease in SPAP during NO inhalation (dSPAP) (r = -0.88). However, negative correlations were observed between bSPAP and percentage increase in CI (%CI) (r = -0.61) and between bSPAP and percentage increase in DO2I (%DO2I) (r = -0.48). Moreover, positive relationships were observed between dSPAP and %CI (r = 0.62) and between dSPAP and %DO2I (r = 0.45). Hemoglobin (Hb) increased significantly from 11.0 to 11.4 g/dl. There were no significant changes in Fio2, pH, PacO2, or base excess (BE) during NO inhalation. The level of methemoglobin measured during the study period remained within the normal range (0.86+/-0.23%). In conclusion, NO inhalation could be an efficient and alternative assist for the circulation in patients whose oxygen delivery deteriorates after cardiovascular surgery. 相似文献
105.
This paper examines the amount of variation among centres and estimates the overall effect of therapy in a multi-centre cancer clinical trial with censored failure time data. To investigate the centre effects, the variation in the treatment effect must be taken into consideration in addition to the variation in the baseline risk. We treat centre effects as random ones and extend the penalized partial likelihood approach proposed by McGilchrist to estimate the treatment-by-centre interaction as well as the baseline risk. This method is applied to data from a superficial bladder cancer clinical trial investigating the efficacy of intravesical chemotherapy after transurethral resection. In this trial, although there exists some degree of centre variation, especially in the baseline risk, the treatment is effective in preventing recurrence among the participating centres. This result indicates that the treatment effect is generalizable to the target population. 相似文献
106.
The effect of tulobuterol tape on histamine-induced bronchoconstriction in conscious guinea pigs: long duration of action 总被引:2,自引:0,他引:2
Musoh K Kawamura K Miyake I Shimada S Ohashi T Iwanaga Y Morikawa K Kato H 《Japanese journal of pharmacology》1999,79(3):401-402
The objective of the present study was to determine the action duration of tulobuterol tape within a 24-hr period in conscious guinea pigs. The bronchoconstriction induced by histamine-inhalation was significantly inhibited by tulobuterol tape in comparison with its placebo tape 8 and 12 hr after binding, and the inhibitory rate was 50+/-11% and 35+/-13%, respectively. Twenty-four hours after binding, the inhibitory effect of tulobuterol tape gradually diminished, but the inhibitory rate was maintained at 30+/-14%. These results suggest that tulobuterol tape has a long lasting bronchodilatory action. 相似文献
107.
Tetsumi Sato Kazuyoshi Hirota Akitomo Matsuki Elemer K. Zsigmond Sara F. Rabito 《Journal canadien d'anesthésie》1996,43(2):172-178
Purpose
Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca++-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of α-adrenoceptors to the relaxant effect of D in vitro.Methods
Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode’s solution, aerated with a mixture of 95% O2 and 5% CO2 at 37°C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph.Results
We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 × 10?6 M D blocked the effect of 10?4 M 5-HT by 44.1 ± 4.3% and at 2.5 × 10?6 M by 63.8 ± 3.8%. Similarly, at 5.0 × 10?6 M concentration, D blocked the effect of 10?5 M H by 27.7 ± 5.3% and at 10?5 M by 56.2 ± 2.6%. Furthermore, 5 ×10?6 M of D reduced the contractions produced by 10?7 M C by 37.1 ± 3.0% and 70?5 M of D by 76.1 ± 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (70?6 M) affected neither 5-HT-induced contractions nor the inhibition by D.Conclusion
Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways. 相似文献108.
J. Y. Lew F. Hata T. Ohashi M. Goldstein 《Journal of neural transmission (Vienna, Austria : 1996)》1977,41(2-3):109-121
Summary Bromocriptine and lergotrile, which are clinically used as antiparkinsonian (AP) agents, compete for the binding of H3-dopamine, H3-apomorphine, and H3-haloperidol to striatal membrane sites. Lergotrile has a higher affinity for the H3-dopamine binding to bovine striatal membranes than bromocriptine. Lergotrile and bromocriptine are almost equipotent in competing for the binding of H3-apomorphine to rat striatal membranes, but bromocriptine is more potent in competing for the binding of H3-haloperidol than lergotrile. These results indicate that lergotrile and bromocriptine are mixed putative agonist-antagonist with respect to the postsynaptic dopamine receptors. Lergotrile and bromcriptine at higher concentrations inhibit synaptosomal tyrosine hydroxylase activity, and reverse the apomorphine elicited enzyme inhibition. Thus, these ergot alkaloids behave as mixed agonist-antagonist also with respect to the presynaptic dopamine receptors. Bromocriptine and lergotrile, as well as other tested DH-ergot alkaloids and neuroleptics, compete for the binding of the-antagonist H3-WB-4101 to rat cerebral cortical membranes. The displacing potencies of the tested DH-ergot alkaloids and of the neuroleptics indicate that they have a high affinity for the-adrenoreceptors in the CNS. 相似文献
109.
Recent researches on the rickettsial group microorganisms are summarized in their comparative aspects of morphology, cultivation and multiplication, susceptibility to chemotherapeutics, chemical structure of envelopes, nucleic acid, protein constitution, and gene structures. From this overview, Rickettsia tsutsugamushi seems to have different properties from the others and should be reclassified into a new genus, and a new species name as Orientia tsutsugamushi is proposed.Presented at the 4th International Symposium on Rickettsiae and Rickettsial Diseases, Pietany, C.S.F.R., 1–6 October, 1990. 相似文献
110.
E Suzuki E Okamoto K Kuwata I Sugawara S Ohashi T Hida A Kyo A Shu T Muraji 《Nippon Heikatsukin Gakkai zasshi》1979,15(4):309-314
A simultaneous manometric monitoring of the common bile duct (CBD) and the duodenum were performed 2 weeks after choledocholithotomy on 15 patients whose common bile ducts were explored without sphincteroplasty and 30 patients with sphincteroplasty. These manometric studies were carried out by open-tip catheters intubated into the CBD and duodenum through the T-tube at the operation. In patients without sphincteroplasty, no effects of the duodenal pressure on a CBD pressure profile were recognized, while a synchronized pressure profile of the CBD and the duodenum was obtained in patients with sphincteroplasty. By stimulation with morphine (Morphine sulfate; 0.17 mg/Kg iv bolus), waxing and waning of the pressured in the CBD without sphincteroplasty were observed with 20 cmH2O in maximum at about 13 minutes after injection. However, in the CBD with sphincteroplasty, scale-over increase of the pressure curve was seen immediately after duodenal contraction caused by morphine stimulation. A direct infusion of 5 ml of 0.1 N hydrochloride to the duodenum causes hyperperistalsis of the duodenum, which made a synchronized pressure profile in the CBD with sphincteroplasty but made no remarkable change in a pressure profile of the CBD without sphincteroplasty. These findings conclude that the sphincter of Oddi plays an important role as a "pressure barrier" between the CBD and the duodenum, and that with the destruction of this sphincter by sphincteroplasty, a pressure profile of the CBD becomes close to that of the duodenum. This simultaneous manometric study of the CBD and the duodenum might be one of most valuable methods for evaluation of completeness of the sphincteroplasty. 相似文献