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1.
P. V. Luoma A. Rautio J. Steng»rd E. A. Sotaniemi J. Marniemi 《European journal of clinical pharmacology》1990,38(6):625-627
Summary Serum high density lipoprotein (HDL) subfractions HDL2 and HDL3, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL2 cholesterol concentrations and HDL cholesterol/cholesterol and HDL2/HDL3 cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL. 相似文献
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Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were
subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received
ICV infusions with 100 μg corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at
the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene, glycol)
did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (≈0.5 g/kg per day), also showed a
robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (≈3.0 g/kg per
day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular
mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol
consumption by acting in the brain, probably by way of neuronal membrane mechanisms. 相似文献
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Sven Ove Ögren H»kan Hall Christer Köhler Olle Magnusson Sven-Erik Sjöstrand 《Psychopharmacology》1986,90(3):287-294
The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50=32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50>100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50>100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat. 相似文献
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Summary In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o. d. as a controlled release formulation, and omeprazole 40 mg o. d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism.As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family. 相似文献
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Early experiences with laparoscopic fundoplication using the Rosetti technique are presented and compared with retrospective results from conventional fundoplication procedures. A 360° floppy fundoplication was laparoscopically constructed without division of short gastric vessels. We have performed 60 consecutive procedures. Conversion to open surgery was done in seven cases due to anatomical reasons and in two due to progressive subcutaneous emphysema and CO2-retention. The complication rate was low. The range of postoperative hospital stay is 1–4 days for non-converted patients. Symptomatic follow up has hitherto been performed in 41 patients with a follow-up time of 3–9 months. Regurgitation and heartburn had disappeared in all but one patient. The follow-up results do not differ from those achieved in patients operated upon with the conventional open Nissen (N=41), Toupét (N=9) or Rosetti (N=36) technique. Pre and postoperative control of 24h pH and lower esophageal sphincter pressure (LESP) in 19 laparoscopically treated patients showed normalisation of LESP in all cases and postoperative 24h pH<4 ranging between 0 and 3%. Assessment of quality of life showed postoperative results in accordance with normal population for all treated groups. 相似文献
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L. St»hle 《European journal of clinical pharmacology》1993,45(5):477-481
Summary The calculation of classical pharmacokinetic parameters from microdialysis data has been described in a previous paper. In this paper I have derived methods for calculating AUMC and AUC from the time-integral type of data that are generated in microdialysis pharmacokinetics experiments. The method derived to estimate AUC is elementary, but is given a theoretical basis using principles of mathematical real analysis, clearly stating the assumptions.The method derived to estimate AUMC is a numerical approximation method based on the linear trapezoidal method. A simulation study was performed to evaluate the precision of the methods and to compare them with corresponding methods for analysis of blood sample data.The estimates from the presently derived methods have a small bias and a small variance. In the simulation study I investigated the influence of model parameters, number of samples, size of statistical error, and the size of the AUC beyond the last sample. Finally, I have given numerical examples from real data to illustrate the use of the method. 相似文献
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The present study investigated effects of methylphenidate on spatio-temporal distributions of responses generated by a fixed interval 60-s schedule of reinforcement. A response panel with 20 different response locations (holes) made it possible to distinguish effects of the drug on the procedurally-correct response (correct according to the contingencies) and effects on other topographically similar responses acting as functionally-adequate responses. Detailed flow charts show how the dynamics of responding changed with dose and segment of the fixed interval. The number of holes visited was increased after low and medium doses, but decreased after high doses. The spatial differences between responses in the initial and the final parts of the fixed interval gradually disappeared after 6 mg/kg or higher doses as the functionally-adequate responses moved to earlier segments of the fixed interval. Few results could, however, be described as response rate dependent. Distributions of responses around the correct hole illustrated differences between procedurally-correct and functionally-adequate classes. The number of holes included in the latter class changed by dose in an inverted U-shaped fashion. Perseverations and stereotyped responding increased with increasing dose. Most of the effects may be described as motor stimulatory. One way of explaining the stimulatory effect is in terms of a lengthened delay-of-reinforcement gradient. The rate-dependent effect of methylphenidate on the procedurally-correct class after some doses may have been due to the combined effects of a lengthened delay gradient increasing the response rates early in the interval and interference from perseverations having their most detrimental effects on the high rates late in the interval.
Offprint request to: T. Sagvolden 相似文献