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991.
992.
S Roman FS Cusdin E Fonfria JA Goodwin J Reeves SC Lappin L Chambers DS Walter WC Clay AD Michel 《British journal of pharmacology》2009,158(6):1513-1526
Background and purpose:
Human and rodent P2X7 receptors exhibit differences in their sensitivity to antagonists. In this study we have cloned and characterized the dog P2X7 receptor to determine if its antagonist sensitivity more closely resembles the human or rodent orthologues.Experimental approach:
A cDNA encoding the dog P2X7 receptor was isolated from a dog heart cDNA library, expressed in U-2 OS cells using the BacMam viral expression system and characterized in electrophysiological, ethidium accumulation and radioligand binding studies. Native P2X7 receptors were examined by measuring ATP-stimulated interleukin-1β release in dog and human whole blood.Key results:
The dog P2X7 receptor was 595 amino acids long and exhibited high homology (>70%) to the human and rodent orthologues although it contained an additional threonine at position 284 and an amino acid deletion at position 538. ATP possessed low millimolar potency at dog P2X7 receptors. 2′-&3′-O-(4benzoylbenzoyl) ATP had slightly higher potency but was a partial agonist. Dog P2X7 receptors possessed relatively high affinity for a number of selective antagonists of the human P2X7 receptor although there were some differences in potency between the species. Compound affinities in human and dog blood exhibited a similar rank order of potency as observed in studies on the recombinant receptor although absolute potency was considerably lower.Conclusions and implications:
Dog recombinant and native P2X7 receptors display a number of pharmacological similarities to the human P2X7 receptor. Thus, dog may be a suitable species for assessing target-related toxicity of antagonists intended for evaluation in the clinic. 相似文献993.
994.
腹腔镜和开腹开窗术治疗肝囊肿的对照性研究 总被引:1,自引:0,他引:1
目的:研究腹腔镜和开腹开窗术治疗肝囊肿的疗效比较。方法:收集本院2006年5月~2010年8月外科收治的42例肝囊肿患者,随机分为腹腔镜肝囊肿开窗术22例(A组),开腹肝囊肿开窗术20例(B组),对两组手术过程中的住院时间、术中出血量、手术时间、功能恢复时间、症状的复发率以及囊肿的复发率进行统计学分析。结果:两组差异住院时间、术中出血量、手术时间以及功能恢复时间比较,差异有统计学意义(P〈0.05),两组复发率以及囊肿复发率比较无统计学意义(P〉0.05)。结论:腹腔镜开窗引流术与开腹开窗术比较具有手术时间短、术中出血量少、功能恢复时间较快且住院时间短等优点,在症状复发率及囊肿复发率与开腹手术相似,因此可以逐步取代传统的开腹手术,值得临床广泛推广。 相似文献
995.
CF Samer Y Daali M Wagner G Hopfgartner CB Eap MC Rebsamen MF Rossier D Hochstrasser P Dayer JA Desmeules 《British journal of pharmacology》2010,160(4):907-918
Background and purpose:
There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored.Experimental approach:
A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg−1 and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session.Key results:
CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and Cmax (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone Cmax was 62% and 75% lower in PM than EM and UM. Noroxymorphone Cmax reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone Cmax by 40% and 80%, and increased noroxycodone AUC∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition.Conclusions and implications:
Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. 相似文献996.
目的观察硫酸镁联合地塞米松治疗爆震性耳聋的临床疗效。方法选择已确诊为爆震性耳聋患者35例,随机分为联合治疗组20例和糖皮质激素组15例。联合治疗组给予硫酸镁加地塞米松治疗;糖皮质激素组给予地塞米松治疗。两组治疗前、后均行纯音测听、听性脑干反应测听(ABR)检查。对检查结果进行统计学分析。结果治疗后两组患者听力水平都有显著改善,且两组之间对比存在非常显著性差异(P<0.01)。结论硫酸镁联合地塞米松可有效治疗爆震性耳聋,疗效明显优于单纯使用地塞米松。 相似文献
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