Antinociceptive effects of tramadol in co-administration with metamizol after single and repeated administrations in rats

Opiate addiction is a chronic recrudescent disorder characterized by a high rate of relapse. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance extracted from Corydalis and Stephania and is contained in a number of traditional Chinese herbal preparations. Compared to other dopamine receptor antagonists, l-THP has lower affinity for D2 receptors than for D1 receptors, and a recent study showed that l-THP also binds to D3 receptors, possibly functioning as an antagonist. The unique pharmacological profile of l-THP suggests that l-THP may be effective for the treatment of opiate addiction. In this study, we investigated the effects of l-THP on heroin self-administration and reinstatement triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin under an extinction/reinstatement protocol, and found that l-THP (2.5 and 5 mg/kg, i.p.) decreased heroin self-administration on the fixed-ratio 1 schedule and dose-dependently (1.25, 2.5 and 5 mg/kg, i.p.) inhibited heroin-induced reinstatement of heroin-seeking behavior. Importantly, l-THP (1.25 and 2.5 mg/kg, i.p.) did not affect locomotion, indicating that the observed effects of l-THP on reinstatement do not appear to be due to motor impairments. The present results demonstrated that dopamine receptor antagonist l-THP attenuates heroin self-administration and heroin-induced reinstatement.     

Serotonin syndrome associated with polypharmacy in the elderly

The increasing use of serotonergic agents, alone and in combination, across multiple disciplines, makes it likely that the prevalence of serotonin syndrome will rise. Caution should be used, especially in the elderly, to avoid unnecessary and potentially harmful polypharmacy. We describe a case of serotonin syndrome in a 79-year-old man taking mirtazapine, venlafaxine and quetiapine. As this case illustrates, serotonin syndrome can be caused by combinations of direct serotonin agonists (e.g., serotonergic antidepressants) and indirect serotonin agonists (e.g., atypical antipsychotics).     

黄体期使用生长激素在高龄卵巢储备功能减退患者中的临床应用

目的探讨黄体期使用生长激素(GH)对高龄卵巢储备功能减退(DOR)患者超促排卵治疗的影响。方法选择接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)且高龄(年龄≥35岁)DOR不孕患者156例为研究对象,均采用拮抗剂方案,分为研究组(加用GH)和对照组(不加用GH)。分析GH对促性腺激素(G n)使用总量、G n使用时间、获卵数、移植前内膜厚度、双原核(2 P N)率、优质胚胎率、着床率的影响。结果 Gn使用时间、Gn使用总量、移植前内膜厚度组间有统计学差异(P0.05)。h CG注射日E 2水平、获卵数、2 P N受精率、优质胚胎率、着床率、临床妊娠率及累积妊娠率组间无统计学差异(P0.05)。研究组临床妊娠率为28.0%、对照组为19.4%,研究组累积妊娠率为33.3%、对照组为20.0%,组间均无统计学差异(P0.05),但研究组临床妊娠率及累积妊娠率有上升趋势。结论 GH对年龄≥35岁DOR患者可明显降低Gn的使用总量及使用时间,增加子宫内膜的厚度,临床妊娠率及累积妊娠率有提高的趋势。     

血小板源性生长因子与系膜细胞增殖研究进展

血小板源性生长因子(PDGF)作为重要的促细胞生长因子,具有促进系膜细胞增殖、细胞外基质积聚等作用.系膜细胞的增殖与细胞周期调控密切相关.PDGF各配体作用于系膜细胞产生不同的效应.该文就近年来有关PDGF诱导系膜细胞增殖的相关机制以及临床应用研究进展作一综述.     

DC260126, a small-molecule antagonist of GPR40, improves insulin tolerance but not glucose tolerance in obese Zucker rats

GPR40 is a G-protein-coupled receptor specifically expressed in pancreatic islets, which maybe mediate both acute and chronic effects of free fatty acids (FFAs) on β-cell function. However, it is still a matter of debate whether GPR40 represents a novel therapeutic target for type 2 diabetes. To this aim, we evaluated the effect of DC260126, a small-molecule antagonist of GPR40, on glucose and lipid metabolism in obese Zucker rats. Rats were treated intraperitoneally with 6 mg/kg of DC260126 for 8 weeks. DC260126 could significantly decrease serum insulin levels, improve insulin tolerance and increase Akt phosphorylation levels in liver, suggesting improved insulin sensitivity in DC260126-treated rats. However, DC260126 did not affect food intake, body weight, blood glucose and lipids. Throughout the experimental period, no significant difference in glucose tolerance was observed between the vehicle and DC260126-treated rats. These results indicate that GPR40 antagonists may not be beneficial for the treatment of type 2 diabetes, although GPR40 antagonists could improve insulin tolerance and increase insulin signaling in vivo.     

牛磺酸拮抗铅对骨髓间充质干细胞生长的影响

目的:为进一步阐明铅对儿童骨髓造血系统的毒作用机制及采取相应的防治措施提供依据,观察研究牛磺酸(Tau)作为铅的拮抗剂对体外铅作用的小鼠骨髓间充质干细胞生长的影响。方法:应用骨髓间充质干细胞体外培养法,在培养体系中分别加入不同浓度的Tau溶液,观察各组骨髓成纤维细胞集落生成单位(CFU-F)成集落率的变化;在培养体系中加入上述不同浓度的Tau溶液作用15 min,再分别加入60μmol/L醋酸铅进行培养,观察各组骨髓CFU-F集落率的变化。结果:培养体系中加入不同浓度的Tau,各组CFU-F成集落率与对照组相比无显著性差异(P>0.05),各组间比较差异亦无统计学意义(P>0.05);加入Tau作用后再用醋酸铅染毒,与未加Tau对照组比较CFU-F成集落率增加,差异有统计学意义(P<0.05),且CFU-F成集落率随Tau浓度的增加而增大,CFU-F与Tau浓度之间成正相关(rs=0.810,P=0.000)。结论:Tau对正常骨髓CFU-F集落率影响不明显,但能够拮抗铅对骨髓CFU-F集落率的抑制作用,并随浓度的增加,拮抗作用逐渐增强。表明Tau是一种很好的铅的拮抗剂,对骨髓间充质干细胞有保护作用。     

Pharmacokinetics and tissue distribution of the new non-imidazole histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy) propyl]piperidine in rats

Abstract

1.?The aim of this study was to evaluate pharmacokinetics and tissue distribution of novel histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (compound DL76).

2.?Following intravenous administration of DL76 at the dose of 3?mg/kg, pharmacokinetic parameters were calculated using non-compartmental analysis. The systemic serum clearance was 10.08?L/h/kg and the estimated blood clearance was 5.64?L/h/kg. The volume of distribution at steady state was 16.1?L/kg which was greater than total body water, terminal half-life and MRT equalled 1.41?h and 1.6?h, respectively. The two-compartment pharmacokinetic model with enterohepatic circulation was also successfully fitted to the experimental data.

3.?After systemic administration, DL76 was rapidly distributed into all organs studied (liver, kidney, brain, and lung). The highest AUC of DL76 was observed in lungs followed by brain, where the exposure to the investigated compound expressed as AUC was almost 30 times higher than in serum.

4.?Bioavailability, calculated based on the area-under-the-concentration–time curve extrapolated to infinity after intravenous and intragastric administration of the dose 3?mg/kg, equalled 60.9%.     

β3肾上腺素能受体阻滞剂SR59230A对心力衰竭大鼠心功能及β3肾上腺素能受体表达的影响

目的：评价β3肾上腺素能受体（β3-AR）阻滞剂SR59230A（SR）对心力衰竭大鼠心功能及β3-AR表达的影响。方法：♂Wistar大鼠85只，取8只设立对照组，其余77只应用异丙基肾上腺素成功建立20只心力衰竭模型后随机分为安慰剂组和SR组，并分别腹腔注射生理盐水和SR，7周后检测超声心动图、血流动力学各指标及β3-AR蛋白表达水平。结果：与安慰剂组比较，SR组短轴缩短率、射血分数、左室收缩末压、左室压力最大上升及下降速率明显增加（P〈0．01或P〈0．05），而心率、左室舒张末压及β3-AR蛋白表达水平显著降低（P〈0．05或P〈0．01）。结论：β3-AR阻滞剂SR能够改善心力衰竭大鼠心功能，该作用可能与其直接阻滞并下调β3-AR表达有关。