利鲁唑对吗啡镇痛、耐受和依赖作用的影响(英文)

目的　研究利鲁唑对阿片镇痛、耐受及躯体功能的调节。方法　采用冰醋酸扭体 ,5 5℃热板法和热辐射甩尾法观察利鲁唑对小鼠痛阈及吗啡镇痛效应的影响 ;采用小鼠急性和慢性吗啡耐受模型及小鼠吗啡依赖模型 ,观察利鲁唑对吗啡耐受和依赖的作用。结果　单独皮下注射利鲁唑 2 .5～ 10mg·kg- 1在以上 3种模型无镇痛作用 ,然而能剂量依赖性地增强吗啡镇痛效应。利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地对抗吗啡引起的急性和慢性耐受。在小鼠吗啡依赖模型中 ,利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地抑制吗啡戒断症状的产生。结论　利鲁唑自身无镇痛作用 ,但能显著增强吗啡镇痛效应 ,并能预防吗啡所引起的耐受和依赖     

电针对吗啡成瘾大鼠戒断-复吸行为影响的初步观察

目的 观察针刺对实验动物戒断及复吸期间操作行为的影响。方法 建立大鼠吗啡自身给药模型，随机分模型对照组、绑缚对照组、针刺治疗组。熄灭期(3d)做相应处理，d4吗啡引燃(2mg／kg体重)，观察动物熄灭踏板数(LPE)、复吸踏板数(LPR)。结果 模型对照组观察到典型熄灭-复吸曲线(ERC)；绑缚对照组该曲线发生变异，主要是缩短了熄灭的过程；针刺治疗组彻底改变了熄灭-复吸曲线的形状，使熄灭反跳现象消失，但复吸值变大。以吗啡平台期平均踏板数(ALPP)为基准值，各组间熄灭平均踏板数(ALPE)和复吸踏板数(LPR)无明显差异。结论 相对于自然戒断，针刺及绑缚在熄灭期间均具有较明显的抑制渴求效果，且针刺比绑缚作用更快．效果更明显；短期(3d)的针刺治疗未达到抗短期复吸(d4)效果。更多结果有待后续观察和进一步验证。     

A chimeric opioid peptide with mixed μ agonist/δ antagonist properties

Abstract: There is evidence to indicate that opioid compounds with mixed μ agonist/δ antagonist properties are analgesics with low propensity to produce tolerance and physical dependence. A chimeric peptide containing the potent and selective μ agonist H‐Dmt‐D‐Arg‐Phe‐Lys‐NH₂ ([Dmt¹]DALDA) (Dmt = 2′,6′‐dimethyltyrosine) and the potent and selective δ antagonist H‐Tyr‐TicΨ[CH₂‐NH]Cha‐Phe‐OH (TICP[Ψ]) (Cha = cyclohexylalanine), connected ‘tail‐to‐tail’ via a short linker, was synthesized using a combination of solid‐phase and solution techniques. The resulting peptide, H‐Dmt→D‐Arg→Phe→Lys‐NH‐CH₂‐CH₂‐NH‐Phe←Cha[NH‐CH₂]ΨTic←Tyr‐H, showed the expected μ agonist/δ antagonist profile in the guinea‐pig ileum and mouse vas deferens assays. Its μ and δ receptor binding affinities were in the low nanomolar range, as determined in rat brain membrane binding assays.     

四川省凉山地区静脉吸毒人群药物滥用及其行为特征调查

目的:了解四川省凉山地区静脉吸毒人群药物滥用及行为特征情况,为采取有针对性的戒毒干预措施预防艾滋病病毒的传播提供数据.方法:以社区为基础招募了379名静脉吸毒人员,调查其人口学特征,艾滋病病毒感染情况,药物滥用的种类、吸毒方式和频率,口吸和静脉吸毒时间,共用注射器具情况等.结果:静脉吸毒人群艾滋病病毒感染率为11.3%(43/379).379名被调查者全部为海洛因滥用者,其中247人(65.2%)单独使用过海洛因,297人(78.4%)混合注射过海洛因与安定,滥用过的其他药物有安定(8.2%)和鸦片(1.3%).300人(79.2%)每天静脉注射吸毒一次及以上;曾经共用注射器具静脉吸毒的为247人(65.2%),87人(35.2%)首次静脉注射吸毒即与他人共用注射器具;初次口吸吸毒和静脉注射吸毒的平均年龄分别为22.37岁和25.35岁,口吸吸毒和静脉注射吸毒的平均时间分别为6.41年和3.42年.结论:加强青少年、吸毒人员关于毒品危害和拒绝毒品的健康教育活动,以及开展美沙酮或丁丙诺啡口服治疗海洛因依赖者,降低静脉注射吸毒行为,控制艾滋病病毒的传播.     

吗啡依赖小鼠脑组织cAMP系统的变化及腺苷酸环化酶磷酸化调节

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加味参附汤对吗啡依赖戒断小鼠免疫功能的影响

吗啡依赖小鼠自然戒断后可见脾脏、胸腺萎缩，巨噬细胞Fc受体阳性百分率及吞噬功能、外周血T淋巴细胞总数、T淋巴细胞对PHA的殖反应、脾T淋巴细胞CD4^ 百分率及CD4^ /CD8^ 比值均明显下降；吗啡继续成瘾而未戒断的小鼠的以上指标进一步损伤；加味参附汤（MSFD）治疗小鼠以上指标均有不同程度的恢复；而丁丙诺啡治疗后免疫功能状态仍低于或相当于自然戒断时。提示MSFD能促进吗啡依赖戒断小鼠损伤的免疫功能的恢复，这一作用可能与其对神经内分泌系统的调节有关。     

Prevention of precipitated withdrawal symptoms by activating central cholinergic systems during a dependence-producing schedule of morphine in rats

Previous studies in this and other laboratories have suggested an important role for central cholinergic neurons in the expression of morphine withdrawal symptoms. This study was designed to determine whether the symptoms of withdrawal could be mitigated by normalization of the effect of morphine on cholinergic neurons. Since this effect is generally inhibitory, we used centrally acting cholinergic agonists to augment central cholinergic tone during chronic morphine infusion. Rats were made dependent following the intra-arterial (i.a.) infusion of increasing concentrations (35-100 mg kg(-1) day(-1)) of morphine over 5 days. I.a. injection of 0.5 mg/kg of naloxone precipitated a profound withdrawal response that included a dramatic increase in mean arterial pressure (MAP) which was maintained over the 60-min observation period, a short duration increase in heart rate (HR), and characteristic opiate withdrawal symptoms. In separate groups of rats, non-toxic doses (50 and 250 microg/kg) of the acetylcholinesterase (AChE) inhibitor, diisopropylflurophosphate (DFP) were administered as single daily injections concomitant with the morphine infusion. DFP treated rats, exhibited significantly reduced expression of the naloxone-evoked pressor response. The apparent anti-withdrawal effect of DFP was not reproduced by the selective peripherally acting AChE inhibitor, echothiophate, although both compounds effectively reduced the expression of certain other withdrawal symptoms. The centrally acting muscarinic cholinergic receptor agonist, arecoline, resulted in an even more impressive suppression of withdrawal symptoms. While not all symptoms associated with morphine withdrawal are mediated via central cholinergic pathways, these results suggest that physical dependence on morphine can be suppressed to a significant degree by the augmentation of central cholinergic activity during morphine administration.     

Total versus tube-related additional work of breathing in ventilator-dependent patients

BACKGROUND: In tracheally intubated or tracheostomized spontaneously breathing patients, tube resistance can highly increase the patient's work of breathing. In this study we focused upon the relationship between total (WOBtot) and tube-related additional inspiratory work of breathing (WOBadd) and compared different ventilatory modalities for proper tube compensation. METHODS: In ten tracheostomized spontaneously breathing patients we measured WOBtot and WOBadd in the continuous positive airway pressure (CPAP) mode, under inspiratory pressure support of 5, 10, and 15 cmH2O in the pressure support ventilation (PSV) mode, and under flow-adjusted pressure support in the automatic tube compensation (ATC) mode. WOBadd and WOBtot were calculated on the basis of measured tracheal pressure and esophageal pressure, respectively. Inspiratory peak tracheal pressure above PEEP was taken as an estimate of pressure support beyond mere tube compensation (i.e., overcompensation). RESULTS: The percentage of the tube-related WOBadd on WOBtot in the CPAP mode was 52%. It decreased with increasing pressure support in the PSV mode from 32% (PSV 5 cmH2O) to 17% (PSV 15 cmH2O). WOBadd was only 15% of WOBtot in the ATC mode. In contrast to the other ventilatory modes, reduction of WOBadd in the ATC mode was achieved with the smallest amount of overcompensation, i.e. with minimal pressure assist beyond mere tube compensation. CONCLUSION: In tracheally intubated or tracheostomized spontaneously breathing patients, adequate compensation of tube resistance (i.e. with minimal overcompensation and minimal undercompensation) is best done by the ATC mode.     

吸毒母亲新生儿临床特点及治疗

目的 探讨吸毒母亲所生新生儿的临床特点及治疗措施。方法 分析54例吸毒母亲所生新生儿临床特点，并就相关治疗措施疗效和转归进行评价。结果 1990～2002年12年间我科共收治吸毒母亲新生儿54例，其中早产儿28例，低出生体重儿32例，新生儿窒息14例，新生儿呼吸窘迫综合征(NRDS)12例，颅内出血8例，先天畸形2例。54例中16例患儿均有不同程度的新生儿戒断综合征表现，29例出现低血钙、低血糖等内环境紊乱。其中母亲吸毒2年以上组中早产、低出生体重、窒息及NRDS的发生率明显高于吸毒2年以下组。经止惊、维持水电解质平衡及对症支持治疗，54例中44例(81％)症状控制出院，8例(15％)死亡，2例(4％)放弃治疗出院。结论 吸毒对于新生儿危害极大，早产、低出生体重、窒息、NRDS等发生率与吸毒时间密切相关。综合治疗有助于患儿康复。     

吗啡对PC12细胞嘌呤核苷酸代谢相关酶基因表达的影响

目的：研究吗啡对神经细胞模型PC12嘌呤核苷酸补救合成酶与分解代谢关键酶基因表达的影响。方法：采用逆转录聚合酶链反应（RT-PCR）方法检测暴露于吗啡不同时间的PC12细胞次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRT）、腺苷激酶（AK）和腺苷脱氨酶（AD A）mRNA的表达水平。结果：与相应时段对照组相比，PC12细胞暴露于吗啡12及24 h时，HGPRT mRNA水平均明显增高(P<0.05)，作用48 h时HGPRT mRNA水平显著降低(P<0.05)，72 h后HGPRT mRNA水平再次升高(P<0.05)；吗啡处理的PC12细胞于12和24 h时，AK mRNA水平均明显降低(P<0.05)，作用48 h时AK mRNA水平升高(P<0.05)，72 h后AK mRNA水平恢复正常；ADA mRNA水平均表现为轻度降低，12 h差异有显著性(P<0.05)。结论：吗啡影响神经细胞嘌呤核 苷酸代谢，使细胞内腺苷酸及腺苷水平增高，这可能是吗啡依赖和耐受形成的机理之一 。