Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: −7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m²). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.     

吗啡增强备用根大鼠脊髓后角组织提取液对培养鸡胚背根节的促神经突起生长的作用

用组织培养方法，探讨备用很大鼠手术侧和非手术侧脊髓后角组织提取液对鸡胚背根节（ＤＲＧ）神经突起的促生长作用，以及应用吗啡对此作用的影响。结果显示：备用根大鼠手术侧脊髓后角组织提取液作用的ＤＲＧ神经突起密度（３６．４２±４．６９），比非手术侧的（２３．９６±３．４７）明显增大。提示去初级传入纤维的脊髓后角组织具有促进ＤＲＧ神经突起生长的神经营养活性作用。应用吗啡的备用根大鼠手术侧脊髓后角组织提取液作用的ＤＲＧ神经突起密度（６４．１９±９．２４），又比备用根大鼠手术侧的大。这表明，吗啡具有进一步增强去初级传入纤维支配的脊髓后角组织提取液促进培养的ＤＲＧ神经突起生长的效应。     

Pharmacological options for management of opioid dependence

Methadone is currently the only opioid available for the pharmacotherapy of opioid dependence. Cross-tolerance between methadone and other opioids constitutes the pharmacological basis for substitution and attenuating the effects of illicit opioid use. However, these principles limit the utility of methadone. Potential alternative opioids include long-acting partial agonists such as buprenorphine and pure antagonists such as naltrexone. Buprenorphine is an alternative to methadone with intermediate intrinsic efficacy. It has a large margin of safety, yet displays some agonist actions similar to methadone. It has greater potential than methadone to safely and effectively block the actions of illicit opioids. Naltrexone is a safe, convenient opioid-antagonist for use following detoxification from opioid agonists. Its main use is to block the actions of other opioids, thereby attenuating or eliminating illicit use during treatment. However, it is poorly accepted by many clients, limiting its application to a sub-group who are highly motivated to detoxify. The distinct pharmacological properties of these opioids can overcome some of the drawbacks of methadone, but other limitations may emerge. Non-opioid adjuncts such as alpha2-adrenoceptor agonists can also have a role during detoxification. These drugs might be of use for specific groups of opioid users, providing therapists with the flexibility to tailor pharmacotherapy to the individual needs of clients.     

Aversion instead of preference learning indicated by nicotine place conditioning in rats

Although nicotine is a drug of abuse for millions of smokers, it has been difficult to demonstrate clearly the motivational properties of nicotine with rats using the conditioned place preference (CPP) paradigm. The first experiment attempted to replicate CPPs reported by other researchers using nicotine doses of 0.4, 0.8, and 1.2 mg/kg. There was a trend for all three doses to produce aversions, but it was significant only for the 0.8 mg/kg dose. Exposures to the CS alone extinguished aversions, but a priming dose (0.2 mg/kg) of nicotine given after extinction produced aversions only in animals exposed to 1.2 mg/kg. Experiment 2 tested whether preexposure to morphine or nicotine would sensitize animals to nicotine's reinforcing effects. In this experiment, rats were exposed to either six nicotine (0.6 mg/kg) or morphine (1.0 mg/kg) dosings prior to preference conditioning. Neither preferences nor aversions were observed in any group following subsequent conditioning with 0.6 mg/kg nicotine. The results suggest that previous observations of preference effects may have been due to specific procedural factors or may have depended on negative reinforcement due to stress reduction.     

不同方法使用东莨菪碱脱毒效果的比较

目的：观察东莨菪碱（scopolamine,Spm)和氯丙嗪（chloprmazine,Clo)对吗啡戒断反应的影响。方法：采用吗啡依赖大鼠模型,不同剂量单多次皮下注射（sc)东莨菪碱及合并使用氯丙嗪处理动物后,腹腔注射（ip)纳洛酮5mg/kg诱发戒断反应,观察戒断症状。结果：单次sc东莨菪碱1.0mg/kg及多次sc东莨菪碱0.5mg/kg可明显抑制吗啡依赖大鼠的身体戒断反应,合并注射氯丙嗪20.0mg/kg时的效果更好.结论:东莨菪碱通过Ach受体可以抑制吗啡戒断反应,氯丙嗪则可能通过作用于蓝斑墙 枢部位α2受体与东莨菪碱起到协同作用.     

穴位体表电刺激对术后PCEA的强化效应

目的　观察穴位体表电刺激对术后患者硬膜外自控镇痛（PCEA）效果、镇痛药用量、血清皮质醇浓度和不良反应的影响。方法　 选择经腹全宫切除术患者40例（ASAⅠ～Ⅱ级）,随机分成二组,每组20例。A组：于术后第4,8小时 Han's各刺激30 min,术后行PCEA。B组：单纯行术后PCEA（对照组）。术后随访镇痛效果、镇静评分、布氏舒适评分（BCS）,分段记录24 h镇痛药用量及总按压次数/实进次数（D1/D2）比值,血清皮质醇含量,肛门恢复排气时间和不良反应情况。结果　两组镇痛效果满意,A组BCS评分高于B组（P＜0.05）。A组镇痛药用量为（31.7±1.9）ml,与对照组（34.2±2.1）ml相比差异有显著性（P＜0.01）。血清皮质醇浓度两组均较术前下降,但A组术后8 h的下降幅度大于对照组。A组恢复肛门排气时间快于B组,而且恶心、呕吐与对照组相比有所减少。结论　术后患者硬膜外腔自控镇痛（PCEA）复合应用穴位体表电刺激,可增强镇痛效果,减少用药量,降低不良反应,是安全有效的复合镇痛方法。     

肾上腺切除对强迫游泳大鼠吗啡成瘾行为的影响

为探索应激和肾上腺切除在药物成瘾行为中的作用机制 , 将40只雄性Wista r大鼠随机分为肾上腺切除组、糖皮质激素Ⅰ组(肾上腺切除+氢化考的松20mg/kg)、糖皮质激素Ⅱ组(肾上腺切除+氢化考的松40mg/kg)及生理盐水对照组,每组各10只, 观察肾上腺切除及给予糖皮质激素对强迫游泳大鼠条件性位置偏爱形成的影响.结果: ①肾上腺切除组动物在药物搭配侧箱体中停留的时间与在对侧箱体中停留时间相比无明显差异(t=1.84 , P＞0.05),而其它3组中均存在显著性差异(P＜0.05或P＜0.01);②与其它3 组相比,肾上腺切除组动物在药物搭配侧箱体中停留时间明显缩短,而其它3组之间则无明显差异.由此表明,切除肾上腺能够减弱强迫游泳对大鼠吗啡条件性位置偏爱的强化作用, 而给予外源性糖皮质激素能够逆转这种作用.