Time-dependent changes in sensitivity to apomorphine and monoamine receptors following withdrawal from continuous cocaine administration in rats

The effects of withdrawal from continuous administration of cocaine on behavioral sensitivity to apomorphine and monoamine receptor density were examined in rats. Subdermal minipumps that delivered either saline or 20 mg/kg/day cocaine hydrochloride were implanted for 2 weeks. Apomorphine-induced stereotypy (0.5 mg/kg, SC) was examined in separate groups of rats either 4 hr or 7, 28, or 60 days after removal of the minipumps. Transient enhanced sensitivity to apomorphine-induced stereotypy occurred during the course of withdrawal. Animals withdrawn from cocaine for 4 hours did not differ from controls in their sensitivity to apomorphine, whereas animals withdrawn from cocaine for 7 days exhibited an increase in apomorphine-induced oral stereotypy relative to controls. However, the enhanced stereotypy response was no longer evident in animals withdrawn for 28–60 days. The animals were sacrificed after behavioral testing, and their brains were assayed for changes in monoamine receptor density in the frontal cortex, caudate-putamen, and nucleus accumbens. The density of ³H-SCH-23390-labeled D1 receptors was altered in all three regions examined in a time-dependent manner that paralleled the changes in behavioral sensitivity to apomorphine. There was a transient decrease in D1 receptor density that was evident by 7 days following withdrawal from continuous cocaine administration and was no longer evident 28 or 60 days posttreatment. There were no changes in ³H-spiroperidol-labeled D2 receptors, ¹²⁵-pindolol-labeled β-adrenergic receptors, or ³H-ketanserin-labeled 5-HT₂ receptors in any of the regions examined at both 4 hr and 7 days after termination of the cocaine infusion. These findings are discussed in terms of their relevance to developing pharmacologic treatments for withdrawal from cocaine. © 1994 Wiley-Liss, Inc.     

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide). METHODS: During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis. RESULTS: Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.     

渗透压微泵恒速给药丙戊酸在小鼠体内的时间药物动力学

以渗透压微泵植入小鼠皮下恒速给予丙戊酸钠，在达到理论稳态浓度时间后，血浆药浓呈昼夜变化，白昼高于夜间，峰值位于明期末。药动学研究揭示丙戊酸血药浓度的昼夜差异可能与其清除率及分布容积的昼夜变化有关。     

Using Queueing Theory to Increase the Effectiveness of Emergency Department Provider Staffing

Objectives: Significant variation in emergency department (ED) patient arrival rates necessitates the adjustment of staffing patterns to optimize the timely care of patients. This study evaluated the effectiveness of a queueing model in identifying provider staffing patterns to reduce the fraction of patients who leave without being seen. Methods: The authors collected detailed ED arrival data from an urban hospital and used a Lag SIPP queueing analysis to gain insights on how to change provider staffing to decrease the proportion of patients who leave without being seen. The authors then compared this proportion for the same 39‐week period before and after the resulting changes. Results: Despite an increase in arrival volume of 1,078 patients (6.3%), an average increase in provider hours of 12 hours per week (3.1%) resulted in 258 fewer patients who left without being seen. This represents a decrease in the proportion of patients who left without being seen by 22.9%. Restricting attention to a four‐day subset of the week during which there was no increase in total provider hours, a reallocation of providers based on the queueing model resulted in 161 fewer patients who left without being seen (21.7%), despite an additional 548 patients (5.5%) arriving in the second half of the study. Conclusions: Timely access to a provider is a critical dimension of ED quality performance. In an environment in which EDs are often understaffed, analyses of arrival patterns and the use of queueing models can be extremely useful in identifying the most effective allocation of staff.     

“分步给药”在低氧易感患者无痛苦胃镜检查中安全性的探讨

目的 探讨在低氧易感患者无痛苦胃镜检查中采用分步给药的安全性和镇静/镇痛效果.方法 接受胃镜检查的180例患者,其中有鼾症、或咳嗽、咳痰症状的患者120例单双号随机入选Ⅰ组(分步给药组)和Ⅱ组(普通组),60例无鼾症、咳嗽、咳痰症状的患者为Ⅲ组(常规给药组),Ⅰ组采用分步给药法,Ⅲ组采用常规给药法对患者实施胃镜检查前的镇静/镇痛术,Ⅱ组则进行普通胃镜检查,分析2种镇静法对SBP、DBP、SpO2、HR、清醒时间、患者反应、患者对检查过程的感受以及是否愿意再次接受检查的影响,评价分步给药法在低氧易感患者无痛苦胃镜检查中的安全性和镇静/镇痛效果.结果 Ⅰ组、Ⅲ组检查中SBP、DBP变化无明显差异(均P＞0.05),Ⅰ组检查前、中SpO2的变化小于Ⅲ组(均P＜0.01);Ⅰ组进镜时咽部受刺激产生的恶心咽吐、流涎、咳嗽、躁动反应多于Ⅲ组(均P＜0.01),但较Ⅱ组少(均P＜0.01);Ⅰ组对胃镜检查的评价与Ⅲ组无明显差异(P＞0.05),与Ⅱ组相比有明显差异(P＜0.01).结论 分步给药法是一种适用于低氧易感患者无痛胃镜检查的安全、有效的镇静/镇痛方法.     

复合维生素E,C,B组合物面膜治疗寻常痤疮117例的疗效和安全性(英文)

目的:了解维生素E,C,B组合物面膜治疗寻常痤疮的疗效及安全性。方法:117例13a以上、痤疮严重程度分级在2级以上且主要表现于脸部的病人,予维生素E,C,B组合物面膜治疗,每日1次,共8wk。观察治疗前后痤疮数量及性质,包括粉刺、丘疹、脓疱及囊肿之数目,并评估整体疗效。结果:治疗后,粉刺、丘疹、脓疱及囊肿数目下降了13±s13,10±12,5±7及3±3,均P<0.01。7例(6.0%)病人症状完全改善,44例(37.6%)中度改善,56例(47.9%)轻度改善,10例(8.6%)无改善。59例(50.4%)病人无红肿、搔痒、灼热及脱皮等现象发生。结论:维生素E,C,B组合物面膜治疗痤疮有效,超过半数的受试者无不良反应发生,可作为传统治疗寻常痤疮药物的替代。     

川芎嗪对P2X3受体介导的大鼠伤害性兴奋传入的作用

通过动物痛行为反应(缩足反射)确定局部和鞘内应用川芎嗪(TMP)对ATP等P2X受体激动剂所致大鼠足底急性伤害性行为反应的影响。P2X3受体拮抗剂TNP-ATP(0．3μmol／L)明显抑制P2X受体激动剂ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的大鼠足底急性伤害性反应。大鼠足底局部应用TMP(0．1-10mmol／L)剂量依赖性地对ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的伤害性反应具有抑制作用。鞘内应用TMP(50mmol／L)对ATP(1μmol／L)或α，β-meATP(0．6μmol／L)引起的伤害性反应具有抑制作用。结果表明，TMP可通过阻断P2X3受体介导的伤害性兴奋传入抑制P2X受体激动剂引起的大鼠足底急性伤害性反应。     

极低出生体重儿两种喂养效果观察

目的:探讨极低出生体重儿(VLBW)的早期微量持续鼻饲喂养(CNG)与间断鼻饲喂养(ING)的喂养耐受性及喂养效果.方法:将60例VLBW进行随机分组,CNG组起始奶量1-2ml/h,以后泵速增加1-2ml/h.ING组奶量以1-2ml/kg开始, 以后每天增加1-2ml/kg/次.所有VLBW均同时进行部分静脉营养,直至达到完全胃肠道喂养时间(FEF).对比两组喂养不耐受性、达到FEF、停止静脉补液时间及黄疸持续时间.结果:CNG组较ING组患儿发生腹胀、呕吐者明显减少(P＜0.05),黄疸持续时间、吸吮动作出现时间及住院时间较对照组明显缩短(P＜0.05),但两组体重增长情况统计学无差异(P＞0.05).结论:CNG更适合VLBW的早期微量喂养.