氢溴酸高乌甲素大鼠在体胃肠的吸收动力学研究

 目的：考察氢溴酸高乌甲素(LH)在大鼠胃肠道的吸收动力学特征及促进剂对其的吸收促进效果。方法：采用大鼠在体胃肠吸收实验模型,用HPLC法测定循环液中药物的浓度。结果：LH在胃、十二指肠、空肠、回肠、结肠的吸收百分率分别为9.67%,19.61%,11.83%,12.95%,9.51%;不同质量浓度的LH(10～40 mg?L-1)与小肠吸收量呈线性关系,吸收速率常数Ka几乎不变。P-糖蛋白抑制剂维拉帕米可增加药物从小肠的吸收。促进剂对药物在小肠内的吸收促进效果均比较明显,癸酸钠吸收促进效果最好。组织病理学观察结果显示,癸酸钠对小肠黏膜造成的损伤最小。结论：药物在整个胃肠道中的吸收均比较有限,在小肠中的吸收呈一级动力学过程,吸收机制有可能为被动扩散;吸收促进剂癸酸钠吸收促进效果最好,且毒性最小,有望作为药用辅料用于口服制剂中提高LH的生物利用度。     

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background:

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

Methods:

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

Results:

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

Conclusions:

We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.     

复方樟柳碱对早期糖尿病视网膜病变多焦视网膜电图的影响

目的：观察复方樟柳碱穴位注射对早期DR的多焦视网膜电图(mfERG)一阶Kernel反应的改变。

方法：连续选取Ⅰ～Ⅱ期糖尿病视网膜病变患者48例48眼,分为对照组和注射组,其中对照组采用控制血糖药物治疗,注射组除采用药物控制血糖外接受复方樟柳碱穴位注射。治疗后行多焦电生理检查,分析参数为mfERG产生的4个象限、6环以及总和反应的波形,对总和反应平均密度、P1和N1的潜伏期与振幅结果进行统计学分析。

结果：注药组和对照组P1波的总和反应平均密度为39.42±6.46、28.50±3.73nV/deg²,N1波为11.12±1.34、6.33±1.14nV/deg²。注药组P1波和N1波总和反应平均密度均高于对照组(P1：t=6.230,P<0.01; N1：t=3.526,P<0.01)。注药组SN、IN、IT和ST象限P1反应波平均密度分别为32.61±9.62、32.31±7.94、29.24±7.84、28.09±5.38nV/deg²,均高于对照组(P<0.05),各象限两组N1反应波平均密度比较均无明显差异。注药组R1～R6 P1、R1～R3 N1反应波平均密度分别为98.11±17.53、73.95±17.20、64.09±14.13、49.43±10.08、40.24±11.55、36.86±6.43、25.27±12.81、21.31±6.76、14.86±5.06nV/deg²,均高于对照组(P<0.05),两组R4～R6 N1反应波平均密度比较无明显差异。注药组IT和ST中P1和N1波幅值1.37±0.35、1.28±0.29、0.31±0.05和0.30±0.10μV,明显高于对照组(P<0.05),两组SN和IN中P1和N1波幅值差异无统计学意义。

结论：复方樟柳碱穴位注射可以改善早期DR部分视网膜功能损伤。     

术前肌注右美沙芬对全麻术后拔管时呛咳反应的影响

目的 观察术前肌注右美沙芬(dextromethorphan,DM)对阻塞性睡眠呼吸暂停综合征(OSAS)患者全麻术后拔管时呛咳反应的影响.方法 选择40例OSAS拟在全麻下行腭咽成型术(UPPD)患者,ASA Ⅰ～Ⅱ级,随机分为对照组及DM组,每组20例,术前30 min分别肌注5 ml生理盐水或DM 0.3 mg/kg,手术结束后拔管过程中观察各组呛咳反应的程度及不良反应.结果 手术结束后拔管时,DM组与对照组比较,DM组呛咳反应程度明显低于对照组.结论 术前30 min肌肉注射DM 0.3 mg/kg可降低OSAS患者全麻下行UPPP术后呛咳反应的程度.     

Differential roles of hypothalamic serotonin receptor subtypes in the regulation of prolactin secretion in the turkey hen

In the turkey, exogenous serotonin (5-hydroxytryptamine, 5-HT) increases prolactin (PRL) secretion by acting through the dopaminergic (DAergic) system. In the present study, infusion of the 5-HT_2C receptor agonist, (R)(−)-DOI hydrochloride (DOI), into the third ventricle stimulates PRL secretion, whereas the 5-HT_1A receptor agonist, (+/−)-8-OH-DPAT hydrobromide (DPAT), inhibits PRL secretion. Using the immediate-early gene, c-fos, as an indicator of neuronal activity, in situ hybridization histochemistry showed preferential c-fos co-localization within tyrosine hydroxylase immunoreactive neurons (the rate limiting enzyme in DA synthesis) in the areas of the nucleus preopticus medialis (POM) and the nucleus premammillaris (PMM), in response to DPAT and DOI, respectively. To clarify the involvement of 5-HT_1A and 5-HT_2C receptors in PRL regulation, their mRNA expression was determined on hypothalamic tissue sections from birds in different reproductive stages. A significant difference in 5-HT_1A receptor was observed, with the POM of hypoprolactinemic short day and photorefractory birds showing the highest expression. 5-HT_2C receptors mRNA did not change during the reproductive cycle. The data presented support the notion that DA neurons in the PMM and POM mediate the stimulatory and inhibitory effects of 5-HT, respectively, on PRL secretion and the 5-HTergic system can both stimulate and inhibit PRL secretion.     

氢溴酸西酞普兰对缺血性脑卒中后抑郁患者的情绪、认知功能和神经功能的影响

目的 探讨氢溴酸西酞普兰联合奥扎格雷钠对缺血性脑卒中后抑郁患者的情绪、认知功能和神经功能的影响.方法 选取我科2017年7月～2019年7月期间收治的119例缺血性脑卒中后抑郁患者作为研究对象,采用随机数字表法分为2组,均给予奥扎格雷钠作为基础治疗,对照组59例增加氟西汀治疗,观察组60例增加氢溴酸西酞普兰治疗,16周...     

联合应用东莨菪碱对家兔急性实验性肝性脑病的治疗作用

目的探讨东莨菪碱对家兔急性实验性肝性脑病的治疗作用及其可能机制,为肝性脑病的临床药物治疗提供实验依据。方法复制急性肝性脑病的动物模型,观察东莨菪碱对家兔抽搐情况、血氨变化以及脂质过氧化损伤的影响。结果东莨菪碱治疗组家兔抽搐症状减轻,血氨降低,MDA含量降低,且可防止SOD减少（P〈0.01）。结论东莨菪碱有明显镇静、止痉作用,并有降血氨作用,对肝脏的脂质过氧化损伤具有部分保护作用。     

Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy

BACKGROUND: Pre-incisional treatment with either N-methyl-D-aspartate (NMDA) receptor antagonists or non-steroidal anti-inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA-receptor antagonist, and tenoxicam, a NSAID, given preoperatively. METHODS: Eighty-eight ASA I or II patients scheduled for LC were entered into a randomized, double-blind study and randomly allocated to one of four groups. Controls received 20 mg (4 ml) of chlorpheniramine maleate (CPM) IM and 4 ml of normal saline (N/S) IV. Group DM received 40 mg of DM (containing 20 mg of CPM) IM and 4 ml of N/S IV. Group T were given CPM 20 mg IM, and tenoxicam 40 mg (4 ml) IV. Group DM + T were given DM 40 mg (containing 20 mg of CPM) IM, and tenoxicam 40 mg IV. All treatments were given 30 min before skin incision. Analgesic effects were evaluated by Visual Analog Scale (VAS) pain scores at rest and during coughing, at 1, 2, 4, 12, 24 and 48 h after surgery. The time to the first request for meperidine for pain relief, and total meperidine consumption, were recorded for 48 h after surgery. RESULTS: Compared to controls, patients given DM and DM + T first requested meperidine significantly later, had lower meperidine consumption, made fewer requests for meperidine, and had lower pain scores. There were significant differences between the DM + T and T groups at 2 and 4 h in both resting and incident VAS pain scores, the incidence of meperidine requests and the time to first meperidine injection. There were significant differences between groups DM and T at 1 h for resting pain and at 2 and 4 h for incident pain. Except for a significant difference in the incident pain score 1 h after surgery, there were no other differences in pain scores between the DM and DM + T groups. Neither synergistic nor antagonistic interaction was observed between DM and tenoxicam. CONCLUSIONS: The results suggest that pretreatment with DM, but not tenoxicam, provides significant pre-emptive analgesia for postoperative pain management in patients after LC surgery. Combining DM and tenoxicam also gives good pain relief.     

浅刺调督法对老年性痴呆模型海马胆碱酯酶活性的影响

目的:探索连续30天对大白鼠腹腔注射氢溴酸东莨菪碱SCOP 3mg/kg能否作为老年性痴呆的造模方法,并探讨浅刺调督法对老年性痴呆的作用机制。方法:模型组、预防组及治疗组采用氢溴酸东莨菪碱腹腔注射3mg/kg,空白组予等量生理盐水腹腔注射,每日1次,连续30天,预防组在实验之日起针刺,治疗组在造模30天后,进行针刺治疗,连续30天。再采用Morris水迷宫检测各组大白鼠的学习与记忆行为。各组实验结束后,抽取大鼠腹腔静脉血5mL,完成后立即快速断头取脑,在冰盘上分离大鼠海马组织,保存在-75℃冰箱内,待进行生化测定。结果:海马胆碱酯酶(CHE)及血液中丙二醛(MDA)检测指标模型组与空白组有显著差别,说明了浅刺调督法对老年性痴呆的部分作用机制,及浅刺调督法对老年性痴呆模型有一定的作用效果。     

Premedication with dextromethorphan provides posthemorrhoidectomy pain relief

PURPOSE: Previous studies have shown that N-methyl-D-aspartate receptor antagonists provide a preemptive analgesic effect in humans. This study was designed to examine whether premedication with dextromethorphan, an N-methyl-D-aspartate antagonist, also provided a preemptive analgesic effect that improved postoperative pain management. METHODS: Sixty patients who were American Society of Anesthesiologists status I and II scheduled for hemorrhoidectomy (modified Whitehead procedure) were included in the study. Patients were randomly assigned to the control and study groups. For the control group patients received chlorpheniramine maleate (20 mg), a component of the injection form of dextromethorphan, intramuscular injection 30 minutes before skin incision. In the study group dextromethorphan 40 mg containing 20 mg chlorpheniramine maleate (intramuscular) was given as premedication 30 minutes before skin incision. Pethidine (1 mg/kg, intramuscular) was given for pain relief as required postoperatively. The time to first pethidine injection, total pethidine consumption, worst pain score, and pethidine-related side effects were recorded for 48 hours postoperatively. RESULTS: The times to first pethidine injection (mean ± standard error of the mean) were 5.2±3 and 19.6±6 hours in the control and study groups, respectively. Total pethidine consumption was 140±11.3 and 63.5±11.8 mg in the control and study groups. The worst visual analog scale pain scores were 7.4±0.2 and 5.6±0.3 in the control and study groups during the two-day observation. The numbers of patients who required pethidine injection were 29 and 20 in the control and study groups, respectively. Two patients suffered pethidine-related side effects, such as nausea, vomiting, dizziness, and headache, in the control group, and no patient complained of any side effect in the study group. CONCLUSION: We found that dextromethorphan premedication provided a preemptive analgesic effect, thus producing reduced postoperative pain and pethidine requirement and improved recovery from hemorrhoidectomy.Supported by grants from the Tri-Service General Hospital (TSGH-C89-057) and National Health Research Institute of Taiwan, Republic of China (NHRI-GT-EX89B909P).