纳洛酮对中重型颅脑损伤病人血浆C-反应蛋白的影响

目的评价纳洛酮对脑外伤的早期疗效及C-反应蛋白(CRP)检测在纳洛酮治疗脑外伤中的应用价值。方法将68例重型脑外伤病人随机分为治疗组30例和对照组38例,对照组给予常规治疗,治疗组在常规治疗的基础上,给予纳洛酮0.4mg·kg-·1d-1治疗。观察病人的GCS评分、颅内压及头颅CT所示脑水肿的变化,并测定治疗前后血清CRP浓度。结果治疗组在提高GCS评分、降低颅内压、控制脑水肿等方面均明显优于对照组(P<0.01)。两组治疗前CRP分别为(73.64±8.64)mg/L(、69.23±7.31)mg/L,差异无统计学意义(P>0.05);治疗后治疗组为(37.25±11.45)mg/L,对照组为(48.54±12.07)mg/L,治疗组明显低于对照组(P<0.01)。结论①纳洛酮综合治疗脑外伤效果明显。②CRP可作为颅脑外伤病情及纳洛酮治疗效果判断的参考指标。     

Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

Effects of repeated doses of benzodiazepines on arterial blood gases and transcutaneous Po2

The effects of repeated doses of benzodiazepines, diazepam and midazolam in combination with meperidine on arterial blood gases and transcutaneous PO2 were studied in eight healthy volunteers. The study was designed to mimic a clinical situation. Initially two doses of either midazolam 0.05 mg/kg or diazepam in fat emulsion 0.15 mg/kg were given in a randomized crossover fashion with a 20-min interval, followed by meperidine 0.5 mg/kg another 20 min later. The opioid effects were then antagonized by naloxone 0.4 mg. The initial doses of benzodiazepines caused an increase in PaCO2 and a decrease in PaO2. The changes in PaO2 were of short duration and recovered to baseline levels between injections. However, they came sooner and were more pronounced after midazolam. The changes in PtcO2 paralleled those in PaO2. The PtcO2 index as a measure of cardiac output and peripheral blood flow adequacy was increased immediately after the first injection of midazolam but was otherwise not different from control. There were no differences between the drugs concerning PtcO2 index. PaCO2 increased after the first benzodiazepine injection and remained so throughout the study. Addition of meperidine caused only small changes in PaO2 and PaCO2. These changes were reversed by naloxone. In spite of different elimination kinetics there was no difference in the duration of respiratory depression between the two benzodiazepines.     

小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

Effect of naloxone on detrusor-sphincter dyssynergia in the chronic spinal cat

Naloxone, an opioid peptide antagonist, has been reported to facilitate voiding in neurologic bladder disorders, but its effects on the neural micturition reflex arc are poorly understood. We studied the effect of naloxone in 34 male adult cats, spinalized at C5-C6 level 7 to 119 days previously. Each cat served as its own control. The following tests were performed: Urethral pressure profiles, cystosphincterograms with the urethro-vesical junction opened and closed and mechanograms of the detrusor, and the circular and longitudinal urethral muscles. The study included (1) the effects of anesthesia of the bladder and pelvic nerve, as well as that of the urethral and pudendal nerves; (2) the action of naloxone; and (3) the action of oxymorphone. Our results demonstrated that naloxone (1) increased somatic (osteotendinous and nociceptive) reflexes and aggravated spasticity; (2) increased vegetative micturitional and sexual reflexes, in particular the urethra-urethral contraction reflex, aggravating the spasmodic contractions of the external sphincter; and (3) increased the frequency and intensity of the mass reflex. In consequence, we suggest that naloxone is contraindicated in cases of spinal cord lesions with detrusor-sphincter dyssynergia syndrome.     

THE INFLUENCE OF CAPTOPRIL AND NALOXONE ON THE VALSALVA MANOEUVRE AND SYSTOLIC TIME INTERVALS IN HEALTHY VOLUNTEERS

1. The aim of the study was to ascertain whether the inhibition of the sympathetic nervous system by angiotensin-converting enzyme (ACE) inhibitors is mediated by endogenous opioids. Naloxone was used to evaluate the effects of the latter on systolic time intervals (STI) and Valsalva manoeuvre-induced blood pressure and heart rate changes. 2. Baseline recordings were done in 12 healthy male volunteers and repeated 2h after oral administration of 75 mg of captopril and again after naloxone 0.4 mg/kg was administered intravenously over 10 min. 3. After captopril there was a significant reduction in systolic (P<0.02) and mean blood pressure (P<0.04) without any changes in heart rate. Furthermore, captopril increased the Valsalva ratio (P<0.06) but did not influence inotropism as indicated by STI. Naloxone did not influence any of these findings. 4. The changes in the Valsalva ratio after captopril were mediated by an increase in the maximum bradycardia in nine of the 12 subjects. 5. The results indicate that endogenous opioids do not play a role in the putative sympatholytic effect of ACE inhibition.     

亮氨酸脑啡肽对脂多糖促血管平滑肌细胞增殖效应的抑制作用

观察亮氨酸脑啡肽和脂多糖对血平滑肌细胞增殖的影响，并观察两者之间的相互作用及阿片受体阻滞剂纳洛酮的影响，方法：实验以离体培养的ＳＤ大鼠胸主动脉ＶＳＭＣ为模型。     

吗啡抑制大鼠多觉型伤害性感受器持续放电

作利用复合致痛剂引起大鼠尾部皮肤多觉型伤害性感受器（ＰＭＮ）持续性放电模型，经股静脉注入吗啡（４ｍｇ／ｋｇ），显抑制ＰＭＮ持续性放电。吗啡抑制ＰＭＮ放电５０％的潜伏期为１０±４．５ｍｉｎ，抑制时程超过３０ｍｉｎ。纳络酮１ｍｇ／ｍｇ ｉｖ，可翻转吗啡的抑制作用。在慢性吗啡耐受大鼠，吗啡几乎失去其抑制作用。吗啡引起的ＰＭＮ放电数变化不呈一致关系。小剂量吗啡（１ｍｇ／ｋｇ）注入支配感受野皮肢的尾动脉