穿心莲内酯对TBHP诱导的椎间盘髓核细胞凋亡的作用及机制研究

目的：探讨穿心莲内酯（andrographolide,ANDRO）对叔丁基过氧化氢（tert-butyl hydroperoxide,TBHP）诱导的椎间盘髓核细胞（nucleus pulposus cells,NPC）凋亡的作用及其机制。方法：用TBHP诱导NPC建立细胞模型。将NPC分为5组：对照组、模型组（100μmol/L TBHP）、ANDRO低剂量组（100μmol/L TBHP+9μmol/L ANDRO）、ANDRO中剂量组（100μmol/L TBHP+18μmol/L ANDRO）和ANDRO高剂量组（100μmol/L TBHP+36μmol/L ANDRO）。流式细胞术检测细胞凋亡和活性氧（reactive oxygen species,ROS）水平,ELISA试剂盒检测氧化应激相关指标超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-PX）和过氧化氢酶（catalase,CAT）水平,JC-1探针法检测线粒体膜电位,Western blot检测动力相关蛋白1(dynam...     

A comparison of residential heroin detoxification patients and methadone maintenance patients

Interviews were conducted with 101 heroin dependent persons entering a residential drug-free detoxification unit in 1989. These self-report data were compared with those previously collected in 1985-6 from 457 methadone maintenance patients. The detoxification patients injected less frequently, used less heroin, had been physically dependent for a shorter period and were more likely to be single, unemployed and to have been charged with a criminal offence in the last 12 months. It is suggested that these findings may indicate that addicts who use more heroin are less likely to seek drug-free detoxification. The wider implication of the finding is that future surveys of injecting drug users should assume that there are significant differences between heroin users entering different modalities of treatment.     

内毒素致家兔氧提取功能障碍的研究

作者复制了家兔病理性氧供依赖性(POSD)模型。采用渐进性低氧法降低总氧运输量(TO_2),从而考察机体氧运输及氧摄取的变化特点。结果表明,在TO_2-VO_2的关系中,对照组可清楚地分为“非依赖”与“依赖”两部分;内毒素组从呼吸空气开始,从未出现坪区,内毒素组和对照组依赖段的斜率,即氧提取率分别为0.473和0.730,两者差别显著(P<0.05)。内毒素组的动静脉血氧含量差值(CaO_2-CVO_2)在渐进性低氧过程中逐渐变小(P<0.01,ANOVA),对照组则呈相反变化趋势,故其组间差别越来越大,表明内毒素组氧提取率降低。     

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.     

吗啡成瘾对大鼠及小鼠学习与记忆能力影响的实验研究

目的 研究吗啡成瘾对大鼠及小鼠学习与记忆能力的影响。方法 将２４只ＳＤ大鼠昆明小鼠分别随机分成３组;即吗啡成瘾组、吗啡成瘾后戒断组和对照组。然后分组对动物进行Ｍorris水迷宫训练。结果（1）在Morris水迷宫掩蔽平台次训练中,吗啡成瘾组动物（大鼠和小鼠）的逃避潜伏期对与对照组及吗啡戒断组动物相比,均明显延长（P＜0．01）;（2）对照组动物的逃避潜伏期最短;（3）在Morris水迷宫可见平台学习中,无论是大鼠还是小鼠,三组动物逃避潜伏期均随着学习训练逐渐缩短,无明显组间差别（P＞0．05）。结论 吗啡成瘾可明显损害动物的学习记忆能力。     

Children's Health and the Environment—The First Herbert L. Needleman Award Lecture

Children today are exposed extensively to toxins in the environment. Prominent among these are exposures to over 70,000 synthetic chemicals, all newly developed in the past 50 years and largely untested for their hazards to children's health. Children are uniquely vulnerable to toxins, and with increasing incidence they are developing chronic, disabling, life-threatening diseases known or suspected to be of environmental origin–asthma, endocrine disruption, cancer, and the diseases caused by tobacco. Pediatricians need to consider toxic etiologies in the differential diagnosis of childhood illness.     

Tolerance,cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps

Previous research has found that drugs with affinity for (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0–30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10–100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1–1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0–3.0 mg/kg), lorazepam (0.3–3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0–30 mg/kg) and zolpidem (0.3–3.0 mg/kg) when tested 3–14 days after pump removal. Differences between compounds highlighted with this model are in agreement with previous observations that these agents possess different pharmacological profiles and different potentials to induce tolerance and dependence.     

Route of administration and adverse effects of amphetamine use among young adults in Syndney, Australia

The relationship between route of administration and the adverse effects of amphetamine use (dependence symptoms, treatment-seeking, adverse psychological symptoms and violence) were examined among 231 Australian amphetamine users, half of whom usually injected amphetamine. Although 87% of users were recruited from non-treatment sources, a third had experienced symptoms of dependence on amphetamine, and a third had experienced an amphetamine-related health problem for which one in four had sought medical attention. There was also a high prevalence of psychological symptoms, such as depression, anxiety, paranoia, hallucinations and violence which were related to frequency of amphetamine use, and use by injection. Amphetamine users need to be better informed about the potential adverse effects of amphetamine use, and about ways in which they can reduce their risks of experiencing these harms by avoiding injecting use, and the regular use of high doses of amphetamines.     

The development of guidelines for drug and alcohol dependence treatment: affecting policy and practice

The rationale and methodology behind the Australian Quality Assurance Project is described. The Project aimed to develop guidelines for treatment content based on three sources of information: research findings, current practice and expert opinion. The issue of the gap between research and practice is discussed, as well as the role of dissemination in altering clinician behaviour.     

Current benzodiazepine issues

This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronicaly, and although this does not appear to result in dose escalation or other evidence of psychological dependence, physiological dependence can result in patient discomfort if drug use is abruptly discontiniued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.This article was supported by USPHS Grant DA-00254 and by funding from Hoffmann-La Roche, Inc.