中脑边缘奖赏系统参与阿片类药物成瘾的环路机制

阿片类药物成瘾发生率高,对个人和社会危害极大。中脑边缘奖赏系统在阿片类药物成瘾中发挥着重要作用,以往研究多集中于中脑边缘奖赏系统中特定脑区的功能变化,而对脑区之间神经元的相互作用研究较少。该文对近年来中脑边缘奖赏系统参与阿片类药物成瘾的环路机制进行综述,以期从更广阔的视野了解阿片类药物成瘾机制。     

电压依赖性钙通道与阿片类药物成瘾之间的关系

阿片类药物成瘾属慢性复发性脑病,主要表现为对成瘾性药物的强迫用药行为及用药量的不可控制性,其机制复杂,治疗困难,复发率高,因此对阿片类药物依赖戒断的机制及治疗的研究一直是医学界关注的热点和难点.大量研究证明电压依赖性钙通道（voltage dependent calcium channels,VDCCs）与阿片类药物成瘾的形成之间存在着密切的关系,VDCCs可通过多种途径参与阿片成瘾的形成.并且临床上,多种钙拮抗剂治疗吗啡戒断综合征也取得了一定的疗效,间接证明了VDCCs与阿片成瘾的形成之间存在着密切的关系.现对VDCCs与阿片类药物成瘾之间的关系综述如下.     

CREB参与慢性应用吗啡引起的神经元和突触的可塑性和适应性

反复应用阿片类药物,机体启动适应机制,神经元及突触功能产生适应性改变,导致神经元及神经网络功能发生长期改变,是机体形成药物依赖和耐受的机制之一[1]。目前研究认为,阿片和其他成瘾药物具有共同的细胞和解剖通路,而受体后细胞、突触和神经网络的适应性改变是成瘾形成的关键[1]。阿片类药物与其受体结合后,     

不规范使用盐酸羟考酮缓释片致成瘾的诊治体会

目的 探讨临床药师参与疼痛治疗的模式,更好地防治阿片类药物成瘾。方法 临床药师作为疼痛规范化治疗团队的成员,通过对患者进行用药监护、用药宣教,提高患者用药依从性,及早发现阿片类药物成瘾,并进行干预,指导脱毒治疗,防治医源性阿片类药物成瘾。结果 临床药师及时对盐酸羟考酮缓释片成瘾患者进行宣教,采用剂量递减法进行脱毒治疗,重新滴定患者所需盐酸羟考酮缓释片的治疗剂量,有效治疗2例由于不规范使用盐酸羟考酮缓释片导致的成瘾患者。结论 临床药师充分参与疼痛治疗,可以有效防治阿片类药物成瘾,保障用药安全性、有效性和规范性。     

药物成瘾治疗新动向

阿片类药物成瘾防复吸一直是作为困扰世界医学界的主题,目前临床上采用阿片类受体激动剂美沙酮、半激动半拮抗剂丁丙喏啡梯度递减替代治疗方案,阿片类药物导致的躯体依赖已经得以解决,临床脱毒基本完成。但吸毒患者复吸率依然很高,导致复吸的因素很多,主要是稽延性症状、心瘾及环境因素,针对复吸原因,许多科研人员正投入大量的工作以研究防复吸的新途径。本文主要介绍药物成瘾治疗的一些新动向。1 阿片类药物受体拮抗剂纳曲酮的应用纳曲酮为纯阿片受体拮抗剂,通过阻断外源性阿片类物质与阿片受体结合,抑制阿片类药物对阿片受体的强化作用,从…     

大视野

海洛因和吗啡成瘾可通过免疫系统阻断近日,物理学家组织网报道,一个国际研究小组获得了重大突破,他们发现了人体免疫系统放大对阿片类药物依赖性的关键机制,并证实可通过药物来阻断吗啡和海洛因成瘾,同时帮助缓解疼痛     

前沿进展

海洛因和吗啡成瘾可通过免疫系统阻断 近日,物理学家组织网报道,一个国际研究小组获得了重大突破,他们发现了人体免疫系统放大对阿片类药物依赖性的关键机制,并证实可通过药物来阻断吗啡和海洛因成瘾,同时帮助缓解疼痛。临床试验预计将在未来18个月内进行。     

论中医药对阿片类药物成瘾者戒断及抗复吸整体序贯疗法

回顾、分析中医药对阿片类药物成瘾者戒断治疗研究现状及存在问题,借助现代生物医学对阿片类药物成瘾机理及戒断后生理变化过程的研究成果及分期概念,运用中医整体、辨证论治学说,论述戒断后辨期与辨证相结合的整体序贯治疗思路与方法,并进行临床示范研究,以期建立中医药戒毒及抗复吸诊疗的理论体系及系统治疗方案     

盐酸丁丙诺啡及曲马多用于腹腔镜泌尿外科术后镇痛的疗效

盐酸丁丙诺啡为阿片受体的部分拮抗一激动剂,其镇痛效果明显。曲马多为弱阿片类药物,无成瘾趋势,呼吸抑制轻微,用于治疗中小手术后疼痛有较好的临床疗效。本研究试用盐酸丁丙诺啡及曲马多治疗腹腔镜下泌尿外科术后疼痛,观察其疗效。     

非靶受体在精神活性物质依赖中的作用

当前精神活性物质滥用和成瘾呈上升趋势,它既是一个严重的社会问题,又是一个非常重要的生物学问题。在我国导致精神依赖的活性物质主要是阿片类。精神活性物质作用的靶受体为阿片受体,非靶受体主要包括多巴胺受体、N-甲基-D-门冬氨酸(NMDA)受体和组胺等。本文主要论述NMDA受体和组胺受体等非靶受体在精神活性物质依赖发生发展过程中功能和结构上的变化,探讨精神活性药物成瘾的机制,研究和开发以NMDA和组胺受体为靶标的新药,为阿片类药物成瘾的防治开辟新的研究领域。     

上海市社区卫生服务中心医务人员伦理学知识调查及建议

目的:调查上海社区卫生服务中心医务人员的伦理学知识认知情况.方法:采取分层抽样方式,于2016年6—8月对上海市245家社区卫生服务中心的7552名医务人员进行问卷调查.结果:医务人员对伦理学知识非常了解、基本了解、了解很少和完全不了解的人数分别为536人(7.1%)、5411人(71.7%)、1536人(20.3%)和69人(0.9%).不同岗位、职称、学历的医务人员之间存在着明显的伦理学知识认知差距.结论:上海社区卫生服务中心医务人员的伦理学知识了解程度仍有待提高,需加强伦理学知识的学习和应用.     

Studies on the receptors involved in the action of the various agents in the phenylbenzoquinone analgesic assay in mice

1. Tolerance to the activity of several narcotic analgesics (morphine, levorphanol, and methadone) and several narcotic-antagonist analgesics (pentazocine, cyclazocine, and nalorphine) was studied in the mouse phenylbenzoquinone stretching test. Virtually complete tolerance was induced by chronic treatment with each of the narcotic agents, while no apparent tolerance was induced by the narcotic antagonists.2. In morphine-tolerant mice there was a high degree of cross-tolerance to the effects of not only the other narcotic drugs but also to those of the narcotic antagonists, acetylsalicylic acid, and physostigmine.3. The effects of morphine and pentazocine were antagonized by naloxone but not by atropine, while the effects of physostigmine were antagonized by atropine but not by naloxone. Neither atropine nor naloxone antagonized the effect of acetylsalicylic acid.4. The results of the tolerance study suggest that there is a fundamental difference in the consequences of receptor interaction for the narcotic and the narcotic-antagonist analgesics. Morphine-tolerant mice exhibit cross-tolerance non-specifically. The selectivity of naloxone and atropine differentiates the narcotic and narcotic-analgesics from the other two agents used in this analgesic test.     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.     

Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse

The ability of ⁹-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E₁ (PGE₁) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED₅₀ in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED₅₀ range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE₁ as the nociceptive agent, 11-OH THC was equipotent to THC while 8,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.     

Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo

Differential pulse voltammetry with carbon fibre electrodes was used to study the effect of central administration of neurotensin on the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum in anaesthetised rats. Intracerebroventricular injection of neurotensin (10 micrograms) increased the peak height for DOPAC 20 min after administration in the nucleus accumbens but only after 40 min in the striatum. The maximum increase was similar in both regions, with 30% and 27% above the pre-injection basal level, respectively. Neurotensin (1 micrograms) however increased the extracellular level of DOPAC in the nucleus accumbens alone. Neurotensin (0.1, 1.0 and 3.0 micrograms/0.5 microliter), injected into the ventral tegmental area, induced a potent and long-lasting elevation of the peak height for DOPAC in the nucleus accumbens, while the same doses in the substantia nigra produced effects on the metabolism of dopamine in the striatum of smaller amplitude and shorter duration. The maximum effect of each dose was about 2.5 times greater in the mesolimbic, compared to the nigrostriatal system. Amphetamine (2 mg/kg, s.c.) decreased the extracellular level of DOPAC with a similar magnitude, both in the nucleus accumbens (52%) and the striatum (47%). Intracerebroventricular administration of neurotensin (1 micrograms), 5 min after amphetamine, did not alter the effect of amphetamine on the extracellular level of DOPAC either in the nucleus accumbens or the striatum. However, neurotensin (10 micrograms) partially reversed the effect of amphetamine in the nucleus accumbens and had a similar but smaller and delayed effect in the striatum. The results from the present study, together with previous neurobehavioural studies, suggest that neurotensin has a relatively selective action on the mesolimbic dopaminergic system in the rat.     

Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

抗生素在预防普外科手术切口感染中的价值分析及其预防

目的:分析抗生素在预防普外手术切口感染中的临床价值.方法:选择我院收治的100例普外科手术患者作为观察对象(2015年2～11月),采用随机分组的方式将100例普外科手术患者分成对照组与实验组,分别在术后使用抗生素及术前1h使用抗生素,观察两组手术切口感染率及患者的疼痛评分.结果:对照组切口感染率(16.00％)明显高于实验组(4.00％),两组之间对比疼痛评分存在显著差异(P＜0.05),有统计学意义.结论:针对普外科手术患者根据患者的切口类型科学、合理选择抗生素及选择适当的使用时间能有效减少术后手术切口感染,有效改善患者预后.     

女性医务人员健康状况的研究

目的探讨女性医务人员健康状况的特点。方法对2877例医院工作人员健康查体资料进行统计学分析。结果①女性医务人员中,41.0%的人员患有不同类型的疾病,略高于男性患病率（36.8%）,二者差异有统计学意义（P=0.029）;②女性医务人员高脂血症为31.9%（212/665）,低于男性（65.9%,274/416）;③脂肪肝患病率女性（32.6%,181/556）,亦低于男性（45.9%,151/329）;④女性相关疾病中,乳腺疾病和子宫肌瘤的患病率分别为4.8%和3.4%;而宫颈糜烂为20.2%;⑤女性医务人员高血糖为11.0%（77/702）,高血压为4.6%（56/1229）。结论女性医务人员中妇科与乳腺疾病是健康体检的重点,代谢性疾病也应加以关注。