慢传输型便秘模型的建立及其机制探讨

目的 :建立实验型慢传输型便秘模型。　方法 :实验组小鼠皮下注射吗啡建立慢传输型便秘模型 ,记录小鼠粪便重量 ,利用炭沫推进试验比较实验组与对照组小鼠结肠传输功能 ;利用免疫组化技术比较两组小鼠结肠组织中Cajal细胞数量。　结果 :实验组小鼠粪便重量减轻 (P <0 .0 1) ,结肠推进率较对照组明显延长 (P <0 .0 1) ,Ca jal细胞数量较对照组明显减少 (P <0 .0 1)。　结论 :吗啡皮下注射诱导小鼠结肠慢传输型便秘模型符合疾病的基本特点 ,其发病机制可能与内源性阿片肽增多和 (或 )肠道Cajal细胞异常改变有关     

针刺对海洛因依赖的脱毒疗效及其防复吸潜力的临床研究

目的 比较针刺、针刺加阿片、阿片加丁丙诺啡及阿片加韩氏戒毒仪4种方法的脱毒疗效及其对脱毒末期稽延性戒断症状和心理渴求的影响。方法 应用戒断症状量表观察脱毒疗效，应用视觉类比量表(VAS)研究心理渴求程度。结果 针刺改善海洛困依赖者戒断症状的优势主要表现在治疗的第6天以后，改善渴求心理的优势表现在第8天以后，且无明显副作用。结论 针刺具有防复吸潜力。可作为解决稽延性戒断症状和消除心理依赖的治疗方法。     

Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.     

Morphine-3-glucuronide: hyperglycemic and neuroendocrine potentiating effects

The greater potency of morphine-6-glucuronide (M6G) as well as the inactivity of morphine-3-glucuronide (M3G) with respect to the antinociceptive effects of the parent molecule, morphine (MOR), have been well established. It has been suggested that M3G is an antagonist of MOR's antinociceptive and respiratory depressive effects. The present study addressed the central nervous system (CNS) interaction of these opiate metabolites on their metabolic and hormonal effects. Whole body glucose kinetics were assessed on conscious, chronically catheterized, unrestrained rats. M3G (5 μg) or H₂O (5 μl) was injected intracerebroventricularly (i.c.v.) 15 min prior to the bolus administration of H₂O (5 μl), M6G (1 μg), or MOR (80 μg). i.c.v. M3G (5 μg) resulted in behavioral excitation, hyperglycemia (+50%), stimulation of glucose rate of appearance (R_a; +100%), glucose rate of disappeaance (R_d; +70%), and metabolic clearance rate (MCR; +33%) within 30 min after injection with no alterations in hormone concentrations. i.c.v. M6G and MOR produced progressive hyperglycemia with significantly high catecholamine and corticosterone levels. M3G pretreatment resulted in enhanced elevations in plasma glucose levels (+52% and +18%), plasma lactate (+138% and +108%), norepinephrine (+96% and +30%), and epinephrine (+62% and +67%) in response to both i.c.v. MOR and M6G administration. These findings suggest a non-opiate and non-hormonal mechanism for M3G-induced hyperglycemia. In contrast, the metabolic and hormonal responses to i.c.v. M6G and MOR are associated with elevations in catecholamine and corticosterone levels, which are remarkably enhanced by M3G pretreatment, most likely through accelerated catecholamine release. Our findings suggest a modulatory role for MOR glucuronidation, not only by rendering it inactive, as in the case of M3G, but by an interplay of the metabolic effects of the parent molecule and its metabolite     

吗啡对机械通气病人的应用

为获得病人在接受呼吸机期间充分的镇静、良好的耐管并与呼吸机合拍达到满意的治疗效果，对６０例不同年龄的患者在进行呼吸机支持治疗期间，采用平均０４５ｍｇ／（ｋｇｄ）的吗啡量持续微量泵静脉注入，间断辅助安定的方法．用药后连续２ｈ观察血压、心率、呼吸、意识等变化．结果：在用药期间病人血压、心率、呼吸平稳，保持清醒，安静耐管，解决了病人与呼吸机拮抗的矛盾．结果表明：该法在临床上有广泛使用价值     

鞘内注射吗啡对大鼠中脑导水管周围灰质、海马和脊髓μ阿片受体mRNA表达的影响

目的研究鞘内注射吗啡对大鼠中脑导水管周围灰质（PAG）、海马和脊髓μ阿片受体（MOR）mRNA表达的影响,探讨大鼠鞘内注射吗啡免疫功能抑制的机制。方法清洁级成年雄性SD大鼠,鞘内置管成功的16只大鼠随机分为2组（n=8）：生理盐水组（NS组）和吗啡组（M组）。M组鞘内持续输注吗啡10μg/h 7 d（生理盐水稀释）,NS组给予等体积的生理盐水。输注7 d后断头处死大鼠,取出大鼠PAG、海马和脊髓标本,采用巢式RT-PCR测定MOR mRNA的表达。结果与NS组比较,M组PAG和海马MOR mRNA表达下调（P〈0.05或0.01）,脊髓MOR mRNA表达无统计学意义（P〉0.05）。结论大鼠PAG和海马MOR表达下调可能是鞘内注射吗啡导致免疫功能抑制的机制之一。     

Antinociceptive Effects of Morphine Were Different Between Experimental and Genetic Diabetes

This study was designed to investigate the effect of morphine on formalin-induced nociceptive responses in streptozotocin (STZ) induced-diabetic mice, noninsulin-dependent genetically diabetic db/db mice and their respective controls (ddY and +/+). In nondiabetic (ddY and +/+) mice, morphine (1–10 mg/kg, PO) dose dependently attenuated the biphasic nociceptive responses induced by SC injection of formalin to the hindpaw, demonstrating equipotency on both the first and second phases. Para-chlorophenylalanine (800 mg/kg × 2, PO) and pindolol (1 mg/kg, IP) reduced the effect of morphine on the first phase, sulpiride (10 mg/kg, IP) abolished the effect on both phases, while ketanserin (1 mg/kg, IP) had no effect. In STZ (200 mg/kg, IP)-diabetic mice, morphine weakly attenuated the nociception in comparison to control ddY mice, whereas it had comparable effects in both the first and second phases of control +/+ mice and db/db mice. The serotonergic agonist, meta-chlorophenylpiperazine (0.32–3.2 mg/kg, PO), dose dependently attenuated the biphasic nociceptive responses to formalin in both phases of diabetic mice; however, FR64822, a dopaminergic compound (0.1–10 mg/kg, PO), had little effect. We speculate that activation of both dopaminergic (DA)- and serotonergic-mediated mechanisms are potentially responsible for the effect of morphine on the first phase, while the DA-mediated effect is involved in the second phase. The DA-mediated mechanism, but not the serotonin-mediated one, appears to be altered in both STZ-diabetic and db/db mice. These results suggest that the attenuated effects of morphine might be due to a dopaminergic dysfunction in STZ mice, and that there might be other mechanisms compensating for this attenuation of dopaminergic function in db/db mice.     

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GAB_A receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABA_A receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc.     

Randomised controlled trial of ondansetron in smoking cessation

A double-blind, placebo controlled trial was undertaken to examine the effect of the 5-HT₃ antagonist, ondansetron .25 mg bd on cigarette withdrawal symptoms and on proportion of individuals maintaining continuous abstinence for 4 weeks in a smoking treatment programme. A total of 111 smokers were allocated to active or placebo conditions and began taking their study medication 2 weeks before the quit date. They attended the smokers clinic for weekly group treatment sessions. The results showed no evidence for less severe withdrawal symptoms or improved abstinence rates in the active medication group. They suggest that inhibiting 5-HT₃ activity is not an effective method of controlling nicotine withdrawal or helping smokers to stop.     

Histamine turnover in the brain of morphine-dependent mice

Summary The turnover of brain histamine was examined in mice implanted subcutaneously with a morphine pellet (50 mg free base). The numbers of naloxone-precipitated jumpings and body shakes were maximum 2 and 3 days after implantation, respectively. The brain tele-methylhistamine level significantly increased (50% to 115%) during 12 h3 days after implantation of a morphine pellet, whereas the histamine level remained unchanged. The accumulation of tele-methylhistamine by pargyline treatment was significantly enhanced when pargyline was administered 12 h after implantation, suggesting an enhancement of histamine turnover. However, a similar degree of the tele-methylhistamine accumulation was induced by pargyline during 1–5 days after implantation, as compared with the accumulation in the control mice implanted with a placebo pellet. In mice undergoing morphine withdrawal by either the removal of morphine pellet or the treatment with naloxone 3 days after implantation, the degree of the pargyline-induced telemethylhistamine accumulation or the (S)--fluoromethylhistidine (-FMH)-induced histamine decrease was similar to that observed in the placebo pellet-control mice. The numbers of naloxone-precipitated jumpings and body shakes occurring in mice 3 days after implantation were not significantly affected by any of l-histidine, -FMH or metoprine. These results suggest that turnover of histamine in the brain is enhanced by acute morphine treatment and returns to the normal rate in the stage of chronic treatment and remains unchanged during the state of withdrawal. Send offprint requests to K. Saeki