过度静脉输液的现状、危害及管控措施

通过分析我国过度静脉输液的现状和危害,结合国外静脉输液管理指南,提出改善我国静脉输液的管控措施,促进我国医疗机构静 脉输液合理使用和管理,保障患者用药安全。     

BIS监测下丙泊酚靶控静脉麻醉与七氟醚麻醉效果比较

目的:比较BIS监测下丙泊酚靶控输注全凭静脉麻醉与七氟醚静吸复合麻醉两种方式下的腹腔镜下子宫切除手术患者麻醉效果。方法:46例择期腹腔镜下子宫切除患者,ASAI`II级,随机分为:丙泊酚靶控全凭静脉麻醉组(TCI组)和七氟醚静吸复合麻醉组(SD组),各23例。术中均监测BIS值(维持在40~60)。记录麻醉诱导前(T1)、手术开始30 min(T2)、术后1 h(T3)患者血压(BP)和心率(HR);记录术后自主呼吸恢复时间、睁眼时间、拔管时间;记录术中知晓发生率和术后24小时恶心呕吐(PONV)发生率。结果:TCI组与SD组患者BP和HR在T1、T2、T3各时间点比较差异均无统计学意义(P0.05);TCI组呼吸恢复时间、睁眼时间、拔管时间均早于SD组,差异有统计学意义(P0.05);两组患者均未发生术中知晓;但术后24小时PONV发生率TCI组明显低于SD组(P0.05)。结论:在BIS监测下,丙泊酚靶控全凭静脉麻醉与七氟醚静吸复合麻醉用于腔镜下子宫切除手术均能够维持术中患者血流动力学平稳,预防术中知晓,但全凭静脉麻醉较静吸复合麻醉患者术后恢复更快,术后24小时恶心呕吐发生率低。     

脑室注射氨茶碱或咪唑对大鼠电针镇痛的影响

我们曾经报道,给大鼠脑室注射 cAMP,外源性地提高脑内 cAMP 水平,引起大鼠的电针镇痛效应显著减弱,并有明显的剂量效应关系。已知裂解 cAMP 的磷酸二酯酶(PDE)抑制剂茶碱能提高脑内 cAMP 含量,而 PDE 激活剂咪唑则能降低脑内 cAMP 水平。因此本文用脑室注射 PDE 抑制剂氨茶碱或 PDE 激活剂咪唑的方法以图改变中枢内源性 cAMP 的水平时对电针镇痛的影响。结果表明氨茶碱能拮抗电针镇痛,而咪唑则对电针镇痛有加强作用。这与外源性注射 cAMP 的结果一致,说明脑内 cAMP 可能是对抗电针镇痛的一个重要因素。     

Ostertagia ostertagi: establishment of patent infections in calves by intravenous inoculation

In two experiments calves raised free of parasite infection were given parenteral injections of Ostertagia ostertagi infective larvae to determine if patent infections might result. Patency was achieved by intravenous injection of larvae. Ten calves of different age (3–8 months) and sex were given intravenous, subcutaneous, and intraperitoneal injections of infective larvae. These calves were not necropsied; patency was based on fecal egg counts. Six calves injected intravenously all achieved patency (17–21 days after inoculation). Two calves each were inoculated subcutaneously and intraperitoneally; patency was observed in none. Calves given primary intravenous inoculation responded with higher levels of ova production to subsequent oral challenge inoculation.In a second experiment, six 2–3-month-old calves were injected intravenously with 186,000 infective larvae. Calves were killed at 2, 7, 12, 20 and 30 days after inoculation and had a tissue reaction in the lungs to migrating larvae characterized by focal granulomas, interstitial thickening of alveolar walls, and some hemorrhage. Infective larvae were recovered from the lungs at 2, 7 and 12 days, fourth stage larvae from the abomasum at 7 and 12 days, and adults only from the abomasum at 20 and 30 days. It was considered that larvae reached the abomasum by way of the trachea and by then being swallowed. Clinical signs of disease were not observed.     

家兔伏核注射吗啡引起的镇痛可被中脑导水管周围灰质注射纳洛酮或甲啡肽抗体所阻断

本实验室以往的资料表明,在家兔中脑导水管周围灰质(PAG)到伏核之间存在一条与镇痛有夫的神经通路,该通路以5-羟色胺(5-HT)和甲啡肽(ME)为其递质。本工作进一步探讨从伏核到PAG的下行镇痛通路。 以辐射热照射家兔嘴侧部皮肤,测量其躲避反应的潜伏期(ERL)作为痛反应阈,简称痛阈。通过预先埋植的慢性套管向伏核内微量注射吗啡,20min后向PAG内双侧注射纳洛酮(NX)或脑啡肽抗血清,观察ERL的变化。(1)伏核内注射吗啡20μg/1μl,引起ERL升高80％以上,作用持续50min以上。(2)PAG内注射NX(每侧0.5、1.0或2.0μg)可不同程度地阻断伏核内注射吗啡的镇痛效应,且呈明显的剂效关系。(3)PAG内注入甲啡肽抗血清(每侧1μl)可部分阻断伏核内注射吗啡的镇痛效应,而注入亮啡肽抗血清或正常兔血清则无效。 实验结果提示,从伏核到PAG存在一条下行镇痛通路,在PAG内可能以ME为其递质。该通路与PAG到伏核的上行镇痛通路构成一个环形的“中脑边缘镇痛回路”,并在针刺镇痛和吗啡镇痛中发挥重要作用。     

5,6-DHT损毁大鼠蓝斑内5-HT能神经末梢对电针镇痛的影响

在大鼠蓝斑注射5.6-DHT 以破坏其5-HT 末梢,然后观察电针镇痛效应的变化。动物分注药组和对照组,注药组在注射5.6-DHT 后7天,针刺镇痛效应比注药前显著下降。与此同时,蓝斑内的5-HT 末梢发生变性,产生逆行性荧光积累,从荧光积累的末梢走向来看,蓝斑内被5.6-DHT 损毁的5-HT 末梢主要来源于中缝背核。随着蓝斑内5-HT 末梢的变性,脑桥区5-HT 含量下降,下降率达27%P<0.01。对照组动物,蓝斑内5-HT 末梢保持正常,其镇痛效应与注药前相比也无明显改变。鉴于一般认为蓝斑核的活动削弱针刺镇痛效应,以上结果提示,在电针镇痛过程中,支配蓝斑的5-HT 神经末梢,对该核 NA 能神经元可能有抑制性影响。     

Drug-primed reinstatement of cocaine seeking in mice: increased excitability of medium-sized spiny neurons in the nucleus accumbens

To examine the mechanisms of drug relapse, we first established a model for cocaine IVSA (intravenous self-administration) in mice, and subsequently examined electrophysiological alterations of MSNs (medium-sized spiny neurons) in the NAc (nucleus accumbens) before and after acute application of cocaine in slices. Three groups were included: master mice trained by AL (active lever) pressings followed by IV (intravenous) cocaine delivery, yoked mice that received passive IV cocaine administration initiated by paired master mice, and saline controls. MSNs recorded in the NAc shell in master mice exhibited higher membrane input resistances but lower frequencies and smaller amplitudes of sEPSCs (spontaneous excitatory postsynaptic currents) compared with neurons recorded from saline control mice, whereas cells in the NAc core had higher sEPSCs frequencies and larger amplitudes. Furthermore, sEPSCs in MSNs of the shell compartment displayed longer decay times, suggesting that both pre- and postsynaptic mechanisms were involved. After acute re-exposure to a low-dose of cocaine in vitro, an AP (action potential)-dependent, persistent increase in sEPSC frequency was observed in both NAc shell and core MSNs from master, but not yoked or saline control mice. Furthermore, re-exposure to cocaine induced membrane hyperpolarization, but concomitantly increased excitability of MSNs from master mice, as evidenced by increased membrane input resistance, decreased depolarizing current to generate APs, and a more negative Thr (threshold) for firing. These data demonstrate functional differences in NAc MSNs after chronic contingent versus non-contingent IV cocaine administration in mice, as well as synaptic adaptations of MSNs before and after acute re-exposure to cocaine. Reversing these functional alterations in NAc could represent a rational target for the treatment of some reward-related behaviors, including drug addiction.     

昆明小鼠和DBA/2小鼠尾静脉注射L1210细胞的比较研究

目的:通过尾静脉注射L1210细胞建立昆明小鼠及DBA/2小鼠的白血病模型,观察肿瘤细胞的迁移情况以及小鼠存活时间,为后续L1210细胞迁移的细胞内信号通路研究及抗肿瘤药物筛选奠定基础。方法:常规培养小鼠白血病细胞L1210系,将昆明小鼠及DBA/2小鼠随机分为对照组(A、C)和实验组(B、D),实验组尾静脉注射5×10^6L1210细胞,对照组注射等体积的PBS。昆明小鼠组饲养56d,DBA/2小鼠组饲养14d。定期测量小鼠体重并观察小鼠形态,取濒死小鼠以及最后解剖的小鼠的心、肝、脾、肺等脏器称重并测量,统计结果。结果:A、B、C、D组小鼠的平均存活天数分别为56、56、13.83±0.37、10.33±3.40d。昆明小鼠实验组脾脏明显肿大,肺脏有少量白细胞浸润,心脏和肝脏无明显变化,无死亡现象;DBA/2小鼠注射L1210细胞后第7d开始出现死亡,随着饲养时间的延长,死亡率不断上升。结论:昆明小鼠或DBA/2小鼠尾静脉注射L1210细胞均可引起肿瘤细胞的体内浸润。昆明小鼠尾静脉注射L1210细胞存活时间长,适合长期观察或周期比较长的实验;DBA/2小鼠尾静脉注射L1210细胞存活时间短,但实验现象明显。后期研究可以针对不同的研究目的和实验周期来选择合适的实验模型。     

Synthesis and evaluation of in vivo anti‐hypothermic effect of all stereoisomers of the thyrotropin‐releasing hormone mimetic: Rovatirelin Hydrate

We discovered the orally active thyrotropin‐releasing hormone (TRH) mimetic: (4S,5S)‐5‐methyl‐N‐{(2S)‐1‐[(2R)‐2‐methylpyrrolidin‐1‐yl]‐1‐oxo‐3‐(1,3‐thiazol‐4‐yl)propan‐2‐yl}‐2‐oxo‐1,3‐oxazolidine‐4‐carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100‐fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti‐hypothermic effect of all stereoisomers of 1 , which has the (4S),(5S),(2S),(2R) configuration from the N‐terminus to the C‐terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)‐isomer 16 did not show any anti‐hypothermic effect. Only the (4S),(5S),(2S),(2S)‐isomer 10 , which has the (2S)‐2‐methylpyrrolidine moiety at the C‐terminus showed the anti‐hypothermic effect similar to 1 . Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N‐terminus and the (2R) configuration at the middle‐part, showed a much lower anti‐hypothermic effect than that of 1 . On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N‐terminus or the (2S) configuration of the C‐terminus, have little influence on the anti‐hypothermic effect.     

腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量的临床研究

目的:确定腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量(ED50),观察蛛网膜下腔注射半数有效剂量芬太尼的效果和副作用,并与蛛网膜下腔注射半数有效剂量的布比卡因进行对比。方法:首先,确定芬太尼用于分娩镇痛的半数有效剂量,筛选50例符合的产妇行腰硬联合分娩镇痛,蛛网膜下腔注射芬太尼的剂量始于25μg,如果镇痛有效,下一病例减少2.5μg芬太尼;如果无效则下一病例增加2.5μg芬太尼。用Probit回归分析计算芬太尼蛛网膜下腔注射行分娩镇痛的半数有效剂量和95%可信区间(95%CI)。第二步,筛选100例需要进行分娩镇痛的产妇,随机分入ED50芬太尼组(F组)和ED50布比卡因组(B组),比较两组药物镇痛效果及起效时间、产妇下肢运动阻滞程度及血压心率变化、胎心变化和镇痛全程药物追加次数。结果:芬太尼蛛网膜下腔注射分娩镇痛的ED50为11.5μg,95%CI为3.5-15.4μg。F组镇痛的平均起效时间为(12.0±3.8)min,两组镇痛的成功率没有统计学差异(P=0.218),F组需要追加PCA的病例百分率明显少于B组(P=0.018)。F组下肢运动阻滞程度轻于B组(P=0.018)。两组镇痛方法对产妇的血压、心率均无明显影响。两组胎心下降的发生率没有明显差异(P0.05)。F组皮肤瘙痒的发生率明显增加(P=0.000)。结论:腰硬联合分娩镇痛蛛网膜下腔注射芬太尼的ED50为11.5μg,95%CI为3.5-15.4μg。蛛网膜下腔注射半数有效剂量的芬太尼可以提供简便、持久、满意和安全的镇痛效果,并且对下肢运动阻滞程度较小,但其所致皮肤瘙痒的发生率升高。