吗啡和胆碱能拮抗剂联合给药对小鼠Y迷宫空间记忆提取及活动性的影响(英文）

吗啡和胆碱能系统的相互作用已在多项研究中提到,本实验想查明吗啡是否能和胆碱能拮抗剂、东莨菪碱以及阿托品共同作用对小鼠的Y迷宫空间识别记忆提取产生影响。采用测试前腹腔给药的方法,选用3种剂量的吗啡(5、1.5、0.5mg/kg),两种剂量的东莨菪碱(1、0.1mg/kg),以及两种剂量的阿托品(0.5、0.1mg/kg),剂量由高到低相配对作为联合给药的手段。其结果表明:1)0.5mg/kg低剂量吗啡与0.1mg/kg低剂量的东莨菪碱,或与0.1mg/kg低剂量的阿托品联合给药的小鼠,在记忆提取测试中,空间探查行为(各臂停留时间百分比)对新异臂没有偏好,而新奇探索行为(各臂访问次数百分比)仍保持了对新异臂的偏好,而相应剂量药物单独给药的小鼠记忆提取均没有被损害;2)吗啡能和东莨菪碱相互作用使小鼠的活动性显著增强。暗示吗啡和胆碱能拮抗剂对小鼠空间记忆提取的破坏存在一定程度的相互作用。     

Neuropharmacological actions of some binuclear lanthanide(III) complexes

Binuclear lanthanide(III) compounds are of great interest because of the potential of their mutual Ln(3+)-Ln(3+) electronic couplings to produce unusually sharp images in magnetic resonance and fluorescence imaging of biological tissue. The toxicity and neuropharmacological properties of the water soluble and stable neutral binuclear complex [La(api)](2) were compared with those of binuclear complexes with lower water stability, and the components used in their syntheses. The order of the 24-h LD(50) (mg/kg body wt.) of the compounds in mice was: salicylaldehyde (2.24)160). These compounds induced convulsions, urination and defecation in mice. Due to the relatively very low toxicity of [La(api)](2), its mode of action was explored. Its proconvulsant action may possibly involve an interaction of undissociated complex with muscarinic receptors, and is reversed by atropine.     

重度有机磷农药中毒致多器官功能障碍综合症死亡因素的探讨

目的:探讨重度有机磷农药中毒发生多脏器功能障碍综合症的死亡因素。方法:分析78例急性有机磷农药中毒发生多脏器功能障碍综合症的临床资料,分为治愈组和死亡组,分别对两组的一般资料、治疗过程、并发症等情况进行比较。结果:治愈组64.5%的中毒物为中低毒性,而死亡组50%的患者中毒物为高毒类,两组中毒物毒性程度的构成比比较差异有统计学意义(P0.05)。死亡组患者中毒后至洗胃的时间间隔较治愈组明显延长(6.8±4.1 vs 4.2±3.5h,p=0.038),入院24小时内氯磷定用量明显低于治愈组(6.2±3.8 vs 8.6±2.6,P=0.045)。两组阿托品总用量及24小时总用量比较未见显著性差异(669.4±393.1 vs 427.9±290.7,P=0.956),但死亡组阿托品日均用量明显高于治愈组(120.2±96.31 vs 39.5±62.0,P=0.042)。入院第1天,死亡组Pa O2/Fi O2、MAP明显低于治愈组,Scr、HR及CK-MB明显高于治愈组;治疗3天后,死亡组MAP仍明显低于治愈组,Scr、HR较高,且Ach E明显低于治愈组,差异均有统计学意义(P0.05)。结论:中毒物的毒性程度、未能早期足量的应用肟类复能剂、过量使用阿托品或阿托品中毒、发病初期缺少足够的多器官功能支持治疗可能是AOPP合并MODS的患者死亡的重要因素。     

Proinsulin C-peptide activates vagus efferent output in rats

The aim of this study was to examine the effect of proinsulin C-peptide on the autonomic nervous systems in rats. Intravenous administration of C-peptide gradually increased electrophysiological activity of the vagus nerves into the stomach and pancreas for at least 90 min. It also slightly increased gastric acid secretion that was suppressed by the treatment with atropine. Intraperitoneal injection of C-peptide did not affect the basal and stress-induced norepinephrine (NE) turnover rate, a biochemical index of sympathetic nerve activity. These results indicate that C-peptide increases parasympathetic nerve activity without affecting sympathetic nerve activity. This could explain, at least in part, the ameliorating effects of C-peptide on impaired cardiac autonomic nerve functions in patients with type 1 diabetes.     

Selective Blocking Effects of Tropisetron and Atropine on Recombinant Glycine Receptors

Some serotonin 5-HT3 receptor ligands of tropeine structure have been recently shown to modulate ionophore function and binding of glycine receptors. This led us to study the effects of the tropeines tropisetron and atropine on recombinant human glycine receptors transiently expressed in Xenopus oocytes by using whole-cell voltage-clamp electrophysiology. Glycine currents were inhibited by atropine in an apparently competitive manner and with considerable selectivity of the tropeines for alpha2 versus alpha1 subunits. Coexpression of beta with alpha subunits and replacement of the N-terminal region of the alpha1 subunits by the corresponding beta segment resulted in similar increases in the inhibitory potencies. Our data suggest common sites of the tropeines for inhibition on the N-terminal region of glycine receptors. The point mutations R271K and R271L of the alpha1 subunit decreased, whereas a T112A substitution increased, the inhibition constants (Ki) of the tropeines. These changes in the Ki values of the tropeines were associated with opposite changes in the EC50 of glycine. Selectivities for the tropeines versus glycine (EC50/Ki) varied within three orders of magnitude. These results, when expressed in terms of free energy changes, can be interpreted according to a two-state receptor model.     

脑室注射GABA对小鼠盐酸诱导型胃溃疡的抑制效应

小白鼠脑室注射ＧＡＢＡ（２、４、６μｍｏｌ）对盐酸诱导型胃溃疡产生一种明显的剂量－效应依赖的抑制效应，腹腔注射ＧＡＢＡ（１００μｍｏｌ）对盐酸诱导型胃溃疡无影响，荷包牡丹碱（ｉ．ｃ．ｖ．０．２μｍｏｌ）、β－氯苯氨丁酸（ｉ．ｃ．ｖ．４μｍｏｌ）或荷包牡丹碱（ｉ．ｃ．ｖ０．２μｍｏｌ）加β－氯苯氯丁酸（ｉ．ｃ．ｖ．４μｍｏｌ）对盐酸诱导型胃溃疡均无影响，但荷包牡丹碱（ｉ．ｃ．ｖ．０．２μｍｏｌ）可以     

近视的药物治疗及手术治疗研究进展

近视是最常见的眼病之一,近年来,由于近视的发病率逐年上升,已成为世界性医学问题,近视眼的治疗也成为研究重点。药物研究和手术治疗是近视的治疗目前的研究热点,并已经取得一定得成果。药物方面,阿托品,托品酰胺,哌仑西平,消旋山莨菪碱对近视的控制作用都有被证实,但由于应用上还有一定的副作用,远期效果也不明确,需要进一步研究。手术方面,近视眼手术主要分为角膜屈光手术和眼内屈光手术。LASIK手术是目前应用最广泛的角膜屈光手术方法,SBK手术,飞秒激光手术等技术也日趋成熟。但是,角膜手术存在着一定的风险,应用范围也较为局限,需要进一步研究。眼内屈光手术主要为有晶体眼的人工晶体植入术(PIOL)和屈光性晶状体置换术,矫正的范围更加大,但是眼内手术并发症较多,也需要进一步研究和改进。     

阿托品压抑疗法和遮盖疗法在治疗小儿弱视中的效果观察

目的:探讨遮盖疗法与阿托品压抑疗法治疗儿童弱视后视功能的变化差异。方法:90例单纯屈光参差弱视儿童随机分为压抑组和遮盖组各45例,两组弱视眼均佩带适矫眼镜,压抑组采用优势眼采用阿托品完全压抑法,遮盖组优势眼6h/日遮盖治疗,均连续治疗6个月,比较两组患儿视力变化情况。结果:治疗后压抑组的视力-0.044±0.137显著优于遮盖组视力-0.217±0.196(P0.05)。压抑组治疗后的P-VEP潜时、P-VEP振幅分别为105.3±4.9(ms)、14.8±3.6(uv)显著优于遮盖组(P0.05)。压抑组的立体视重建疗效分布显著的优于遮盖组(P0.05),压抑组的有效率80%显著的高于遮盖组的60%(P0.05)。压抑组的疗效分布显著的优于遮盖组(P0.05),压抑组的有效率84.44%显著的高于遮盖组的57.78%(P0.05)。结论:阿托品压抑疗法治疗弱视儿童较遮盖疗法具有更加显著的治疗效果。     

Involvement of cholinergic neurons in the regulation of the ghrelin secretory response to feeding in sheep

We previously demonstrated that a transient surge in plasma levels of ghrelin occurs just prior to a scheduled meal and that this surge is modified by the feeding regimen. This suggests that the ghrelin secretion is regulated by the autonomic nervous system, especially the cholinergic projections to the stomach. To test this hypothesis, we investigated changes in plasma ghrelin levels at feeding time in rams by administering cholinergic blockers (atropine and hexamethonium) and a cholinergic accelerator (metoclopramide). The average food intake in each group infused with atropine, hexamethonium, metoclopramide, and saline was 150+/-28, 137+/-46, 153+/-50, and 1075+/-25g, respectively. Plasma ghrelin concentrations increased (P<0.05) after i.v. infusion of hexamethonium and gradually decreased (P<0.05) after i.v. infusion of metoclopramide. Plasma ghrelin levels in hexamethonium-treated animals were greater (P<0.05) than those of atropine-treated animals. Plasma ghrelin levels were significantly (P<0.05) higher in sheep given i.v. infusions of atropine or hexamethonium than the levels in normal- or pair-fed sheep infused with saline. Plasma ghrelin levels were similar in metoclopramide-treated, pair-fed, and control animals. These results support the possibility that ghrelin secretion is regulated by cholinergic neurons of the vagus and that cholinergic activity suppresses ghrelin secretion in sheep.     

Involvement of cholinergic mechanisms in the central control of respiration in the cane toad, Bufo marinus

Chemical substrates, central sites and central mechanisms underlying the regulation of breathing in lower vertebrates have not been well characterized. The present study was undertaken to determine the effect of pH changes and cholinergic agents on the central control of respiration in the cane toad, Bufo marinus. Adult toads were anesthetized, catheterized and unidirectionally ventilated before exposing the brainstem. An airtight buccal cannula was also inserted through the tympanum to record buccal pressure. The animal was decerebrated, anesthetic removed and the responses to pH changes of solutions bathing the ventral surface of the medulla (VSM) were tested by superfusing the VSM with mock cerebrospinal fluid (mCSF) of pH 7.8-normal, 7.2-acidic and 8.4-basic. The acidic solution increased respiratory activity, the basic solution decreased activity and the normal solution had no effect. In addition, cholinergeric agents (acetylcholine-ACh, physostigmine-Phy, nicotine-Nic, and atropine-Atr) dissolved in mCSF were applied bilaterally onto the VSM using filter paper pledgets. ACh, Phy and Nic increased episodic breathing frequency by 14.3+/-9.7, 9.4+/-5.4 and 29.1+/-11.8 %, respectively, whereas, Atr caused a decrease (-26.6+/-16.6%). These agents had no effect on blood pressure. It is therefore, concluded that the VSM is pH sensitive and a cholinergic mechanism is involved in the central modulation of respiration in Bufo.