川楝素对大白鼠膈肌神经肌肉接头超微结构的影响

本实验用电子显微镜观察了大鼠肌注川楝素后,膈肌神经肌肉接头超微结构的改变。给药后3小时,在突触前看到明显的结构改变,主要是突触小泡数量显著减少。其次是长管形泡增多、自噬体样结构经常出现,以及线粒体较分散、较趋近于突触前膜等。川楝素对突触后结构的影响则不明显。仅看到部分神经肌肉接头在接头区有肌原纤维Z-线消失和Schwann细胞突起伸入突触间隙的现象。本实验可能为阐明川楝素的作用机理提供了一点形态学依据。     

丙烯酰胺抑制大鼠肌注A型肉毒毒素后的神经芽生

目的观察丙烯酰胺是否能抑制肉毒毒素肌注后的神经芽生,以延长其治疗肌肉过强活动疾病的疗效。方法SD大鼠随机分为肉正常对照组、丙烯酰胺组、肉毒毒素组和毒毒素+丙烯酰胺组。每只大鼠右肢腓肠肌分别肌肉注射A型肉毒毒素5U或生理盐水1次(0.2mL),肌注后d3,6,9,12,15,18及21分别ip3%丙烯酰胺或生理盐水,每次0.1mL。肌肉注射肉毒毒素后1,2,3,4,6,8,10及12周的8个时间点评定大鼠右后肢肌力,观察单纤维肌电图和形态学计数神经纤维。结果肉毒毒素组右后肢肌力下降,单纤维肌电图纤维密度测定和病理形态神经纤维计数结果均显示A型肉毒毒素肌肉注射后神经芽生现象;单纤维肌电图动作电位平均连续差结果提示出现神经肌肉接头传导异常,12周可基本恢复正常。加用丙烯酰胺可延缓芽生高峰的时间和抑制芽生程度,并延缓神经肌肉接头功能的恢复。结论应用丙烯酰胺可抑制A型肉毒毒素局部注射后神经芽生,延迟肌力恢复。     

经含川楝素溶液培养后PC12细胞的SNARE蛋白的表达增加

川楝素是来源于传统中药，楝属植物川楝韧皮的一种三帖化合物。已有研究证明，它是一个作用于神经递质释放环节的特异性突触前阻断剂；并具有抑制人的多种肿瘤细胞增殖和引发细胞凋亡的效应；虽与同为突触前阻断剂的肉毒神经毒素在许多方面有相似的作用特点，但川楝素却又显示有效的抗肉毒效应。本工作利用免     

FDA批准肉毒杆菌毒素治疗皱纹

FDA于 2 0 0 2年 4月 12日批准肉毒杆菌A型增加治疗面部皱纹的新适应证。肉毒杆菌毒素是由A型肉毒杆菌分泌的纯化神经毒素复合物 ,其药理作用是阻断神经———肌肉接头间突触前膜乙酰胆感的释放 ,阻断神经冲动向肌肉的传递 ,从而缓解肌肉痉挛 ,导致其收缩无力。最早治疗使用肉毒杆菌可以追溯到 2 0世纪 6 0年代 ,FDA于 1989年 11月批准其治疗眼内肌内痉挛和功能紊乱 (睑痉挛和斜视 ) ,2 0 0 0年 11月批准肉毒杆菌毒素治疗颈部肌肉张力障碍 ,以及运动神经功能紊乱所致的严重的颈部、肩部肌肉痉挛。此次批准爱尔兰Allergan制药有限公司美…     

肉毒杆菌毒素食物中毒4例护理体会

肉毒杆菌毒素食物中毒是由于误食肉毒杆菌毒素污染的食品而引起的.其中毒机制,毒素主要作用于脑神经核、神经肌肉接头和自主神经末梢,抑制神经末梢乙酰胆碱的释放,导致肌肉麻痹和神经功能不全[1].     

肉毒毒素临床应用现状

肉毒毒素是由肉毒杆菌产生的一种神经毒素 ,能抑制神经肌肉接头以及胆碱能交感和副交感神经元乙酰胆碱释放。近 15年来肉毒毒素已被用于有效地治疗斜视和各种运动障碍 ,且治疗范围正在不断扩大。本文介绍了肉毒毒素的作用方式、治疗依据、实际治疗问题、副作用和适应证。     

A型肉毒毒素治疗疼痛的机制研究进展

A型肉毒毒素(botulinum toxin-A,BTX-A)是由100 ku的重链和50 ku的轻链通过二硫键相连形成的双链多肽式结构,其中轻链是一种蛋白酶可与神经肌肉接头处的融合蛋白结合,防止突触小泡锚定在细胞膜上释放乙酰胆碱,从而干扰神经冲动传递,因此在临床中作用效果广泛。近年来针对BTX-A临床应用范围的讨论也一直是热点,研究显示,A型肉毒毒素(BTX-A)能有效治疗疼痛,具有可持续性发挥疗效和无成瘾性等特点,但对于BTX-A作用机制仍旧存有争议。本篇文章将分别对BTX-A在外周神经系统和中枢神经系统中作用机制的相关研究进行综述。     

A-型肉毒素在面部除皱中的应用

随着人们生活水平的不断提高,为减轻岁月的痕迹,如何减少面部的皱纹一直是皮肤美容医师共同追求的目标。肉毒素注射除皱是其中之一,现就A-型肉毒素在面部除皱中的应用就有关文献综述如下。1肉毒毒素概念肉毒毒素(botulinum toxin)是由厌氧芽胞杆菌属中的肉毒杆菌分泌的一种毒性极强的神经毒素[1]。其中根据其血清抗原性的不同,可分为A、B、Cα、Cβ、D、E、F、和G 8个型[2],其中A型肉毒素(BT-A)因其稳定性最好、易于制备和保存而普遍用于临床。2肉毒素的作用机理肉毒毒素能从多方面作用于神经肌肉接头,阻断神经对肌肉的传导,导致肌肉…     

A型肉毒素在去皱应用中常见的副反应

肉毒素，又名肉毒杆菌肉毒素A，是肉毒梭菌生长繁殖过程中产生的一种细菌外毒素，是一种神经毒素蛋白，作用于周围神经运动末梢，抑制周围运动神经突触前膜释放乙酰胆碱，引起肌肉暂时性松弛性麻痹，3～6个月后失活的神经末梢产生神经轴突芽生，重新激发神经．肌肉传导。近几年来肉毒素用于治疗面部皱纹，被证明是有效的生物制剂。     

克痛宁注射液

本品系从眼镜蛇蛇毒中分离提纯的一种低分子量蛋白质(神经毒素)并配以无机盐的制剂。【作用特点】眼镜蛇神经毒素是作用非常专一的碱性毒素。它特异地作用于神经肌肉接头的突触后膜,产生箭毒样神经肌肉阻断作用。本品突出的特点是非麻醉性镇痛药,镇痛效果比吗啡强,具有不成瘾、无耐药性、无明显副作     

Synaptic terminal degeneration and remodeling at the rat neuromuscular junction resulting from a single exposure to acrylamide

Repetitive exposure to low doses of acrylamide results in extensive pathological changes at the neuromuscular junction (NMJ), but it remains undetermined if a single exposure to a larger dose will produce a similar neuropathological outcome. In the present study, morphometric and ultrastructural analyses of rat soleus NMJ were performed to determine early pathological effects of an intraperitoneal injection of 100 mg/kg acrylamide. Widespread nerve terminal degeneration, terminal sprouting, and endplate lengthening were evident as early as 4 days after injection. Degenerating terminal branches were swollen and exhibited enhanced argyrophilia. Ultrastructurally, the majority of terminals exhibited axolemmal abnormalities, neurofilament accumulations, and a paucity of synaptic vesicles; occasional swollen terminals lacked neurofilaments but contained increased numbers of tubulovesicular profiles. This early morphological pattern of nerve terminal changes suggests that acrylamide may disrupt both synaptic vesicle recycling and neurofilament degradation. These findings indicate that a single high dose of acrylamide triggers pathological lesions and remodeling in motor nerve terminals virtually identical to those resulting from multiple low doses.     

Ultrastructural alterations of mouse diaphragm nerve endings induced by purified scorpion venom, titysustoxin

Five mice were injected intraperitoneally with 4–16 μg of tityustoxin. The ultrastructure of their diaphragm nerve endings were studied using as controls three normal mice. Pathological alterations found in all treated animals consisted of: (1) rarefaction of the fibrillar structure, shrinkage and/or gross vacuolization in the cytoplasm of axons of less than 5 μm diameter; (2) mitochondrial edema, irregular distribution and 18–26 per cent diminution of the synaptic vesicles in the motor end-plates. These lesions resemble those induced by batrachotoxin, black widow spider venom and beta-bungarotoxin. The results seem to support the vesicle hypothesis and suggest that tityustoxin effects directly the nerve terminals.     

D-半乳糖葡胺增敏小鼠对非致死剂量细菌脂多糖致死作用与肝脏DNA片段化的高度相关性

目的：本实验研究了以非致死剂量脂多糖（Lipopolysaccharide,LPS）攻击半乳糖葡胺（D-galactosamine,D-GalN）增敏小鼠的残废是否伴有重要器官的凋亡特征。方法：实验小鼠以LPS（0.05μg）与D-GalN(20mg)直接攻击,而对照组小鼠仅仅以LPS或D-GalN,在规定实验时间经乙醚麻醉后,取出脑、肾、心、脾、肺、肝,并立即匀浆和抽提DNA,对所抽提的各器官的DNA以常规琼脂糖凝胶电泳分析是否存在DNA梯度现象;并测定血浆中乳酸脱氢酶和谷氨酸草酰乙酸转移酶,同时将DNA片段化现象与小鼠致死作用的关联性在实验组和对照组间做比较。结果：LPS攻击D-GalN增敏的小鼠4h时,在所检测的器官中,仅仅肝脏可见重叠凋亡特征DNA片段化现象,至7h时小鼠死亡,而仅用LPS或D-GalN攻击的对照组小鼠,不仅全部存活而且肝脏DNA分子完整。结论：LPS攻击D-GalN增敏的小鼠,肝脏是唯一出现DNA片段化的靶器官,由细菌LPS引发小鼠的死亡,肝脏的损伤可能是关键的原因。     

用去势小鼠提肛肌-海棉球肌测定类固醇蛋白同化作用的方法

本文研究去势小鼠肾脏、提肛肌和海绵球肌对同化类固醇的反应敏感性,同时比较去势小鼠提肛肌、提肛肌-海绵球肌和大鼠提肛肌对17α-甲基睾丸素反应的差别.结果指出,去势小鼠的肾脏,无论从反应所需剂量,反应出现的快慢和反应持续时间的长短看,均系三种组织最不敏感者.提肛肌和海绵球肌对药物的敏感度大致相同.从去势小鼠和大鼠提肛肌及精囊反应上看,对药物的敏感度也大致相同.所不同者,大鼠提肛肌对药物的反应随剂量的增加而递增,不同剂量组的同化作用和雄性素样作用比值也较接近;而小鼠提肛肌的反应与剂量的关系不恒定,甚至大小颠倒,不同剂量组的比值变化也大.将去势小鼠提肛肌和海绵球肌合并后,则其反应即随剂量的增加而递增,不同剂量组的比值也很稳定.以上结果说明,用去势小鼠提肚肌-海绵球肌和精囊重量增加作为测定类固醇同化作用和雄性素样作用的指标是值得采用的.     

Lecithin vesicular carriers for transdermal delivery of cyclosporin A

Two kinds of vesicles with and without the presence of sodium cholate (flexible vesicles and conventional vesicles) were prepared, using cyclosporin A as model drug. When applied onto the excised abdominal skin of mice non-occlusively, the enhancing effects of vesicles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. The effect of sodium cholate micelles was also studied. In vivo study was carried out by topical application of vesicles onto the mice skin and drug serum concentration was detected. Results showed that after 8 h of administration, flexible vesicles transported 1.16 microg of cyclosporin A through per cm(2) mice skin and amounted to 1.88 microg 24 h later. The residual amount in the skin was 1.78+/-0.51 microg/cm(2). However, flexible vesicles failed to transport measurable amount of drug through pre-hydrated skin while deposited 2.39+/-0.26 microg/cm(2) into the skin. Conventional vesicles failed to transfer cyclosporin A into the receiver while accumulated 0. 72+/-0.19 microg/cm(2) of drug in the skin. Furthermore, 1 and 40% sodium cholate micelles precluded the transport of cyclosporin A. In vivo studies indicated that with the application of flexible vesicles, serum drug concentration of 53.43+/-9.24 ng/ml was detected 2 h later. After the stratum corneum of mouse skin has been destroyed by shaving, flexible vesicles transferred large amount of drug into blood, up to 187.32+/-53.21 ng/ml after 1 h of application. Conventional vesicles failed to deliver measurable amount of drug into the blood under normal skin condition. In conclusion, flexible vesicle is better than conventional vesicle as the carrier for transdermal delivery of cyclosporin A. Penetration and fusion have been suggested to be two major functional mechanisms. Hydration is detrimental to the enhancement effect. Stratum corneum constitutes main barrier to the transport of lipophilic cyclosporin A.     

AMPLIFIED PROINFLAMMATORY CYTOKINE EXPRESSION AND TOXICITY IN MICE COEXPOSED TO LIPOPOLYSACCHARIDE AND THE TRICHOTHECENE VOMITOXIN (DEOXYNIVALENOL)

A single oral exposure to the trichothecene vomitoxin (VT) has been previously shown in the mouse to increase splenic mRNA levels for several cytokines in as little as 2 h. Since one underlying mechanism for these effects likely involves superinduction of transiently expressed cytokine genes, VT may also potentially amplify cytokine responses to inflammatory stimuli. To test this possibility, the effects of oral VT exposure on tumor necrosis factor- (TNF- ), interleukin-6 (IL-6), and IL-1 expression were measured in mice that were intraperitoneally injected with lipopolysaccharide (LPS), a prototypic inflammatory agent. As anticipated, VT alone at 1, 5, and 25 mg/kg body weight increased splenic mRNA expression of all three cytokines after 3 h in a dose-response fashion. LPS injection at 1 and 5 mg/kg body weight also induced proinflammatory cytokine mRNA expression. There was a synergistic increase in TNF- splenic mRNA levels in mice treated with both VT and LPS as compared to mice treated with either toxin alone, whereas the effects were additive for IL-6 and IL-1 mRNA expression. When relative mRNA levels were examined over a 12-h period in mice given LPS (1 mg/kg) and/or VT (5 mg/kg), significant enhance ment was observed up to 6, 12, and 3 h for TNF- , IL-6, and IL-1 , respectively. When plasma cytokine concentrations were measured, TNF- was found to peak at 1 h and was significantly increased at 1, 3, and 6 h if mice were given LPS and VT, whereas LPS or VT alone caused much smaller increases in plasma TNF- . Plasma IL-6 peaked at 3 h in LPS, VT, and LPS/VT groups, with the combined toxin group exhibiting additive effects. Plasma IL-1 was not detectable. The potential for VT and LPS to enhance toxicity was examined in a subsequent study. Mortality was not observed up to 72 h in mice exposed to a single oral dose of VT at 25 mg/kg body weight or to an intraperitoneal dose of LPS at 1 or 5 mg/kg body weight; however, all mice receiving VT and either LPS dose became moribund in less than 40 h. The principal histologic lesions in the moribund mice treated with VT and LPS were marked cell death and loss in thymus, Peyer's patches, spleen, and bone marrow. In all of these lymphoid tissues, treatment-induced cell death had characteristic histologic features of apoptosis causing lymphoid atrophy. These results suggest that LPS exposure may markedly increase the toxicity of trichothecenes and that the immune system was a primary target of these interactive effects.     

An electrophysiological analysis of the effects of reserpine on adrenergic neuromuscular transmission.

1 An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles less than 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release. 2 Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%. 3 Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone. 4 During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady-state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 5 These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis.     

Effects of cannabinoids on function of testis and secondary sex organs in the Fischer rat

Chronic oral treatment of young adult male Fischer rats with delta 9-tetrahydrocannabinol (THC), 1, 5 and 25 mg kg-1 day-1, or crude marihuana extract (CME), 3, 15 and 75 mg kg-1 day-1, reduced body weight gain by about 50-80% at the high CME or THC dose and was correlated with decreased food intake. When cannabinoid was administered early in the light cycle (9-11 a.m.), cauda epididymis sperm count and seminal vesicle fluid and fructose content were depressed to 50-65% at the high dosages but were not significantly different from those of pair-fed controls. Administration late in the light cycle (4-5 p.m.) depressed epididymal sperm count, seminal vesicle fluid content, and weight of testis, seminal vesicles and epididymis to 40-80% below that seen for pair-fed controls. 24 h after the last treatment, serum testosterone was unchanged in intubated control and low-dose treated rats, compared with untreated controls, but was elevated nearly twofold in medium-dose-treated rats (p less than 0.05). The results indicate that time of cannabinoid administration as well as feeding pattern are critical in studies of the rat reproductive system.     

Core proteins of the secretory machinery

Members of the Rab, SM- and SNARE-protein families play key roles in all intracellular membrane trafficking steps. While SM- and SNARE-proteins become directly involved in the fusion reaction at a late stage, Rabs and their effectors mediate upstream steps such as vesicle budding, delivery, tethering, and transport. Exocytosis of synaptic vesicles and regulated secretory granules are among the best-studied fusion events and involve the Rab3 isoforms Rab3A-D, the SM protein munc18-1, and the SNAREs syntaxin 1A, SNAP-25, and synaptobrevin 2. According to the current view, syntaxin 1A and SNAP-25 at the presynaptic membrane form a complex with synaptic vesicle-associated synaptobrevin 2. As complex formation proceeds, the opposed membranes are pulled tightly together, enforcing the fusion reaction. Munc18-1 is essential for regulated exocytosis and interacts with syntaxin 1A alone or with SNARE complexes, suggesting a role for munc18-1 in controlling the SNARE-assembly reaction. Compared to other intracellular fusion steps, special adaptations evolved in the synapse to allow for the tight regulation and high membrane turnover rates required for synaptic transmission. Synaptic vesicle fusion is triggered by the intracellular second messenger calcium, with members of the synaptotagmin protein family being prime candidates for linking calcium influx to fusion in the fast phase of exocytosis. To compensate for the massive incorporation of synaptic vesicles into the plasma membrane during exocytosis, special adaptations to endocytic mechanisms have evolved at the synapse to allow for efficient vesicle recycling.