Effect of treatment with botulinum toxin on neurogenic blepharospasm.

Botulinum toxin type A creates temporary localised flaccid paralysis after injection into skeletal muscle. Thirty four patients with blepharospasm, of whom 28 also had the oromandibular dystonia syndrome, were treated with injections of botulinum toxin type A into the orbicularis oculi, and 28 showed functional improvement after the treatment. A high incidence of local side effects occurred, especially partial ptosis, which was well tolerated. There were no systemic side effects. The average period of relief was 2.5 months, increasing to 2.8 months after a second injection. Functional improvement was limited in patients with severe associated dystonia.     

Growing old disgracefully: the cosmetic use of botulinum toxin

The explosive growth in the use of botulinum toxin for cosmetic purposes has undoubtedly had an impact on the number of animals used in the potency testing of this product. The test used is a classical LD50, a severe procedure during which animals experience increasing paralysis until the occurrence of death. The enthusiastic adoption by the general public of the use of botulinum toxin as an anti-wrinkle treatment has, at least in Europe, paradoxically taken place against a background of moves to stop animal testing of cosmetics and cosmetic ingredients. There appears to be a dearth of information aimed at the public concerning botulinum toxin testing. Botulinum toxin does have important medical applications; however, the question arises whether a blanket licence for the testing can be justified, when a large proportion of the product is being used cosmetically. A further question is why death continues to be the endpoint of the potency test, when a more-humane endpoint has been proposed. In addition, a number of alternative methods have been developed, which could have the potential to replace the lethal potency test altogether. These methods are discussed in this paper, and the importance of establishing a strategy for their validation is emphasised, a need that has become even more urgent in the light of the recently published draft monograph on botulinum toxin by the European Pharmacopoeia Commission.     

A型肉毒毒素治疗偏侧面肌痉挛和头颈部肌张力障碍的疗效观察

为评估Ａ型肉毒毒素治疗偏侧面肌痉挛和头颈部肌张力障碍的疗效,本文对４２例偏侧面肌痉挛及３４例头颈部肌张力障碍（后者包括１８例眼睑痉挛,１２例Ｍｅｉｇｅ氏病、４例痉挛性斜颈）病人进行Ａ型肉毒毒素肌肉多点注射治疗,并治疗前后的病情分级对比。结果表明,Ａ型肉毒毒素治疗有效率为１００％,疗效持续８～２６周,可重复注射,并再次取得疗效。部分病人局部出现轻度肌无力,数周后均可恢复,无全身毒副作用。结论认为Ａ型肉毒毒素能治疗偏侧面肌痉挛和头颈部局限性肌张力障碍,不失为一种有效安全简便易行的治疗手段。     

Use of botulinum toxin

In an extensive survey of postgraduate physicians in two teaching hospitals (N = 141) for their humanistic attitudes, values and behavior, all ratings of physicians'' humanistic performance, including physicians'' own scores on self-report measures, supervising faculty, nurses and patient ratings, were modestly but significantly correlated with each other. Sex, ethnic or racial background, year of training, marital status, number of children, Alpha-Omega-Alpha membership or number of articles published were unrelated to physicians'' humanistic behavior. Several measures of humanism were positively correlated with having taken more courses in the social sciences and humanities, having had more early person-centered work experience and reporting that before medical school others had confided in them or sought their advice more frequently.     

Action of botulinum A toxin and tetanus toxin on synaptic transmission

Intracellular recordings of the spontaneous activity from mammalian spinal cord neurons in culture demonstrated different sensitivities of excitatory and inhibitory synaptic transmission for the action of tetanus toxin (Tetx) and botulinum toxin type A (Botx). The effects of Tetx and Botx on spontaneous and nerve-evoked transmitter release were compared under identical experimental conditions in experiments on in vitro poisoned mouse diaphragms. At 37 degrees C completely paralyzed endplates are characterized by a very low frequency of spontaneous miniature endplate potentials (m.e.p.p.s) and by a 100% failure to evoke endplate potentials (e.p.p.s) in response to single nerve stimuli. Striking differences in the action of both toxins have been observed when the very low transmitter release probabilities of paralyzed nerve-muscle preparations were increased by tetanic nerve stimulation and/or application of potent K+-channel blockers and/or by reduction of temperature to 25 degrees C. While Botx did not change the short latency between nerve impulse and postsynaptic response, Tetx produced a temporal dispersion of the quantal release suggesting that the toxins act at different sites in the chain of events that result in transmitter release. To find further evidence to support the different actions of the toxins the spontaneous transmitter release was studied in more detail. Tetx blocked preferentially the release of so-called large mode m.e.p.p.s without affecting the frequency of the small mode ones. In contrast, Botx strongly inhibited both the small and large mode m.e.p.p.s.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of botulinum toxin type A in aesthetic mandibular contouring

The lower third of Asian faces is wider than that of Caucasians and it is determined by the size and width of the mandibular bone and the thickness of muscles and subcutaneous fat tissues surrounding it. Efforts to create an aesthetically slim and smooth facial contour line in nonobese people have led the authors to focus on two approaches: surgical resection of the masseteric muscle and modeling ostectomy of the square-angled mandibular bone. Because these procedures present some problems, the authors adopted a nonsurgical concept that chemically denervates muscles and reduces the bulk of the muscle. The authors have conducted a total of 1021 clinical cases from March of 2001 through September of 2002, in which patients were treated with botulinum toxin type A (Dysport; Ipsen Ltd, Slough, United Kingdom) for remodeling the lower facial contour line; 383 of those cases were followed up for at least 3 months after the initial injection. A database was made by measuring the change in the thickness of the injected muscle with an ultrasonogram. Eleven patients underwent resection of the mandibular angle before injection. The preinjection ostectomy group was involved in the study as a result of their dissatisfaction with the surgical results; they had a rather thick masseter muscle and not a bone problem. Some had both bone problems and a thick masseter muscle. Three months after the botulinum toxin injection, the thickness of the muscle was reduced by 31 percent on average. The atrophic effect of injection was observed after 2 to 4 weeks for most patients. Seventy percent of the 383 patients tracked were greatly satisfied with the result, with another 23 percent generally satisfied. No long-term side effects were reported. Masseteric hypertrophy is frequent in Asians because of racial characteristics and dietary habits. Botulinum toxin type A has made a new epoch in facial contouring for Asians. Considering that Asians have a prominent malar and a prominent mandible angle, the reduction in the thickness of the masseter can provoke relative prominence of the malar and mandible angle. Therefore, precise indication and anatomy of the facial muscle should be thoroughly understood, which will decrease the incidence of side effects and problems. Botulinum toxin type A (Dysport) injection is simple in technique, has few side effects, and promises a rapid return to daily life. The authors conclude that the injection of botulinum toxin type A can replace surgical masseter resection.     

Properties and use of botulinum toxin and other microbial neurotoxins in medicine.

Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders following 10 or more years of experimental treatment on human volunteers. Botulinum toxin exerts its action on a muscle indirectly by blocking the release of the neurotransmitter acetylcholine at the nerve ending, resulting in reduced muscle activity or paralysis. The injection of only nanogram quantities (1 ng = 30 mouse 50% lethal doses [U]) of the toxin into a spastic muscle is required to bring about the desired muscle control. The type A toxin produced in anaerobic culture and purified in crystalline form has a specific toxicity in mice of 3 x 10(7) U/mg. The crystalline toxin is a high-molecular-weight protein of 900,000 Mr and is composed of two molecules of neurotoxin (ca. 150,000 Mr) noncovalently bound to nontoxic proteins that play an important role in the stability of the toxic unit and its effective toxicity. Because the toxin is administered by injection directly into neuromuscular tissue, the methods of culturing and purification are vital. Its chemical, physical, and biological properties as applied to its use in medicine are described. Dilution and drying of the toxin for dispensing causes some detoxification, and the mouse assay is the only means of evaluation for human treatment. Other microbial neurotoxins may have uses in medicine; these include serotypes of botulinum toxins and tetanus toxin. Certain neurotoxins produced by dinoflagellates, including saxitoxin and tetrodotoxin, cause muscle paralysis through their effect on the action potential at the voltage-gated sodium channel. Saxitoxin used with anaesthetics lengthens the effect of the anaesthetic and may enhance the effectiveness of other medical drugs. Combining toxins with drugs could increase their effectiveness in treatment of human disease.     

肉毒毒素作用机制的研究进展

肉毒毒素(botulinum toxin,BTX)是肉毒梭状芽胞杆菌在生长繁殖过程中产生的一种外毒素,其通过抑制神经递质的释放而引起肌肉松弛型麻痹。在世界范围内,肉毒中毒的案例时有发生,病情严重的患者最终因呼吸衰竭而死亡。肉毒毒素相关产品在临床痉挛性疾病、腺体分泌过度、神经性疼痛的治疗及美容除皱等领域展现出广阔的应用前景。因而,肉毒毒素作用机制的研究在肉毒中毒的治疗以及临床新适应症的开发等方面具有重要意义。就肉毒毒素跨越小肠上皮细胞屏障的吸收及神经毒性作用机制的研究现状作一概述。     

Effect of botulinum D toxin on human neutrophilic leukocytes and localization of its substrates

Botulinum D toxin has been shown to ADP-ribosylate 22-kD proteins in neutrophilic leukocytes, but the function of these GTP-binding proteins remains unknown. In analogy to small GTP-binding proteins like SEC4 to YPT1, it has been suggested that botulinum D toxin substrates might be involved in secretory process of myeloid cells. Three main findings lead to the opposite conclusion. First of all, in human neutrophils, botulinum D toxin does not modify the release of azurophilic and specific granules induced by a chemoattractant (a formylpeptide) or a phorbol ester. Second, botulinum D toxin ADP-ribosylates 24 to 26-kD proteins that are only present in plasma membranes of human neutrophils. The membrane location of these substrates differs largely from that of the GTP-binding proteins involved in exocytosis and located in granules. Finally, since the same quantity of the toxin substrates is present in neutrophils as in their precursors, HL60 cells (which are devoid of specific granules and characterized by immature azurophilic granules and NADPH oxidase), it is unlikely that endogenous botulinum D toxin substrates are directly involved in the secretory responses of neutrophils.