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首页> 外文学位 >The biological activity of botulinum toxins A and F in the chronically implanted rat.
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The biological activity of botulinum toxins A and F in the chronically implanted rat.

机译：慢性植入大鼠中肉毒杆菌毒素A和F的生物活性。

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摘要

Intramuscular injection of Botox type A is largely successful in the treatment of focal dystonias, however, patients who become immunoresistant to Botox A no longer benefit from therapy. For these individuals, the shorter-acting Botox F may provide a reasonable treatment alternative. The present investigation compared the time course and extent of neuromuscular blockade and recovery of Botox A and F.;Thirty-three rats were implanted with a stimulus cuff around the sciatic nerve and recording electrodes in the gastrocnemius muscle and near its origin and insertion, the Achilles tendon and knee. Evoked potentials (EPs) were recorded three times weekly. The gastrocnemius muscle of implanted animals was injected with 0.625, 1.25, 2.5, 5 or 10 units of Botox type A or type F, or a saline placebo. EPs were recorded tri-weekly over 22 weeks time until EMG values recovered maximally and were stable for one month. Gastrocnemius muscles were weighed and evaluated histologically.;Results determined that the degree of neuromuscular blockade significantly differed between A and F, with more complete blockade observed with type A. Regardless of toxin type, doses of 2.5-10 units depressed neurotransmission by 75-97%. The effect of type A lasted three months, while type F animals recovered within 30 days. The extent of final recovery was dependent on both type and dose of Botox. EMG activity fully recovered to baseline in all type F and low-dose type A animals. EPs recorded from animals injected with 2.5 or more units of type A never recovered to preinjection values. Delayed onset of recovery in high-dose type A animals may have allowed time for denervative changes to prevent a full reversal of toxin effect. Histological analysis confirmed atrophy in higher-dose type A muscles. The rapid recovery of type F animals made questionable nerve terminal sprouting as the mechanism by which neurotransmission was restored. Clinical implications and applications of findings are discussed.
机译：肌注A型肉毒杆菌毒素在局灶性肌张力障碍的治疗中取得了很大的成功，但是，对Botox A产生免疫抗性的患者不再从治疗中受益。对于这些人，作用较短的肉毒杆菌毒素F可提供合理的治疗选择。本研究比较了肉毒杆菌毒素A和F的神经肌肉阻滞和恢复的时间过程和程度; 33只大鼠在坐骨神经周围植入了刺激袖套，并在腓肠肌及其近端起源和插入处记录了电极，跟腱和膝盖。每周记录3次诱发电位（EPs）。向植入动物的腓肠肌注射0.625、1.25、2.5、5或10个单位的肉毒杆菌A型或F型肉毒杆菌，或盐水安慰剂。在22周的时间内每三周记录一次EP，直到EMG值最大程度恢复并稳定一个月。对腓肠肌进行称重并进行组织学评估。结果确定A和F之间的神经肌肉阻滞程度存在显着差异，而A型则观察到更完全的阻滞。不论毒素类型如何，剂量为2.5-10单位的神经阻滞剂均以75-97抑制了神经传递。 ％。 A型影响持续三个月，而F型动物则在30天内恢复。最终恢复的程度取决于肉毒杆菌素的类型和剂量。在所有F型和低剂量A型动物中，EMG活性已完全恢复至基线。从注射了2.5个或更多单位A型动物的动物记录的EP从未恢复到注射前的值。高剂量A型动物的恢复延迟发作可能已经为神经变性的改变留出了时间，以防止毒素作用的完全逆转。组织学分析证实高剂量A型肌肉萎缩。 F型动物的快速恢复使可疑的神经末梢发芽成为恢复神经传递的机制。讨论了临床意义和发现的应用。

著录项

  • 作者

    Rainey, Cheryl Lee.;

  • 作者单位

    Vanderbilt University.;

  • 授予单位 Vanderbilt University.;
  • 学科 Speech therapy.;Animal Physiology.;Toxicology.;Cellular biology.
  • 学位 Ph.D.
  • 年度 1997
  • 页码 142 p.
  • 总页数 142
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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