筛选抗帕金森活性的方法:已发表文献中的错误

J. Prabhakaran, S. Oommen, Alwar Mc
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摘要

1817年,英国医生詹姆斯·帕金森(James Parkinson)描述了帕金森病的典型症状,其特征是震颤、僵硬和运动障碍。[1]可用于治疗帕金森氏症的药物数量可观,但这些药物中的大多数具有各种其他作用,而且发现抗帕金森氏症活性是偶然的。[2]检测抗帕金森活性的筛选方法是间接的。1962年,Morpurgo描述了一种直接筛选这些化合物的方法。[3]Morpurgo从1958年由Writh等人进行的一项研究中得出了这些结果,他们描述了老鼠的四个阶段。紧张症是一种神经源性运动不动和行为异常的状态,表现为麻木。[4]通过皮下注射吩噻嗪后2、4、6和22小时的试验来确定阶段。在第一阶段,动物没有任何动作的欲望;它静静地坐在它被放置的地方。然而,轻轻推一下动物就能引起短暂的运动。在第二阶段,动物和第一阶段一样,但推力不再引起动作。在第三阶段,动物摆出一些姿势,比如把前腿放在3厘米高的木块上。在第四阶段,动物保持固定的位置,用后腿坐着,将一只前腿放在9厘米高的木块上,另一只前腿自由悬挂。Morpurgo于1962年采用大鼠腹膜内给药5mg/Kg体重的perphenazine诱导紧张症,以评价抗帕金森药物引起锥体外系症状的效果。然而,第一阶段和第二阶段与最初的研究不同。文章描述了动物在I阶段的自由运动,得分率为0.5或零分。这是错误的理解,并且出现了在动物完全不动的阶段给多少分的问题。根据with等人的说法,在阶段2中,动物仍然保持在阶段1中,推不引起任何反应。在修改版本中,这个阶段也被改为“动物只有在被推动时才会移动”。[5]Morpurgo法是医学研究中常用的评价方法。在已发表的文章中发现这种错误可能有多种原因。因此,它被观察到使研究人员能够在他们的研究工作中理解原始的方法,而没有任何科学空白。研究者和同行评议人员应采取进一步措施避免今后出现此类错误,并遵循原有的研究方法。
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Method used in screening antiparkinson activity:errors in published literature
Dear Editor In 1817, James Parkinson an English physician, described the classical symptoms of Parkinson disease, that was characterized by tremor, rigidity and akinesia.[1] An appreciable list of drugs useful in treating parkinsonism is available, but most of these drugs had various other actions and finding of antiparkinson activity was by accident.[2] Screening methods for the detection of antiparkinson activity is indirect. Morpurgo in 1962 described a direct method to screen these compounds.[3] Morpurgo derived these results by a study conducted by Writh et al in 1958, who have described four stages in the rat. Catatonia is a state of neurogenic motor immobility and behavioral abnormality manifested by stupor.[4] The stages are determined by tests at 2, 4, 6 and 22 hours after subcutaneous injection of the phenothiazine. In the stage I, the animal has no desire to make any movements; it sits quietly where it has been placed. However, a light push against the animal can elicit brief movements. In the stage II, the animal remains as in stage I but a push no longer elicits movements. In the stage III, the animal assumes postures as for example when its foreleg is placed on a wooden block 3centimetre high. In the stage IV, the animal maintains its fixed position when, while sitting on its hind legs, one of its forelegs is placed on a wooden block 9 centimetre high and the other foreleg is allowed to hang free. This study was adopted by Morpurgo in 1962 toinduce catatonia by administering perphenazine at a dose of 5mg/Kg of body weight intra peritoneally in rats to evaluate antiparkinson drugs by causing extrapyramidal symptoms. However the stage 1 and stage 2 differ from the original study. The article describes the free movement of the animal in stage I with scoring rate of 0.5 or zero point. This is wrongly understood and the questions arise as to what score to be given in stage I when the animal does not move at all. According to Writh et al, in stage 2, animal remains as in stage 1 and a push does not elicit any response. This stage has been also been changed to “animal moves only when pushed” in modified versions.[5] Method of Morpurgo is often practiced in medical research for such evaluation. There may be various reasons for finding this kind of errors in the published articles. So it was observed to enable the researchers understand the original methodology in their research work without any place for scientific lacunae. Further measures should be taken by the researchers and peer reviewers to avoid such errors in future and follow the original research methodology.
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