对左旋多巴长期治疗帕金森病的评价

很多研究证明长期应用左旋多巴(L-dopa)治疗帕金森病(PD),可明显改善PD患者的症状,而且应该在PD的早期应用适量的左旋多巴进行治疗,以改善患者的早期症状。长期应用左旋多巴治疗PD与长期应用多巴胺受体激动剂对疾病导致的病死率相同。长期应用多巴胺受体激动剂治疗PD的疗效与长期应用左旋多巴相同,前者并未显示出优越性。     

A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson''s disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.     

新发帕金森病的急性多巴反应性评价

目的：建立急性左旋多巴负荷试验用于鉴别新发帕金森病（PD）与新发帕金森综合征（PDS）患者,并筛选评价指标的临界值。方法：选择89例有PD样表现但未服用过左旋多巴的患者,根据临床诊断分为PD组（n=48）和PDS组（n=41）,进行了急性左旋多巴／卡比多巴（100／25mg）试验。根据两组患者统-PD评分运动分量表（UPDRS—Ⅲ）评分的平均最大改善率进行比较,并建立受试者工作特征（ROC）曲线,以该曲线上最大Youden指数对应的运动评分最大改善率作为临界值。结果：PD组在服用左旋多巴-卡比多巴后的平均UPDRS-Ⅲ评分平均最大改善率高于PDS组,差异有统计学意义（P〈0．01）。建立的ROC曲线在鉴别PD和PDS差异具有统计学意义,ROC曲线下面积为0．827（P〈0．01）,对应上网UPDRS运动评分改善率的最佳临界值为12．45％（Youden指数0．565,敏感度80．9％,特异度75．6％）。结论：急性左旋多巴-卡比多巴试验可作为PD疗效和诊断的一种辅助参考方法。     

小剂量左旋多巴上调pCREB及CD39蛋白表达发挥抗氧化应激损伤作用的研究

目的明确左旋多巴对PC12细胞生长及应激状态下存活的影响,探讨其抗氧化应激损伤的机制。方法不同浓度左旋多巴处理PC12细胞,用MTT法检测PC12细胞增长率及加入过氧化氢后细胞存活率;免疫荧光、Western blot方法测定磷酸化环单磷酸腺苷反应元件结合蛋白(pCREB)及CD39蛋白表达。结果低浓度左旋多巴(20μmol·L-1)促进PC12细胞生长,且可抗氧化应激损伤,而蛋白激酶抑制剂减弱此保护作用。免疫荧光及Western blot结果显示CD39及pCREB表达升高。结论低浓度左旋多巴可通过上调CD39及pCREB表达发挥抗氧化应激神经保护作用。     

左旋多巴激发试验对儿童生长激素缺乏症的临床价值

目的:探讨左旋多巴激发试验在诊断儿童生长激素缺乏症(GHD)的临床价值。方法:对330例身材矮小儿童应用左旋多巴激发试验,采用化学发光法进行生长激素(GH)检测。以测得的GH最高值为峰值,峰值≥10ng/ml为GH不缺乏,激发试验阳性;10ng/ml>峰值≥5ng/ml为GH部分缺乏,峰值<5ng/ml为GH缺乏,激发试验阴性。结果:激发后峰值强度为(12.23±8.10)ng/ml;峰值出现在(30～90)min者占96%,出现在120min者占4%(阳性3例),两者峰值有显著性差异(P<0.01);GH完全缺乏者占21%,部分缺乏者占22%,完全不缺乏者占57%。结论:左旋多巴激发试验可应用于临床GHD的诊断,但其诊断敏感度低,需要联合其它激发方式和其它指标对GHD患者进行综合评价。     

Endocrine ablation in breast cancer patients who have failed cytotoxic therapy

Between 1972 and 1979, forty-six women underwent endocrine ablative surgery, having failed combinations of chemotherapy, radiation, and surgery (including oophorectomy). All had clinically measurable disease; nearly half were afflicted with bone pain. Each was judged to be a candidate for the procedure by estrogen receptor studies (52%), response to L-dopa (39%), or response to prior oophorectomy (8%). All were followed to their death or to the present, with a minimum of 12 months for those alive. Thirty-one (67%) were improved, and disease was arrested in five (11%) for a median time of 13.5 months. There was no difference in response rates or intervals between estrogen receptor-positive and L-dopa-positive groups. Response was not correlated with disease-free interval or menopausal status. Best results were achieved in those with metastases confined to an organ system, particularly the skeletal complex. The procedure is withheld in those with brain metastases. Postablative chemotherapy appeared to prolong the control interval, though numbers are small. The low morbidity and mortality (one death) of midline adrenaloophorectomy combined with the high incidence of recapture of disease leads us to recommend this procedure in appropriately selected patients who have previously failed other therapeutic modalities.     

油麻藤组织培养产生左旋多巴的研究

本研究选用油麻藤属三种植物进行组织培养,诱发愈伤组织,建立了基本方法并测定了愈伤组织的生长量和愈伤组织中左旋多巴的含量,结果表明:愈伤组织的生长量、生长速度和左旋多巴含量在种间有明显差异。愈伤组织中左旋多巴含量高于原种子中的含量,同一种培养材料不同继代愈伤组织中左旋多巴含量相对稳定并略有提高的趋势,愈伤组织中左旋多巴能从组织中排入培养基中。此外,讨论了用组织培养方法生产左旋多巴的可能性和固定化细胞培养等问题。     

Striatal L-dopa metabolism studied in vivo in rats with nigrostriatal lesions

Summary We have used cerebral dialysis to monitor striatal metabolism of exogenously administered L-dopa (L-dihydroxyphenylalanine) in rats with unilateral lesions of the substantia nigra. The concentration of extracellular dopamine (DA) increased in both striata following L-dopa administration but the increase was markedly attenuated in the lesioned striatum. The formation of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the major DA metabolites, was also reduced in the lesioned striata following L-dopa administration; however, the reduction was not as great as was that of DA formation. A significant metabolism of exogenous L-dopa to 3-O-methyldopa occurred in both striata. L-dopa administration transiently increased extracellular levels of 5-hydroxyindoleacetic acid (5 HIAA) in both the lesioned and intract striata.These results suggest that the striatum with a reduction in DA nerve terminals is deficient both in the capacity to synthesize DA and in the storage mechanisms necessary to protect the newly synthesized DA from oxidative metabolism.     

Effect of L-dopa on dementia-related rigidity

L-dopa 100 mg plus benserazide 25 mg versus placebo were given 3 times daily to 14 consecutive patients with dementia and rigidity. The treatment was crossed over to the alternative therapy after a 7-day period. Despite a mean 60% raise in CSF-HVA during L-dopa administration, no patient responded to the treatment. These data suggest that dementia-associated rigidity differs, at least, pharmacologically from parkinsonian rigidity.