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1.
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.  相似文献   
2.
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。  相似文献   
3.
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。  相似文献   
4.
帕金森病(PD)是一种神经系统退行性疾病,左旋多巴仍是治疗PD的金标准用药,但是随着疾病的发展,长期服用左旋多巴会出现左旋多巴诱发异动症(LID),LID是常见的运动并发症。文中主要讨论LID的临床表现及治疗问题。  相似文献   
5.
First line treatment for Parkinson’s disease (PD) is typically either L-dopa or a non-ergot dopamine agonist (DA). However, the options for the treatment of motor symptoms in PD patients have increased in the last thirty years, which have seen several new classes of PD medications introduced onto the market. The purpose of this study is to examine the changes in first line therapy of newly diagnosed Parkinson’s patients between 2000 and 2016 in Wales.A population-based study evaluated data from the Secure Anonymised Information Linkage (SAIL) Databank of residents in Wales, aged 40 years or older, newly treated with PD medications between 2000 and 2016. The data was compared across three intervals: 2000–2005, 2006–2011 and 2012–2016. Patients were classified by age at diagnosis into young: 40–60 years; mid, 61–80 years; and older >80 years. Logistic regression was undertaken to determine the predictors of PD medication prescribing.For the whole study period, the profiles of 9142 newly diagnosed PD patients were analysed. L-dopa was the most common first line therapy (80.6%), followed by non-ergot DAs (12.9%) and monoamine oxidase B (MAO-B) inhibitors (7.9%). Odds of L-dopa prescribing were greater in patients >80 years (OR = 20.46 95%CI: 16.25–25.76) and in the period 2012–2016 (OR = 1.98 95% CI: 1.70–2.29). Prescribing of non-ergot DAs significantly declined in 2012–2016 (OR = 0.42 95% CI: 0.35–0.49). Additional factors influencing first line therapy were deprivation, presence of diabetes and prior use of antidepressants. For example, PD patients residing in the least deprived area were less likely to be prescribed L-dopa compared to patients residing in the most deprived area (OR = 0.77 95% CI: 0.65–0.93).First line therapy in PD in Wales has undergone a significant switch towards L-dopa over the last 16 years. The data indicates reasonable compliance with guidelines on efficacy and safety issues related to Parkinson’s medications.  相似文献   
6.
左旋多巴甲酯对剥夺性弱视猫视皮层17区神经细胞的影响   总被引:1,自引:0,他引:1  
目的观察不同剂量的左旋多巴甲酯对剥夺性弱视猫模型视皮层17区神经细胞凋亡情况以及神经生长因子(NGF)和FOS蛋白表达的影响,探讨左旋多巴甲酯对弱视的治疗效果及其作用机制。方法健康的幼猫30只随机分成6组:左旋多巴甲酯高(LDMEH)、中(LDMEM)、低(LD-MEL)剂量组、阳性对照组(PC)、模型对照组(MC)及正常对照组(NC),每组5只。除了正常组,于4周龄时参照Hubel经典实验方法对各组幼猫进行麻醉后的左眼单纯上下睑缝合建立剥夺性弱视,12周后打开缝合眼并开始给药,每天灌胃左旋多巴甲酯20,40,80 mg.kg-1,阳性对照组为左旋多巴40 mg.kg-1,正常组与模型组为等剂量生理盐水,每天1次持续30 d。进行Nissl染色观察,TUNEL检测法观察视皮层神经细胞的凋亡情况,经免疫组化技术检测视皮层17区神经细胞中NGF以及FOS蛋白的表达情况。结果左旋多巴甲酯有效地降低了弱视眼视皮层17区中的神经细胞凋亡率。模型对照组弱视眼视皮层17区NGF和FOS免疫阳性细胞数量明显低于正常对照组,差异有统计学意义(P<0.01)。给药治疗后各组视皮层17区NGF和FOS免疫阳性细胞密度较模型对照组均为增加,差异有统计学意义(P<0.01或P<0.05)。结论左旋多巴甲酯对视皮层17区中神经细胞有保护作用,通过上调内源性NGF和FOS蛋白的表达来修复剥夺性弱视造成的结构与功能缺陷,可能与它们共同协调作用下重塑中枢视觉通路有关。  相似文献   
7.
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。  相似文献   
8.
Recent studies suggest that the initial expression of adrenal phenylethanolamine N-methyltransferase (PNMT) and epinephrine (E) are dependent upon stimulation of adrenal glucocorticoid receptors. However, evidence suggests that the expression of heart and brain PNMT is independent of glucocorticoids. We measured PNMT activity and E levels in adrenal, heart and head over the latter half of gestation in rat fetuses treated chronically with glucocorticoids, and in normal controls. Chronic glucocorticoid treatment ending on embryonic day (e)12 did not affect heart, head or trunk PNMT activity or E levels. In contrast, chronic glucocorticoid exposure ending e19 or e20 resulted in marked increases in both PNMT and E in adrenal, heart and head tissues. The elevation of E in all three tissues was unaffected by maternal adrenalectomy, indicating enhanced fetal E synthesis. In the absence of exogenous glucocorticoid treatment heart PNMT activity peaked on e12, prior to the earliest reported appearance of glucocorticoid receptors. We conclude that expression of PNMT in all three tissues is glucocorticoid independent until the latter part of gestation when it is readily enhanced by glucocorticoids.  相似文献   
9.
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.  相似文献   
10.
目的观察经侧脑室注射左旋多巴对帕金森病(PD)大鼠的影响。方法应用“羟基多巴胺立体定向脑内注射制备偏侧损毁的PD大鼠模型,并用阿扑吗啡(APO)皮下注射诱发大鼠向健侧旋转。将24只PD大鼠随机分为4组(n=6),经侧脑室注入生理盐水组为对照组,余3组分别经侧脑室注射浓度为0.1μg/μl、1μg/μl和5μg/μl的左旋多巴1μl,4μl/d,连续1周;观察在注射后不同时间大鼠旋转行为以及中脑黑质多巴胺能神经元数量的变化。结果经侧脑室注射1μg/μl和5μg/μl的左旋多巴后。与对照组相比,PD大鼠向健侧的旋转圈数明显减少(P〈0.01),左旋多巴效果在2h左右达到高峰,且中脑黑质多巴胺能神经元的数量也明显增多(P〈0.01)。结论经侧脑室注射适当剂量的左旋多巴可有效地改善PD大鼠的旋转行为,并增加中脑黑质多巴胺能神经元数量。  相似文献   
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