Melatonin inhibits 6-hydroxydopamine production in the brain to protect against experimental parkinsonism in rodents

Abstract:  We tested the hypothesis that melatonin regulates formation of 6-hydroxydopamine (6-OHDA) in the brain and thereby protects animals from dopaminergic neurotoxicity and the development of parkinsonism in animals. Employing a ferrous-ascorbate-dopamine (FAD) hydroxyl radical (^•OH) generating system, in the present study we demonstrate a dose-dependent attenuation of 6-OHDA generation by melatonin in vitro. Intra-median forebrain bundle infusion of FAD caused significant depletion of striatal dopamine (DA), which was blocked by melatonin. Per-oral administration of l -3,4-dihydroxyphenylalanine (l -DOPA) for 7 days caused a dose-dependent increase in the formation of 6-OHDA in the mouse striatum, which was increased synergistically by the systemic administration of the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the 7th day of l -DOPA treatment. Melatonin treatment significantly attenuated both the l -DOPA and MPTP-induced increases in the levels of striatal 6-OHDA, and protected against striatal DA depletion caused by the neurotoxin. These observations suggest a novel mode of melatonin-induced dopaminergic neuroprotection in two models of Parkinson's disease, and suggest the possible therapeutic use of this well-known antioxidant indoleamine neurohormone in parkinsonism.     

Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation

Abstract:  Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine–Tryptophan–Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival ( P  < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39–71% ( P  < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity.     

Melatonin protects against experimental reflux esophagitis

Abstract:  Reflux esophagitis (RE), a major gastrointestinal disorder results from excess exposure of the esophageal mucosa to acidic gastric juice or bile-containing duodenal contents refluxed via an incompetent lower esophageal sphincter. Recent studies implicated oxygen derived free radicals in RE induced esophageal mucosal damage resulting in mucosal inflammation. Thus, control over free radical generation and modulation of inflammatory responses might offer better therapeutic effects to counteract the severity of RE. In this context we investigated the effect of melatonin against experimental RE in rats. Melatonin pretreatment significantly reduced the haemorrhagic lesions and decreased esophageal lipid peroxidation aggravated by RE. Moreover, the depleted levels of superoxide dismutase and glutathione observed in RE were replenished by melatonin signifying its free radical scavenging properties and antioxidant effects resulting in the improvement of esophageal defense mechanism. Further melatonin repressed the upregulated levels of expression of proinflammatory cytokines like, TNF-α, IL-1β and IL-6 in RE. However, increased levels of the anti-inflammatory cytokine IL-10 remained unaltered after melatonin administration signifying its immunomodulatory effect through suppression of Th1-mediated immune responses. The involvement of receptor dependent actions of melatonin against RE were also investigated with MT2 receptor antagonist, luzindole (LUZ). LUZ failed to antagonize melatonin's protective effects against RE indicating that melatonin mediated these beneficial effects in a receptor-independent fashion. Thus, esophageal mucosal protection elicited by melatonin against experimental RE is not only dependent on its free radical scavenging activity but also mediated in part through its effect on the associated inflammatory events in a receptor-independent manner.     

两种方法测定尿游离皮质醇的结果分析

目的 比较分析化学发光免疫测定法(CLIA)和酶联免疫吸附分析法(ELISA)测定尿游离皮质醇(UFC)结果.方法 用上述两种方法分别测定68例住院病人(肾上腺疾病20例,非.净上腺疾病48例)2 4小时UFC,结果进行配对t检验和相关分析.结果 两种方法检测UFC的结果无统计学差异(t=0.023,P>0.05),两者具有良好的相关性(r=0.85),且与临床诊断符合率高.但在UFC浓度大于1000nmol/L时两结果有一定差别.结论 两种方法均可用于检测UFC,CLIA实现了自动化,具有方便、快速、无毒等优点.     

褪黑激素抗氧化作用的研究进展

褪黑激素是松果体分泌的一类激素,对其研究起初主要集中在调节睡眠的作用,但近年发现其具有强大的抗氧化应激作用。实验研究表明,褪黑激素不仅本身具有明显的抗氧化作用,且被氧化后的多级代谢产物亦有强大的抗氧化功能;还具有同时清除氧族和氮族自由基的双重功效及上调多种抗氧化酶活性的功能。目前对于它在缺血再灌注损伤、抗癌、抗退行性变等领域的应用研究取得众多进展。本文主要综述近年来褪黑激素抗氧化机制及其应用的研究进展。     

吸烟、硝酸甘油对动脉粥样硬化家兔血管平滑肌细胞钙浓度的影响

目的研究吸烟、硝酸甘油对动脉粥样硬化血管平滑肌细胞胞内游离钙浓度([Ca2+]i)的影响,探讨吸烟对动脉粥样硬化形成及硝酸甘油的生物效应的作用。方法复制家兔动脉粥样硬化模型,分离血管平滑肌细胞。Fluo-3/AM负载细胞,应用流式细胞仪检测血管平滑肌细胞[Ca2+]i,激光扫描共聚焦显微系统测定单个血管平滑肌细胞内Ca2+的时空变化。结果各组动物主动脉壁均见到程度不同的动脉粥样硬化斑块形成。动脉粥样硬化家兔血管平滑肌细胞[Ca2+]i明显升高(48.45±5.31,与生理盐水对照组38.09±2.57比较,P<0.01);吸烟能增加动脉粥样硬化家兔血管平滑肌细胞[Ca2+]i(56.48±2.99,与单纯动脉粥样硬化组48.45±5.31比较,P<0.01);硝酸甘油则能明显降低动脉粥样硬化家兔血管平滑肌细胞[Ca2+]i(41.91±3.16,与单纯动脉粥样硬化组48.45±5.31比较,P<0.05);吸烟能明显抑制硝酸甘油降低血管平滑肌细胞[Ca2+]i的作用(47.99±5.10,与硝酸甘油组41.91±3.16比较,P<0.05)。结论吸烟能明显增加动脉粥样硬化血管平滑肌细胞[Ca2+]i,硝酸甘油则能明显降低动脉粥样硬化血管平滑肌细胞[Ca2+]i,吸烟能抑制硝酸甘油的生物学效应。     

采用聚酰胺除辛芍冻干粉针中赤芍提取物鞣质的工艺研究

目的:研究注射用辛芍冻干粉针聚酰胺法除鞣质工艺。方法:以有效成分芍药苷转移率、鞣质检查、局部刺激性和小鼠异常毒性试验为评价指标,通过聚酰胺除鞣质吸附、解析工艺优化,比较传统除鞣质法和聚酰胺除鞣质法除鞣质效果。结果:聚酰胺法能有效去除样品中的鞣质,芍药苷的转移率明显高于其他方法,而且异常毒性显著降低,制剂的安全性得到有效保证。结论:聚酰胺法除鞣质为中药注射剂除鞣质技术提供了实验依据。     

维脑康胶囊对慢性脑低灌注大鼠脑内胆碱能系统及清除自由基能力的影响

目的:观察维脑康胶囊(WNK)对慢性脑低灌注所致大鼠认知障碍的干预作用及机制。方法:结扎大鼠双侧颈总动脉,4周后分为:假手术组,模型组,达纳康组,WNK 8.25,16.5,33.0mg·kg^-1组;同时灌胃给药,给药周期8周,测定大鼠在MORRIS水迷宫中寻找平台的持续时间,同时HPLC-ECD测定脑组织中乙酰胆碱(ACh)含量,比色法测定乙酰胆碱酯酶(AChE)活性、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果:与模型组比较,给药4~8周,WNK组大鼠寻找平台时间明显缩短,脑内AChE活性明显降低(P<0.05),ACh含量明显增加(P<0.05~0.01),SOD活性明显增强(P<0.05)。结论:WNK对慢性脑低灌注引起的认知障碍的改善作用可能与增强清除自由基能力以及保护胆碱能系统有关。     

腔镜辅助下保留乳头乳腺癌改良根治术的探讨

目的：探讨腔镜辅助下保留乳头乳腺癌改良根治术的方法和疗效。方法：2004年9月～2006年4月,对24例患者行腔镜辅助下保留乳头乳腺癌改良根治术。结果：24例患者无明显手术并发症,且美容效果良好。术后随访时间最长18.6个月,中位平均随访时间为9.2个月,全组无局部复发和远处转移。结论：腔镜辅助下保留乳头乳腺癌改良根治术可作为早期乳腺癌手术治疗的选择术式。     

前列腺癌根治手术的进展

前列腺癌根治术是治疗局限性前列腺癌的标准方法。经过20多年的发展，目前此手术的并发症发生率已明显下降，它已成为患者的最佳选择，术后极少影响患者的生活质量。本文结合自己的经验体会对目前开展最为广泛并且为大多数学者所推崇的开放性耻骨后前列腺癌根治术作了详尽的探讨。对腹腔镜下和机器人辅助腹腔镜下前列腺癌根治术作了简要阐述。主要讨论的焦点集中于近年来在手术技巧方面的创新和在降低手术并发症方面的改进。