骨髓单个核细胞移植对不同Child—Pugh分级肝硬化血清胆碱酯酶的影响

目的 探讨肝动脉插管自体骨髓单个核细胞移植对不同Child～Pugh分级肝硬化患者血清胆碱酯酶（CHE）的影响。方法201例肝硬化患者,其中131例行自体骨髓单个核细胞移植,70例为对照。骨髓穿刺采集自体骨髓,体外分离纯化骨髓单个核细胞,经肝动脉插管将其移植入肝脏。分别于移植后4、8、12、24周观察血清CHE变化情况,比较不同Child—Pugh分级肝硬化患者CHE改变,并观察患者并发症发生情况。结果移植组患者移植前血清CHE为2387．4U／L,移植后4周、8周、12周和24周分别升至2875．9U／L、3190．6U／L、3216．0U／L和3066．5U／L。患者移植后24周内血清CHE水平较移植前显著升高,而对照组无明显升高,两组比较差异有统计学意义。移植组中,Child—PughA级和B级患者血清CHE改善程度优于C级患者。两组患者24周内主要并发症发生率差异无统计学意义。移植后无严重不良事件发生。结论自体骨髓单个核细胞移植能提高肝硬化患者血清CHE水平,对Child—PughA级和B级患者改善明显。     

Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.     

旺拉提取物对胆碱能损伤大鼠脑胆碱酯酶的影响

【目的】研究藏药旺拉提取物对胆碱能损伤大鼠脑胆碱酯酶活性和表达的影响。【方法】采用基底前脑注射鹅蒿蕈氨酸的方法建立胆碱能损伤大鼠模型。实验动物分为假手术组、模型组、CE 5 mg/kg组,连续灌胃给药28 d。取大鼠脑额叶皮层、基底前脑区,观察大鼠脑病理改变,化学法测定胆碱酯酶和乙酰胆碱酯酶活性,免疫组化染色法检测乙酰胆碱酯酶表达。【结果】与假手术组相比,模型组大鼠脑额叶皮层、基底前脑神经元细胞发生坏死等病理变化,胆碱酯酶和乙酰胆碱酯酶活性明显下降(P<0.05),乙酰胆碱酯酶表达水平下降[P<0.05,脑额叶皮层乙酰胆碱酯酶的累积光密度为(4.6±0.4)×104,基底前脑乙酰胆碱酯酶的累积光密度为(2.5±0.2)×104]。与模型组大鼠比,CE 5 mg/kg可抑制胆碱能损伤大鼠脑的病理改变,对乙酰胆碱酯酶和胆碱酯酶活性影响不大,但可明显提高乙酰胆碱酯酶的表达水平[P<0.05,脑额叶皮层乙酰胆碱酯酶的累积光密度为(6.2±0.4)×104,基底前脑乙酰胆碱酯酶的累积光密度为(3.2±0.2)×104]。【结论】CE对胆碱能神经系统有一定的保护作用,这可能是CE改善学习记忆能力的途径之一。     

Aerosolized delivery of oxime MMB-4 in combination with atropine sulfate protects against soman exposure in guinea pigs

We evaluated the efficacy of aerosolized acetylcholinesterase (AChE) reactivator oxime MMB-4 in combination with the anticholinergic atropine sulfate for protection against respiratory toxicity and lung injury following microinstillation inhalation exposure to nerve agent soman (GD) in guinea pigs. Anesthetized animals were exposed to GD (841?mg/m³, 1.2 LCt₅₀) and treated with endotracheally aerosolized MMB-4 (50 µmol/kg) plus atropine sulfate (0.25?mg/kg) at 30?sec post-exposure. Treatment with MMB-4 plus atropine increased survival to 100% compared to 38% in animals exposed to GD. Decreases in the pulse rate and blood O₂ saturation following exposure to GD returned to normal levels in the treatment group. The body-weight loss and lung edema was significantly reduced in the treatment group. Similarly, bronchoalveolar cell death was significantly reduced in the treatment group while GD-induced increase in total cell count was decreased consistently but was not significant. GD-induced increase in bronchoalveolar protein was diminished after treatment with MMB-4 plus atropine. Bronchoalveolar lavage AChE and BChE activity were significantly increased in animals treated with MMB-4 plus atropine at 24?h. Lung and diaphragm tissue also showed a significant increase in AChE activity in the treatment group. Treatment with MMB-4 plus atropine sulfate normalized various respiratory dynamics parameters including respiratory frequency, tidal volume, peak inspiratory and expiratory flow, time of inspiration and expiration, enhanced pause and pause post-exposure to GD. Collectively, these results suggest that aerosolization of MMB-4 plus atropine increased survival, decreased respiratory toxicity and lung injury following GD inhalation exposure.     

Chlorpyrifos: Weight of evidence evaluation of potential interaction with the estrogen,androgen, or thyroid pathways

Chlorpyrifos was selected for EPA’s Endocrine Disruptor Screening Program (EDSP) based on widespread use and potential for human and environmental exposures. The purpose of the program is to screen chemicals for their potential to interact with the estrogen, androgen, or thyroid pathways. A battery of 11 assays was completed for chlorpyrifos in accordance with test guidelines developed for EDSP Tier 1 screening. To determine potential endocrine activity, a weight-of-evidence (WoE) evaluation was completed for chlorpyrifos, which included the integration of EDSP assay results with data from regulatory guideline studies and the published literature. This WoE approach was based on the OECD conceptual framework for testing and assessment of potential endocrine-disrupting chemicals and consisted of a systematic evaluation of data, progressing from simple to complex across multiple levels of biological organization. The conclusion of the WoE evaluation is that chlorpyrifos demonstrates no potential to interact with the estrogen, androgen, or thyroid pathways at doses below the dose levels that inhibit cholinesterase. Therefore, regulatory exposure limits for chlorpyrifos, which are based on cholinesterase inhibition, are sufficient to protect against potential endocrine alterations. Based on the results of this WoE evaluation, there is no scientific justification for pursuing additional endocrine testing for chlorpyrifos.     

Chemistry and functional properties in prevention of neurodegenerative disorders of five Cistus species essential oils

The chemical composition of Cistus creticus, Cistus salvifolius, Cistus libanotis, Cistus monspeliensis and Cistus villosus essential oils has been examined by GC and GC–MS analysis. Height-nine constituents were identified in C. salvifolius oil, sixty in C. creticus, fifty-six in C. libanotis, fifty-four in C. villosus, forty-five in C. monspeliensis. Although the five species belong to the same genus, the composition showed interesting differences. Essential oils were screened also for their potential antioxidant effects (by DPPH, ABTS, FRAP and β-carotene bleaching test) and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, useful for prevention and treatment of Alzheimer’s disease. C. monspeliensis exhibited the most promising activity in β-carotene bleaching test (IC₅₀ of 54.7 μg/mL). In FRAP test C. libanotis showed a value of 19.2 μM Fe(II)/g. C. salvifolius showed the highest activity against AChE (IC₅₀ of 58.1 μg/mL) while C. libanotis, C. creticus, C. salvifolius demonstrated a good inhibitory activity against BChE with IC₅₀ values of 23.7, 29.1 and 34.2 μg/mL, respectively. Overall our results could promote the use of the essential oil of different Cistus species as food additives and for formulation of herbal infusion or nutraceutical products.     

血清前白蛋白、总胆汁酸和胆碱酯酶联合检测在乙型肝炎进展中的临床价值

目的明确血清前白蛋白(PA)、总胆汁酸(TBA)和胆碱酯酶(CHE)在乙型肝炎进展中的临床价值。方法 141例临床确诊的乙型肝炎及进展期患者及42例职工体检的HBsAg阴性的正常人群,均于清晨空腹采集静脉血,采用日立7600-020全自动生化分析仪测定PA、TBA和CHE。结果与对照组比较,肝硬化组、肝癌介入术后组和HBeAg(+)乙肝组PA、CHE及TBA均有显著性差异(P<0.05),HBeAg(-)乙肝组与对照组比较,PA及CHE差异无统计学意义(P>0.05),TBA差异具有统计学意义(P=<0.05);PA及CHE下降程度依次为肝癌介入术后组>肝硬化组>HBeAg(+)乙肝组,而TBA的上升程度依次为肝硬化组>肝癌介入术后组>HBeAg(+)组>HBeAg(-)组。结论 PA、TBA和CHE联合检测是反映肝脏的合成和损害程度,预测肝脏的储备功能的良好指标,可以为临床的治疗和监测提供参考。     

78例有机磷中毒患者心肌酶谱和心电图分析

目的通过早期检测有机磷中毒（AOIP）患者血清心肌酶谱及心电图变化,探讨其临床意义。方法监测78例AOIP患者不同时间点心电图及心肌酶谱的变化水平并与30例健康对照组比较。结果中度及重度中毒患者心肌酶显著高于对照组（P〈O．01）。结论定期检测患者心肌酶谱对于临床治疗、观察愈后具有重要意义。     

肺部疾病引发全身炎症反应综合征的老年患者死亡因素分析

目的分析肺部疾病引发全身炎症反应综合征（SIRS）的老年患者病情死亡因素。方法选择2009年9月至2010年12月入住浙江大学医学院附属第一医院中心重症监护病房因肺部疾病引发SIRS的老年患者50例,根据预后情况分为存活组（18例）和死亡组（32例）。检测所有入院患者24h内的血清胆碱酯酶（ChE）、白蛋白（ALB）、D-二聚体、乳酸及C反应蛋白（CRP）水平,并进行急性病生理学和长期健康评价（APACHE）Ⅱ评分。结果存活组和死亡组之间比较,肺部疾病引发SIRS患者的血乳酸、ALB及APACHEⅡ评分差异无统计学意义（P均〉0.05）,而年龄、血浆D-二聚体、CRP及ChE方面,差异均具有统计学意义（P均〈0.05）。Logistic回归结果表明,影响肺部疾病引起SIRS的老年患者预后的独立危险因素仅有ChE一项（β=-0.016,P=0.040）。受试者工作特征曲线（ROC）分析显示,以ChE预测SIRS的老年患者预后的ROC曲线下面积为0.839,S.E.=0.057,P=0.000;当ChE=98.5U/L时,敏感度为88.9;1-特异度为0.25,以此切点对患者的预后具有较好的预测价值。结论 ChE可能参与了老年SIRS的发生和发展过程,对这类患者的病情发展转归有一定的预测作用,指标稳定,受干扰因素少。     

总抗氧化状态对AD患者认知功能的影响

目的探讨总抗氧化状态对阿尔茨海默病（AD,即人们常说的老年痴呆症）患者认知功能的影响。方法病例来自聊城市第四人民医院住院和门诊的AD患者共107例,随机抽取54倒服用多奈哌齐作为治疗组,53例应用安慰剂作为对照组。入组后检测红细胞内超氧化物歧化酶（简称SoD）和谷胱甘肽过氧化物酶（简称GPX）,测定血浆总抗氧化状态（简称TAs）和胆碱酯酶活力（简称CHE）。在治疗前及治疗后1、3、6个月分别检测一次,并进行MMsE（简易智力状况检查法）评分。结果治疗前CHE、GPX、TAS、SOD浓度对照组及治疗组无明显差异（P〉0．05）。治疗6个月后,治疗组CHE浓度较对照组比较明显降低（P〈0．05）;两组GPX血浓度治疗后无显著差异（P〉0．05）;治疗组TAs浓度较对照组比较明显增高,有明显差异（P〈0．05）;治疗组SOD浓度较对照组有咦显差异（P〈0．05）;治疗组的MMSE得分随着治疗时间的延长而增高,但治疗组与治疗前有明显差异（P〈0．05）,而对照组治疗前后无明显差异,两组在治疗6个月后有明显差异（P〈0．05）。结论总抗氧化水平提高,认知水平亦有所提高,改善抗氧化水平对于提高AD患者的认知功能有一定的作用,但远期效果有待进一步观察。