小儿地高辛代谢及合理临床应用研究进展

地高辛是儿科临床最常用的强心苷类药物.由于地高辛治疗窗窄,治疗剂量与中毒剂量接近,个体差异大,临床中有关地高辛中毒或者剂量不足的病例时有报道,其影响因素众多.有研究表明,年龄、体重、肝肾功能、肠道微生态及药物间相互作用等均可影响地高辛的代谢动力学.临床应用时除观察有无中毒的表现外,需综合各种影响因素,个体化调整用药,并严密监测地高辛血药浓度.     

MEMBRANE Na &#180 +;-K &#180 +; ATPase MEDIATED CASCADE IN BIPOLAR MOOD DISORDER,MAJOR DEPRESSIVE DISORDER,AND SCHIZOPHRENIA RELATIONSHIP TO HEMISPHERIC DOMINANCE

The isoprenoid pathway produces digoxin, an endogenous membrane Na &#180 +;-K &#180 +; ATPase inhibitor and regulator of neurotransmitter transport. The objective of the study was to relate digoxin status and hemispheric dominance to the pathogenesis of psychiatric disorders--bipolar mood disorder, major depressive disorder, and schizophrenia. The following parameters were assessed in bipolar mood disorder during the manic phase and depressive phase of the illness as well as in major depressive disorder, and schizophrenia: HMG CoA reductase activity, tryptophan and tyrosine catabolic patterns, red blood cell (RBC) Na &#180 +;-K &#180 +; ATPase activity, and serum magnesium. These parameters were compared to individuals of dif fering hemispheric dominance. The levels of serum digoxin and HMG CoA reductase activity were found to be decreased in the depressive phase of bipolar mood disorder and major depressive disorder with a cor responding increase in RBC Na &#180 +;-K &#180 +; ATPase activity and serum magnesium levels. There was increase in tyrosine and tyrosine catabolites, and a reduction in tryptophan and its catabolites, in the serum in the depressive phase of bipolar mood disorder and major depressive disorder. The neurotransmitter patterns and digoxin levels in the depressive phase of bipolar mood disorder/major depressive disorder correlated with those in right-handed/left hemisphere dominant individual. The neuro transmitter patterns and digoxin levels in the manic phase of bipolar mood disorder and schizophrenia correlated with those in left-handed/right hemisphere dominant individuals. Digoxin status and hemispheric domi nance could correlate with the pathogenesis of psychiatric disorders--schizophrenia, major depressive disorder, and bipolar mood disorder.     

Rapid detection of convallatoxin using five digoxin immunoassays

Context. Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. Objective. We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. Materials and methods. Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. Results. Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. Conclusion. Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.     

地高辛标记DNA探针快速筛选肿瘤细胞株基因表达差异

目的建立寡核苷酸探针正向斑点杂交技术,快速筛选不同细胞株同一基因HIF-1a表达差异,探讨斑点杂交筛选基因表达的可行性。方法将多种培养肿瘤细胞株提取总RNA后,点样于尼龙膜上,与地高辛标记的HIF-1a基因探针杂交,结果与半定量RT-PCR结果比较。结果斑点杂交实验结果与RT-PCR结果一致,无统计学差异(P>0.05)。结论用随机引物地高辛标记DNA探针可以快速筛查不同细胞株同一基因表达差异,可以作为研究肿瘤基因表达差异的工具。     

Na+-K+ pump inhibition caused by chronic amiodarone in guinea pig myocardium

Summary Although it is known that amiodarone inhibits myocardial Na⁺-K⁺ pump activity, the potency and the time course of this inhibition are unknown. The aim of this study was to investigate these aspects with reference to digoxin, using guinea pigs treated with either intraperitoneal amiodarone (20mg/kg per week, up to 12 weeks,n = 26) or the same amount of vehicle as a control (n = 24). ECG recording and microelectrode experiments were conducted every 2 weeks. QT interval corrected by heart rate and action potential duration were prolonged as a function of the time of exposure to amiodarone. Hyperpolarization observed immediately after the overdrive (1.0Hz) termination or K⁺-replenishment following K⁺-depletion in the presence of 0.1mM Ba²⁺ was compared in the amiodarone-treated and untreated groups, as an index of the Na⁺-K⁺ pump activity. The resting membrane potential recovery from overdrive-induced depolarization was slower and the amplitude of K⁺-induced hyperpolarization was smaller in the amiodarone-treated group than in the untreated group. These changes were evident as the chronic amiodarone treatment progressed, although the changes in these parameters were greater in the case of acute application of 50µM digoxin. In conclusion, this study indicates that treatment with amiodarone for longer than several weeks moderately inhibits the myocardial Na⁺-K⁺ pump.This work was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (11877125).     

血浆地高辛浓度危急值的应用与评估

目的 对血浆地高辛浓度危急值进行回顾性分析,为持续改进该项目危急值报告制度提供依据.方法 从实验室信息系统中筛选出血浆地高辛浓度危急值数据,经数据处理,统计出该项目危急值的发生率、天内分布、周内分布、科室分布,评估危急值范围和报告的周转时间.结果 血浆地高辛浓度危急值的发生率占该项目测试数的2.98％,科室分布以心内科为主.83.3％危急值报告的实验室周转时间在3小时之内.评估该项目频数分布图、临床症状符合率后,认为可以继续使用原定的血浆地高辛浓度危急值.结论 定期分析评估（一年一次）,持续改进血浆地高辛浓度危急值报告工作程序,可以提高检验科和临床科室的工作效率和质量,满足患者的安全要求.     

地高辛-PLGA抗肿瘤纳米粒子的制备及其抗肿瘤活性的初步研究

目的 制备载地高辛的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒子,提高地高辛的生物利用度,降低其毒副作用.方法 建立测定地高辛-PLGA纳米粒子载药量和包封率的高效液相色谱法;采用乳化溶剂挥发法制备地高辛-PLGA纳米粒子,并通过单因素实验优化制备条件;采用噻唑蓝法评价地高辛和地高辛-PLGA纳米粒子的抗肿瘤能力.结果 以粒径为筛选条件的单因素实验结果表明,制备地高辛-PLGA纳米粒子的最佳条件为PLGA 30 mg,地高辛2 mg,二氯甲烷3 ml,聚乙烯醇质量分数0.5％,超声功率200 W.此制备条件下得到的地高辛-PLGA纳米粒子的粒径约231 nm,包封率为74.61％,载药量为5.37％,且其抗肿瘤活性优于地高辛,差异具有统计学意义(P＜0.05).结论 以PLGA为载体材料制备地高辛-PLGA纳米粒子可增强地高辛的抗肿瘤作用.     

地高辛血药浓度监测及分析

目的分析地高辛血药浓度监测结果,为临床合理用药提供参考依据。方法采用荧光免疫偏振法监测使用地高辛的72例患者血药浓度,对监测结果进行比较分析。结果 0.5-2.0μg/L为地高辛安全有效血药浓度,共监测72例,其中在有效血药浓度范围内共50例（占69.44%）,低于治疗浓度下限的共9例（占12.50%）,高于治疗浓度上限的共13例（占18.06%）。结论由于地高辛安全范围窄,个体差异大,故应对使用地高辛的患者进行血药浓度监测,并制订个体化给药方案,为临床安全、有效、合理地使用地高辛提供依据。     

慢性肾病对老年慢性心力衰竭患者地高辛治疗的影响研究

目的探讨慢性肾病(CKD)对老年慢性心力衰竭(CHF)患者地高辛治疗的影响,以及监测血清地高辛浓度的临床意义。方法我院2007年1月—2009年6月收治的100例CHF伴CKD应用地高辛治疗的老年患者,按肾脏病生存质量指导(K-DOQI)的标准分为4个组(CKDⅠ～Ⅱ期、Ⅲ期、Ⅳ期和Ⅴ期),观察CKD分期和地高辛不良反应与地高辛浓度间的关系。结果 4组血药浓度比较,差异有统计学意义(P<0.05)。4组心率减慢、心律失常、胃肠道反应、中枢神经系统的不良反应发生率比较,差异均有统计学意义(P<0.05)。结论 CHF伴CKD的患者应用地高辛前有必要评估肾功能;CKDⅢ期和Ⅳ期的老年CHF患者服用地高辛必须监测血药浓度;而CKDⅤ期的老年CHF患者应用地高辛治疗必须谨慎,即使监测血清地高辛浓度也难以避免不良反应,需密切观察临床表现,并进行个体化治疗。