Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic Acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

α-溴-2、3、4、5、6五氟甲苯衍生气相色谱同时测定吲-3-乙酸和脱落酸

用α-溴-2、3、4、5、6五氟甲苯作衍生剂,在55℃反应90分钟可与吲哚-3-乙酸和脱落酸生成酯。这两种酯可用气相色谱分离,电子捕获检测器测定。本方法操作简单、灵敏度高。最小检测量:吲哚-3-乙酸和脱落酸分别为10^(-14)g 和10^(-13)g。

尿液中5-甲氧基吲哚乙酸的方波伏安法快速检测研究

研究了5-甲氧基吲哚乙酸(MIAA)的电化学行为和机理,并采用方波伏安法建立了尿液中MIAA的快速分析方法。在0.2mol/L的NH3-NH4Cl缓冲溶液(pH=9.2)中,MIAA在+0.5V(vs.Ag/AgCl)电位处产生一个吸附控制的不可逆阳极氧化峰。峰电流与MIAA浓度在4.0×10-6～1.0×10-4mol/L范围内呈良好的线性关系;检出限为9.8×10-7mol/L,RSD为3.5%。将本法应用于尿样中MIAA含量的快速检测,回收率为91%～99%,样品全分析在10min以内,具有快速、简便和低成本的特点,可以用于松果体腺功能评价。

5-(3-甲基-1-氢-吲哚)乙酸的合成研究

以2-(3-溴苯基)乙酸为原料,经过酯化、硝化、还原、取代、Heck反应和酯水解反应成功合成了标题化合物,总收率18.62%。关键步骤是取代反应和Heck反应。该方法操作简单、成本低、收率高,适合于工业化生产。

改进HPLC法测定吲哚美辛肠溶片中的有关物质

目的：改进高效液相色谱法测定吲哚美辛肠溶片中2-甲基-5-甲氧基-1H-吲哚-3-乙酸（以下简称杂质I）和4．氯苯甲酸（以下简称杂质Ⅱ）的含量。方法：色谱柱为PhenomenexPhenyl．Hexyl，流动相为10g／L醋酸溶液．乙腈（梯度洗脱），流速为1．0ml/min，检测波长为254nm，柱温为40℃，进样量为20μl。结果：杂质Ⅰ和杂质Ⅱ的检测质量浓度线性范围分别为0.2622～5．2430、0．2525～5．0500μg／ml（r均为0．9998）；定量限分别为1．12、0．48ng，检测限分别为0.340、0．146ng；精密度、稳定性、重复性试验的RSD〈2％；杂质Ⅰ和杂质Ⅱ的加样回收率分别为99．71％～100．52％（RSD：0．28％。n=9）、100．84％～102．14％（RSD=0．47％，n=9）。结论：该方法准确、快速，可用于吲哚美辛肠溶片中杂质Ⅰ和杂质Ⅱ的含量测定。

Effects of Gender, Age, and Clot Formation on the Measurements of Tryptophan Metabolites in Blood

Background: Tryptophan metabolism plays important roles in health and diseases. Although simultaneous measurements of tryptophan metabolites are successfully measured, influences of age, gender, and clot formation on the measurements have not been reported. Methods: We took blood from young and old Japanese men and women and compared plasma levels of tryptophan metabolites. We also took plasma and serum from the blood of middle-aged men (n = 10). Metabolites analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). Body mass index (BMI) and TRP metabolites have been measured in healthy young men (n = 48), young women (n = 47), old men (n = 44), and old women (n = 39). TRP metabolites were measured by using the ultrahigh speed liquid chromatography-mass spectroscopy (Shimadzu Corporation). Results: Tryptophan and its metabolites such as serotonin, 5-hydroxyindole acetic acid, indole-3-acetic acid, kynurenine, anthranilic acid, were higher in young women and old men than young men and old women. Plasma levels of 3-hydroxykynurenine and xanthurenic acid were lower in young women and old men. Comparison of plasma and serum indicates that most of metabolites were higher in serum than plasma except for 3-hydroxy-kynurenine and quinolinic acid. Conclusion: Metabolites of the upper stream of degradation of tryptophan were higher in young women and old men than young men and old women, which suggests that the degradation of tryptophan was accelerated in young men and old women than young women and old men. Serum preparation may activate tryptophan degradation resulting in higher levels of metabolites in serum than in plasma.

Comparison of Age and Gender Differences of Tryptophan Metabolites in Patients of Major Monopolar and Bipolar Depression

Background: No research has been done for the determination of plasma levels of tryptophan metabolites in patients of monopolar and bipolar depression. Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: No significant age and gender differences were shown in monopolar depressive patients and some differences were shown in bipolar patients. The administration of drugs such as antidepressants, antipsychotics, mood stabilizers do not seem to have affected the results. Conclusion: In patients of major monopolar depression age and gender differences of plasma levels of tryptophan metabolites disappear although significant differences are observed in healthy volunteers. Some differences of age and gender differences were shown between monopolar and bipolar depressive patients.

6-羟基多巴胺诱导的帕金森病大鼠纹状体 5-羟吲哚乙酸、褪黑素与多巴胺的关系

目的观察6-羟基多巴胺（6-OHDA）诱导的帕金森病（PD）大鼠纹状体透析液中，5-羟吲哚乙酸（5-HIAA）和褪黑素的动态变化及其与多巴胺的关系。方法脑内单侧双点注射6-OHDA至大鼠右侧黑质致密部和前脑内侧束建立PD模型。用脑微透析术分别于建模后1周、2周、3周、4周的10：00收集毁损侧纹状体透析液，高效液相色谱检测多巴胺、5-ttlAA和褪黑素浓度。结果建模1周PD大鼠的多巴胺浓度为[（1．19±0．22）ng／m1]，明显低于溶剂对照组[（8．62±0．73）ng／m1]和假手术组[（8．73±0．78）ng／m1]（P〈0．01）；PD组的5-HIAA水平呈低于溶剂对照组和假手术组的趋势；PD组褪黑素水平在建模后4周为[（43．31±11．37）pg／m1]，明显高于溶剂对照组[（19．13±5．38）pg／m1]和假手术组（19．80±6．96）pg／m1（p〈0．05）；PD组透析液中多巴胺和5-HIAA浓度具有显著的正相关性（r=0．867，P〈0．01）。结论6-OHDA诱导的PD大鼠纹状体多巴胺减少的同时伴有5-HIAA和褪黑素的变化，这些变化可能与PD的进展相关。

新型胰岛素增敏剂2-甲基-1(-4-氯苯甲酰基)-5-苄氧基-1H-吲哚-3-乙酸在大鼠体内的药动学研究

目的:研究新型胰岛素增敏剂2-甲基-1(-4-氯苯甲酰基)-5-苄氧基-1H-吲哚-3-乙酸(GY3)在大鼠体内的药动学特征。方法:采用反相高效液相色谱法,检测8只大鼠灌胃给予GY3溶液45mg/kg后0.25、0.5、1.5、2.5、4.0、5.0、7.0、9.0、12.0、16.0、20.0、24.0、28.0、36.0h的血药浓度,用DAS2.0药动学软件计算其药动学参数。色谱条件:色谱柱为ShimadzuC18,流动相为甲醇-0.1%磷酸(76∶24),流速为1ml/min,检测波长为253nm,柱温为25℃,进样量为20μl。结果:GY3检测质量浓度的线性范围为5.0～160.0μg/m(lr=0.9996),绝对回收率为96.96%～100.22%。药动学参数tmax为(2.75±2.32)h、cmax为(22.34±9.61)μg/ml、AUC0-∞为(187.85±115.08)μg·h/ml、t1/2β为(6.99±0.99)h。结论:GY3在大鼠体内的药-时曲线特征符合血管外给药一级吸收二室模型。

加味酸枣仁汤治疗肝血亏虚证失眠患者60例临床观察

目的观察加味酸枣仁汤治疗肝血亏虚证失眠的临床疗效及其对单胺类神经递质的影响。方法将120例失眠患者随机分为中医治疗组和西医对照组各60例,同时征集60例睡眠正常人群为正常对照组。中医治疗组给予加味酸枣仁汤中药配方颗粒剂,每日1剂;西医对照组给予艾司唑仑片,每次1mg,睡前30min口服,两组均治疗2周。正常对照组不作特殊处理。两组分别于治疗前后填写匹兹堡睡眠指数量表(PSQI)、睡眠状态自评量表(SRSS)。两治疗组患者分别于治疗前后,健康对照组于入组时检测5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)和β-内啡肽(β-EP)水平。观察两治疗组的临床疗效。结果两组患者治疗后SRSS、PSQI量表评分均较治疗前降低(P<0.01);治疗后中医治疗组SRSS、PSQI量表评分低于西医对照组(P<0.05)。治疗前与正常对照组比较,两组患者5-HT、β-EP水平明显降低,5-HIAA水平明显升高(P<0.01);治疗后两组患者5-HT、β-EP水平较本组治疗前明显升高,5-HIAA水平明显降低(P<0.05或P<0.01);中医治疗组治疗后与西医对照组比较,5-HT、β-EP水平明显升高,5-HIAA水平明显降低(P<0.05或P<0.01)。中医治疗组临床综合疗效总有效率(86.67%)明显高于西医对照组(75.00%)(P<0.05)。结论肝血亏虚证失眠患者单胺类递质紊乱,加味酸枣仁汤可以改善失眠患者及调节神经递质。