正常中国汉人红细胞中儿茶酚氧位甲基转移酶的活性测定

目的测定正常中国人群红细胞儿茶酚氧位甲基转移酶(COMT)活性浓度值,为研究COMT活性变化在疾病诊断中的应用提供依据。方法采用高效液相色谱法测定279名正常健康人(其中男性134例,女性145例)红细胞中COMT的活性浓度,用SPSS统计软件对性别间测定结果进行检验比较。结果男性和女性红细胞中COMT活性浓度分别为:(16.5±7.4)、(15.5±5.3)nmol.mL RBC-1.h-1。活性频率分布男性在6.0~37.4nmol.mL RBC-1.h-1,女性为5.4~37.2 nmol.mL RBC-1.h-1,男女之间COMT活性浓度的差异无统计学意义(P>0.05)。结论本法灵敏,简便,准确,重复性好,且测定结果与国外一些报道一致,适用于临床应用测定研究。本结果可作为中国健康人红细胞COMT活性正常值及今后研究的重要参考数据。     

A new meroditerpenoid from Mayodendron igeum

A new meroditerpenoid, igeumone (1), together with 18 known compounds (2-19), were isolated from ethanolic extract of the bark of Mayodendron igeum. Their structures were determined by analysis of spectral data or comparison with authentic samples. X-ray crystallographic analysis was employed to unambiguously determine the structure of 1.     

干扰素引起面部泛发型痤疮

患者女,28岁。于2003年10月因发现肝功能异常,在当地医院检测发现抗HCV阳性,诊断为丙型肝炎,自2003年10月开始持续在我院门诊就诊。检测:ALT600U/L,HCV RNA( ),给予干扰素α-2b300万u,隔日1次皮下注射。治疗2个月后:ALT56U/L,HCV RNA(-),治疗5个月时,患者面部出现多个痤疮,未加以注意,继续治疗。面部痤疮明显加重,至2004年7月3日,来我院复查,面部密布痤疮,且涉及到颈部和胸部;痤疮大者如蚕豆,小者如黄豆,呈结节状,周围红肿;痤疮愈后,面部留下明显疤痕。几乎达到毁容的程度,患者不敢外出。检测自身抗体均为阴性,患者拒绝痤疮活检…     

Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.     

左旋千金藤啶碱对外周血管多巴胺DA_1和DA_2受体亚型的作用

用家兔离体血管环方法，研究左旋千金藤啶碱（ｌＳＰＤ）对外周血管ＤＡ１和ＤＡ２受体亚型的作用。结果表明，ｌＳＰＤ使ＤＡ１受体激动剂ＦＯＤＡ诱发的肾、肺和肠动脉以及ＤＡ２受体激动剂ＰＢＤＡ诱发的肠和股动脉舒张反应的量效曲线非平行右移，最大反应（Ｅｍａｘ）降低，均呈非竞争性拮抗；ｌＳＰＤ本身还可使肾和肺血管产生轻度的浓度依赖性舒张反应，表现为ＤＡ１受体激动剂的作用特性。提示ｌＳＰＤ为外周血管ＤＡ１和ＤＡ２受体的混合性阻滞剂并兼有ＤＡ１受体部分激动剂的双重作用特性。     

Studies on exposure status of inhabitants to water-arsenic valence states in areas with endemic arsenism in the Datong basin in Shanxi

This study aimed to describe the distribution of water-arsenic (As) valence states and its relationship to areas with endemic arsenism in the Datong basin. Drinking water samples of patients with endemic arsenism and a control group were examined using hydride generation atomic fluorescence spectrometry (HG-AFS). We analyzed the data using SPSS10.0 for Windows. The As(III)/As ratio was 52.1% in the water sample, exceeding the national standard of 0.05 mg/L. The As(III)/As ratio significantly varied among the different stages in the disease-state groups, and with the control group (χ ² = 22.4, P<0.01). The As(III)/As(V) ratio significantly varied in the four groups (χ ² = 26.19, P<0.01), with a tendency to increase along with the seriousness of the disease state. The most common type of drinking water arsenic valence state was As(III) in the endemic disease-areas. Endemic arsenism was positively correlated with As(III). This led us to conclude that the fraction of each water-arsenic valence state should be studied when determining the arsenic content of drinking water. Translated from Chinese Journal of Endemiology, 2006, 25(1): 64–66 [译自: 中国地方病学杂志]     

头孢克肟混悬剂与颗粒剂的药物动力学及生物等效性

目的　比较头孢克肟混悬剂与头孢克肟颗粒剂在健康志愿者体内的药物动力学及生物等效性 ,确保临床用药质量。方法　采用开放、随机、1周清洗间歇的二阶段自身交叉对照试验法 ,1 8例健康男性志愿者单剂量口服头孢克肟 2 0 0mg ,于服药 0、0 5、1、2、3、4、5、6、8、1 2、1 6和 2 4h采集血清样品 ,用RP HPLC法测定血清中头孢克肟的浓度 ,并拟合药动学参数 ,以双单侧t检验法比较头孢克肟两种制剂AUC、Cmax和Tmax间的差异。结果　头孢克肟混悬剂与头孢克肟颗粒剂在健康志愿者体内的药 时曲线均符合一级吸收的单室开放模型 ,主要药动学参数 :Tmax(实测值 )分别为 (3 2 1± 0 4 2 )和 (3 2 1± 0 4 2 )h ,Cmax(实测值 )分别为 (3 32± 0 4 1 )和 (3 1 2± 0 4 3) μg/ml,AUC0～ 2 4 分别为 (30 61± 4 0 5)和 (2 8 52± 3 1 3)h·mg/L。经配对双单侧t检验法比较 ,头孢克肟两种制剂各主要药动学参数间均无统计学差异 (P >0 0 5) ,头孢克肟混悬剂对头孢克肟颗粒剂的相对生物利用度为 1 0 7 3 %。结论　头孢克肟两种制剂在健康志愿者体内具有相同的生物效应。     

An evaluation of chemical photoreactivity and the relationship to phototoxicity

The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290–700 nm, and that are either applied locally/topically, or “reach” (EMEA)/“significantly partition” (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed.     

Verification of five pharmacogenomics-based warfarin administration models

Objective:This study aims to screen and validate five individual warfarin dosing models (four Asian model algorithms, namely, Ohno, Wen, Miao, Huang, and the algorithm of International Warfarin Pharmacogenetic Consortium, namely IWPC algorithm) with the aim of evaluating their accuracy, practicality, and safety.Results:The prediction accuracies of the Huang and Wen models were the highest. In terms of clinical practicality, the Huang model rated the highest for the low-dose group, whereas the Ohno and IWPC models rated the highest for the middle-dose group. The models tended to markedly overpredict the doses in the low-dose group, especially the IWPC model. The Miao model tended to severely underpredict the doses in the middle-dose group, whereas no model exhibited severe overprediction.Conclusions:Since none of the models ranked high for all the three criteria considered, the impact of various factors should be thoroughly considered before selecting the most appropriate model for the region''s population.KEY WORDS: Mechanical heart valve replacement, model, pharmacogenomics, verification, warfarin     

华蟾素配合立体定向放射治疗中晚期食管癌28例

目的观察华蟾素配合立体定向伽玛射线放射治疗中晚期食管癌的近期临床疗效。方法将56例患者随机均分为华蟾素联合伽玛刀治疗组（治疗组）和伽玛刀单独治疗组（对照组）。伽玛刀治疗总剂量40～50Gy,次数10～12次,边缘剂量300～420cGy,等剂量曲线55%～85%,每日治疗1次;治疗组加用华蟾素注射液20～30mL静脉滴注,1次/d,连续3～4周。结果 56例患者均顺利完成治疗,治疗组梗阻症状总缓解率、影像学总缓解率均显著高于对照组（P均小于0.05）;治疗组不良反应如急性放射性食管炎、白细胞下降发生率虽低于对照组,但差异无统计学意义（P〉0.05）。结论华蟾素注射液联合伽玛射线立体定向放射治疗中晚期食管癌患者,临床症状缓解率高,毒副作用小,患者耐受性好,近期疗效令人满意。