卡马西平血清样品的稳定性考察

目的考察卡马西平血清样品不同保存条件对血清药物浓度的影响。方法取癫痫患者血清样品,在取血当时、室温（28±3）℃保存1d、2d、3d或冷藏（4±1）℃保存1d、3d、7d后,用荧光偏振免疫法（FPIA）测定血清卡马西平浓度并进行比较,考察其稳定性。结果室温保存1d、2d、3d或冰箱冷藏保存1d、3d、7d的血清测定结果均与取血当时测定结果无统计学差异。结论卡马西平血清样品在室温下可稳定保存三天、冷藏条件下可稳定保存七天。     

血液灌流治疗小儿卡马西平急性中毒疗效观察

目的：分析采用血液灌流治疗急性卡马西平中毒的经验和价值。方法选择2007年5月至2013年7月就诊于西安市儿童医院重症医学科的45例误服卡马西平且入院血药浓度大于15μg/mL的患儿,将其分为血液灌流组（灌流组）24例和常规治疗组（对照组）21例,灌流组在常规治疗的基础上进行血液灌流治疗。两组患儿在治疗0、24、48、72小时测定卡马西平血药浓度。结果血液灌流组血清卡马西平浓度分别为：38．5±23．42μg/mL,17．54±5．56μg/mL,9．80±2．90μg/mL,1．20±1．03μg/mL;常规治疗组血清卡马西平浓度分别为：35．52±5．56μg/mL,30．92±5．53μg/mL,24．38±4．44μg/mL,16．52±4．23μg/mL,灌流组患儿血清卡马西平浓度在24、48、72小时较对照组低,差异有统计学意义（ t值分别为4．832,5．233,3．343,P＜0．05）。结论血液灌流对卡马西平急性中毒有明显疗效,能快速降低卡马西平浓度。     

液质联用法监测癫痫患儿卡马西平血药浓度及结果分析

目的：建立液谱质谱联用法（LC—MS）,对卡马西平（CBZ）进行血药浓度监测,同时探究卡马西平血药浓度与癫痫疗效的关系。方法：以本院小儿神经内科的168例癫痫患者作为研究对象,采用高效液相色谱质谱（1iquidchromatography—massspectrometry,LC—MS）方法对其血药浓度进行监测。结果：卡马西平血药浓度在2．0～40．0mg／L的范同内线性关系良好（r=0．9967）。168例癫痫患者中有104例的CBZ血药浓度为4～12mg／L,其中81例显效或有效,23例效果不明显,有效率为77．9％。48例患者的CBZ血药浓度〈4mg／L,占全部患者的28．6％,其中15例患者有效,其余无效;16例患者的CBZ血药浓度〉12mg／L,全部有效。结论：本文中LC—MS方法专属性强,灵敏度、准确度以及重现性均较好,易于操作,可用于癫痫患者血清中卡马西平血药浓度的监测。卡马西平治疗癫痫的疗效以及不良反应和CBZ血药浓度密切相关。     

肾移植受者环孢素A血药浓度监测的回顾分析

目的 探讨影响肾移植受者术后环孢素A(CsA)血药浓度的因素。方法 197例肾移植受者术后口服CsA达稳态时,用荧光偏振免疫分析法(FPIA)测定其全血CsA浓度,分析各种因素对CsA血药浓度的影响。结果 CsA的个体差异较大,剂量、术后时间、肝肾功能、胆汁排泄、食物吸收、合并用药甚至于患者的性别、年龄等因素都可以影响CsA的吸收、代谢、排泄。结论 每个病人的病情、用药情况都不尽相同。监测CsA血药浓度时必须结合患者的实际情况作具体分析,及时调整用药方案。确保正确地指导临床合理用药,提高治疗水平。     

FPIA法和HPLC法监测丙戊酸血药浓度的比较研究

目的:比较荧光偏振免疫分析法(FPIA)和高效液相色谱法(HPLC)监测丙戊酸血清药物浓度的相关性。方法:收集癫痫患者服丙戊酸后的稳态谷浓度血样,分别用FPIA法和HPLC法进行测定,考察二种测定方法的相关程度。结果:以HPLC法测定结果(x)与FPIA法测定结果(y)所作线性回归方程如下:y=1.8163+0.8407x(r=0.944),二种方法测定丙戊酸血清药物浓度结果差异有统计学意义(P<0.05)。结论:FPIA法和HPLC法测定丙戊酸血药浓度结果差异具有统计学意义,在丙戊酸治疗药物监测中应予以关注并作相应调整。     

血浆同型半胱氨酸测定在冠心病诊断中的应用价值

目的探讨血浆同型半胱氨酸(HCY)水平与冠心病发生的关系.方法用荧光偏振免疫法检测了新乡市100名正常人及50例冠心病患者HCY水平.结果冠心病患者HCY[(16.72±6.75)μmol/L]明显高于正常人[(9.7±3.01)μmol/L](P＜0.05).结论用荧光偏振免疫法检测血浆HCY表明,血浆HCY水平升高与冠心病发生有一定关系.     

血浆同型半胱氨酸与肾移植手术的关系探讨

目的:探讨血浆总同型半胱氨酸(tHCY)水平与肾移植手术的关系。方法:应用荧光偏振免疫法(FPIA)测定40例正常人、47例肾移植术后患者和30例慢性肾功能不全(CRF)患者的血浆tHCY水平,并对20例肾移植患者(连续监测组)手术前后的血浆tHCY水平进行连续1周的检测。结果:各组血浆tHCY水平均以(x±s)表示,对照组为10.12±3.15μmol/L;肾移植后患者为15.78±5.24μmol/L,CRF患者为19.68±6.74μmol/L。连续监测组手术前、下术后 tHCY水平分别为18.46±7.57μmol/L、13.01±5.56μmol/L。肾移植术后患者、CRF患者、连续监测组患者手术前、后血浆tHCY水平与正常对照组相比均有显著性差异(P＜0.001)。连续监测组患者手术前tHCY水平与其手术后相比有显著性差异(P＜0.001)。结论:肾移植术后患者、CRF患者血浆tHCY水平与正常人相比有显著性差异(P＜0.001),肾功能小全是引起肾移植后患者高tHCY血症的主要原因。     

卡马西平缓释片的处方优化研究

目的：通过对卡马西平缓释片中缓释材料种类和用量的筛选,确定最佳辅料及其配比,寻找出释放度和稳定性最优的处方。方法：根据美国上市卡马西平缓释片说明书选择阻滞剂、填充剂、润湿剂、润滑剂。用对比试验,通过调整辅料的品种和用量,制定不同的卡马西平缓释片处方,并通过释放度的比较确定最优处方。结果：确定了卡马西平缓释片的最优化处方及制备工艺。结论：该研究筛选出的卡马西平缓释片的处方及制备工艺,符合《中国药典》2010年版标准,其体外释放度及稳定性皆达到最优。     

反向荧光偏振（FP）检测血清中HBV多聚酶基因突变

目的:建立简便的HBV多聚酶基因序列中拉米呋啶耐药性相关的基因突变的检测方法.方法:利用pfu酶的3'-5'外切校正功能和荧光偏振光检测技术进行点突变的检测.首先PCR扩增HBV多聚酶基因,然后用3'标记荧光分子FAM的探针与扩增产物中待测核苷酸的下游序列杂交,使探针3'第一个碱基与靶序列中待测点的碱基配对.若碱基配对正确,pfu酶可以沿探针的3'端延伸;若碱基配对错误,pfu酶须将探针3'标有荧光分子的核苷酸切掉,然后再沿探针3'端延伸.由于第一种情况,荧光分子与DNA链相连,分子量增加,则荧光偏振光值增大;而第二种情况,荧光分子与探针分离,荧光分子的整体分子量减小,则荧光的偏振光值减小,这样可以通过荧光偏振光值的大小判断待测点核苷酸的改变.结果:该方法可以检测出HBV多聚酶基因序列中特定位置的核苷酸类型,可以检测1×10~1个拷贝的模板量.对30例经过6个月以上拉米呋啶治疗的患者血清进行检测,检测出其中有3例是甲硫氨酸(M)密码子ATG中的A→G变异;2例是ATG中的G→C变异;1例是ATG中的C→T.结论:该技术可以对血清中HBV多聚酶基因序列中点突变以及其他基因突变进行检测.     

卡马西平治疗癫痫的血液浓度监测

目的探讨卡马西平治疗癫痫的疗效与血药浓度的关系,为临床用药提供参考.方法采用荧光偏振免疫法测定119例癫痫患者卡马西平的血药浓度.结果96例血药浓度在4～12 μg/ml范围内,抗癫痫有效81例,有效率约84.38%,17例血药浓度低于4μg/ml,3例有效,其余无效.6例血药浓度高于12 μg/ml,全部有效,但有4例患者有明显的不良反应.结论卡马西平治疗癫痫的疗效与不良反应和血药浓度密切相关.     

Effect of Repeated Freezing and Thawing on Biomarker Stability in Plasma and Serum Samples

Objectives

The stability of circulating proteins can be affected by repeated freezing and thawing. The aim of our study was to identify the effect of repeated freezing and thawing on the plasma and serum concentrations of eight proteins [interferon-γ, interleukin (IL)-8, IL-15, IL-17A, matrix metalloproteinase (MMP)-7, tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGF-R2)].

Methods

We assessed the concentration changes of these proteins in 30 plasma and serum samples subjected to three, four, or five freeze–thaw cycles, and compared these with the concentration changes in the samples that were subjected to two freeze–thaw cycles before analysis.

Results

Repeated freezing and thawing by up to five cycles did not modify the plasma and serum concentrations of interferon-γ, IL-8, and VEGF-R2, while levels of MMP-7, tumor necrosis factor-α, and VEGF were significantly changed in both plasma and serum samples. Moreover, MMP-7 and VEGF concentrations tended to increase with freeze–thaw cycles. They were more elevated in plasma samples (up to about 15%) than in serum samples (up to about 7%), suggesting that serum is the preferred sample type for the analysis of circulating proteins.

Conclusion

This is the first report on the effect of repeated freezing and thawing on plasma concentrations of MMP-7 and VEGF-R2. Our findings propose that researchers should consider the number of freeze–thaw cycles to select plasma or serum samples, depending on the type of analyte.     

Serum Concentrations of Selected Persistent Organic Pollutants in a Sample of Pregnant Females and Changes in Their Concentrations during Gestation

Objectives

In this study we evaluated the concentrations of selected persistent organic pollutants in a sample of first-time pregnant females residing in the United States and assessed differences in these concentrations in all pregnant females during gestation.

Methods

We reviewed demographic and laboratory data for pregnant females participating in the National Health and Nutrition Examination Survey, including concentrations of 25 polychlorinated biphenyls (PCBs), 6 polychlorinated dibenzo-p-dioxins (PCDDs), 9 polychlorinated dibenzofurans (PCDFs), and 9 organochlorine pesticides. We report serum concentrations for first-time pregnant females (2001–2002; n = 49) and evaluate these concentrations in all pregnant females by trimester (1999–2002; n = 203) using a cross-sectional analysis.

Results

The chemicals with ≥ 60% detection included PCBs (congeners 126, 138/158, 153, 180), PCDDs/PCDFs [1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (1234678HpCDD), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (123678HxCDD), 1,2,3,4,6,7,8-heptachlorodibenzofuran (1234678HpCDF), 1,1′-(2,2-dichloroethenylidene)-bis(4-chlorobenzene) (p,p′-DDE)], and trans-nonachlor. The geometric mean concentration (95% confidence intervals) for 1234678HpCDD was 15.9 pg/g lipid (5.0–50.6 pg/g); for 123678HxCDD, 9.7 pg/g (5.5–17.1 pg/g); and for 1234678HpCDF, 5.4 pg/g (3.3–8.7 pg/g). The differences in concentrations of these chemicals by trimester were better accounted for with the use of lipid-adjusted units than with whole-weight units; however, the increase in the third-trimester concentration was greater for PCDDs/PCDFs (123678HxCDD, 1234678HpCDF) than for the highest concentration of indicator PCBs (138/158, 153, 180), even after adjusting for potential confounders.

Conclusion

The concentrations of these persistent organic pollutants in a sample of first-time pregnant females living in the United States suggest a decline in exposures to these chemicals since their ban or restricted use and emission. The redistribution of body burden for these and other persistent organic pollutants during pregnancy needs to be more carefully defined to improve the assessment of fetal exposure to them based on maternal serum concentrations. Additional studies are needed to further the understanding of the potential health consequences to the fetus from persistent organic pollutants.     

The Baseline Serum Lipoprotein Profile Is Related to Plant Stanol Induced Changes in Serum Lipoprotein Cholesterol and Triacylglycerol Concentrations

Objective: Baseline characteristics of subjects might be related to the effect of plant stanols on the serum lipoprotein profile. The aim of the study was to examine effects of subjects’ baseline characteristics (baseline serum concentrations of lipids and lipoproteins at the start of the study, lathosterol, campesterol and sitosterol; gender, age, BMI, smoking, use of oral contraceptives and menopause) on the effects of plant stanol esters on the serum lipoprotein profile.

Methods: We used data of five studies performed at our Department. A random intercept model was used for statistical analysis, using serum lipid and lipoprotein concentrations after plant stanol ester consumption, as dependent variables.

Results: After plant stanol ester consumption, higher baseline serum concentrations of total and LDL cholesterol resulted in larger absolute decreases in their respective serum concentrations. For the ratio of total to HDL cholesterol and triacylglycerol, higher baseline serum levels resulted in larger absolute and relative decreases in their serum levels. HDL cholesterol concentrations increased in subjects with low baseline concentrations and decreased in those with high baseline concentrations. Effects however were small. No relationships were observed with baseline serum cholesterol-standardized lathosterol and campesterol concentrations, although LDL cholesterol concentrations tended to decrease more at higher baseline sitosterol concentrations. No effects of other baseline characteristics were found.

Conclusions: People with an unfavorable serum lipid and lipoprotein profile benefit even more of plant stanols than people with a more favorable profile.     

Genome-Wide Association Study of Serum Selenium Concentrations

Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10⁻⁵. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10⁻⁷ and 4.04 × 10⁻⁷ in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.     

Stability of Mercury Concentrations in Frozen Avian Blood Samples

It is unclear whether mercury concentration in wildlife tissues changes appreciably after lengthy frozen storage. To test whether such freezer-archived samples are stable, small (~10–50 μL) avian blood samples stored in capped glass capillary tubes were analyzed for total mercury concentration, and then reanalyzed after being frozen for up to 3 years. Mercury concentrations increased 6% on average over the 3 year period, but time spent frozen explained only 11% of the variation between measurements. This small amount of change suggests that archived blood samples remain useful for at least several years.     

鼠疫免疫血清制备及抗体效价稳定性的研究

目的　探讨鼠疫弱毒菌株免疫家兔制备高效价抗鼠疫免疫血清的方法 ,及免疫血清冷冻保存时间对其效价的影响。方法　 (1)用鼠疫弱毒菌株 3 7℃ 48h培养物制成 10亿 /ml菌悬液 ,以不同的免疫途径分别接种被试动物 4～6次 ,放血分离血清。 (2 )分别测定冷冻保存 1、3、6、12、18个月的抗血清菌凝效价 ,判断其效价稳定性。结果　 (1)静脉全程免疫获得的免疫血清菌凝效价 ,明显高于多途径免疫获得的免疫血清 ,平均高 2个滴度。 (2 )免疫血清的效价随着保存时间的延长而有所下降。但 1年内下降不超过 2个滴度。结论　鼠疫弱毒菌株的静脉全程免疫可获得高效价的免疫血清 ,鼠疫免疫血清保存 1年菌凝效价相对稳定。     

奥氮平和丙戊酸钠治疗急性躁狂发作的短期疗效与血药浓度分析

目的探讨奥氮平与丙戊酸钠治疗急性躁狂发作的短期疗效及血药浓度的相互影响。方法将44例躁狂发作患者,随机均分为奥氮平组和丙戊酸钠组,治疗第8天时改为同剂量联合治疗1周。分别测定1周和2周时血药浓度,以YMRS减分率和TESS评定临床疗效和不良反应。结果奥氮平组治疗2周末显效率显著高于丙戊酸钠组(P<0.05);YMRS评分第1周相对基线均有明显下降,奥氮平组下降更明显(P<0.05);奥氮平显效浓度显著高于非显效患者的血浓度(P<0.05)。结论奥氮平单一或联合丙戊酸钠治疗急性躁狂发作均有较好疗效,起效快,安全性高和耐受性良好。血药浓度监测具有重要的临床意义。     

丙烯酰胺中毒大鼠神经组织及血清中Na~+、K~+、Ca~(2+)离子的变化

用高分辨质谱计测定丙烯酰胺中毒大鼠神经组织及血清中Na~+、K~+、Ca~(2+)离子的变化,结果表明:急性中毒时,小脑中三种离子的含量均明显下降(P<0.05);亚急性中毒时,血清中K~+明显下降(P<0.05)。