癫患儿血清中丙戊酸的稳定性

丙戊酸钠(sodium valproate, SVPA)为临床常用广谱抗癫药物,因其丙戊酸(valproate acid, VPA)治疗血药浓度范围窄(50～100 μg/ml),需进行常规的治疗血药浓度监测(TDM)[1～3].我院自1995年至今共有500多人次的VPA血药浓度监测,均为当天取样当天测定.在常规TDM中,患者的血清样品未能即时测定而需储存.VPA血清样品要求放在低温冰箱-20 ℃条件下,可存放2 wk保持稳定[3,4].但由于低温冰箱价格贵,且样品解冻至室温所需时间长.本实验探讨癫患儿单用SVPA治疗时,其血清样品在冷处(2～10 ℃)密闭储存7 d的稳定性.     

癫癎患儿血清中丙戊酸的稳定性

丙戊酸钠 (sodium valproate,SVPA)为临床常用广谱抗癫药物 ,因其丙戊酸 (valproate acid,VPA)治疗血药浓度范围窄 (50～ 1 0 0︼g/ml) ,需进行常规的治疗血药浓度监测 (TDM) [1～ 3] 。我院自1 995年至今共有 50 0多人次的 VPA血药浓度监测 ,均为当天取样当天测定。在常规 TDM中 ,患者的血清样品未能即时测定而需储存。VPA血清样品要求放在低温冰箱 - 2 0℃条件下 ,可存放 2 wk保持稳定[3,4 ] 。但由于低温冰箱价格贵 ,且样品解冻至室温所需时间长。本实验探讨癫患儿单用 SVPA治疗时 ,其血清样品在冷处 (2～ 1 0℃ )密闭储存…     

高效液相色谱法测定新生儿咖啡因血药浓度及临床应用

目的:建立测定新生儿血清中咖啡因血药浓度的高效液相色谱法,并对使用咖啡因治疗原发性呼吸暂停新生儿的血药浓度进行测定。 方法:色谱柱为 ZORBAX Extend C18 柱,流动相为乙腈-水(19 ∶ 81,V/ V),柱温 25 ℃ ,流速 1 mL/ min,检测波长273 nm。 结果:咖啡因血药浓度在 1. 0~160. 0 μg / mL 范围内呈良好的线性关系(r = 0. 998 9),平均回收率 98. 40% ~ 102. 40%,日内与日间相对标准差(RSD)≤9. 63%,检测 10 例患儿给药 7 d 后咖啡因血药浓度为(20. 53±11. 12)μg / mL。 结论:建立的高效液相色谱法准确、快速,经验证适用于新生儿血清中咖啡因血药浓度测定。     

HPLC法测定人血浆中拉莫三嗪的浓度及其影响因素研究

目的:建立测定人血浆中拉莫三嗪(LTG)浓度的方法,分析LTG血药浓度的相关影响因素。方法:血浆样品以甲醇处理后采用高效液相色谱(HPLC)法进行测定,其中内标为氯霉素,流动相为乙腈-磷酸盐缓冲液(30∶70),色谱柱为Luna C18,流速为1ml/min,检测波长为306 nm。对收集的病例进行分组,应用逐步回归法分析影响LTG血药浓度的各类因素;应用相关分析法分析不同组别中的影响因素。结果:拉莫三嗪的血药浓度在0.5²0.0μg/ml范围内线性关系良好(r=0.999 5),最低检测限为0.5μg/ml;低、中、高3种质量浓度的平均方法回收率分别为(94.39±1.57)%、(95.57±2.22)%、(91.81±2.11)%;LTG血药浓度与LTG给药剂量、联用丙戊酸(VPA)呈正相关(r分别为0.641 7、2.568 0,P<0.05),与联用苯巴比妥(PB)呈负相关(r=-2.048 2,P<0.05);性别、年龄及体质量与其不存在显著的相关关系(P>0.05)。结论:本试验建立的HPLC法操作简便、快捷、回收率高、精密度好,适用于临床上常规监测LTG的血药浓度;LTG血药浓度可受LTG给药剂量、联合应用VPA及PB等因素的影响,因此在临床有必要开展其血药浓度监测,实行个体化给药。     

荧光偏振免疫法检测不同储存条件血清丙戊酸浓度

目的 考察不同储存条件对血清丙戊酸浓度的影响, 并对丙戊酸稳定性进行考察. 方法 利用荧光偏正免疫分析仪（TDXFLX）对不同储存条件下的丙戊酸患者血清进行测定. 结果 血清在－30, －80 ℃储存24, 48 h, 与0 h（室温）比较, 血清丙戊酸浓度变化较大, 样品在－80 ℃冰箱储存较－30 ℃冰箱储存血药浓度稳定. 患者丙戊酸血样在－80 ℃冰箱储存达120 h后, 与0 h比较变异系数<15%. 结论 该 方法 操作简便, 快速, 结果 可靠, 可为临床患者血样监测提供便利.     

苯巴比妥治疗新生儿缺氧缺血性脑病的血药浓度监测

目的监测苯巴比妥(PB)治疗新生儿缺氧缺血性脑病(HIE)的血药浓度,探讨苯巴比妥对其的疗效及合理用法.方法 HIE患儿使用PB负荷疗法抗惊厥,静注首次负荷量15～20 mg/kg,分1-2次,24 h后给予维持量3～5 mg/kg,分1-2次,连用5 d.应用荧光偏振免疫法监测5l例HIE患儿的PB血药浓度.结果:达有效血药浓度范围(15～40μg/ml)占62.73%(32/51),低于15μg/ml的占9.8%(5/51),高于40 μg/ml的占27.5%(14/51).结论:结果表明我院PB治疗HIE的给药方案是基本合理的;建议在给予负荷剂量24 h后进行PB血药浓度监测,以确定维持剂量.     

儿童万古霉素血药浓度监测及初始剂量优化

目的 通过分析某院0～6岁患者万古霉素血药浓度达标率及用药剂量的关系,探讨优化儿童患者万古霉素给药方案。方法 根据纠正胎龄后的年龄将患儿分为A(年龄<7 d),B(年龄7～28 d),C(年龄>28 d)3组,分析不同年龄组患儿万古霉素血药浓度水平和达标率情况,比较说明书推荐剂量、指南推荐剂量与实际剂量的差别。结果 106例0～6岁患儿监测万古霉素血药浓度168例次,以5～15 mg·L-1为目标谷浓度的万古霉素达标率为57.74%(98/168)。A、B、C 3组的血药浓度达标率分别为43.59%(17/39),54.00%(27/50)和67.09%(53/79),A、B组达标率低于C组,差异有统计学意义(P<0.05)。A、B、C 3组的平均血药浓度分别为(15.88±1.36),(13.51±0.82)和(11.10±0.69),C组的平均血药浓度低于另外2组,差异有统计学意义(P<0.05)。A组浓度达标患者的实际用量高于指南推荐剂量,差异有统计学意义(P<0.05),与说明书推荐的最大剂量差异无统计学意义(P>0.05)。B组浓度达标患者...     

反相高效液相色谱法测定盐酸伪麻黄碱血药浓度

报道用反相高效液相色谱外标法测定体内盐酸伪麻黄碱血药浓度的分析方法.血清样品用乙醚/正己烷(1:1)提取,以0.5%硫酸铵-甲醇(65:35)为流动相,紫外λ210nm检测,最低检出浓度为25ng/ml,平均提取回收率为80.4%.本法操作简便、迅速,适用于盐酸伪麻黄碱的血药浓度测定.     

217例次癫痫患儿血清奥卡西平代谢物浓度监测分析

目的 对血清奥卡西平活性代谢物(MHD)浓度监测结果 进行分析. 方法 采用高效液相色谱(HPLC)法测定血清MHD浓度,色谱柱为Inertsil ODS-3柱(4.6 mm×250 mm,5 μm),流动相为甲醇:水(45:55),流速1 mL.min^-1,检测波长225 nm. 结果 在217例次癫痫患儿MHD的血药浓度测定结果 中,有65.0%患儿血药浓度在治疗窗内,35.0%血药浓度偏低. 结论 儿童癫痫患者服用奥卡西平后,血清MHD浓度个体差异较大,及时监测血药浓度有助于及时调整用药剂量,促进奥卡西平个体化给药方案的实施.     

SDS增敏荧光光度法测定人血清中左氧氟沙星的残留量

目的 建立人血清中左氧氟沙星(LOX)残留量的快速测定方法.方法 采用十二烷基硫酸钠(SDS)增敏荧光光度法.结果 用无水乙醇沉淀蛋白,对血清进行预处理,利用LOX-SDS体系测定,人血清中LOX在0.1～5.0 μg·ml-1时,荧光强度与浓度呈线性关系,其回归方程为:F＝5.552 40.019C(r＝0.9990),平均回收率为99.72%,RSD＝0.68%.结论 所建方法简便、准确、快速,可用于人血清中LOX的测定.     

联合检测血清Hcy和Lp (a)与UA对冠心病患者预后评估的价值探讨

目的 探讨血清同型半胱氨酸(Hcy)、脂蛋白a[Lp(a)]和尿酸(UA)联合检测对冠状动脉粥样硬化性心脏病(CHD)的病情及预后的评估价值.方法 选取CHD患者96例(疾病组)和体检健康者50例(正常组),采集清晨空腹静脉血,检测血清Hcy、Lp(a)和UA.观察组(疾病组)随访1年,91例病情缓解或无进展,5例发展为急性心肌梗死(AMI).采用受试者工作特征曲线分析血清Hcy、Lp(a)和UA单独及联合检测对CHD患者预后的诊断价值.结果 疾病组血清Hcy、Lp(a)和UA水平均高于正常组(均P＜ 0.05);随访发展为AMI患者入院时血清Hcy、Lp(a)和UA水平均高于病情缓解或无进展者(均P＜ 0.01).Hcy、Lp(a)和UA联合检测对CHD患者预后评估的AUC为0.855、敏感性为89.4％、特异性为80.2％、阳性预测值86.4％,均高于3项单独检测.结论 冠状动脉粥样硬化性心脏病患者血清Hcy、Lp (a)和UA水平均升高,其水平变化可反映冠状动脉粥样硬化性心脏病病情,三者联合检测可提高对患者预后的判断价值.     

Comparison of the inhibition potential of parthenolide and micheliolide on various UDP-glucuronosyltransferase isoforms

Abstract

1. Parthenolide (PTL) and micheliolide (MCL) are sesquiterpene lactones with similar structures, and both of them have been reported to exhibit multiple biochemical and pharmacological activities. This study aims to investigate the inhibition of these two compounds on the activity of UDP-glucuronosyltransferases (UGTs).

2. In vitro incubation mixture for recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition kinetics (including inhibition type and parameters) were determined, and in silico docking was employed to elucidate the inhibition difference between PTL and MCL on UGT1A1.

3. MCL showed no inhibition toward all the UGT isoforms, and PTL showed strong inhibition toward UGT1A1. The half-maximal inhibitory concentration (IC₅₀) of PTL on the activity of UGT1A1 was determined to be 64.4?μM. Inhibition kinetics determination showed that PTL exerted noncompetitive inhibition toward UGT1A1, and the inhibition kinetic constant (K_i) was determined to be 12.1?μM. In silico docking method has been employed to show that hydrogen bonds between PTL and the activity cavity of UGT1A1 contributed to the stronger inhibition of PTL on the activity of UGT1A1 than MCL. In conclusion, PTL can more easily induce drug–drug interaction (DDI) with clinical drugs mainly undergoing UGT1A1-catalyzed glucuronidation.

     

The effect of halothane on the stability of Ca2+ transport activity of isolated fragmented sarcoplasmic reticulum

The effects of the inhalation anaesthetic agent, halothane (CF₃CHBrCl), on the stability of the calcium transport system of isolated rabbit white skeletal muscle sarcoplasmic reticulum have been studied. Calcium transport activity was unaffected when suspensions of sarcoplasmic reticulum vesicles were preincubated at 37° and pH 6.8 at concentrations of halothane below 5 mM, but was progressively inactivated at higher concentrations. (Ca²⁺,Mg²⁺)-ATPase activity was enhanced during inactivation of calcium transport. At pH 6.3 and 5.8, halothane increased the first order rate constants of inactivation and effects were noted in the anaesthetic range of concentration (1–2 mM). The inulin inaccessible space of membrane vesicles did not change appreciably during the period of treatment with halothane, excluding increased permeability as an explanation of the inhibition of calcium accumulation. Inactivation was irreversible and highly temperature dependent, with an activation energy of 52.7 kcal/mol. Calcium ions had a protective effect against inactivation (K_{0.5 (Ca2+) = 1.5 × 10^?6M}), as did ATP ($\text{K}{}_{\mathrm{<mtext>0.5\; (</mtext><mtext>Atp</mtext><mtext>)</mtext>}}\text{? 10}{}^{\mathrm{?6}}\text{M}$). It is concluded that mild acid conditions and halothane act synergistically during inactivation of the calcium transport system of sarcoplasmic reticulum membranes. These studies suggest that halothane interacts with the (Ca²⁺, Mg²⁺)-ATPase protein at the ATP-specific binding site or that it disrupts protein-lipid associations in the membrane. In either case the destabilizing effect of halothane may be modified by the conformational state of the protein.     

运动对糖尿病肾病早期相关指标的影响

目的研究运动对糖尿病肾病(DN)早期诊断指标如尿微量白蛋白(Alb)、尿转铁蛋白(TRF)、尿铜蓝蛋白(CP)、尿视黄醇结合蛋白(RBP)的影响。方法对45名2型糖尿病患者做次极量运动试验,运动前后分别测尿Alb、尿TRF、尿CP、尿RBP及尿肌酐(Cr),并以26名非糖尿病人做对照。结果糖尿病患者运动后尿Alb/Cr较运动前增加(P>0.01),尿TRF/Cr,CP/Cr,RBP/Cr运动前后无明显改变;非糖尿病人运动后尿Alb/Cr也较运动前增加(P>0.05),尿TRF/Cr,CP/Cr,RBP/Cr运动前后也无明显改变。而在相关分析中发现,尿RBP/Cr与Alb/Cr无显著相关性。尿TRF/Cr,CP/Cr与Alb/Cr有显著相关性。结论尿Alb/Cr受运动影响而尿TRF/Cr、CP/Cr不受运动影响,可作为DN早期诊断指标之一。     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

AFP、AFU、DSA-GGT联合检测对原发性肝癌的诊断价值

目的探讨甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)和欧蔓陀罗凝集素(DSA)强结合的γ-谷氨酰转移酶(DSA-GGT)联合检测对原发性肝癌(PHC)的诊断价值。方法对58例PHC和167例良性肝病患者,以及36例其它肿瘤患者,进行AFP、AFU和DSA-GGT指标联合检测,分析3项指标对PHC的诊断价值。结果PHC组的AFP、AFU、DSA-GGT的阳性率均明显高于良性肝病和其它肿瘤组(P<0.01);AFP、AFU和DSA-GGT对PHC的诊断敏感性分别为68.97%、67.24%和65.52%,特异性分别为90.64%,89.66%和91.13%;PHC患者血清AFP、AFU、DSA-GGT之间无相关性,联合检测对PHC有互补诊断价值,阳性率达96.55%。结论AFP、AFU和DSA-GGT等3个指标联合应用,可提高PHC的诊断灵敏度,提高诊断水平。     

GC法检测浙八味药材中有机氯农药的残留

目的 测定与分析白术、白芍、玄参等8种药材中9种有机氯农药残留量.方法 以混合溶剂超声提取样品、浓硫酸磺化净化,采用毛细管气相色谱,用HP-5弹性石英毛细管柱程序升温分离,微电子捕获检测器检测,峰面积外标法定量.结果 延胡索、麦冬和杭白菊均检出滴滴涕,含量分别为0.439、45.017、5.434 ng·g<'-1>;杭白菊检出五氯硝基苯,含量为1.030 ng·g<'-1>;其余药材均未检出有机氯农药残留.结论 浙八味药材大部分未检出有机氯农药残留或含量较低,均在规定的安全范围内.     

吸烟对血液过氧化与抗氧化平衡的影响

比较吸烟与不吸烟人静脉血血浆及红细胞脂质过氧化物-丙二醛（MDA）含量，血浆及红细胞超氧化物歧化酶（SOD）活力、全血谷胱甘肽过氧化物酶（GSH－Px）活力及血浆总抗氧化能力（AOA）．结果表明：吸烟组血浆及红细胞MDA的含量高于不吸烟组（P＜0．01），红细胞SOD含量高于不吸烟组（P＜0．01），血浆SOD、全血GSH－Px活力．血浆AOA均低0于不吸烟组（P＜0．01，P＜0．05，P＜0.05）．提示长期吸烟可使血中氧化与抗氧化失去平衡。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

Anti-ischemic effects of nimesulide, a cyclooxygenase-2 inhibitor on the ischemic model of rabbit induced by isoproterenol

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.