D1 Dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior

The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons.     

Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.     

高效液相色谱法检测血中表阿霉素的研究

用ＺｏｒｂａｘＣ－８柱成功地分离了阿霉素、表阿霉素及其代谢产物。在此基础上建立了用阿霉素作内标物定量测定表阿霉素的分析方法，其最低检测限为２ｎｇ／ｍｌ，线性范围１０－３００ｎｇ／ｍｌ。     

盐酸齐拉西酮在中国健康志愿者中的药代动力学研究

目的评价国产盐酸齐拉西酮胶囊的人体药代动力学特点;初步评价国产盐酸齐拉西酮胶囊的安全性。方法采用HPLC法测定血浆中齐拉西酮浓度。10位男性健康受试者进食时单剂量口服40mg盐酸齐拉西酮胶囊。于服药前及服药后0.5、1、2、3、4、5、6、8、10、12、24、36、48小时采集5m l血样。抗凝处理取血浆,-20℃保存,用于血药浓度的测定。安全性评价包括体检、实验室检查(心电图、血常规、生化常规及尿常规等)及不良事件的记录。结果主要药动学参数:Cm ax为(175.0±63.73)ng/m l;Tm ax为(3.80±1.32)h;MRT为(9.37±1.53)h;t1/2为(6.10±1.65)h;Ka为0.1831±0.0708/h;Kel为0.1219±0.0349/h;Vd为(685.3±325.4)L;C l为(83.30±34.50)L/h;AUC0→t为(1312±261.3)ng/m l/h,AUC0→∝为(1339±261.1)ng/m l/h。药物不良事件主要为嗜睡、口干、头昏、静坐不能、体位性低血压等,程度多为轻至中度,均能在短时间内缓解。结论研究结果显示了国产盐酸齐拉西酮在中国人中药代动力学特点,单剂量口服胶囊40mg是安全的。     

Active surfactant in pharyngeal aspirates of term neonates: lipid biochemistry and surface tension function

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air–liquid interface to values below 5 mN m^?1. In addition, it has been suggested that surfactant is also present in the airways, particularly in the perinatal period. We isolated surfactant from pharyngeal aspirates obtained from 33 neonates immediately after delivery and analysed it for both phospholipid (PL) composition and surface tension function. PL classes and phosphatidylcholine (PC) molecular species were determined by normal and reversed-phase high-performance liquid chromatography (HPLC), respectively. Static and dynamic surface properties of the surfactant were studied in a pulsating bubble surfactometer. Sample volume was 1.3 ± 0.5 mL (mean ± SD) with a total amount of 2.5 ± 1.3 μmol of PL and a concentration of 2.1 ± 1.0 μmol mL^?1 PL. HPLC analyses of PL classes revealed a composition identical with surfactant prepared from alveolar washes, i.e. PC 83.6 ± 2.1%, sphingomyelin 1.4 ± 0.5%, phosphatidylglycerol 8.1 ± 1.6%, phosphatidylethanolamine 2.1 ± 0.5% and phosphatidylinositol 2.6 ± 1.1%. Thin-layer chromatography showed almost identical results but was more time-consuming and needed more material for analysis. Analysis of PC molecular species revealed a composition typical of human alveolar surfactant with 54.7 ± 3.9% dipalmitoyl PC, 10.3 ± 1.9% palmitoyloleoyl PC and 9.1 ± 1.5% palmitoylmyristoyl PC. Minimal surface tension fell to values below 5 mN m^?1 within 5 min of cycling in all subjects. The methods used in this study allowed for complete PL and surface tension analyses of surfactant obtained during routine pharyngeal suctioning after delivery at term. Whether they are also applicable to preterm neonates with respiratory distress remains to be determined.     

丹酰氯柱前衍生人尿液多胺高效液相色谱(HPLC)快速测定

建立了丹酰氯柱前衍生HPLC法测定人尿中多胺含量的方法。以己二胺为内标 ,uBondapak -C18(2 5 0× 4.6mm ,10um)为固定相 ,甲醇和水为流动相 ,梯度洗脱 ,柱温 5 0℃ ,流速 1ml/min ,荧光检测器测得腐胺 (PUT)、精脒 (SPD)和精胺(SP)三者回收率为PUT 97%、SPD 98%、SP 10 3% ,回归方程线性良好 ( 均大于 0 99) ,分析时间约 9min。该法简洁 ,快速 ,灵敏度高 ,重现性好 ,可有效分析人尿及其他生物样品中的多胺含量     

Handling of biological samples in the determination of the anti-neoplastic drug mitomycin C

A study to ascertain suitable conditions for handling biological samples from patients, treated with the antibiotic mitomycin C (MMC), with the objective of improving the accuracy and reliability of the determination is described. Situations frequently occurring in medical practice are simulated to optimize procedures for reliable and reproducible sampling, sample treatment and determination of MMC. Continuation of drug partitioning in whole blood after sampling can be prevented by immediate cooling in ice before the separation of plasma from cells. The adjustment of the pH of urine samples is shown to be particularly important since a low urinary pH causes decomposition of MMC; moreover, it may decrease extraction recovery. Furthermore, long-term exposure of samples to daylight induces drug decomposition. Frozen storage of plasma and urine samples for periods greater than 3 weeks is to be avoided as this results in a considerable drop in MMC concentration. Repeated cycles of freezing and thawing are shown to have no effect upon the analytical results (6 cycles tested). The analysis of extracts of biological samples may take place up to at least 24 h after their preparation without measurable loss of analyte.     

高效液相色谱-串联质谱法测定蜂蜜中氯霉素、甲砜霉素、氟甲砜霉素及甲硝唑

目的 建立蜂蜜中氯霉素、甲砜霉素、氟甲砜霉素及甲硝唑残留的高效液相色谱-串联质谱同时测定方法。方法 以乙酸乙酯作为提取剂,经涡旋混匀提取后,氮吹至干,用5%甲醇水溶解,Oasis HLB固相萃取柱净化。经甲醇洗脱,洗脱液经45℃水浴氮吹至干,流动相涡旋溶解,上机测定。高效液相色谱分离、串联质谱检测,采用多离子反应监测（MRM）模式,内标法定量。结果 在优化条件下,4种抗生素浓度在0.1～5.0μg/L范围内,线性关系良好,相关系数（r）≥0.9953,方法检出限≤0.015μg/kg,不同基质中平均加标回收率为78.5%～95.1%,相对标准偏差（RSD）为2.8%～10.7%。结论 该方法快速、灵敏、准确,适用于蜂蜜中氯霉素、甲砜霉素、氟甲砜霉素及甲硝唑的同时测定。     

侧金盏花中强心甙的高效液相色谱分离和相对含量测定

作者研究了侧金盏花中强心甙的反相高效液相色谱测定方法,并对吉林产的侧金盏花中强心甙的相对含量进行了测定。测定结果表明,吉林产的侧金盏花中主要含甙元A、甙元B、加拿大麻甙、铃兰毒甙和毒毛旋花子甙元等强心成分。