气相色谱法同时测定帕洛诺司琼中的8种有机溶剂残留量

[目的]测定帕洛诺司琼中甲醇、甲苯、乙酸乙酯、乙醇、四氢呋哺、丙酮、异丙醇、正己烷的含量。[方法]采用毛细管气相色谱法，色谱系统：HP-5色谱柱、程序升温、载气为氮气、检测器为FID，外标法计算含量。[结果]在选定的色谱条件下，测得各有机溶剂的线性良好（r〉0．99）；平均回收率96．35％～103．67％，RSD1．37％～3．04％，最低检出限0．27～0．38ng，3批样品中8种有机溶剂残留量均符合要求。[结论]经方法学试验验证，该方法灵敏、准确、可靠，适用于本品有机溶剂残留量的测定。     

高尿酸血症大鼠肾小管上皮细胞OAT3表达的变化

目的 研究高尿酸血症状态下Wistar大鼠肾小管上皮细胞有机阴离子转运体3(OAT3)表达水平的变化.方法 20只雄性Wistar大鼠随机分为对照组和高尿酸血症组,高尿酸血症组饲以高酵母饲料并给予腺嘌呤100 mg/(kg·d)灌胃,定期监测大鼠血尿酸、肌酐、尿素氮水平,应用免疫组织化学技术检测大鼠肾脏近端小管上皮细胞OAT3的表达水平.结果 实验第14天,高尿酸血症组大鼠血尿酸水平显著高于对照组(t′=-15.00,P<0.01);高尿酸血症组OAT3的吸光度值较对照组明显降低(t=3.299,P<0.01),灰度值较对照组明显升高(t=-3.337,P<0.01).结论 高尿酸血症大鼠肾小管上皮细胞中OAT3 蛋白表达水平显著降低,OAT3可作为研发治疗高尿酸血症药物作用靶点.     

扶绥肝癌高发与饮水有机污染关系的研究

文本扶绥是我胃直癌发县之一，病区居民主要饮用严重有机物污染的塘水，塘水中的有机污染指标和某些有机组分均委高，如ＣＯＤ、ＢＯＤ、ＮＯ＾－２、腐酸和亚硝胺等，而且与发病率呈显著的正相关关系。而石灰岩层中的深井水则相反，水质好，发病率很低。废弃塘水改饮石灰岩层深井水，可截水中的有害物和致癌物进入人本，以达到增进居民健康，预防肝癌的目的。     

An exploratory analysis of risk factors for childhood malignant germ-cell tumors: report from the Childrens Cancer Group (Canada,United States)

A study of 105 patients with childhood malignant germ-cell tumors (MGCT) and 639 community controls was conducted utilizing a large epidemiologic database collected by the Childrens Cancer Group from 25 member institutions in the United States and Canada. This study was designed to explore the risk factors of this malignancy whose etiology remains poorly understood. A structured, self-administered questionnaire was used to collect exposure information, and data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term. Parental, particularly maternal, self-reported exposure to chemicals or solvents (odds ratio [OR]=4.6, 95 percent confidence interval [CI]=1.9–11.3) and OR=2.2, CI=1.1–4.7 for maternal and paternal exposure, respectively) and plastic or resin fumes (OR=12.0, CI=1.9–7.5.0 [maternal] and OR=2.5, CI=1.0–6.5 [paternal]) were associated with elevated risk of MGCT. New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI=1.5–6.6) associated with maternal urinary infections during index pregnancy. Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT.Drs Shu, Nesbit, and Robison are affiliated with the Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN, USA. Drs Buckley and Krailo are affiliated with the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA. Contributing Childrens Cancer Group Investigators, Institutions, and Grant Numbers are given in the Appendix. Address correspondence to Dr Shu, Childrens Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA. Grant support is from the US National Cancer Institute and the US Department of Health and Human Services.     

Seven years of experience with selective screening for organic acidurias

Between 1975 and 1981 nearly 9000 patients with suspected inherited metabolic diseases were investigated by a selective screening procedure including, apart from simple tests for ketone bodies, sugars and SH-containing compounds, high voltage electrophoresis of amino acids as well as gas liquid chromatography and gas liquid chromatography-mass spectrometry of the organic acids. Fifty-two cases with 18 different inborn errors of metabolism were detected. The effectivity index was calculated to be 0.6% or 1 case in about 170 requests. From the presented and from already existing data in the literature the overall incidences for all organic acidurias together and for propionic acidemia separately were appraized to be 1:10000 and 1:50000, respectively. About half of the patients diagnosed by this screening may benefit from the diagnosis.     

Hepatobiliary transport of bile acids and organic anions

Recent studies have elucidated the mechanism and regulation of hepatic transport of bile acids and organic anions. Bile acids are taken up into hepatocytes by basolateral transporters, Na⁺-dependently by Na⁺/taurocholate cotransporting polypeptide (NTCP) and Na⁺-independently by organic anion transporting polypeptide (OATP) families. Organic anions are taken up into hepatocytes by OATP families. These compounds are then transported in hepatocytes bound to cytosolic binders, and subjected to transport by ATP binding cassette (ABC) transporters at the canalicular membrane. Amidated bile acids are excreted into bile by bile salt export pump (BSEP), and organic anions and bile acid sulfates and glucuronides are excreted by multidrug resistance protein 2 (MRP2). Hepatic transporters are downregulated under cholestasis in rats and humans, except for MRP3, a basolateral ABC transporter, which is upregulated and may have a role in removing bile acids and organic anions from hepatocytes to the blood under cholestatic conditions. Nuclear receptors, which bind bile acids, have been shown to regulate the expression of hepatic transporters. Farnesoid X receptor (FXR), which downregulates CYP7A1, the rate-limiting enzyme of bile acid biosynthesis, upregulates BSEP and downregulates NTCP. MRP2 is upregulated by both FXR and pregnane X receptor (PXR), which upregulates CYP3A. Received: February 19, 2002 / Accepted: March 8, 2002 Offprint requests to: H. Takikawa     

Interaction of human organic anion transporters with various cephalosporin antibiotics

Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs). The purpose of this study was to elucidate the interaction of human-OATs with various cephalosporin antibiotics, using proximal tubule cells stably expressing human-OAT1, human-OAT3 and human-OAT4. Human-OAT1 and human-OAT3 are localized to the basolateral side of the proximal tubule, whereas human-OAT4 is localized to the apical side. The cephalosporin antibiotics tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. All of these cephalosporin antibiotics significantly inhibited organic anion uptake mediated by human-OAT1, human-OAT3 and human-OAT4. Kinetic analysis revealed that these inhibitions were competitive. The inhibition constant (K(i)) values of cefoperazone, cefazolin, ceftriaxone and cephaloridine for human-OAT1 were much lower than those for human-OAT3 and human-OAT4, whereas the K(i) values of cephalothin and cefotaxime for human-OAT3 were much lower than those for human-OAT1 and human-OAT4. Human-OAT4 mediated the bidirectional transport of estrone sulfate, an optimal substrate for human-OAT4. These results suggest that human-OAT1, human-OAT3 and human-OAT4 interact with various cephalosporin antibiotics, and that human-OAT1 and human-OAT3 play a distinct role in the basolateral uptake of cephalosporin antibiotics. Since the K(i) value of cephaloridine for human-OAT4-mediated organic uptake was much higher than that for human-OAT1, the results indicate the possibility that human-OAT4 limits the efflux of cephaloridine, leading to the accumulation of cephaloridine and the induction of nephrotoxicity.     

Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells,an in vitro model of the blood-brain barrier

The transport of L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid), a compound known to be transported by the organic cation transporter/carnitine transporter OCTN2, was studied in immortalized rat brain endothelial cells (RBE4). The cells were found to take up L-carnitine by a sodium-dependent process. This uptake process was saturable with an apparent Michaelis-Menten constant for L-carnitine of 54+/-10 microM and a maximal velocity of 215+/-35 pmol/mg protein/h. Besides L-carnitine, the cells also took up acetyl-L-carnitine and propionyl-L-carnitine in a sodium-dependent manner and TEA in a sodium-independent manner. RT-PCR with primers specific for the rat OCTN2 transporter revealed the existence of OCTN2 mRNA in RBE4 cells. Screening of a cDNA library from RBE4 cells with rat OCTN2 cDNA as a probe identified a positive clone which showed, when expressed in HeLa cells, the functional characteristics of OCTN2. The HeLa cells expressing the RBE4 OCTN2 cDNA showed a sixfold increase in L-carnitine uptake and a fourfold increase in TEA uptake in a sodium-containing buffer. Typical inhibitors for organic cation transporters (e.g. MPP(+) or TEA) showed an inhibitory effect on the transport of L-carnitine and TEA into the transfected cells. Similarly, unlabeled L-carnitine inhibited the transport of [3H]-L-carnitine and [14C]TEA in transfected HeLa cells. It is concluded that RBE4 cells, a widely used in vitro model of the blood-brain barrier (BBB), express the organic cation/carnitine transporter OCTN2.     

有机磷中毒洗胃后置管引流的研究

目的:观察有机磷农药中毒洗胃后置胃管负压引流的临床效果。方法:60例口服有机磷农药中毒患者随机分成引流组与对照组各30例。对照组常规洗胃,应用特殊解毒药及对症处理。引流组在常规洗胃后经鼻插入胃管负压引流2~4d,其它治疗方法同对照组。结果:引流组达到阿托品化的时间早,阿托品的用量少,胆碱酯酶活力恢复正常的时间提前,住院时间短,反跳、呼吸肌麻痹、中间型综合征、重要器官损害等并发症少,治愈率高,各项统计结果均优于对照组(P<0.05)。结论:有机磷农药中毒患者常规洗胃后置胃管负压引流抢救成功率高,值得推广。     

均匀设计优化二元溶剂分散法制备莪术油纳米粒的研究

目的优化二元溶剂分散法制备莪术油纳米粒（ZTO-NP）的制备工艺技术条件，探讨其可行性。方法以形态、粒径、包封率为指标，采用均匀设计，考察分散剂浓度、载体材料用量、有机相体积和搅拌时间等影响因素，筛选出比较理想的制备工艺。结果最佳工作条件为：聚氧乙烯-聚氧丙烯共聚物（普朗尼克F68）0．1％，乳酸-乙醇酸共聚物（PLGA）0．01g，搅拌时间4h，丙酮体积1mL。所制得的纳米粒为圆整的类球形粒子，表面光滑，平均粒径为233．1nm（PDI值为0．047），zeta电位为-22．1mV，包封率为70．01％，载药量为57．55％。结论二元溶剂分散法可用于薮术油类液体药物纳米粒的制备。