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21.
目的 建立一种快速、灵敏的高效液相色谱-串联质谱(HPLC-MS/MS)方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1~8.0 μg·mL-1范围内线性良好(r2 > 0.99),最低检测限为 0.1 μg·mL-1,提取回收率为91.0%~98.7%,日内和日间准确度分别为98.8%~111.3% (精密度:CV ? 9.03%)和94.9%~102.6% (精密度:CV ? 10.68%)。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%~105.79%,94.25%~101.54%和93.24%~101.02%,均落在生物等效可接受标准80.00%~125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。 相似文献
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Susan WS Leung Hwee Teoh Adrian Quan Ricky YK Man 《Clinical and experimental pharmacology & physiology》1997,24(12):984-986
1. Current evidence suggests that lysophosphatidylcholine (LPC), a component found in oxidized low-density lipoprotein (Ox-LDL), inhibits endothelium-dependent relaxation (EDR) mediated by endothelium-derived relaxing factor (EDRF) and endothelium-derived hyperpolarizing factor (EDHF). An objective of the present study was to characterize the roles of the different elements of EDR in LPC-induced impairment within the porcine coronary artery. Concomitantly, we sought to determine whether impairment of one component of EDR would increase the sensitivity of the endothelium to LPC. 2. Bradykini. (0.1 nmol/L-0.3 μmol/L) relaxed U46619 (30 nmol/L)-precontracted porcine coronary artery rings in a concentration-dependent manner. A reduction in the bradykinin-elicited response was observed in NG-nitro-L-arginine methyl ester (L-NAME; 300 μmol/L)- and ouabain (50 μmol/L)-treated rings. Pretreatment with LPC (20 μmol/L), which on its own had no effect on normal endothelial relaxation, resulted in further inhibition of EDRF- and EDHF-induced relaxations. 3. Our results demonstrate that EDRF and EDHF are the primary mediators of EDR in the porcine coronary artery. Our data also show that while a low concentration of LPC (20 μmol/L) does not impair EDR, it can evoke vascular dysfunction following blockade of either the effects of EDRF or EDHF. Therefore, these data suggest that the partially damaged vascular endothelium could be more sensitive to threshold levels of this atherogenic phospholipid. 相似文献
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Lalit?DandonaEmail author Pratap?Sisodia SG?Prem?Kumar YK?Ramesh A?Anod?Kumar M?Chalapathi?Rao Elliot?Marseille M?Someshwar Nell?Marshall James?G?Kahn 《BMC public health》2005,5(1):98
Background
Female sex workers and their clients play a prominent role in the HIV epidemic in India. Systematic data on the outputs, cost and efficiency for HIV prevention programmes for female sex workers in India are not readily available to understand programme functioning and guide efficient use of resources. 相似文献26.
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OBJECTIVE: To investigate the cancer-promoting effect of Taiwan betel quid in hamster buccal pouch carcinogenesis.
MATERIALS AND METHODS: Two hundred and fifty-two non-inbred mate adult Syrian golden hamsters were randomly divided into six groups, each containing forty-two animalS. A treatment regimen over a 14-week experimental period was employed with six animals per group being killed at seven different periods (every 2 weeks). The right buccal pouch of each animal was painted three times a week with various combinations of 7, 12-dimethylbenz[a]anthracene (DMBA), Taiwan betel quid extract, dimethyl sulfoxide (DMSO) and mineral oil.
RESULT: Both the number and size of tumors in animals concurrently treated with DMBA and betel quid were significantly higher than those in animals treated with DMBA alone in each killing period of 8, 10, 12 and 14 weekS. No visible tumors but hyperkeratosis and acanthosis were observed in pouches treated with betel quid alone for all killing periods.
CONCLUSION: Our results indicate Taiwan betel quid may be a co-carcinogen in human oral carcinogenesis, if extrapolation can be made from the current animal study. 相似文献
MATERIALS AND METHODS: Two hundred and fifty-two non-inbred mate adult Syrian golden hamsters were randomly divided into six groups, each containing forty-two animalS. A treatment regimen over a 14-week experimental period was employed with six animals per group being killed at seven different periods (every 2 weeks). The right buccal pouch of each animal was painted three times a week with various combinations of 7, 12-dimethylbenz[a]anthracene (DMBA), Taiwan betel quid extract, dimethyl sulfoxide (DMSO) and mineral oil.
RESULT: Both the number and size of tumors in animals concurrently treated with DMBA and betel quid were significantly higher than those in animals treated with DMBA alone in each killing period of 8, 10, 12 and 14 weekS. No visible tumors but hyperkeratosis and acanthosis were observed in pouches treated with betel quid alone for all killing periods.
CONCLUSION: Our results indicate Taiwan betel quid may be a co-carcinogen in human oral carcinogenesis, if extrapolation can be made from the current animal study. 相似文献
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DNA amplification by Polymerase Chain Reaction (PCR) of a repetitive sequence specific for Mycobacterium tuberculosis, from clinical samples of extra pulmonary origin were evaluated. The 123 base pair fragment of the insertion element IS 6110 in Mycobacterium tuberculosis was amplified. A total of 50 samples were analysed by PCR and compared with culture on Lowenstein-Jensen medium (LJ) and the clinical findings of the patient. Out of the total 26 samples were positive by PCR, while only seven grew the bacilli in culture. 24 samples were negative by PCR and culture. All the seven samples that grew the bacilli on culture were positive by PCR. In remaining 19 cases that were positive by PCR but did not grow the bacilli clinical features, radiological findings and Mantoux test were strongly suggestive of M. tuberculosis. All the amplification negative cases had no positive evidence of tuberculosis but were being followed up. When correlated with culture and clinical history the sensitivity of PCR for the diagnosis of active tuberculosis was 100%. However, the specifity was only 55.8% as culture on LJ (Gold Standard) was positive in only 7 samples out of 26 samples that were positive by PCR.KEY WORDS: DNA Amplification, IS 6110, Mycobacterium tuberculosis. 相似文献