肾脏损伤时有机阴离子转运子表达变化及其意义

有机阴离子转运子(OAT)在机体清除各种内、外源性有机阴离子的过程中发挥极其重要的作用.在肾脏,OAT参与排泄许多外源性有机阴离子,如药物、环境中的化学物质、生物毒素以及许多内源性有机阴离子包括多种尿毒症毒素等.近年研究发现,各种肾脏疾病条件下OAT表达发生变化,并由此而产生相应病理生理效应.本文讨论了OAT在近端肾小管上皮细胞的生物学特征、肾脏病变状态下的表达变化及其病理生理学意义.     

The Effect of a High Salt Diet and Gender on Blood Pressure,Urinary Protein Excretion and Renal Pathology in Shr Rats

A high salt diet produced increases in SBP, urinary protein excretion (UPE) and renal vascular lesions (RVL) across groups of male and female SHR rats which were allowed to develop moderate or excessive increases in SBP. A highly significant linear relationship between SBP and log-transformed UPE was found when the data from all groups were analyzed together. Males developed high blood-pressure more rapidly, and exhibited more severe RVL and greater UPE than females. Two results prevent the conclusion that the elevated UPE was simply due to the adverse effects of high BP on the kidney. First, the relationship between SBP and UPE across groups could not be demonstrated when regression analyses were performed within individual dietary sub-groups. Secondly, gender differences in UPE were highly significant by analysis of covariance adjusting for individual differences in SBP. The increases in SBP and UPE may be independent consequences of ingestion of a high salt diet.     

Biological exposure limits estimated from relations between occupational styrene exposure during a workweek and excretion of mandelic and phenylglyoxylic acids in urine

Summary Styrene exposure of 18 workers in fiber-glass reinforced plastic industries was measured for 30-min periods throughout each workday for a week. The styrene uptake was estimated using pulmonary ventilation measurements. All urine voidings were collected separately and the styrene metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA) were determined. The relationship between both exposure and uptake versus excretion of these metabolites was studied. Styrene metabolite concentrations and excretion rates (with 95% tolerance limits) were calculated to correspond to a constant 8-h exposure at the Swedish exposure limit level (25 ppm) or an uptake of an exposure limit related styrene dose (6.3 mmol). The tightest tolerance limits were obtained for excretion rate of MA + PGA per 24 h. The calculated biological exposure limit was 3.4 (± 0.7) mmol MA + PGA/24 h for a dose of 6.3 mmol styrene.     

羟基红花黄色素A脂质载体及水溶液在大鼠体内的代谢、排泄、生物利用度研究

目的：研究不同的羟基红花黄色素A（HSYA）剂型对HSYA代谢、排泄、生物利用度的影响。方法：大鼠灌胃给予HSYA脂质制剂和水溶液,采用HPLC及LC-MS检测血浆、胆汁、粪便、尿液样品。结果：大鼠灌胃给予HSYA脂质制剂和水溶液后,在大鼠胆汁中均发现HSYA及其II相代谢产物;HSYA原药的质荷比为611,而两个II相代谢产物的质荷比分别为918和691,结合酶降解实验表明这两个代谢产物分别为HSYA的谷胱甘肽结合物和硫酸酯结合物。但是同水溶液相比,HSYA脂质制剂显著性降低了HSYA及其II相代谢产物从胆汁的排泄量。大鼠灌胃给予HSYA脂质制剂后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为（0.05±0.03）%、（8.80±2.30）%、（37.99±17.50）%,其cmax、AUC0-8h分别为2.79μg·mL^-1、402.51μg·min·mL^-1;而大鼠灌胃给予HSYA水溶液后,HSYA原药从胆汁、粪便、尿液中24h的累积排泄量分别为（0.32±0.22）%、（44.66±8.00）%、（5.58±1.30）%,其cmax、AUC0-8h分别为0.08μg·mL^-1、10.73μg·min·mL^-1。结论：实验结果表明脂质制剂可能不会改变HSYA的代谢机制,但是显著性降低了HSYA从粪便和胆汁的排泄量,提高了其生物利用度。     

曲克芦丁及其代谢产物在大鼠体内的排泄动力学研究

目的研究曲克芦丁及其代谢产物在大鼠体内的排泄情况。方法大鼠腹腔注射曲克芦丁,收集尿液、粪便和胆汁样品,应用 HPLC方法测定曲克芦丁在大鼠尿液、粪便和胆汁样品的含量,测定曲克芦丁代谢产物在大鼠粪便中的含量。结果曲克芦丁在大鼠尿液、粪便和胆汁中的累积排泄率分别为( 16.17±10.28)%、(0.54±0.47)%和( 58.94±13.37)%。与此同时,粪便中约有( 22.69±12.48)%的代谢产物曲克芦丁苷元生成。结论曲克芦丁主要通过胆汁进行排泄,以原型和代谢产物的形式排出体外。     

Biological fate and interaction with cytochromes P450 of the nanocarrier material,d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.     

铊在大鼠体内的吸收,分布和排泄

以碳酸亚铊１０ｍｇ／ｋｇ经口给大鼠灌胃染毒，，５分钟后，可在大部份组织中测到铊，半小时，除胃以外，肝中含量最高；１小时后，除胃以外，脾和肾中含量最高，次为心和睾丸；２小时肾中浓度居首位，其高峰期在４－８小时，４小时后，骨中含量增高，仅次于胃，脑，肌肉。     

Effect of nafenopin (SU-13, 437) on liver function

Summary Administration of nafenopin (SU-13-437) to male rats for two days leads to a doubling of bile production and a 50% increase in liver weight. These two effects have been shown not to be directly interrelated. A marked decrease in biliary bile salt concentration suggests that the bile salt independent flow is stimulated. The extra bile produced is probably of canalicular origin since bile to plasma concentration ratios of erythritol are unchanged. At least three polar metabolites of nafenopin have been observed in rat bile. Obervations in rats with partial biliary fistulas indicate that the drug and its metabolites undergo extensive enterohepatic circulation. Our studies support the view that much of the enhanced bile flow is associated with the presence of nafenopin and/or its metabolites within the hepatobiliary system. However, the response is too extensive to be explained merely by osmotic choleresis. Induced structural changes in the liver may also account for some of this effect.This research was supported by U.S. Public Health Service Grant CA 14231 from the National Cancer Institute     

Pantothenic acid status of free living adolescent and young adults

The objective of the current study was to compare estimated dietary pantothenic acid of adolescent and adult humans on self-selected diets with urinary excretion and blood levels of pantothenic acid in order to gain insights on apparent pantothenic acid nutritional status of these individuals. In Study I, 11 adolescent boys and girls ranging in age from 10–16 years participated. Subjects were interviewed on past dietary practices. During the 4-day test period, subjects kept daily records of food intakes and made complete collections of urine. Fasting blood samples were drawn at the end of the study. Study II was similar to Study I except that 23 adult subjects participated. Pantothenic acid contents of urine and blood serum from both studies were determined microbiologically using Lactobacillusplantarum. Intakes of pantothenic acid were calculated from dietary diaries and from the check forms. For adolescent subjects, a strong, statistically significant correlation between pantothenic acid intake and blood serum pantothenic acid was found. However, no statistically significant positive correlation was found between pantothenic acid intake and either pantothenic acid excretion expressed in terms of mg/day or mg/g creatinine. In the latter case, the correlation was directionally negative. For adults, a strong, statistically significant positive correlation was found between pantothenic acid intake and urinary pantothenic acid excretion. However, the relationship between pantothenic acid intake and blood serum pantothenic acid was not statistically significant.