MBL途径补体激活与糖尿病肾病进展的相关性研究

目的观察Ⅱ型糖尿病患者血清甘露聚糖结合凝集素(MBL)和尿膜攻击复合物(MAC)的表达及与糖尿病肾病发生和进展的相关性。方法选择60例Ⅱ型糖尿病患者,按照尿白蛋白排泄率(UAER)分为正常白蛋白尿组(NA,UAER<30mg/24h,n=20),微量白蛋白尿组(MA,UAER 30～300mg/24h,n=20)和临床蛋白尿组(CA,UAER>300mg/24h,n=20)。采用双抗体夹心酶联免疫吸附实验(ELISA)检测血清MBL、尿MAC水平,并检测各组患者的血清肌酐(SCr)等指标。结果 CA组血清MBL和尿MAC明显高于MA组(P<0.05),MA组也高于NA组(P<0.05);所有患者的血清MBL与尿MAC呈高度正相关关系(P<0.05);血清MBL及尿MAC与患者的UAER及血清肌酐均存在正相关关系(P<0.05)。结论 MBL途径补体激活可能与糖尿病肾病的发生及进展密切相关。     

舒洛地特治疗糖尿病肾病Ⅲ期的疗效研究

目的研究舒洛地特对治疗2型糖尿病肾病Ⅲ期尿微量白蛋白排泌率(UAER)的疗效。方法 93例糖尿病肾病Ⅲ期患者被随机分为三组,常规组29组,舒洛地特组33例,福辛普利组31例。疗程均为8周。结果治疗8周后,舒洛地特组UAER(63.54±23.39)μg/min较正常组(110.74±37.52)μg/min相比,有显著统计学意义(P<0.001);较福辛普利组(69.56±21.47)μg/min相比,无统计学意义(P>0.05)。结论舒洛地特可有效降低2型糖尿病肾病Ⅲ期患者的尿微量蛋白排泌率。     

阿特拉津及其代谢物在大鼠尿液中的排泄动力学研究

目的:建立大鼠尿液中阿特拉津(ATR)及其代谢物脱乙基阿特拉津(DEA)、脱异丙基阿特拉津(DIA)及脱乙基脱异丙基阿特拉津(DEDIA)的分析方法,并考察其排泄特征。方法:采用乙腈沉淀蛋白、SFC柱富集等对尿液样品预处理;以高效液相色谱法测定大鼠尿液中ATR及其代谢物的含量,色谱柱为WelchromTM C18,流动相为0.5%冰醋酸甲醇液-0.5%冰醋酸水溶液梯度洗脱,检测波长为225nm;大鼠按25、50、125mg·kg-1灌服给予ATR溶液,于给药前和给药后6、12、18、24、48、72h收集尿液测定并计算其72h累积排泄量占给药量比。结果:ATR、DEA、DIA、DEDIA检测浓度线性范围分别为0.5～50、1～100、1～100、15～1500μg·mL-(1r=0.994～0.998),各样本高、中、低浓度的回收率为96.76%～99.03%,日内、日间RSD均<5%;大鼠灌服ATR后,尿样中主要以代谢物DEDIA为主(>75%),而原型、DEA和DIA排泄量均较少(<10%)。结论:所建立的分析方法准确、灵敏、重复性好,适用于尿液中ATR及其代谢物的分析;ATR在大鼠体内以代谢物DEDIA排泄占绝对优势,降解更趋完全。     

Pharmacokinetics,tissue distribution and excretion study of tetrandrine in rats

As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root of Stephania tetrandra S. Moore, tetrandrine (Tet) is widely used for the treatment of malignant tumor due to its properties of reversing the multidrug resistance and apoptosis induction. In the present study, we aimed to evaluate the pharmacokinetics, tissue distribution and excretion of Tet in rats. Drug concentration in plasma and tissues was measured by high performance liquid chromatography (HPLC), and the experimental data were analyzed using pharmacokinetic software DAS 2.0. The results showed that the plasma protein binding rate of Tet was 68.7%, indicating a higher protein binding drug. Tissue distribution was found in a descending order as follows: lung>heart>liver>kidney>spleen. Renal excretion was a major route of excretion, and the urine, bile and fecal excretion accounted for 25.73% of the administered dose. AUC_0–∞ of Tet in the liver was 20 times greater than that in plasma, indicating that Tet had a higher affinity for the liver. Moreover, CL in the liver was the lowest among all tissues, indicating that Tet with slow elimination might result in the accumulation. Therefore, we need to adjust the dose for patients who have dysfunction in liver and kidney. In addition, therapeutic drug monitoring in long-term clinical treatment, if necessary, should be carried out.     

Addition of castor oil as a booster in colon capsule regimens significantly improves completion rates and polyp detection

BACKGROUND Incomplete excretion rates are problematic for colon capsule endoscopy(CCE). Widely available booster regimens are suboptimal. Recently published data on one day preparation CCE protocol using castor oil appeared effective.AIM To assess the impact of adding castor oil to a standard split-dose(2-d) preparation in an unselected Western patient cohort.METHODS All patients aged 18 or more referred to our unit for a CCE over a 5-mo period were prospectively recruited. Controls were retrospectively identified from our CCE database. All patients received split bowel preparation with Moviprep~? [polyethylene glycol(PEG)-3350, sodium sulphate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution; Norgine B. V, United States], a PEG-based solution used predominantly in our colonoscopy practice. Control booster regimen included Moviprep~? with 750 m L of water(booster 1) on reaching the small bowel. A further dose of Moviprep~? with 250 m L of water was given 3 h later and a bisacodyl suppository(Dulcolax~?) 10 mg after 8 h, if the capsule was not excreted. In addition to our standard booster regimen, cases received an additional 15 m L of castor oil given at the time of booster 1. A nested case control design with 2:1 ratio(control:case) was employed. Basic demographics, completion rates, image quality, colonic transit time, diagnostic yield and polyp detection were compared between groups, using a student t or chi-square tests as appropriate.RESULTS One hundred and eighty-six CCEs [mean age 60 years(18-97), 56% females, n = 104], including 62 cases have been analysed. Indication breakdown included 96 polyp surveillance(51.6%), 42 lower gastrointestinal symptoms(22.6%), 28 due to incomplete colonoscopy(15%), 18 anaemia(9.7%) and 2 inflammatory bowel disease surveillance(1.1%). Overall, CCE completion was 77%(144/186), image quality was adequate/diagnostic in 91%(170/186), mean colonic transit time was 3.5 h(0.25-13), and the polyp detection rate was 57%(106/186). Completion rates were significantly higher with castor oil, 87% cases(54/62) vs 73% controls(90/124), P = 0.01. The number needed to treat with castor oil to result in an additional complete CCE study was 7, absolute risk reduction = 14.52%, 95% confidence interval(CI): 3.06-25.97. This effect of castor oil on excretion rates was more significant in the over 60 s, P 0.03, and in females, P 0.025. Similarly, polyp detection rates were higher in cases 82%(51/62) vs controls 44%(55/124), P = 0.0001, odds ratio 5.8, 95%CI: 2.77-12.21. Colonic transit times were similar, 3.2 h and 3.8 h, respectively. Image quality was similar, reported as adequate/diagnostic in 90%(56/62) vs 92%(114/124).CONCLUSION In our capsule endoscopy centre, castor oil addition as a CCE booster significantly improved completion rates and polyp detection in an unselected Western cohort.     

Kinetics of styrene urinary metabolites: a study in a low-level occupational exposure setting in Singapore

Summary Biological monitoring of styrene exposure commonly involves measurement of styrene metabolites, mainly mandelic acid (MA) and phenylglyoxylic acid (PGA), in the urine of exposed subjects. Previous studies on the kinetics of styrene metabolites in urine were mostly conducted in a controlled environment on subjects exposed to high concentrations of styrene. In this study, we examined subjects exposed to low levels of styrene in a fiber-reinforced plastics (FRP) plant to see whether the excretion kinetics of styrene metabolites are similar under field conditions. Eight healthy Chinese male volunteers were exposed to styrene for 4 h with a mean environmental concentration of 11 ppm. Urine samples were collected continuously for 20 h after termination of the exposure and concentrations of urinary MA and PCA were determined. The results showed that MA was rapidly excreted in urine after the exposure, with a half-life of 2.1 h or 1.9 h when corrected with urine creatinine. The excretion of PGA followed that of MA and the half-life was 8.1 h or 5.1 h after correction with creatinine. The half-lives are considerably shorter compared to those in previous reports, suggesting that environmental factors, exposure conditions, or ethnic differences may affect the excretion kinetics of styrene metabolites. The fast excretion of styrene metabolites is also consistent with the observation that urine MA and PGA levels correlated better with the half-day time-weighted average (TWA) concentration of environmental styrene than with the whole-day TWA concentration. Our findings thus underscore the need for information on excretion kinetics in order to develop an appropriate biological monitoring scheme for specific exposure settings and subjects.     

Reassessment of Criteria for the Selection of Perfluorochemicals for Second-Generation Blood Substitutes: Analysis of Structure/Property Relationships

The criteria for the selection of perfluorochemicals destined to serve as oxygen carriers in second-generation blood substitutes are critically discussed in light of the presently available body of data. The need for pure, well-defined, reproducible, industrially feasible perfluorochemicals, in order to attain the degree of reliability desirable for their use in medicine, is stressed. Particular attention is given to the inverse excretion rate versus emulsion stability relationship and to its sharp dependence on molecular weight. The range of acceptable molecular weights is established as 460-520. Oxygen-dissolving capacity, rheologic characteristics, and intravascular persistence are also discussed. The need for standard methodology and experimental protocols is reaffirmed. Perspectives are evaluated, in particular, with the aim of easing certain of the present limitations.     

Metabolism of tritiated angiotensin II in anaesthetized rats

Summary The metabolic fate of small doses of a newly prepared, highly radioactive angiotensin II has been studied in anaesthetized rats. Doses of 25 or 100 ng were administered in a single injection and the following parameters were studied: 1. The variation with time of the concentration of total radioactivity in plasma and urine. 2. The nature of this radioactivity, classifying it as protein-bound, free immunoreactive (angiotensin, 2–8 heptapeptide or 3–8 hexapeptide) or free nonimmunoreactive (smaller tyrosine-containing fragments). 3. The distribution of radioactivity in various tissues, including a detailed study of different regions of the brain.The main results are that: 1. angiotensin II and/or metabolites are rapidly removed from the circulation, mainly by tissue uptake and to a lesser extent by urinary excretion (which reached 12% of the dose injected after 1 hour); 2. remaining angiotensin II circulating in the blood is rapidly degraded, presumably by tissue peptidases; 3. radioactivity concentrates in the adrenal glands, kidney, liver and pituitary and does not readily pass the blood-brain barrier; 4. there is a possible binding of angiotensin and metabolites on to plasma proteins.     

Study of the Excretion Mechanism of a Perfluorochemical Emulsion

The excretion mechanism of perfluorochemicals (PFC) via the lung has been studied by physicochemical and histochemical methods. Monocytes that had phagocytized PFC particles were found in the lung capillaries, and alveolar macrophages that had phagocytized PFC particles were found in the alveoli. Vacuolated macrophages were observed microscopically in the alveolar space of rats injected with PFC emulsions. The PFC content in alveolar macrophages reached a maximum level of 1.44 mg/l x 10(8) cells 72 h after injection. It was confirmed by means of a wavelength dispersive x-ray analyzer that fluorine atoms were present in the vacuolated alveolar macrophages. The peroxidase activity of the PFC-phagocytizing macrophages suggest that monocytes phagocytize PFC particles in the circulation and migrate to the alveolar space. This study shows that the monocyte/macrophage system is related to one mechanism for excretion of PFC after intravenous injection of PFC emulsions.     

Simultaneous determination by gas chromatography of phenol, 2-chlorophenol, 2,4- and 2,6-dichlorophenol, 2,4,6 trichlorophenol,and 2, 3, 5, 6-tetrachlorophenol in the Urine of Industrially Exposed Workers

Summary An analytical method is described which has suitable sensitivity and specificity for analyzing urine samples from workers who are exposed to chlorinated phenols. The phenolic compounds are separated by steam distillation and then extracted into isopropyl ether. Without derivatizing the material, it is analyzed by gas chromatography on a 180 cm x 2 mm i.d. glass column containing 60/80 mesh Tenax GC (ENKA NV, The Netherlands) using flame ionization detectors. The detection limits in urine range from 0.1 mg/l urine for phenol to 1 mg/l for the di- and trichlorophenols. The coefficient of variation for each component is less than 4%.The naturally occurring metabolites cresol and 4-heptanone are also isolated and can be quantified by this method.