• 【在独特的人类模型中探讨植酸盐摄入,植酸盐尿液排泄和肾结石风险之间的潜在关系:没有确凿的证据支持植酸盐作为结石抑制剂。】 复制标题 收藏 收藏
    DOI:10.1053/j.jrn.2019.10.006 复制DOI
    作者列表:Fakier S,Rodgers A
    BACKGROUND & AIMS: OBJECTIVE:Dietary phytate (IP6) enjoys a reputation as an inhibitor of calcium renal stone formation, although there are very few human studies to support this notion. In South Africa, urolithiasis occurs in the white (W) but is rare in the black (B) population. We undertook this unique human model to further investigate the IP6 theory. METHODS:Healthy W and B males completed baseline food-frequency recall questionnaires. Dietary intake of IP6 was restricted for 18 days. An IP6 dietary supplement was ingested on days 15-18. Twenty-four-hour urinary phytate and other urinary components were determined. Relative supersaturations of calcium salts were calculated. The urinary metastable limit (MSL) of calcium oxalate (CaOx) and its crystallisation kinetics were determined experimentally. RESULTS:Habitual dietary intake of IP6 and its urinary excretion were significantly higher in B than in W (1650 ± 202 vs. 640 ± 134 mg/d, P = .0002 and 1.13 ± 0.12 vs. 0.75 ± 0.13 μM, P <.05, respectively). In B, urinary phytate decreased significantly after 15 days of IP6 restriction, but in W, its excretion remained constant. After supplementation, urinary IP6 increased significantly in both groups reaching levels commensurate with the baseline value in B. No significant differences occurred in B in any of the routine urinary risk factors throughout the trial. However, in W, urinary citrate excretion increased on day 18 relative to day 0. There were no significant intragroup or intergroup changes in relative supersaturation, metastable limit, or crystallization kinetics. CONCLUSIONS:Despite notable differences in the renal handling of ingested IP6, there were no changes in any of the well-established urinary risk factors for calcium renal stone formation in either of our uniquely different test groups. We conclude that, in the absence of hard evidence, claims that IP6 is a stone inhibitor remain unproven.
    背景与目标: 目的:膳食植酸(IP6)作为抑制肾结石形成的钙素而享有盛誉,尽管很少有人类研究支持这种观点。在南非,尿石症发生在白人(W)人群中,但在黑人(B)人群中很少见。我们采用了这种独特的人类模型来进一步研究IP6理论。
    方法:健康的W和B男性完成了基线食物频率召回问卷。 IP6的饮食限制为18天。在第15-18天摄入IP6膳食补充剂。测定了二十四小时的尿肌醇六磷酸和其他尿液成分。计算了钙盐的相对过饱和度。草酸钙(CaOx)的尿亚稳态极限(MSL)及其结晶动力学是通过实验确定的。
    结果:B的日常饮食摄入IP6及其尿排泄量显着高于W(1650±202 vs. 640±134 mg / d,P = .0002和1.13±0.12 vs. 0.75±0.13μM,P <。分别为05)。在B中,IP6限制15天后,尿肌醇六磷酸显着减少,但在W中,其排泄量保持恒定。补充后,两组的尿中IP6均显着升高,达到与B的基线值相当的水平。在整个试验中,B中的任何常规尿液危险因素均无显着差异。但是,在W中,相对于第0天,第18天尿液中柠檬酸盐的排泄量增加。相对过饱和度,亚稳态极限或结晶动力学方面,组内或组间无明显变化。
    结论:尽管摄入的IP6在肾脏处理方面存在显着差异,但在我们两个不同的测试组中,任何公认的尿钙钙结石形成的危险因素均无变化。我们得出的结论是,在没有确凿证据的情况下,声称IP6是结石抑制剂的说法仍未得到证实。
  • 【17α-炔雌醇对胆汁酸胆汁排泄的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0304-4165(75)90213-5 复制DOI
    作者列表:Watanabe H
    BACKGROUND & AIMS: :The effect of 17alpha-ethinylestradiol on biliary bile acids has been investigated. The ratio of cholate to chenodeoxycholate was diminished by the estrogen in cholestyramine-treated rats. With low doses, this effect was due to increased excretion of chenodeoxycholate. With the highest dose, the decreased ratio was due to a reduction in the levels of cholic acid. In the intermediate dosage range, both factors contributed to the decreased ratio. Prolonged treatment with 500 mug daily of 17alpha-ethinylestradiol produced a reduction in the excretory rate of both bile acids in animals treated or not treated with cholestyramine.
    背景与目标: :已经研究了17α-炔雌醇对胆汁胆汁酸的作用。在胆甾醇胺处理的大鼠中,雌激素降低了胆酸盐与鹅去氧胆酸盐的比例。在低剂量下,这种作用是由于鹅去氧胆酸盐的排泄增加所致。在最高剂量下,比率降低是由于胆酸水平降低。在中等剂量范围内,这两个因素均导致比率降低。每天用500马克杯的17α-乙炔雌二醇进行长时间治疗,会降低或降低胆甾胺的动物两种胆汁酸的排泄率。
  • 【胰岛素的肾脏代谢:突变胰岛素综合征(和歌山胰岛素)患者的尿中胰岛素排泄。】 复制标题 收藏 收藏
    DOI:10.1053/meta.2001.24885 复制DOI
    作者列表:Hanabusa T,Oki C,Nakano Y,Okai K,Nishi M,Sasaki H,Sanke T,Nanjo K
    BACKGROUND & AIMS: :Many studies have shown that the kidney plays an important role in the metabolism of many proteins and small peptides. To understand insulin handling in the kidney, we examined urinary insulin excretion under several conditions in patients with mutant insulin syndrome (MIS; insulin Wakayama). Urinary excretion of insulin was studied using high-performance liquid chromatography analysis in patients with MIS. In these patients, most of the insulin extracted from a 24-hour urine collection and from urine collected after stimulation of insulin secretion by glucose or glucagon was normal insulin, whereas 90% of serum insulin is structurally abnormal (Leu-A3 insulin). On the other hand, arginine, which is known as an inhibitor of renal tubular reabsorption, increased urinary excretion of Leu-A3 insulin. The ratio of Leu-A3 and normal insulin in urine after arginine was similar to that in serum. A large amount of Leu-A3 insulin is excreted in urine when reabsorption of insulin at renal tubules is inhibited by arginine. These data indicate that normal and Leu-A3 insulin are filtered through the glomerulus with relatively little restriction. Using the fact that basal urine has a high concentration of normal insulin and an extremely low concentration of Leu-A3 insulin, which has less receptor-binding affinity, we speculated some possibilities. One possibility is that both forms of insulin are reabsorbed by the tubular cells, but with different efficiencies. Leu-A3 insulin absorption in more complete, and this suggests differences in the uptake pathways that may account for the differences in response to arginine infusions. Another possibility is that only normal insulin is secreted from tubules into urine which is mediated by receptors. Our results provide new insight into renal metabolism of insulin and showed that MIS is a useful model for studying it.
    背景与目标: :许多研究表明,肾脏在许多蛋白质和小肽的代谢中起着重要作用。为了了解肾脏中胰岛素的处理方法,我们在突变胰岛素综合征(MIS;和歌山胰岛素)的患者中检查了几种情况下的尿中胰岛素排泄。使用高效液相色谱分析对MIS患者的尿液中的胰岛素进行了研究。在这些患者中,从24小时尿液收集以及葡萄糖或胰高血糖素刺激胰岛素分泌后收集的尿液中提取的大多数胰岛素是正常胰岛素,而90%的血清胰岛素在结构上是异常的(Leu-A3胰岛素)。另一方面,作为肾小管重吸收抑制剂的精氨酸可增加Leu-A3胰岛素的尿排泄。精氨酸后尿液中Leu-A3和正常胰岛素的比例与血清中的相似。当精氨酸抑制肾小管对胰岛素的重吸收时,尿中会分泌大量Leu-A3胰岛素。这些数据表明正常和Leu-A3胰岛素通过肾小球滤过的情况相对较少。利用基础尿液中高浓度的正常胰岛素和极低浓度的Leu-A3胰岛素(具有较少的受体结合亲和力)这一事实,我们推测了一些可能性。一种可能性是两种形式的胰岛素都被肾小管细胞吸收,但效率不同。 Leu-A3胰岛素吸收更完全,这表明摄取途径的差异可能解释了精氨酸输注反应的差异。另一种可能性是仅正常胰岛素从肾小管分泌到尿液中,这是由受体介导的。我们的结果为胰岛素的肾脏代谢提供了新的见识,并表明MIS是研究胰岛素的有用模型。
  • 【高度暴露于二硝基甲苯的矿工中尿蛋白的病理排泄模式。】 复制标题 收藏 收藏
    DOI:10.1097/00043764-200107000-00007 复制DOI
    作者列表:Brüning T,Thier R,Mann H,Melzer H,Bröde P,Dallner G,Bolt HM
    BACKGROUND & AIMS: :A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as biomarkers for damage of the proximal tubule and glutathione-S-transferase pi (GST pi) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1-microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.
    背景与目标: :对前德意志民主共和国铜矿开采行业中高度暴露于二硝基甲苯(DNT)的161名地下矿工进行了重新研究,以寻找亚临床肾脏损害的迹象。该研究包括通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)排泄的尿蛋白的筛查,以及定量特定尿蛋白α1-微球蛋白和谷胱甘肽-S-转移酶α(GSTα)的生物标志物,以检测尿液的损害。远端小管和谷胱甘肽-S-转移酶pi(GST pi)用于远端小管的损伤。根据与DNT专业接触的类型和持续时间,将暴露量半定量分类(低,中,高和非常高)。观察到病理蛋白排泄模式与DNT暴露的半定量排名具有直接的剂量依赖性。先前报道的大多数泌尿道癌症病例,尤其是那些暴露程度较高的人群,都局限于病理性尿蛋白排泄模式。 DNT的损害直接指向了管状系统。在许多情况下,注意到出现了Tamm-Horsfall蛋白(105 kD蛋白标记)的出现。有关生物标志物α1-微球蛋白,GSTα和GST pi的数据始终表明肾小管损伤呈剂量依赖性增加,这证实了SDS-PAGE筛选的结果,并明确表明在给定的暴露条件下DNT的肾毒性作用。在暴露于DNT的工人中观察到的癌症患者群体中,仅在例外情况下才发现正常的生物标志物排泄物。
  • 【经皮肝穿刺胆道引流患者氟莫昔夫的胆汁排泄量的日变化。】 复制标题 收藏 收藏
    DOI:10.1046/j.0306-5251.2001.01418.x 复制DOI
    作者列表:Hishikawa S,Kobayashi E,Sugimoto K,Miyata M,Fujimura A
    BACKGROUND & AIMS: AIMS:To examine diurnal variation in biliary excretion of flomoxef. METHODS:Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction. RESULTS:Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times. CONCLUSIONS:These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.
    背景与目标: 目的:研究氟莫昔夫的胆汁排泄量的日变化。
    方法:对8例经皮经肝穿刺胆道造影术的患者静脉注射氟洛昔芬(1 g),并在09.00 h和21.00 h采用交叉设计,冲洗时间为36 h,进行引流。每次给药后6小时收集排出的胆汁。这些患者仍患有轻度至中度肝功能障碍。
    结果:给药后6 h的胆汁流量和胆汁酸排泄在09.00 h和21.00 h处理之间无显着差异。在21.00 h剂量后,胆汁氟莫昔芬的最大浓度明显更高,其总排泄量6 h趋于更大[最大浓度(microg ml(-1)):34.2 /-29.9(09.00 h剂量)vs 43.5 /- 28.3(21.00小时剂量)(差异的95%置信区间:2.6约为15.9,P = 0.013);总排泄量(mg 6 h(-1)):1.4 /-1.3(09.00 h剂量)vs 1.6 /-1.2(21.00 h剂量)(差异的95%置信区间:-26.8,313.7,P = 0.087)]。在两个治疗时间之间,氟莫昔夫保持高于最低抑菌浓度的时间段无显着差异。
    结论:这些结果表明氟莫昔夫的胆汁排泄表现为昼夜变化。但是,由于差异相对较小,可以在一天中的任何时间使用氟莫昔芬,而无需进行任何剂量调整。
  • 【透析方式和其他处方因素对腹膜透析中腹膜蛋白排泄的影响。】 复制标题 收藏 收藏
    DOI:10.3265/Nefrologia.pre2012.Jul.11465 复制DOI
    作者列表:Rodríguez-Carmona A,Pérez-Fontán M,Pértega-Díaz S,López-Calviño B,López-Muñiz A,García-Falcón T
    BACKGROUND & AIMS: BACKGROUND:There is a deficit of information regarding the factors that influence peritoneal protein excretion (PPE) during PD therapy. In particular, the effects of the modality of PD and other conditions of the dialysis prescription remain unclear. METHOD:This prospective, observational study analysed the effects of prescription characteristics on 24-hour PPE (study variable) in a cohort of patients starting PD. Our statistical analysis included a multi-level mixed model and standardised estimations of peritoneal protein transport during serial four-hour peritoneal equilibrium tests in order to control for disparities in the characteristics of patients managed on different regimens. RESULTS:We evaluated 284 patients, 197 on CAPD and 87 on automated PD (APD), at the start of PD treatment. The two groups differed in terms of clinical characteristics and peritoneal function. Univariate, serial estimates of 24-hour PPE were marginally higher in CAPD patients, and remained essentially stable over time in both groups. Multivariate analyses identified CAPD (B=888.5mg, 95% CI: 327.5/1448.6), total dialysate volume infused per day (B=275.9 mg/Ll; 153.9/397.9) and ultrafiltration (B=0.41 mg/mL; 0.02/0.80) as independent predictors of 24-hour PPE. The model also revealed a minor trend for a lower 24-hour PPE as time on PD increases. CONCLUSIONS:The individual characteristics of peritoneal protein transport are the major determinants of 24-hour PPE. The use of CAPD as the dialysis modality is associated with higher PPE rates than the APD technique, although this difference is counterbalanced by a direct correlation between PPE and the volume of dialysate infused per day. Ultrafiltration and time on dialysis also act as minor independent predictors of PPE during PD therapy.
    背景与目标: 背景:关于PD治疗期间影响腹膜蛋白排泄(PPE)的因素的信息不足。特别是,PD方式和透析处方其他条件的影响仍不清楚。
    方法:这项前瞻性观察性研究分析了处方特征对一群开始PD的患者24小时PPE(研究变量)的影响。我们的统计分析包括一个多级混合模型和一系列连续四个小时的腹膜平衡测试过程中的腹膜蛋白运输的标准化估计,以控制采用不同方案治疗的患者的特征差异。
    结果:在PD治疗开始时,我们评估了284例患者,其中CAPD为197例,自动PD为87例。两组的临床特征和腹膜功能不同。 CAPD患者24小时PPE的单变量,系列估计略高,两组随时间的推移基本保持稳定。多变量分析确定了CAPD(B = 888.5mg,95%CI:327.5 / 1448.6),每天注入的总透析液体积(B = 275.9 mg / Ll; 153.9 / 397.9)和超滤(B = 0.41 mg / mL; 0.02 / 0.80 )作为24小时个人防护装备的独立预测指标。该模型还显示出随着PD持续时间的增加,PPE降低的趋势很小。
    结论:腹膜蛋白运输的个体特征是24小时PPE的主要决定因素。使用CAPD作为透析方式比使用APD技术具有更高的PPE率,尽管这种差异可以通过PPE和每天注入的透析液量之间的直接相关性来抵消。超滤和透析时间也是PD治疗期间PPE的次要独立预测指标。
  • 【18至39岁成年人24小时尿钠排泄预测方程的有效性。】 复制标题 收藏 收藏
    DOI:10.3945/ajcn.113.059436 复制DOI
    作者列表:Cogswell ME,Wang CY,Chen TC,Pfeiffer CM,Elliott P,Gillespie CD,Carriquiry AL,Sempos CT,Liu K,Perrine CG,Swanson CA,Caldwell KL,Loria CM
    BACKGROUND & AIMS: BACKGROUND:Collecting a 24-h urine sample is recommended for monitoring the mean population sodium intake, but implementation can be difficult. OBJECTIVE:The objective was to assess the validity of published equations by using spot urinary sodium concentrations to predict 24-h sodium excretion. DESIGN:This was a cross-sectional study, conducted from June to August 2011 in metropolitan Washington, DC, of 407 adults aged 18-39 y, 48% black, who collected each urine void in a separate container for 24 h. Four timed voids (morning, afternoon, evening, and overnight) were selected from each 24-h collection. Published equations were used to predict 24-h sodium excretion with spot urine by specimen timing and race-sex subgroups. We examined mean differences with measured 24-h sodium excretion (bias) and individual differences with the use of Bland-Altman plots. RESULTS:Across equations and specimens, mean bias in predicting 24-h sodium excretion for all participants ranged from -267 to 1300 mg (Kawasaki equation). Bias was least with International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) equations with morning (-165 mg; 95% CI: -295, 36 mg), afternoon (-90 mg; -208, 28 mg), and evening (-120 mg; -230, -11 mg) specimens. With overnight specimens, mean bias was least when the Tanaka (-23 mg; 95% CI: -141, 95 mg) or Mage (-145 mg; -314, 25 mg) equations were used but was statistically significant when using the Tanaka equations among females (216 to 243 mg) and the Mage equations among races other than black (-554 to -372 mg). Significant over- and underprediction occurred across individual sodium excretion concentrations. CONCLUSIONS:Using a single spot urine, INTERSALT equations may provide the least biased information about population mean sodium intakes among young US adults. None of the equations evaluated provided unbiased estimates of individual 24-h sodium excretion.
    背景与目标: 摘要背景:建议收集24小时尿液样本以监测平均人群钠摄入量,但实施起来可能很困难。
    目的:目的是通过使用现货尿钠浓度预测24小时钠排泄来评估已发布方程的有效性。
    设计:这是一项横断面研究,于2011年6月至8月在华盛顿特区进行,研究对象是407位18-39岁,48%黑色的成年人,他们将每个尿液收集在一个单独的容器中24小时。从每个24小时收集中选择四个定时的空隙(早晨,下午,晚上和过夜)。已发布的方程式用于通过标本计时和不同种族的亚组来预测尿液中24小时钠的排泄。我们通过测量的24小时钠排泄量(偏差)检查了平均差异,并使用Bland-Altman图检查了个体差异。
    结果:在方程和样本中,所有参与者预测24小时钠排泄的平均偏差为-267至1300 mg(川崎方程)。对于盐,其他因素和血压(INTERSALT)方程的国际合作研究,使用上午(-165 mg; 95%CI:-295,36 mg),下午(-90 mg; -208,28 mg)的国际合作研究中的偏倚最少。和晚上(-120 mg; -230,-11 mg)标本。对于过夜样本,当使用Tanaka(-23 mg; 95%CI:-141,95 mg)或Mage(-145 mg; -314,25 mg)方程式时,平均偏差最小,但在使用Tanaka时具有统计学意义女性(216至243 mg)之间的方程式和黑人以外的其他种族之间的Mage(-554至-372 mg)方程式。各个钠排泄浓度之间发生明显的高估和低估。
    结论:使用单点尿液,INTERSALT方程可提供有关美国年轻成年人中人群平均钠摄入量的偏差最小的信息。所评估的方程式均未提供单个24小时钠排泄的无偏估计。
  • 【京尼平对大鼠胆汁化合物胆汁排泄的影响。】 复制标题 收藏 收藏
    DOI:10.1111/j.1872-034X.2007.00309.x 复制DOI
    作者列表:Mikami M,Takikawa H
    BACKGROUND & AIMS: AIM:Genipin, a metabolite of geniposide, is reported to stimulate the insertion of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, and to cause choleresis by increasing the biliary excretion of glutathione, which has been considered to be a substrate of Mrp2. In the present study, the effect of colchicine on the choleretic effect of genipin was investigated. The effect of genipin on the biliary excretion of the substrates of bile salt export pump and Mrp2 was also studied. METHODS:After bile duct cannulation into rats, genipin was administered at the rate of 0.2 mumol/min/100 g, and the effect of colchicine pretreatment (0.2 mg/100 g) was examined. Metabolites of genipin in the bile were examined by a thin layer chromatography. Taurocholate (TC), sulfobromophthalein (BSP), and pravastatin were infused at the rate of 1.0, 0.2 and 0.3 mumol/min/100 g, respectively, and the effect of genipin co-administration was examined. RESULTS:Genipin increased bile flow and the biliary glutathione excretion, and those increases were not inhibited by colchicine. The biliary excretion of genipin glucuronide was less than 10% of the genipin excreted into bile. The biliary excretion of TC, BSP, and pravastatin was unchanged by genipin co-administration. CONCLUSION:It was indicated that colchicine-sensitive vesicular transport has no role on the genipin-induced insertion of Mrp2 to the canalicular membrane. Choleresis of genipin is considered to be mainly due to the increased biliary glutathione excretion by genipin, not by the biliary excretion of glucuronide. TC had no effect on the biliary glutathione excretion.
    背景与目标: 目的:Genipin是子苷的一种代谢产物,据报道可刺激胆道膜中插入多药抗性蛋白2(Mrp2),并通过增加谷胱甘肽的胆汁排泄来引起胆汁淤积,后者被认为是谷胱甘肽的底物。 Mrp2。在本研究中,研究了秋水仙碱对Genipin的胆汁收缩作用的影响。还研究了京尼平对胆盐输出泵和Mrp2的胆汁排泄的影响。
    方法:在大鼠胆管插管后,以0.2μmol/ min / 100 g的速率给予genipin,并检查秋水仙碱预处理(0.2 mg / 100 g)的效果。通过薄层色谱法检查了胆碱中京尼平的代谢产物。分别以1.0、0.2和0.3 mumol / min / 100 g的速度输注牛磺胆酸盐(TC),磺基溴酞(BSP)和普伐他汀,并检查了genipin共同给药的效果。
    结果:Genipin增加了胆汁流量和胆汁谷胱甘肽排泄,而秋水仙碱没有抑制这些增加。 genipin葡萄糖醛酸苷的胆汁排泄量少于genipin排入胆汁中的10%。 genipin并用时,TC,BSP和普伐他汀的胆汁排泄没有改变。
    结论:秋水仙碱敏感的囊泡转运对Genipin诱导的Mrp2插入小管膜没有作用。 genipin的胆汁淤积被认为主要是由于genipin所增加的胆汁谷胱甘肽排泄,而不是由于葡糖苷酸的胆汁排泄。 TC对胆汁谷胱甘肽排泄没有影响。
  • 【尿中6-巯基氧基褪黑素的质谱定量分析:年龄依赖性排泄和生物学变异。】 复制标题 收藏 收藏
    DOI:10.1515/cclm-2020-0455 复制DOI
    作者列表:van Faassen M,van der Veen A,van Ockenburg S,de Jong H,de Vries EGE,Kema IP
    BACKGROUND & AIMS: Objectives:Regulators of circadian rhythm, including melatonin, influence fundamental biological processes. Measuring the melatonin metabolite 6-sulfatoxymelatonin in urine can estimate melatonin production. 6-sulfatoxymelatonin is mainly analyzed by immunoassays, but these methods are hampered by cross-reactivity and poor reproducibility when used to analyze small molecules. Therefore, we validated a high-throughput liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify 6-sulfatoxymelatonin in urine. We evaluated age-dependent 24-h excretion of 6-sulfatoxymelatonin into urine and the biological variation of urinary excretion in healthy individuals. Methods:The online solid phase extraction method combined with LC-MS/MS was validated according to international guidelines, and used to measure the excretion of 6-sulfatoxymelatonin into urine of 240 healthy individuals. Biological variation of 6-sulfatoxymelatonin excretion was examined in 10 healthy individuals. Results:Urinary 6-sulfatoxymelatonin results were well within the validation criteria (interassay coefficient of variation: <5.4%, quantification limit: 0.2 nmol/L). There was an age-related decrease in 6-sulfatoxymelatonin excretion into 24-h urine [F(5, 234)=13.9; p<0.001]. Within-subject variation of 6-sulfatoxymelatonin was 39.2% in day urine, 15.1% in night urine, and 12.2% in 24-h urine. Between-subject variation was 39.1% in day urine, 37.9% in night urine, and 36.8% in 24-h urine. Conclusions:This MS-based method enables straightforward, reproducible, and sensitive quantification of 6-sulfatoxymelatonin in urine. Urinary 6-sulfatoxymelatonin levels decreased with age. Biological variation of 6-sulfatoxymelatonin excretion into urine was high between subjects and lower within subjects, indicating that repeated measurements of 6-sulfatoxymelatonin in 24-h urine are needed in future studies.
    背景与目标: 目的:昼夜节律的调节剂,包括褪黑激素,影响基本的生物学过程。测量尿液中的褪黑素代谢物6-硫酸根氧基褪黑素可以估计褪黑激素的产生。主要通过免疫测定法分析6-硫酸氧褪黑素,但这些方法在用于分析小分子时受到交叉反应性和重现性差的困扰。因此,我们验证了串联质谱法(LC-MS / MS)进行的高通量液相色谱法定量尿液中的6-磺酰氧基褪黑素。我们评估了健康个体中6-巯基氧基褪黑激素随年龄的24小时排泄和尿液排泄的生物学变化。
    方法:按照国际指南对在线固相萃取结合LC-MS / MS方法进行了验证,并用于测定240名健康人尿液中6-磺酰氧基褪黑素的排泄量。在10名健康个体中检查了6-硫氧嘧啶褪黑素排泄的生物学变化。
    结果:尿6-磺酰氧基褪黑激素的结果完全符合验证标准(测定间变异系数:<5.4%,定量极限:0.2nmol / L)。与24小时尿液中的6-巯基氧基褪黑激素的排泄量存在年龄相关性的降低[F(5,234)= 13.9; p <0.001]。受试者体内6-硫酸氧褪黑激素的日间变异为39.2%,夜间尿为15.1%,24小时尿为12.2%。受试者之间的差异为白天尿液为39.1%,夜间尿液为37.9%,24小时尿液为36.8%。
    结论:这种基于质谱的方法可对尿液中的6-磺酰氧基褪黑素进行直接,可重现和灵敏的定量。尿中的6-硫酸酯化褪黑激素水平随着年龄的增长而降低。受试者之间尿中6-巯基氧基褪黑激素排泄的生物学变化较高,而受试者中则较低,这表明在未来的研究中需要对24小时尿液中的6-巯基氧基褪黑激素进行重复测量。
  • 【NIDDM伴有微量白蛋白尿的尿白蛋白排泄率和24小时动态血压:单不饱和饮食的影响。】 复制标题 收藏 收藏
    DOI:10.1007/BF00402177 复制DOI
    作者列表:Nielsen S,Hermansen K,Rasmussen OW,Thomsen C,Mogensen CE
    BACKGROUND & AIMS: :Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean +/- SD: 145/78 +/- 25/10 vs 143/79 +/- 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 +/- 16/8 vs 143/79 +/- 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean x/divided by tolerance factor) 32.4 x/divided by 2.1 to 36.0 x/divided by 1.9 micrograms/min (NS) vs from 34.2 x/divided by 1.9 to 32.1 x/divided by 2.1 micrograms/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p < 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: :先前的研究表明,非胰岛素依赖型糖尿病(NIDDM)患者中,富含不饱和脂肪的饮食可能会对血压产生有益影响,而对蛋白尿的影响知之甚少。在为期3周的交叉设计中,我们比较了目前推荐的高碳水化合物饮食(50%碳水化合物,30%脂肪[10%单不饱和脂肪])与富含单不饱和脂肪(30%碳水化合物,50%脂肪)的饮食效果脂肪[30%单不饱和脂肪])对10例持续性微量白蛋白尿患者的尿白蛋白排泄率,24小时动态血压和代谢控制的影响。高碳水化合物饮食前后的24小时动态血压相似(平均/-SD:145/78 /-25/10 vs 143/79 /-19/10 mmHg(NS)和单不饱和脂肪饮食:140/78 /-16/8 vs 143/79 /-15/8 mmHg(NS)。白天或夜间血压均无变化,饮食治疗3周后尿白蛋白排泄率未受影响:从(几何平均值x /除以公差系数)32.4 x /除以2.1至36.0 x /除以1.9微克/分钟(NS),从34.2 x /除以1.9至32.1 x /除以2.1微克/分钟(空腹血糖,血清果糖胺和HbA1c以及脂质和脂蛋白的浓度在两种饮食中均保持稳定,与高碳水化合物饮食相比,单不饱和脂肪饮食中LDL / HDL胆固醇比率降低(p < 0.03)。总的来说,与高碳水化合物饮食相比,单不饱和脂肪饮食治疗3周不会影响24小时的轻便微白蛋白尿NIDDM患者的血压或白蛋白尿(摘要截断为250个字)
  • 【食用大豆后,口服抗生素可减少儿童尿中类黄酮的排泄。】 复制标题 收藏 收藏
    DOI:10.1080/01635580701586747 复制DOI
    作者列表:Halm BM,Franke AA,Ashburn LA,Hebshi SM,Wilkens LR
    BACKGROUND & AIMS: :How oral antibiotics (OABX) alter isoflavones (IFLs) in soy-consuming children is unknown. We evaluated OABX effects on urinary IFL excretion rates (UIERs) in 17 children, ages 4 to 17 yr, who provided 2 urine collections in pairs of a baseline urine and an overnight urine collection after consuming a body-weight-adjusted dose of soy nuts. The first collection was during OABX treatment for a bacterial infection and the second when healthy and off antibiotics. IFL food levels and UIERs were measured for nonmetabolites (NM), namely, daidzein, genistein (GE), and glycitein, and the metabolites (M) dihydrodaidzein, dihydrogenistein, equol, and O-desmethylangolensin (DMA), by liquid chromatography mass spectrometry. Urinary IFLs were hypothesized to change after OABX due to intestinal microflora alterations. A total of 11 children completed the study correctly. During OABX use, UIER (nmol/h/kg) for GE (6.4 +/- 1.0 vs. 10.1 +/- 1.6), all NM (27.5 +/- 4.8 vs. 36.2 +/- 4.7), and total IFLs (all NM + all M; 29.4 +/- 5.0 vs. 38.8 +/- 4.8) was reduced (P < 0.05) vs. when healthy. In contrast, a trend toward more DMA production during OABX was observed (1.2 +/- 0.6 vs. 0.4 +/- 0.3, P = 0.13). The reduction in urinary IFL appearance could be due to the changes of intestinal bacteria by OABX and/or due to processes related to the infection.
    背景与目标: :口服抗生素(OABX)如何改变食用大豆的儿童中的异黄酮(IFL)。我们评估了17岁的4至17岁儿童的OABX对尿液IFL排泄率(UIER)的影响,他们在摄入体重调整剂量的大豆坚果后,以基线尿液的形式提供了2次尿液收集,并收集了过夜尿液。 。第一个收集是在OABX处理期间用于细菌感染的,第二个收集是在健康和不使用抗生素的情况下。通过液相色谱质谱法测量了非代谢物(NM)的黄豆苷元,染料木黄酮(GE)和甘氨酸素以及代谢物(M)二氢黄豆苷元,二氢染料木黄酮,雌马酚和O-去甲基Angolensin(DMA)的IFL食物水平和UIERs 。假设OABX后由于肠道菌群改变,尿中IFL发生改变。共有11名儿童正确完成了这项研究。在使用OABX期间,GE的UIER(nmol / h / kg)(6.4 /-1.0对10.1 /-1.6),所有NM(27.5 /-4.8对36.2 /-4.7)和总IFL(所有NM均为M ;与健康时相比,降低了(29.4 /-5.0对38.8 /-4.8)(P <0.05)。相反,观察到在OABX期间产生更多DMA的趋势(1.2 /-0.6对0.4 /-0.3,P = 0.13)。尿中IFL外观的减少可能是由于OABX引起的肠道细菌变化和/或与感染有关的过程。
  • 【幼年虹鳟鱼(Oncorhynchus mykiss)饥饿期间呼吸气体的交换,含氮废物的排泄以及燃料的使用。】 复制标题 收藏 收藏
    DOI:10.1007/BF00387515 复制DOI
    作者列表:Lauff RF,Wood CM
    BACKGROUND & AIMS: Oxygen consumption, CO2 excretion, and nitrogenous waste excretion (75% ammonia-N and 25% urea-N) were measured daily in 4-g rainbow trout over a 15-day starvation period. Oxygen consumption and CO2 excretion declined while N excretion increased transiently in the mid-part of the starvation period but was unchanged from control levels at the end. Component losses (as percentage of total fuel used) of protein, lipid, and carbohydrate were 66.5, 31.1, and 2.4% respectively, as measured from changes in body weight and body composition, the latter relative to a control group at day 0. Instantaneous fuel use, as calculated from the respiratory quotients and nitrogen quotients, indicated that relative protein use rose during starvation, but contributed at most 24% of the aerobic fuel (as carbon). Lipid metabolism fell from about 68 to 37%, and was largely replaced by carbohydrate metabolism which rose from 20 to 37%. We conclude that the two approaches measure different processes, and that the instantaneous method is preferred for physiological studies. The compositional method is influenced by greater error, and measures the fuels depleted, not necessarily burned, because of possible interconversion and excretion of fuels.

    背景与目标: 在15天的饥饿期内,每天在4克虹鳟鱼中测量耗氧量,CO2排泄量和含氮废物的排泄量(75%氨氮和25%尿素氮)。在饥饿期的中段,耗氧量和CO2排泄量减少,而N排泄量则短暂增加,但与对照期末相比没有变化。从体重和身体组成的变化来衡量,蛋白质,脂质和碳水化合物的成分损失(占所用总燃料的百分比)分别为66.5、31.1和2.4%,后者相对于对照组在第0天有所变化。根据呼吸商和氮商计算的燃料消耗量表明,饥饿期间相对蛋白的消耗量增加了,但最多占有氧燃料的24%(​​以碳计)。脂质代谢从约68%下降到37%,并被碳水化合物代谢从20%上升到37%所取代。我们得出的结论是,这两种方法测量的过程不同,并且瞬时方法是生理学研究的首选。组成方法会受到较大误差的影响,并且由于燃料可能会相互转化和排泄,因此会测量耗尽的燃料(不一定燃烧)。

  • 【单核细胞趋化蛋白-1的尿排泄:肾小球病变患者活动性肾小管间质损害的生物标志物。】 复制标题 收藏 收藏
    DOI:10.1159/000107806 复制DOI
    作者列表:Dantas M,Romão EA,Costa RS,dos Reis MA,Vieira Neto OM,Ribeiro RA,Ravinal RC,Rodrigues Júnior AL,Coimbra TM
    BACKGROUND & AIMS: BACKGROUND/AIMS:The urinary concentration of the monocyte chemoattractant protein-1 (uMCP-1) chemokine is increased in several proteinuric and/or inflammatory renal diseases. In the present study, we evaluated the association between uMCP-1 and renal function, proteinuria, glomerular and interstitial macrophage infiltration, and renal fibrosis in patients with primary and secondary glomerulopathies diagnosed by renal biopsy. METHODS:Thirty-seven patients aged 32.6 +/- 7.7 years were studied. uMCP-1 was determined by ELISA. Renal macrophage expression (CD68 positive cells) is reported as number of macrophages/10(4) microm2 of the cortical tubulointerstitial (TI) area or of glomerular capillary tuft area. Cortical interstitial fibrosis was quantitated by PicroSirius red staining under polarized light by a computerized manner. RESULTS:The uMCP-1 ratio (pg/ml/urinary creatinine mg/ml) was positively correlated (Spearman coefficient) with proteinuria (r = 0.4629; p < 0.005) and number of macrophages in the cortical TI area (r = 0.64; p = 0.0005), and negatively correlated with creatinine clearance (r = -0.4877; p < 0.001). The uMCP-1 ratio was not significantly correlated with number of macrophages/glomerular capillary tuft area (r = 0.27; p = 0.19) or with percent cortical interstitial fibrosis (r = 0.08; p = 0.62). CONCLUSIONS:The uMCP-1 excretion is a biomarker of the inflammatory activity of the TI area, and does not reflect chronic interstitial damage.
    背景与目标: 背景/目的:在几种蛋白尿和/或炎性肾脏疾病中,单核细胞趋化蛋白-1(uMCP-1)趋化因子的尿液浓度增加。在本研究中,我们评估了通过肾活检诊断为原发性和继发性肾小球病变的患者中uMCP-1与肾功能,蛋白尿,肾小球和间质巨噬细胞浸润以及肾纤维化之间的关系。
    方法:对37名年龄在32.6 /-7.7岁的患者进行了研究。通过ELISA确定uMCP-1。肾巨噬细胞表达(CD68阳性细胞)报告为皮质肾小管间质(TI)区域或肾小球毛细血管簇区域的巨噬细胞数/ 10(4)microm2。皮层间质纤维化通过计算机化方式在偏光下通过PicroSirius红染色进行定量。
    结果:uMCP-1比值(pg / ml /尿肌酐mg / ml)与蛋白尿(r = 0.4629; p <0.005)和皮质TI区域巨噬细胞数量(r = 0.64; n = 0.64)呈正相关(Spearman系数)。 p = 0.0005),与肌酐清除率呈负相关(r = -0.4877; p <0.001)。 uMCP-1比率与巨噬细胞/肾小球毛细血管簇面积(r = 0.27; p = 0.19)或皮质间质纤维化百分比(r = 0.08; p = 0.62)没有显着相关性。
    结论:uMCP-1排泄是TI区炎症活动的生物标志物,不能反映慢性间质损伤。
  • 【吲达帕胺和卡托普利对糖尿病微量白蛋白尿患者血压和白蛋白排泄率的比较作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0002-9149(97)89237-5 复制DOI
    作者列表:Donnelly R,Molyneaux LM,Willey KA,Yue DK
    BACKGROUND & AIMS: Nephropathy affects about one third of diabetic patients and its onset can be predicted almost a decade in advance by detecting small quantities of albumin in the urine (microalbuminuria). Thus, detection of proteinuria or microalbuminuria in diabetic patients carries important implications and merits intervention. Strategies for delaying the relentless progression of microalbuminuria to diabetic nephropathy and ultimately end-stage renal failure are focused on improving glycemic control and reducing blood pressure. Studies with beta-blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors in hypertensive diabetics with microalbuminuria have shown a significant reduction in urinary albumin excretion rates (AER), with effective lowering of blood pressure. In a crossover study, we compared the effects of captopril versus indapamide as monotherapy for 12 weeks on AER and blood pressure in 31 diabetic patients with established microalbuminuria. The 2 drugs were equally effective in reducing AER (average reduction 30-40%) and had comparable antihypertensive effects.

    背景与目标: 肾病影响大约三分之一的糖尿病患者,并且可以通过检测尿液中的少量白蛋白(微量白蛋白尿)提前近十年预测其发病。因此,在糖尿病患者中检测蛋白尿或微量白蛋白尿具有重要意义并值得干预。延迟微量白蛋白尿持续发展至糖尿病性肾病并最终导致终末期肾衰竭的策略集中在改善血糖控制和降低血压上。在具有微量白蛋白尿的高血压糖尿病患者中,对β受体阻滞剂,钙拮抗剂,利尿剂和血管紧张素转换酶(ACE)抑制剂的研究表明,尿白蛋白排泄率(AER)明显降低,有效降低了血压。在一项交叉研究中,我们比较了卡托普利和吲达帕胺单药治疗12周对31例已建立微量白蛋白尿的糖尿病患者的AER和血压的影响。这两种药物在降低AER方面同样有效(平均降低30-40%),并且具有可比的降压作用。

  • 【海藻酸盐可增强大鼠排泄,并减少锶和铯的吸收。】 复制标题 收藏 收藏
    DOI:10.1248/bpb.b12-00899 复制DOI
    作者列表:Idota Y,Harada H,Tomono T,Morimoto K,Kobayashi S,Kakinuma C,Miyajima C,Kasahara F,Ogihara T
    BACKGROUND & AIMS: :Alginate (ALA), which is an intercellular polysaccharide associated with brown algae, is used as a food additive, a health food and a medicine. Here, we first examined the adsorption of strontium (Sr) and cesium (Cs) by ALA in vitro, and then evaluated the effects of ALA on absorption and excretion of Sr and Cs in rats, in order to evaluate its potential usefulness for minimizing radiation damage from materials released after a nuclear accident. Both Sr and Cs were concentration-dependently adsorbed by sodium alginate (ALA-Na) in vitro. In rats given diet containing either ALA-Na or calcium alginate (ALA-Ca) for two weeks, the plasma concentration of Sr gradually decreased compared with the controls (normal diet); however, in the case of Cs, the plasma concentration was decreased only in the ALA-Ca group, but not the ALA-Na group. Moreover, we examined the effect of preadministration of diet containing either ALA-Na or ALA-Ca on absorption of Sr and Cs administered orally as the chloride salts to rats. Absorption of both Sr and Cs was reduced in the ALA-Ca group, while absorption of only Sr was reduced in the ALA-Na group. Safety assessments indicated that ALA-Ca is safer than ALA-Na. These results indicate that ALA-Ca reduces absorption and promotes excretion of both Sr and Cs, while ALA-Na does so only for Sr.
    背景与目标: :藻酸盐(ALA)是与褐藻相关的细胞间多糖,被用作食品添加剂,保健食品和药物。在这里,我们首先研究了ALA在体外对锶(Sr)和铯(Cs)的吸附,然后评估了ALA对大鼠中Sr和Cs吸收和排泄的影响,以评估其对最小化辐射的潜在有用性。核事故后释放的材料造成的损坏。海藻酸钠(ALA-Na)在体外对Sr和Cs均具有浓度依赖性的吸附作用。在饮食中含有ALA-Na或海藻酸钙(ALA-Ca)的大鼠中持续2周,与对照组相比,Sr的血浆浓度逐渐降低(正常饮食);在正常饮食中,Sr的血浆浓度逐渐降低。但是,在Cs的情况下,血浆浓度仅在ALA-Ca组中降低,而在ALA-Na组中未降低。此外,我们检查了预先饲喂含有ALA-Na或ALA-Ca的饮食对口服给予大鼠氯化物的Sr和Cs的吸收的影响。在ALA-Ca组中,Sr和Cs的吸收均降低,而在ALA-Na组中,仅Sr的吸收降低。安全评估表明,ALA-Ca比ALA-Na安全。这些结果表明,ALA-Ca减少了Sr和Cs的吸收并促进了排泄,而ALA-Na仅针对Sr了。

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