• 【人体中的生长抑素和水排泄:肾脏内的作用。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2265.1985.tb00212.x 复制DOI
    作者列表:Walker BJ,Evans PA,Forsling ML,Nelstrop GA
    BACKGROUND & AIMS: :Intravenous infusion of somatostatin in six water loaded normal human subjects produced a prompt reduction in urine flow accompanied by a rise in urine osmolality and a decrease in free water clearance. Plasma AVP levels did not change. Somatostatin would seem to exert an antidiuretic effect directly on the kidney.
    背景与目标: :在六只水负荷正常的正常受试者中静脉滴注生长抑素会导致尿液流量迅速减少,并伴随着尿渗透压的升高和游离水清除率的降低。血浆AVP水平未改变。生长抑素似乎直接对肾脏产生抗利尿作用。
  • 【吸烟引起的TSNA暴露:18年的尿NNAL排泄数据。】 复制标题 收藏 收藏
    DOI:10.1016/j.yrtph.2013.07.013 复制DOI
    作者列表:Appleton S,Olegario RM,Lipowicz PJ
    BACKGROUND & AIMS: :The objective of this work was to characterize trends over time in urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) among cigarette smokers in the US. We identified 35 studies presenting data that either reported, or could be converted to, common units of total urinary NNAL excretion as pmol/mg creatinine. The studies spanned 18years, reported urinary NNAL excretion estimates for 61 defined populations, and included a combined total of 3941 study participants. Analyses show that urinary NNAL excretion trends downward with study publication year, and the trend is statistically significant. The trend does not appear to be accounted for by a reduction in cigarettes smoked per day by study participants over the same time period. This trend is consistent with reductions in tobacco specific nitrosamine (TSNA) levels in both cigarette tobacco filler and mainstream cigarette smoke observed over the past decade and with efforts by the tobacco industry and the agricultural community to reduce levels of TSNAs in tobacco and cigarette smoke.
    背景与目标: :这项工作的目的是表征美国吸烟者中4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁醇(NNAL)随时间的排泄趋势。我们鉴定了35项研究,这些研究报告的数据报告或可以转换为总尿液NNAL排泄的常见单位为pmol / mg肌酐。这项研究历时18年,报告了61个特定人群的尿NNAL排泄量估计值,并且总共包括3941名研究参与者。分析显示,随着研究出版年份的增加,尿液NNAL排泄量呈下降趋势,并且该趋势具有统计学意义。研究参与者在同一时期内每天吸烟量的减少似乎不能解释这一趋势。这种趋势与在过去十年中观察到的卷烟烟草填充剂和主流卷烟烟雾中特定于烟草的亚硝胺(TSNA)水平的降低以及烟草业和农业界为降低烟草和卷烟烟雾中TSNA含量所做的努力是一致的。
  • 【Alpha CTX作为乳腺癌骨骼侵袭的生物标志物:免疫定位和尿排泄的负荷依赖性。】 复制标题 收藏 收藏
    DOI:10.1158/1055-9965.EPI-05-0909 复制DOI
    作者列表:Leeming DJ,Delling G,Koizumi M,Henriksen K,Karsdal MA,Li B,Qvist P,Tankó LB,Byrjalsen I
    BACKGROUND & AIMS: :We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of alphaCTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of alphaalphaCTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and alphaCTX (anti-alphaCTX antibody). The association between the extent of metastatic bone disease and urinary excretion of alphaalphaCTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for alphaCTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of alphaCTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of alphaalphaCTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in alphaalphaCTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, alphaalphaCTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection.
    背景与目标: :我们最近发现I型胶原C端肽的交联的,非异构形式的尿排泄增加(αalphaCTX)可能是乳腺癌患者骨转移的敏感指标。本研究旨在调查(a)骨转移附近的alphaCTX表位的定位,以及(b)转移数目与alphaalphaCTX尿液排泄之间的关系。对来自乳腺癌患者的相邻骨切片进行染色,以检查是否存在肿瘤细胞(抗细胞角蛋白抗体),破骨细胞(TRAcP活性)和alphaCTX(抗αCTX抗体)。在90例乳腺癌患者中评估了转移性骨疾病程度与通过ELISA测定的尿αalphaCTX排泄之间的关系(45例发生骨转移,45例未发生骨转移)。免疫组织化学显示,TRAcP阳性破骨细胞的堆积和细胞角蛋白阳性骨转移附近的alphaCTX表位的强烈染色。 alphaCTX染色区域在偏振光下显示出非结构化的骨组织。此外,患有转移性骨病的乳腺癌患者的骨转移数量与尿中的alphaalphaCTX水平之间存在显着的线性关联,与年龄和体重指数无关(r = 0.56,P <0.001)。与一个,两个或三个转移的存在相关的alphaalphaCTX的估计相对增加分别为38%,57%和81%。考虑到该测定的17%的个体差异,alphaalphaCTX可能是敏感的生化标志物,用于密切监测癌症患者,旨在促进早期转移检测。
  • 【虎杖提取物(PCE)口服后白藜芦醇在大鼠中的组织分布和排泄。】 复制标题 收藏 收藏
    DOI:10.1016/j.phymed.2008.02.009 复制DOI
    作者列表:Wang D,Xu Y,Liu W
    BACKGROUND & AIMS: PURPOSE:Polygonum cuspidatum extract as a traditional Chinese medicine is extracted from the dried rhizome and root of Polygonum cuspidatum Sieb.et Zucc. Resveratrol is one of its active components. Studies were performed in rats to define the tissue distribution and excretion of resveratrol in urine and bile, and to characterize (if possible) any metabolites of resveratrol observed in tissues after ig 20mg/kg Polygonum cuspidatum extract. METHOD:For tissue distribution studies, tissues (300 mg) were homogenized and centrifuged with methanol, and metabolites found in selected tissue extract were identified by LC/MS/MS. For urinary and biliary excretion experiments, urine and bile samples were cleaned up by using solid-phase extraction (SPE) with polyamide cartridges. All the concentrations of resveratrol in these biological samples were determined by HPLC with UV detection. RESULT:After a single oral dose of 20mg/kg PCE in rats, resveratrol was mainly distributed in stomach, duodenum, liver and kidney with detectable metabolites resveratrol monoglucuronide and resveratrol monosulfate. The majority of the resveratrol was excreted as metabolites, only 0.59% and 0.027% of the dosage were excreted in urine and bile respectively as unchanged drug within 24h.
    背景与目标: 目的:从虎杖的干燥根茎和根中提取虎杖提取物作为中药。白藜芦醇是其活性成分之一。在大鼠中进行了研究,以确定白藜芦醇在尿液和胆汁中的组织分布和排泄,并表征(如果可能)ig 20mg / kg虎杖提取物后在组织中观察到的白藜芦醇的任何代谢产物。
    方法:对于组织分布研究,将组织(300 mg)匀浆并用甲醇离心,然后通过LC / MS / MS鉴定所选组织提取物中发现的代谢物。对于尿液和胆汁排泄实验,通过使用固相萃取(SPE)和聚酰胺滤筒来清洁尿液和胆汁样品。这些生物样品中白藜芦醇的所有浓度均通过具有紫外检测的HPLC测定。
    结果:大鼠单次口服20mg / kg PCE后,白藜芦醇主要分布在胃,十二指肠,肝脏和肾脏,其代谢产物可检测到白藜芦醇单葡萄糖醛酸和白藜芦醇单硫酸盐。白藜芦醇的大部分以代谢产物的形式排泄,在24h内分别以不变的药物形式排泄了尿液和胆汁中0.59%和0.027%的剂量。
  • 【具有疫苗相关性麻痹性脊髓灰质炎的免疫缺陷患者的脊髓灰质炎病毒排泄时间延长。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Centers for Disease Control and Prevention (CDC).
    BACKGROUND & AIMS: Recently completed molecular studies of poliovirus isolates suggest that viral replication of vaccine-related polioviruses may have persisted for as long as 7 years in a patient with vaccine-associated paralytic poliomyelitis (VAPP) in whom common variable immunodeficiency syndrome (CVID) previously had been diagnosed. This report summarizes the clinical and virologic data and discusses the possible implications of these new findings for the global polio eradication initiative, which include how and when to discontinue vaccination when polio has been eradicated.

    背景与目标: 最近完成的脊髓灰质炎病毒分离株的分子研究表明,疫苗相关性脊髓灰质炎病毒的病毒复制在先前已被诊断出常见可变免疫缺陷综合症(CVID)的疫苗相关性麻痹性脊髓灰质炎(VAPP)患者中可能持续长达7年之久。 。本报告总结了临床和病毒学数据,并讨论了这些新发现对全球根除脊髓灰质炎行动的可能影响,包括根除脊髓灰质炎后如何以及何时停止接种疫苗。

  • 【钠和尿素的排泄决定了常染色体显性多囊肾病患者对V2受体拮抗剂的尿量:饮食干预的影响。】 复制标题 收藏 收藏
    DOI:10.1007/s11255-020-02384-3 复制DOI
    作者列表:Côté G,Asselin-Thompstone L,Mac-Way F,René de Cotret P,Lacroix C,Desmeules S,Agharazii M
    BACKGROUND & AIMS: PURPOSE:Tolvaptan, a vasopressin V2 receptor antagonist, slows the decline in renal function in autosomal dominant polycystic kidney disease (ADPKD). However, it increases urine output such that patient adherence could be compromised. In a cohort of patients with ADPKD on tolvaptan, we aimed to identify the contribution of sodium and urea excretion rate to daily urine output, and to evaluate the effectiveness of dietary counseling on sodium and urea excretion rates. METHODS:Retrospective analysis of 30 ADPKD patients who underwent a single session of personalized dietary counseling to reduce sodium and protein intake before initiation of tolvaptan. Creatinine and 24-h urine were obtained regularly on treatment. Generalized estimation equations were used. RESULTS:Mean age and median eGFR were 44 ± 11 years and 52 (43-74) ml/min/1.73 m2. Tolvaptan increased diuresis from 2.5 to 5.2 l/day. After adjusting for the dose of tolvaptan, an increase in sodium and urea excretion rate by 50 mmol/day was associated with an estimated additional urine volume of 0.6 l/day (95% CI 0.4-0.8 l/day; P < 0.001) and 0.25 l/day (95% CI 0.11-0.39 l/day; P < 0.001), respectively. Dietary counseling resulted in a transient reduction of sodium excretion by 19 mmol/day during the first 4 months (P = 0.016) but resulted in a more sustained reduction in urea excretion by 69 mmol/day (P = 0.008). CONCLUSION:Both sodium and urea excretion rates contribute significantly to daily urine volume in patients treated with tolvaptan, and a single session of dietary counseling was transiently effective in reducing sodium intake but achieved a more sustained reduction in protein intake. Dietary counseling should be considered in the management of ADPKD patients treated by tolvaptan.
    背景与目标: 目的:托伐普坦,一种血管加压素V2受体拮抗剂,可延缓常染色体显性遗传性多囊肾(ADPKD)肾功能的下降。但是,它会增加尿量,从而可能损害患者的依从性。在一群接受托伐普坦治疗的ADPKD患者中,我们旨在确定钠和尿素排泄率对每日尿量的贡献,并评估饮食咨询对钠和尿素排泄率的有效性。
    方法:对30例ADPKD患者进行回顾性分析,这些患者在开始使用托伐普坦之前接受了一次个性化饮食咨询以减少钠和蛋白质的摄入。治疗期间定期获取肌酐和24小时尿液。使用了广义估计方程。
    结果:平均年龄和平均eGFR为44±11岁,52(43-74)ml / min / 1.73m2。托伐普坦的利尿作用从2.5升/天增加到5.2升/天。调整托伐普坦的剂量后,钠和尿素排泄速率增加50 mmol /天与估计的额外尿量0.6升/天有关(95%CI 0.4-0.8升/天; P <0.001)和分别为0.25 l /天(95%CI 0.11-0.39 l /天; P <0.001)。饮食咨询在头四个月内使钠排泄瞬时减少了19 mmol /天(P = 0.016),但导致尿素排泄更持久地减少了69 mmol / day(P = 0.008)。
    结论:托伐普坦治疗的患者每日尿液中钠和尿素的排泄率显着提高,并且一次饮食咨询可以暂时有效地减少钠的摄入量,但可以更持久地减少蛋白质的摄入量。在托伐普坦治疗的ADPKD患者的治疗中应考虑饮食咨询。
  • 【患有高血压家族史的血压正常男性在急性生理盐水负荷期间肾脏钠排泄钝化。】 复制标题 收藏 收藏
    DOI:10.1093/ajh/4.7.570 复制DOI
    作者列表:Widgren BR,Herlitz H,Hedner T,Berglund G,Wikstrand J,Jonsson O,Andersson OK
    BACKGROUND & AIMS: :The natriuretic and intra-arterial blood pressure response to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with positive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 +/- 5 years) control group with negative family histories of hypertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hypertension and in controls matched for BMI as compared with lean controls. Sodium excretion increased in all three groups during the saline infusion, while subjects with positive family histories of hypertension disclosed a diminished natriuretic response as compared with the two control groups. Systolic blood pressure increased significantly during the saline load in subjects with positive family histories of hypertension, while in subjects with negative family histories of hypertension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium excretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive family histories of hypertension exhibit a blunted natriuretic and an exaggerated blood pressure response to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin.
    背景与目标: :在血压家族史为阳性(n = 11)和阴性(n = 21)的血压正常的年轻男性中,研究了急性盐负荷(1000 mL 0.9%NaCl)对利尿钠和动脉内血压的反应。年龄相匹配的(36 /-5岁)高血压家族史阴性的对照组分为两组,一组与体重家族史阳性的受试者(n = 10)相匹配的体重指数(BMI),以及另一个瘦肉对照组(n = 11)。与瘦弱对照组相比,高血压家族史阳性的受试者和与BMI相匹配的对照组的基线血压显着更高。在盐水注入过程中,所有三个组的钠排泄均增加,而高血压家族史呈阳性的受试者与两个对照组相比,其利尿钠反应减弱。高血压家族史呈阳性的受试者在生理盐水负荷期间收缩压显着升高,而高血压家族史呈阴性的受试者的收缩压未见明显变化。在基线时,三组之间的血浆肾素活性,血管紧张素II,血清醛固酮,血浆去甲肾上腺素,血容量和对哇巴因敏感的红细胞钠流出速率常数没有差异。在患有高血压家族史的受试者中,基线钠排泄与钠流出速率常数之间发现显着负相关。我们得出结论,与高血压家族史阴性的两个对照组相比,高血压家族史阳性的受试者表现出钝利钠盐和对急性盐分负荷的夸大血压反应。这可能是神经元和/或激素来源的。
  • 【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。

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