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Sample records for renal clearance concepts

  1. Renal Clearance of Nanoparticles

    PubMed Central

    Choi, Hak Soo; Liu, Wenhao; Misra, Preeti; Tanaka, Eiichi; Zimmer, John P.; Ipe, Binil Itty; Bawendi, Moungi G.; Frangioni, John V.

    2008-01-01

    SUMMARY The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using quantum dots (QDs) as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter (HD) by over 15 nm and prevented renal excretion. A final HD smaller than 5.5 nm resulted in rapid and efficient urinary excretion, and elimination of QDs from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. PMID:17891134

  2. Renal Clearance of Mineral Metabolism Biomarkers.

    PubMed

    van Ballegooijen, Adriana J; Rhee, Eugene P; Elmariah, Sammy; de Boer, Ian H; Kestenbaum, Bryan

    2016-02-01

    CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD. PMID:26047790

  3. Renal Clearance and Degradation of Glutathione-Coated Copper Nanoparticles

    PubMed Central

    Yang, Shengyang; Sun, Shasha; Zhou, Chen; Hao, Guiyang; Liu, Jinbin; Ramezani, Saleh; Yu, Mengxiao; Sun, Xiankai; Zheng, Jie

    2016-01-01

    Degradation of inorganic nanoparticles (NPs) into small molecular complexes is often observed in the physiological environment; however, how this process influences renal clearance of inorganic NPs is largely unknown. By systematically comparing renal clearance of degradable luminescent glutathione coated copper NPs (GS-CuNPs) and their dissociated products, Cu(II)-glutathione disulfide (GSSG) complexes (Cu(II)-GSSG), we found that GS-CuNPs were eliminated through the urinary system surprisingly faster and accumulated in the liver much less than their smaller dissociation counterparts. With assistance of radiochemistry and positron emission tomography (PET) imaging, we found that the observed “nano size” effect in enhancing renal clearance is attributed to the fact that GS-CuNPs are more resistant to serum protein adsorption than Cu(II)-GSSG. In addition, since dissociation of GS-CuNPs follows zero-order chemical kinetics, their renal clearance and biodistribution also depend on initial injection doses and their dissociation processes. Quantitative understanding of size effect and other factors involved in renal clearance and biodistribution of degradable inorganic NPs will lay down a foundation for further development of renal-clearable inorganic NPs with minimized nanotoxicity. PMID:25674666

  4. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance

    NASA Astrophysics Data System (ADS)

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R. James; Whelan, Eoin C.; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-01

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 109 M‑1 cm‑1 and 1.5 × 108 M‑1 cm‑1 respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  5. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance.

    PubMed

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R James; Whelan, Eoin C; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-19

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 10(9) M(-1) cm(-1) and 1.5 × 10(8) M(-1) cm(-1) respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract. PMID:27378394

  6. Contribution of renal and non-renal clearance on increased total clearance of adalimumab in glomerular disease.

    PubMed

    Roberts, Brittney V; Susano, Isidro; Gipson, Debbie S; Trachtman, Howard; Joy, Melanie S

    2013-09-01

    The contribution of renal and non-renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collected from seven patients treated with adalimumab. Renal clearance (ClR ) was measured and non-renal clearance (ClNR ) was calculated as the difference between total clearance and ClR . Differences in cumulative amount in urine, ClR, and ClNR between study weeks 1 and 16 and relationships between proteinuria (protein:creatinine ratio (Up/c)), and ClR and ClNR were evaluated. Up to 13% of the adalimumab dose was lost in urine. ClNR contributed more than ClR to enhanced total clearance. There was a nonlinear relationship between Up/c and ClR (R(2) 0.7059); an increase in ClR beginning at Up/c of 12 mg/mg [slope 1.755, (C.I. -7.825 to 11.34)]. There was a linear relationship between Up/c and ClNR (R(2) 0.5039); for every one unit increase in Up/c, ClNR would increase by 3.5 mL/hr (P = 0.01). Both ClR and ClNR contribute to enhanced total clearance of adalimumab in glomerular disease secondary to FSGS. Additional research is needed to identify mechanisms for the increased ClNR pathways. PMID:23813330

  7. The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

    PubMed

    Vree, T B; Guelen, P J; Jongman-Nix, B; Walenkamp, G H

    1981-07-18

    The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin. PMID:6166414

  8. A porphyrin-PEG polymer with rapid renal clearance.

    PubMed

    Huang, Haoyuan; Hernandez, Reinier; Geng, Jumin; Sun, Haotian; Song, Wentao; Chen, Feng; Graves, Stephen A; Nickles, Robert J; Cheng, Chong; Cai, Weibo; Lovell, Jonathan F

    2016-01-01

    Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with (64)Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function. PMID:26517562

  9. Further Characterization of an Active Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

    2007-01-01

    A new test chamber and precision hydraulic actuation system were incorporated into an active clearance control (ACC) test rig at NASA Glenn Research Center. Using the improved system, a fast-acting, mechanically-actuated, ACC concept was evaluated at engine simulated temperatures and pressure differentials up to 1140 F and 120 psig, on the basis of secondary seal leakage and kinematic controllability. During testing, the ACC concept tracked a simulated flight clearance transient profile at 1140 F, 120 psig, with a maximum error of only 0.0012 in. Comparison of average dynamic leakage of the system with average static leakage did not show significant differences between the two operating conditions. Calculated effective clearance values for the rig were approximately 0.0002 in. at 120 psig, well below the industry specified effective clearance threshold of 0.001 in.

  10. Renal Function Descriptors in Neonates: Which Creatinine-Based Formula Best Describes Vancomycin Clearance?

    PubMed

    Bhongsatiern, Jiraganya; Stockmann, Chris; Yu, Tian; Constance, Jonathan E; Moorthy, Ganesh; Spigarelli, Michael G; Desai, Pankaj B; Sherwin, Catherine M T

    2016-05-01

    Growth and maturational changes have been identified as significant covariates in describing variability in clearance of renally excreted drugs such as vancomycin. Because of immaturity of clearance mechanisms, quantification of renal function in neonates is of importance. Several serum creatinine (SCr)-based renal function descriptors have been developed in adults and children, but none are selectively derived for neonates. This review summarizes development of the neonatal kidney and discusses assessment of the renal function regarding estimation of glomerular filtration rate using renal function descriptors. Furthermore, identification of the renal function descriptors that best describe the variability of vancomycin clearance was performed in a sample study of a septic neonatal cohort. Population pharmacokinetic models were developed applying a combination of age-weight, renal function descriptors, or SCr alone. In addition to age and weight, SCr or renal function descriptors significantly reduced variability of vancomycin clearance. The population pharmacokinetic models with Léger and modified Schwartz formulas were selected as the optimal final models, although the other renal function descriptors and SCr provided reasonably good fit to the data, suggesting further evaluation of the final models using external data sets and cross validation. The present study supports incorporation of renal function descriptors in the estimation of vancomycin clearance in neonates. PMID:26412385

  11. High Temperature Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

    2006-01-01

    A mechanically actuated blade tip clearance control concept was evaluated in a nonrotating test rig to quantify secondary seal leakage at elevated temperatures. These tests were conducted to further investigate the feasibility of actively controlling the clearance between the rotor blade tips and the surrounding shroud seal in the high pressure turbine (HPT) section of a turbine engine. The test environment simulates the state of the back side of the HPT shroud seal with pressure differentials as high as 120 psig and temperatures up to 1000 F. As expected, static secondary seal leakage decreased with increasing temperature. At 1000 F, the test rig's calculated effective clearance (at 120 psig test pressure) was 0.0003 in., well within the industry specified effective clearance goal.

  12. The biodistribution of gold nanoparticles designed for renal clearance

    NASA Astrophysics Data System (ADS)

    Alric, Christophe; Miladi, Imen; Kryza, David; Taleb, Jacqueline; Lux, François; Bazzi, Rana; Billotey, Claire; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2013-06-01

    Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions. However scintigraphy appears better suited for a biodistribution study owing to a great sensitivity. The successful immobilization of radioelements (99mTc, 111In) in the DTDTPA shell, instead of gadolinium ions, renders possible the follow up of Au@DTDTPA by scintigraphy which showed that Au@DTDTPA nanoparticles exhibit a safe behaviour after intravenous injection to healthy rats.Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate

  13. Highly Catalytic Nanodots with Renal Clearance for Radiation Protection.

    PubMed

    Zhang, Xiao-Dong; Zhang, Jinxuan; Wang, Junying; Yang, Jiang; Chen, Jie; Shen, Xiu; Deng, Jiao; Deng, Dehui; Long, Wei; Sun, Yuan-Ming; Liu, Changlong; Li, Meixian

    2016-04-26

    Ionizing radiation (gamma and X-ray) is widely used in industry and medicine, but it can also pose a significant hazardous effect on health and induce cancer, physical deformity, and even death, due to DNA damage and invasion of free radicals. There is therefore an urgent unmet demand in designing highly efficient radioprotectants with synergetic integration of effective renal clearance and low toxicity. In this study, we designed ultrasmall (sub-5 nm) highly catalytically active and cysteine-protected MoS2 dots as radioprotectants and investigated their application in protection against ionizing radiation. In vivo preclinical studies showed that the surviving fraction of MoS2-treated mice can appreciably increase to up to 79% when they were exposed to high-energy ionizing radiation. Furthermore, MoS2 dots can contribute in cleaning up the accumulated free radicals within the body, repairing DNA damage, and recovering all vital chemical and biochemical indicators, suggesting their unique role as free radical scavengers. MoS2 dots showed rapid and efficient urinary excretion with more than 80% injected dose eliminated from the body after 24 h due to their ultrasmall hydrodynamic size and did not cause any noticeable toxic responses up to 30 days. PMID:27018632

  14. Metabolic and renal clearance rates of purified human chorionic gonadotropin.

    PubMed Central

    Wehmann, R E; Nisula, B C

    1981-01-01

    The metabolic clearance rate (MCR) and renal clearance rate (RCR) of human chorionic gonadotropin (hCG) were measured in healthy young men and women using techniques of continuous intravenous infusion and rapid intravenous injection of unlabeled, highly purified hCG. Seven subjects received 4 d of infusion at a rate of 0.2 microgram/min, followed by an additional 4 d of infusion at 0.8 microgram/min. Mean serum levels of hCG established at these rates of infusion were 61.1 +/- 3.3 and 237 +/- 16 ng/ml, respectively (mean +/- SEM). The MCR determined at the low infusion rate was not significantly different from that determined at the higher infusion rate (1.83 +/- 0.09 vs. 1.95 +/- 0.14 ml/min per m2). The mean MCR for all subjects was 1.88 +/- 0.08 ml/min per m2. The MCR was not significantly different between men amd women (2.04 +/- 0.13 vs. 1.76 +/- 0.07 ml/min per m2). The RCR also did not vary between low and high infusion rates (0.40 +/- 0.03 vs. 0.40 +/- 0.04 ml/min per m2). The mean RCR for all subjects was 0.40 +/- 0.02 ml/min per m2. There was no difference in RCR between men and women (0.42 +/- 0.05 vs. 0.39 +/- 0.03 ml/min per m2). Six subjects were given 1.0 mg of highly purified hCG by rapid intravenous injection. Initial serum levels of hCG were 300-400 ng/ml, and the subsequent disappearance curve was multiexponential over 8-10 d. The disappearance curve of hCG in each subject was fitted to a biexponential equation. The rapid component t1/2 was 5.97 +/- 0.63 h and the slow component t1/2 was 35.6 +/- 8.0 h. We conclude that the MCR of purified hCG in man is about 2 ml/min per m2 and the RCR is 0.4 ml/min per m2; these parameters are concentration independent and do not differ significantly between healthy young men and women. PMID:7251859

  15. Applying Organ Clearance Concepts in a Clinical Setting

    PubMed Central

    2008-01-01

    Objective To teach doctor of pharmacy (PharmD) students how to apply organ clearance concepts in a clinical setting in order to optimize dose management, select the right drug product, and promote better patient-centered care practices. Design A student-focused 5-hour topic entitled "Organ Clearance Concepts: Modeling and Clinical Applications" was developed and delivered to second-year PharmD students. Active-learning techniques, such as reading assignments and thought-provoking questions, and collaborative learning techniques, such as small groups, were used. Student learning was assessed using application cards and a minute paper. Assessment Overall student responses to topic presentation were overwhelmingly positive. The teaching strategies here discussed allowed students to play an active role in their own learning process and provided the necessary connection to keep them motivated, as mentioned in the application cards and minute paper assessments. Students scored an average of 88% on the examination given at the end of the course. Conclusion By incorporating active-learning and collaborative-learning techniques in presenting material on organ clearance concept, students gained a more thorough knowledge of dose management and drug-drug interactions than if the concepts had been presented using a traditional lecture format. This knowledge will help students in solving critical patient situations in a real-world context. PMID:19214275

  16. Seal Investigations of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Taylor, Shawn; Oswald, Jay; DeCastro, Jonathan A.

    2006-01-01

    In an effort to improve upon current thermal active clearance control methods, a first generation, fast-acting mechanically actuated, active clearance control system has been designed and installed into a non-rotating test rig. In order to harvest the benefit of tighter blade tip clearances, low-leakage seals are required for the actuated carrier segments of the seal shroud to prevent excessive leakage of compressor discharge (P3) cooling air. The test rig was designed and fabricated to facilitate the evaluation of these types of seals, identify seal leakage sources, and test other active clearance control system concepts. The objective of this paper is to present both experimental and analytical investigations into the nature of the face-seal to seal-carrier interface. Finite element analyses were used to examine face seal contact pressures and edge-loading under multiple loading conditions, varied E-seal positions and two new face seal heights. The analyses indicated that moving the E-seal inward radially and reducing face seal height would lead to more uniform contact conditions between the face seal and the carriers. Lab testing confirmed that moving the balance diameter inward radially caused a decrease in overall system leakage.

  17. Evaluation of "true" creatinine clearance in rats reveals extensive renal secretion.

    PubMed

    Darling, I M; Morris, M E

    1991-10-01

    The renal clearance of endogenous creatinine is widely used to assess glomerular filtration rate (GFR) and renal function in animal investigations. The objective of the present investigation was to evaluate the extent of renal secretion of endogenous creatinine in rats and the effect of probenecid, the classical inhibitor of organic anion transport, on creatinine clearance. Ten female Lewis rats received 3H-inulin (5-muCi i.v. bolus followed by 5 muCi/hr) throughout a 6-hr period. Three hours after initiation of the inulin infusion, probenecid was administered (92.4-mg/kg i.v. bolus followed by 0.59 mg/min/kg). Steady-state serum concentrations of about 500 micrograms/ml probenecid were achieved. Renal clearance was assessed between 1 and 3 hr (control) and between 4 and 6 hr (probenecid treatment). A preliminary study in seven rats demonstrated no time-dependent change in inulin or creatinine clearance between these two study intervals. Creatinine clearances were determined by an alkaline picrate assay which incorporated Fuller's earth (Lloyd reagent) to remove interfering noncreatinine chromogens from serum samples and these values were compared with those using a nonspecific picrate assay. "True" clearance ratios of creatinine to inulin (Clcr/CLin) were greater than unity (2.33 +/- 0.83, mean +/- SD) and were significantly decreased after probenecid treatment (1.26 +/- 0.28, P less than 0.01). Probenecid had no effect on GFR, as assessed by inulin clearance. Using the nonspecific picrate assay, CLcr/CLin was 1.12 +/- 0.41, which was not significantly different from unity and which decreased to 0.53 +/- 0.12 after probenecid treatment. Therefore, creatinine undergoes extensive renal secretion in female Lewis rats. PMID:1796052

  18. Monocarboxylate Transporter Inhibition with Osmotic Diuresis Increases γ-Hydroxybutyrate Renal Elimination in Humans: A Proof-of-Concept Study

    PubMed Central

    Morris, Marilyn E.; Morse, Bridget L.; Baciewicz, Gloria J.; Tessena, Matthew M.; Acquisto, Nicole M.; Hutchinson, David J.; DiCenzo, Robert

    2012-01-01

    Background and objective The purpose of the current study was to demonstrate proof-of-concept that monocarboxylate transporter (MCT) inhibition with L-lactate combined with osmotic diuresis increases renal clearance of γ-hydroxybutyrate (GHB) in human subjects. GHB is a substrate for human and rodent MCTs, which are responsible for GHB renal reabsorption, and this therapy increases GHB renal clearance in rats. Methods Ten healthy volunteers were administered GHB orally as sodium oxybate 50 mg/kg (4.5 gm maximum dose) on two different study days. On study day 1, GHB was administered alone. On study day 2, treatment of L-lactate 0.125 mmol/kg and mannitol 200 mg/kg followed by L-lactate 0.75 mmol/kg/hr was administered intravenously 30 minutes after GHB ingestion. Blood and urine were collected for 6 hours, analyzed for GHB, and pharmacokinetic and statistical analyses performed. Results L-lactate/mannitol administration significantly increased GHB renal clearance compared to GHB alone, 439 vs. 615 mL/hr (P=0.001), and increased the percentage of GHB dose excreted in the urine, 2.2 vs. 3.3% (P=0.021). Total clearance was unchanged. Conclusions MCT inhibition with L-lactate combined with osmotic diuresis increases GHB renal elimination in humans. No effect on total clearance was observed in this study due to the negligible contribution of renal clearance to total clearance at this low GHB dose. Considering the nonlinear renal elimination of GHB, further research in overdose cases is warranted to assess the efficacy of this treatment strategy for increasing renal and total clearance at high GHB doses. PMID:24772380

  19. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

  20. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance (0.001 in. error).

  1. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    PubMed

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  2. Renal tubular receptor imaging with iodine-131-labeled peanut lectin: pharmacokinetics and renal clearance mechanism in animals

    SciTech Connect

    Boniface, G.R.; Suresh, M.R.; Willans, D.J.; Tam, Y.K.; Shysh, A.; Longenecker, B.M.; Noujaim, A.A.

    1986-05-01

    Intravenously administered peanut lectin (PNA), iodinated with /sup 131/I ((/sup 131/I)PNA), is rapidly cleared from the plasma by the kidneys in dogs (clearance (total body) = 17.52 +/- 8.74 ml/min). Dynamic gamma camera renal scintigraphy demonstrated renal accumulation and excretion phases of the (/sup 131/I)PNA renogram in dogs and rabbits (% injection dose-at-peak = 21.8 +/- 3.3% and 19.6 +/- 4.3%, time-to-peak = 44.6 +/- 4.8 min and 37.2 +/- 6.9 min, respectively). Immunoperoxidase staining of kidney sections, following i.v. administered PNA, demonstrated predominant accumulation by the proximal tubules of mice, rabbits, and dogs. The basement membrane was intensely stained at early times p.i. while intracellular and luminal PNA was evident within 1 hr. Urine analysis confirmed the presence of intact (/sup 131/I)PNA in the bladder contents, while protein degradation products, and a small percentage of the free iodide (less than 5%) were noted within 1 hr p.i. The relative proportion of free iodide increased at later times p.i. (greater than 6 hr). A receptor mediated excretion mechanism is proposed for the clearance of PNA and may be useful for the study of renal tubular function.

  3. Quantitative Structure-Pharmacokinetic Relationships for the Prediction of Renal Clearance in Humans

    PubMed Central

    Dave, Rutwij A.

    2015-01-01

    Renal clearance (CLR), a major route of elimination for many drugs and drug metabolites, represents the net result of glomerular filtration, active secretion and reabsorption, and passive reabsorption. The aim of this study was to develop quantitative structure-pharmacokinetic relationships (QSPKR) to predict CLR of drugs or drug-like compounds in humans. Human CLR data for 382 compounds were obtained from the literature. Step-wise multiple linear regression was used to construct QSPKR models for training sets and their predictive performance was evaluated using internal validation (leave-one-out method). All qualified models were validated externally using test sets. QSPKR models were also constructed for compounds in accordance with their 1) net elimination pathways (net secretion, extensive net secretion, net reabsorption, and extensive net reabsorption), 2) net elimination clearances (net secretion clearance, CLSEC; or net reabsorption clearance, CLREAB), 3) ion status, and 4) substrate/inhibitor specificity for renal transporters. We were able to predict 1) CLREAB (Q2 = 0.77) of all compounds undergoing net reabsorption; 2) CLREAB (Q2 = 0.81) of all compounds undergoing extensive net reabsorption; and 3) CLR for substrates and/or inhibitors of OAT1/3 (Q2 = 0.81), OCT2 (Q2 = 0.85), MRP2/4 (Q2 = 0.78), P-gp (Q2 = 0.71), and MATE1/2K (Q2 = 0.81). Moreover, compounds undergoing net reabsorption/extensive net reabsorption predominantly belonged to Biopharmaceutics Drug Disposition Classification System classes 1 and 2. In conclusion, constructed parsimonious QSPKR models can be used to predict CLR of compounds that 1) undergo net reabsorption/extensive net reabsorption and 2) are substrates and/or inhibitors of human renal transporters. PMID:25352657

  4. Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110.

    PubMed

    Zhang, Yan; Warren, Mark S; Zhang, Xuexiang; Diamond, Sharon; Williams, Bill; Punwani, Naresh; Huang, Jane; Huang, Yong; Yeleswaram, Swamy

    2015-04-01

    Serum creatinine is commonly used as a marker of renal function, but increases in serum creatinine might not represent changes in glomerular filtration rate (GFR). INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine was observed after treatment with INCB039110. However, a dedicated renal function study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy volunteers indicated no change in GFR. In vitro studies were therefore conducted to investigate the interaction of INCB039110 with five transporters that are likely involved in the renal clearance of creatinine. Cell systems expressing individual or multiple transporters were used, including a novel quintuple-transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of creatinine. Given the interactions of INCB039110 with multiple transporters affecting creatinine uptake and efflux, an integrated system expressing all five transporters was sought; in that system, INCB039110 caused a dose-dependent decrease in transcellular transport of creatinine with weaker net inhibition compared with the effects on individual transporters. In summary, a molecular mechanism for the increase in serum creatinine by INCB039110 has been established. These studies also underline the limitations of using serum creatinine as a marker of renal function. PMID:25605813

  5. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

    NASA Astrophysics Data System (ADS)

    Liu, Fuyao; He, Xiuxia; Chen, Hongda; Zhang, Junping; Zhang, Huimao; Wang, Zhenxin

    2015-08-01

    An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

  6. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

    PubMed Central

    Liu, Fuyao; He, Xiuxia; Chen, Hongda; Zhang, Junping; Zhang, Huimao; Wang, Zhenxin

    2015-01-01

    An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging. PMID:26245151

  7. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications.

    PubMed

    Liu, Fuyao; He, Xiuxia; Chen, Hongda; Zhang, Junping; Zhang, Huimao; Wang, Zhenxin

    2015-01-01

    An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe(3+), gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging. PMID:26245151

  8. [Evaluation of the renal function in type 2 diabetes: clearance calculation or cystatin C?].

    PubMed

    Dhia, Rym Ben; Hellara, Ilhem; Harzallah, Olfa; Neffati, Fadoua; Khochtali, Ines; Mahjoub, Sylvia; Najjar, Mohamed Fadhel

    2012-01-01

    Screening for diabetic nephropathy is usually done by albuminuria/24h and the use of creatinine clearance. The objective of this study was to evaluate the renal function in Type 2 diabetes by using different formulas of creatinine clearance and to assess the contribution of cystatin C; 83 adults with type 2 diabetes (23 men and 60 women) and 83 adult controls (40 men and 43 women) were studied. Biochemical parameters were determinated on Coba 6000™ (Roche diagnostics). Diabetics showed a significant increase in blood glucose, cholesterol, triglycerides, LDLc, the ApoB, Lp(a), urea, uric acid, creatinine and cystatin C and lower HDLc. Cystatin was increased in patients with degenerative complications and in hypertensive patients. We found strong correlations of cystatin C with creatinine (r = 0.9454), urea (r = 0.8999) and uric acid (r = 0.8325). We found a significant exponentially increase of creatinine and cystatin C from one stage to another. Cystatin C has a strong association with MDRD (r = 0.8086) and CG (r = 0.7915) and a low one with creatinine clearance (r = 0.1044). In conclusion, the use of cystatin C for screening and early treatment of incipient diabetic nephropathy appears to be adequate. CG and MDRD formulas still hold their place, in regards to the classical determination of creatinine clearance, to monitor patients. PMID:22565176

  9. Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

    PubMed Central

    Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

    2015-01-01

    Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

  10. Estimation of renal function in the intensive care unit: the covert concepts brought to light.

    PubMed

    Sunder, Sham; Jayaraman, Rajesh; Mahapatra, Himanshu Sekhar; Sathi, Satyanand; Ramanan, Venkata; Kanchi, Prabhu; Gupta, Anurag; Daksh, Sunil Kumar; Ram, Pranit

    2014-01-01

    Frantic efforts have been made up to this date to derive consensus for estimating renal function in critically ill patients, only to open the Pandora's box. This article tries to explore the various methods available to date, the newer concepts, and the uncared issues that may still prove to be useful in estimating renal function in intensive care unit patients. The concept of augmented renal clearance, which is frequently encountered in critically ill patients, should always be taken into account, as correct therapeutic dosage of drugs sounds vital which in turn depends on correctly calculated glomerular filtration rate. Serum creatinine and creatinine-based formulae have their own demerits that are well known and established. While Cockcroft-Gault and 4-variable modification of diet in renal diseases formulae are highly inadequate in the intensive care setup for estimating glomerular filtration rate, employing isotopic methods is impractical and cumbersome. The 6-variable modification of diet in renal diseases formula fairs better as it takes into account the serum albumin and blood urea nitrogen, too. Jelliffe's and modified Jelliffe's equations take into account the rate of creatinine production and volume of distribution which in turn fluctuates heavily in a critically ill patient. Twenty-four-hour and timed creatinine clearances offer values close to reality although not accurate and cannot provide immediate results. Cystatin C is a novel agent that offers a sure promise as it is least influenced by factors that affect serum creatinine to a major extent. Aminoglycoside clearance, although still in the dark area, may prove a simple yet precise way of estimating glomerular filtration rate in those patients in whom these drugs are therapeutically employed. Optic ratiometric method has emerged as the most sophisticated one in glomerular filtration rate estimation in critically ill patients. PMID:25520843

  11. Iohexol plasma clearance, a simple and reliable method to measure renal function in conscious mice.

    PubMed

    Luis-Lima, Sergio; Rodríguez-Rodríguez, Ana Elena; Martín-Higueras, Cristina; Sierra-Ramos, Catalina; Carrara, Fabiola; Arnau, María Rosa; Alvarez de la Rosa, Diego; Salido, Eduardo; Gaspari, Flavio; Porrini, Esteban

    2016-09-01

    In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice. We used two groups of mice: testing and validation, formed by 16 animals (8 male and 8 female) each. Iohexol was injected intravenously into the tail vein (6.47 mg), and tail tip blood samples were collected at 1, 3, 7, 10, 15, 35, 55, and 75 min. Iohexol plasma clearances were calculated in two ways: (1) two-compartment model (CL2) using all time points and (2) one-compartment model (CL1) using only the last four points. In the testing group, CL1 overestimated the true clearance (CL2). Therefore, CL1 was recalculated applying a correction factor calculated as the ratio between CL2/CL1. The latter was considered as the simplified method. CL2 averaged 223.3 ± 64.3 μl/min and CL1 252.4 ± 76.4 μl/min, which lead to a CF of 0.89. Comparable results for CL2, CL1, and simplified method were observed in the validation group. Additionally, we demonstrated the capacity of the simplified method to quantitatively assess different degrees of renal function in three mouse models: hyperoxaluric-CKD (87.4 ± 28.3 μl/min), heminephrectomized (135-0 ± 50.5 μl/min), and obese (399.6 ± 112.1 μl/min) mice. We have developed a simple and reliable method to evaluate renal function in conscious mice under diverse clinical conditions. Moreover, the test can be repeated in the same animal, which makes the method useful to examine renal function changes over time. PMID:27315812

  12. Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients.

    PubMed

    Perez-Ruiz, Fernando; Aniel-Quiroga, Maria Angeles; Herrero-Beites, Ana María; Chinchilla, Sandra Pamela; Erauskin, Gorka Garcia; Merriman, Toni

    2015-09-01

    Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension. PMID:25763991

  13. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy.

    PubMed

    Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H; Roy, Shuvo

    2016-01-01

    Silicon nanopore membranes (SNMs) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here, we present an initial evaluation of the SNM's mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200 ml/min) and pressures (1,448 mm Hg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25 ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4 hours in an extracorporeal porcine model. The pressure drop across the flow cell was 4.6 mm Hg at 200 ml/min. Mechanical testing showed that SNM could withstand up to 775.7 mm Hg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extracorporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1-fold increase and 1.8-fold increase over polyethylene glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401

  14. Probenecid inhibits the renal clearance of frusemide and its acyl glucuronide.

    PubMed Central

    Vree, T B; van den Biggelaar-Martea, M; Verwey-van Wissen, C P

    1995-01-01

    The effect of oral probenecid (1 g) on the pharmacokinetics of frusemide (80 mg p.o.) and its acyl glucuronide was studied in nine healthy subjects. Probenecid significantly increased the t1/2,z of frusemide from 2.01 +/- 0.68 to 3.40 +/- 1.48 h (P = 0.0015) and significantly decreased oral clearance from 164 +/- 67.0 to 58.3 +/- 28.1 ml min-1 (P = 0.0001). No effect of probenecid on the plasma protein binding of frusemide was detected. Probenecid significantly increased the tmax of the metabolite frusemide acyl glucuronide from 1.4 to 2.6 h, but had no effect on the tlag, Cmax, t1/2,z and plasma protein binding. The urinary recoveries of unchanged frusemide (39.2 +/- 10.2 vs 34.4 +/- 8.6%, P = 0.28) and its acyl glucuronide (12.1 +/- 2.7 vs 11.8 +/- 3.7%, P > 0.8) were not altered by probenecid. However, probenecid decreased the renal clearance of both frusemide (128 +/- 49 vs 44.0 +/- 18.6 ml min-1, P = 0.0002) and the acyl glucuronide (552 +/- 298 vs 158 +/- 94.0 ml min-1, P < 0.0001). The non-renal clearance of frusemide (36.7 +/- 21.0 vs 15.2 +/- 13.4 ml min-1, P = 0.0068) was also decreased. The clinical relevance of the study relates to the possible conjugation of frusemide in the kidney and the role of the conjugate in the pharmacodynamic effect. PMID:7654491

  15. The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients.

    PubMed

    Kiser, J J; Carten, M L; Aquilante, C L; Anderson, P L; Wolfe, P; King, T M; Delahunty, T; Bushman, L R; Fletcher, C V

    2008-02-01

    We determined the effects of lopinavir/ritonavir on tenofovir renal clearance. Human immunodeficiency virus-infected subjects taking tenofovir disoproxil fumarate (TDF) were matched on age, race, and gender and were enrolled into one of the following two groups: group 1: subjects taking TDF plus lopinavir/ritonavir plus other nucleoside reverse transcriptase inhibitors (NRTIs); group 2: subjects taking TDF plus NRTIs and/or non-NRTIs but no protease inhibitors. Twenty-four-hour blood and urine collections were carried out in subjects for tenofovir quantification. Drug transporter genotype associations with tenofovir pharmacokinetics were examined. In 30 subjects, median (range) tenofovir apparent oral clearance, renal clearance, and fraction excreted in urine were 34.6 l/h (20.6-89.5), 11.3 l/h (6.2-22.6), and 0.33 (0.23-0.5), respectively. After adjusting for renal function, tenofovir renal clearance was 17.5% slower (P=0.04) in subjects taking lopinavir/ritonavir versus those not taking a protease inhibitor, consistent with a renal interaction between these drugs. Future studies should clarify the exact mechanism and whether there is an increased risk of nephrotoxicity. PMID:17597712

  16. Plasma Creatinine Clearance in the Dog

    ERIC Educational Resources Information Center

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  17. Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics.

    PubMed

    Hobbs, Athena L V; Shea, Katherine M; Roberts, Kirsten M; Daley, Mitchell J

    2015-11-01

    Augmented renal clearance (ARC) has been reported in approximately 30-65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50-85%. Risk factors for ARC include the following: age younger than 50-55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8-hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population. PMID:26598098

  18. Passive Tumor Targeting of Renal Clearable Luminescent Gold Nanoparticles: Long Tumor Retention and Fast Normal Tissue Clearance

    PubMed Central

    Liu, Jinbin; Yu, Mengxiao; Zhou, Chen; Yang, Shengyang; Ning, Xuhui; Zheng, Jie

    2014-01-01

    Glutathione-coated luminescent gold nanoparticles (GS-AuNPs) of ~ 2.5 nm behave like small dye molecules (IRdye 800CW) in physiological stability and renal clearance, but exhibit much longer tumor retention time and faster normal tissue clearance than the dye molecules, indicating that well-known enhanced permeability and retention (EPR) effect, a unique strength of conventional nanoparticles (NPs) in tumor targeting, still exists in such small NPs. These merits enable the AuNPs to more rapidly detect tumor than the dye molecules without severe accumulation in reticuloendothelial system (RES) organs, holding great promise in cancer diagnosis and therapy. PMID:23506476

  19. Tikhonov adaptively regularized gamma variate fitting to assess plasma clearance of inert renal markers

    PubMed Central

    Puetter, Richard C.; Ling, Lin; Babyn, Paul S.

    2010-01-01

    The Tk-GV model fits Gamma Variates (GV) to data by Tikhonov regularization (Tk) with shrinkage constant, λ, chosen to minimize the relative error in plasma clearance, CL (ml/min). Using 169Yb-DTPA and 99mTc-DTPA (n = 46, 8–9 samples, 5–240 min) bolus-dilution curves, results were obtained for fit methods: (1) Ordinary Least Squares (OLS) one and two exponential term (E1 and E2), (2) OLS-GV and (3) Tk-GV. Four tests examined the fit results for: (1) physicality of ranges of model parameters, (2) effects on parameter values when different data subsets are fit, (3) characterization of residuals, and (4) extrapolative error and agreement with published correction factors. Test 1 showed physical Tk-GV results, where OLS-GV fits sometimes-produced nonphysical CL. Test 2 showed the Tk-GV model produced good results with 4 or more samples drawn between 10 and 240 min. Test 3 showed that E1 and E2 failed goodness-of-fit testing whereas GV fits for t > 20 min were acceptably good. Test 4 showed CLTk-GV clearance values agreed with published CL corrections with the general result that CLE1 > CLE2 > CLTk-GV and finally that CLTk-GV were considerably more robust, precise and accurate than CLE2, and should replace the use of CLE2 for these renal markers. PMID:20865304

  20. Renal failure in cirrhosis: Emerging concepts

    PubMed Central

    Bittencourt, Paulo Lisboa; Farias, Alberto Queiroz; Terra, Carlos

    2015-01-01

    Acute renal failure, now termed acute kidney injury (AKI), is frequently found in patients with cirrhosis. The occurrence of AKI, irrespective of the underlying cause, is associated with reduced in-hospital, 3-mo and 1-year survival. Hepatorenal syndrome is associated with the worst outcome among AKI patients with cirrhosis. Several definitions for AKI that have been proposed are outlined and evaluated in this paper. Among these, the International Club for Ascites-AKI criteria substantially strengthen the quality of early diagnosis and intervention according to underlying cause of AKI. PMID:26413223

  1. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF. PMID:27144905

  2. Caffeine renal clearance and urine caffeine concentrations during steady state dosing. Implications for monitoring caffeine intake during sports events.

    PubMed Central

    Birkett, D J; Miners, J O

    1991-01-01

    1. Relationships between the plasma and urine concentrations and clearances of caffeine over successive dosage intervals at steady-state were investigated in six healthy volunteers administered caffeine, 150 mg 8 hourly for 6 days. 2. There was marked inter-individual variability in the urine (15.9-fold range) and steady-state plasma (8.1-fold range) concentrations of caffeine. 3. Urine caffeine concentrations were similar to those in plasma, with mean ratios (plasma:urine) ranging from 1.10 to 1.74. There was a good correlation (r = 0.93, P less than 0.01) between caffeine urine and plasma concentrations. 4. There was a good correlation between caffeine renal clearance and urine flow rate (r = 0.89, P less than 0.01). Caffeine renal clearance was not significantly different from the product of fu and urine flow rate, where fu is the fraction of caffeine unbound in plasma. Urine caffeine concentration and urine flow rate were not correlated (r = 0.14, P greater than 0.05). 5. The results indicate that caffeine is reabsorbed from the renal tubule to equilibrium with unbound caffeine in plasma. 6. A regulatory urine caffeine concentration limit of 12 mg 1(-1) may be exceeded by some individuals with coffee intake in the range 3 to 6 cups per day. PMID:2049248

  3. The renal concentrating mechanism: fundamental theoretical concepts.

    PubMed

    Stephenson, J L

    1983-05-15

    Five theoretical principles that follow from qualitative consideration of renal architecture and tubular permeabilities are proposed to explain the concentration of urine in the mammalian kidney. These are: 1) The medullary loop of the doubly folded S-shaped configuration of the nephron permits solute supplied by ascending Henle's limb (AHL) to extract water from descending Henle's limb (DHL) and collecting duct (CD). 2) The cortical loop allows the diluted AHL fluid to return to isotonicity with cortical plasma before returning to the medulla. 3) The folded vasa recta and surrounding interstitium (the central core) provide an expansion chamber for the performance of osmotic work and a mixing chamber for salt and urea. This mixing induces passive salt transport out of AHL. 4) Overall, the system acts as a solute cycling multiplier from the AHL to vascular core and the osmotically equilibrated DHL and CD. 5) The short-looped nephrons provide urea to drive salt transport out of AHL of long nephrons in the inner medulla. PMID:6840288

  4. Cancer Theranostic Nanoparticles Self-Assembled from Amphiphilic Small Molecules with Equilibrium Shift-Induced Renal Clearance

    PubMed Central

    Ma, Yuan; Mou, Quanbing; Sun, Mo; Yu, Chunyang; Li, Jianqi; Huang, Xiaohua; Zhu, Xinyuan; Yan, Deyue; Shen, Jian

    2016-01-01

    Nano drug delivery systems have emerged as promising candidates for cancer therapy, whereas their uncertainly complete elimination from the body within specific timescales restricts their clinical translation. Compared with hepatic clearance of nanoparticles, renal excretion of small molecules is preferred to minimize the agent-induced toxicity. Herein, we construct in vivo renal-clearable nanoparticles, which are self-assembled from amphiphilic small molecules holding the capabilities of magnetic resonance imaging (MRI) and chemotherapy. The assembled nanoparticles can accumulate in tumor tissues for their nano-characteristics, while the small molecules dismantled from the nanoparticles can be efficiently cleared by kidneys. The renal-clearable nanoparticles exhibit excellent tumor-inhibition performance as well as low side effects and negligible chronic toxicity. These results demonstrate a potential strategy for small molecular nano drug delivery systems with obvious anticancer effect and low-toxic metabolism pathway for clinical applications. PMID:27446502

  5. [Evaluation of a modified exogenous creatinine clearance as a suitable renal function test for the small animal practice].

    PubMed

    Höchel, Joachim; Finnah, Anke; Velde, Karsten; Hartmann, Helmut

    2004-01-01

    A suitable method in the routine veterinary practice for the quantitative determination of the glomerular filtration rate (GFR) in dogs and cats has not been available until to date. Therefore, we modified the known plasma clearance model (=P-CL). The resulting P-CLterminal was assessed concerning its diagnostic value. P-CL of exogenous creatinine (P-CLcrea) and of inulin were determined in dogs (n=12, Beagle, 6 months of age) and cats (n=11, Domestic Short Hair, 14 months of age). The marker substances were administered as a bolus injection. In fasted dogs, P-CLcrea was 84.3 +/- 14.85 ml/min/m2 after a creatinine dose of 2.4 g/m2. An electrolyte infusion during the clearance determination did not alter the resulting values (p>0.05). In fasted cats, P-CLcrea was 54.7 +/- 5.8 ml/min/m2 (creatinine dose 2.0 g/m2). The inulin clearance, determined at the same time, was 104.5 +/- 19.81 ml/min/m2. Feeding the cats just before and during the test increased P-CL of both markers significantly (p<0.05). In order to adapt the clearance method for diagnostic assessment of GFR in the small animal practice, we aimed at minimizing the number of required blood samples (3 instead of 7 or more) and introduced the modified exogenous creatinine clearance (P-CLterminal). These values determined were 108.4 +/- 20.81 ml/min/m2 in fasted dogs and 66.3 +/- 11.81 ml/min/m2 in fasted cats. An electrolyte infusion (dogs) and feeding (cats) had the same effect on P-CLterminal values as described above for P-CL. In conclusion,the modified exogenous creatinine clearance is a suitable renal function test for the early diagnosis of renal disease in dogs and cats presented in small animal practices. PMID:15495934

  6. Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.; Erker, Arthur H.

    2004-01-01

    The objectives of the research presented in this viewgraph presentation are to 1) Design a mechanical ACC system for HPT tip seal clearance management; 2) Design a test rig to evaluate ACC system concepts. We have focused our efforts on designing mechanical ACC systems that articulate the seal shroud via mechanical linkages connected to actuators that reside outside the extreme environment of the HPT. We opted for this style of design due to a lack of high temperature/low profile actuators that are presently available. We have also selected multiple hydraulic actuators for this first generation ACC system. Fuel-draulic actuators are already a well established technology.

  7. [Renal functional reserve in children with a history of hemolytic uremic syndrome through technetium-99m diethylene-triamine-penta-acetic acid clearance].

    PubMed

    Bruno, Guillermo O A; Diéguez, Stella Maris; Voyer, Luis E

    2012-01-01

    Protein loads in normal subjects increase glomerular filtration rate (GFR), which implies a renal functional reserve (RFR). Patients who have suffered a loss in the number of nephrons may show normal values of GFR due to hyperfiltration of remnant nephrons, with subsequent loss of RFR. This could be an early sign of renal damage, and probably a contributory factor to renal damage progress. The objective of this study is to determine the RFR through technetium-99m diethylene-triamine-penta-acetic acid (99m Tc-DTPA) clearance in patients who have recovered from hemolytic uremic syndrome. Renal functional reserve was determined in 33 children from 2 to 16 years old, with normal values of proteinuria, serum creatinine and creatinine clearance after over a year of having suffered hemolitic uremic syndrome. For that purpose 99m Tc-DTPA clearance was determined in basal condition and following protein load. In 17 patients DTPA clearance increased 20% or more after protein load compared to basal condition, and they were considered to have normal RFR, a probably index of totally recovered renal function; in the remaining 16 patients the increases were lower than 20%, and were considered to have no RFR, condition that was postulated as a contributing factor to renal damage progress. There was not significant differences either in age or basal GFR between both groups. Being the test easier than inuline clearance and more accurate than creatinine clearance, it proves particularly useful for early diagnosis of patients that need special follow-up and treatment. PMID:22307424

  8. Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

    PubMed

    De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

    2015-11-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].). PMID:26349821

  9. Augmented Renal Clearance Implies a Need for Increased Amoxicillin-Clavulanic Acid Dosing in Critically Ill Children

    PubMed Central

    Standing, Joseph F.; Barker, Charlotte I. S.; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G.; Delanghe, Joris R.; Robays, Hugo; De Paepe, Peter

    2015-01-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].) PMID:26349821

  10. The role of plasma volume, plasma renin and the sympathetic nervous system in the posture-induced decline in renal lithium clearance in man.

    PubMed

    Smith, D F; Shimizu, M

    1978-01-01

    Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity. PMID:692834

  11. A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders

    SciTech Connect

    Mueller-Suur, R.B.; Bois-Svensson, I.; Mesko, L. )

    1990-11-01

    The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ((123I)OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and (123I)OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function.

  12. Reduced Renal Clearance of Cefotaxime in Asians with a Low-Frequency Polymorphism of OAT3 (SLC22A8)

    PubMed Central

    Yee, Sook Wah; Nguyen, Anh Nguyet; Brown, Chaline; Savic, Radojka M.; Zhang, Youcai; Castro, Richard A.; Cropp, Cheryl D.; Choi, Ji Ha; Singh, Diment; Tahara, Harunobu; Stocker, Sophie L.; Huang, Yong; Brett, Claire M.; Giacomini, Kathleen M.

    2014-01-01

    Organic anion transporter 3 (OAT3, SLC22A8), a transporter expressed on the basolateral membrane of the proximal tubule, plays a critical role in the renal excretion of organic anions including many therapeutic drugs. The goal of this study was to evaluate the in vivo effects of the OAT3-Ile305Phe variant (rs11568482), present at 3.5% allele frequency in Asians, on drug disposition with a focus on cefotaxime, a cephalosporin antibiotic. In HEK293- Flp-In cells, the OAT3-Ile305Phe variant had a lower maximum cefotaxime transport activity, Vmax, [159 ± 3 nmol*(mg protein)−1/min (mean ± SD)] compared with the reference OAT3 [305 ± 28 nmol*(mg protein)−1/min, (mean ± SD), p < 0.01], whereas the Michaelis-Menten constant values (Km) did not differ. In healthy volunteers, we found volunteers that were heterozygous for the Ile305Phe variant and had a significantly lower cefotaxime renal clearance (CLR; mean ± SD: 84.8 ± 32.1 mL/min, n = 5) compared with volunteers that were homozygous for the reference allele (158 ± 44.1 mL/min, n = 10; p = 0.006). Furthermore, the net secretory component of cefotaxime renal clearance (CLsec) was reduced in volunteers heterozygous for the variant allele [33.3 ± 31.8 mL/min (mean ± SD)] compared with volunteers homozygous for the OAT3 reference allele [97.0 ± 42.2 mL/min (mean ± SD), p = 0.01]. In summary, our study suggests that a low-frequency reduced-function polymorphism of OAT3 associates with reduced cefotaxime CLR and CLsec. PMID:23649425

  13. Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

    PubMed

    Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

    2016-04-01

    After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. PMID:26944791

  14. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    PubMed

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

  15. The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors

    PubMed Central

    Schück, Otto; Teplan, Vladimir; Maly, Jan; Franekova, Janka; Malinska, Hana; Stollova, Milena; Latova, Irena; Urbanova, Jana; Skibova, Jelena; Viklicky, Ondrej

    2014-01-01

    It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 – 2.50) mL/s/1.73 m2. Total bias when using the CKD-EPI formula was –0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 – 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution. PMID:25345381

  16. Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.

    2003-01-01

    Improved blade tip sealing in the high pressure compressor and high pressure turbine can provide dramatic improvements in specific fuel consumption, time-on-wing, compressor stall margin and engine efficiency as well as increased payload and mission range capabilities of both military and commercial gas turbine engines. The preliminary design of a mechanically actuated active clearance control (ACC) system for turbine blade tip clearance management is presented along with the design of a bench top test rig in which the system is to be evaluated. The ACC system utilizes mechanically actuated seal carrier segments and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. The purpose of this active clearance control system is to improve upon current case cooling methods. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, re-burst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). The active turbine blade tip clearance control system design presented herein will be evaluated to ensure that proper response and positional accuracy is achievable under simulated high-pressure turbine conditions. The test rig will simulate proper seal carrier pressure and temperature loading as well as the magnitudes and rates of blade tip clearance changes of an actual gas turbine engine. The results of these evaluations will be presented in future works.

  17. Renal clearance studies of effect of left atrial distension in the dog.

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1972-01-01

    Investigation of the water diuresis of left atrial distension in 16 dogs on the basis of clearance studies employing hydration, chronic and acute salt loading, deoxycorticosterone (DOCA) in excess, and distal tubular nephron blockade with diuretics. The diuresis was found in hydrated and salt-loaded dogs and was independent of DOCA and presumed renin depletion. It was not found in five dogs after distal tubular blockade. No significant reproducible saluresis was ever documented. The water diuresis was always stopped by exogenous vasopressin (seven dogs). Antidiuretic hormone inhibition with distal tubular nephron water permeability changes appears to be the sole mechanism of the diuresis of left atrial distension in the dog.

  18. Servo-control of water and sodium homeostasis during renal clearance measurements in conscious rats.

    PubMed

    Thomsen, Klaus; Shirley, David G

    2007-01-01

    Servo-controlled fluid and sodium replacement during clearance studies is used in order to prevent loss of body fluid and sodium following diuretic/natriuretic procedures. However, even under control conditions, the use of this technique is sometimes associated with increases in proximal tubular fluid output (assessed by lithium clearance) and excretion rates. The present study examined the reason for these increases. The first series of experiments showed that one cause is volume overloading. This can occur if the servo system is activated from the start, i.e., during the establishment of a suitably high urine flow rate by constant infusion of hypotonic glucose solution. The second series of experiments showed that replacement of blood samples with donor blood can also lead to increases in fractional lithium excretion and accompanying increases in water and sodium excretion, a problem not seen when blood samples are replaced with the animal's own red blood cells resuspended in isotonic saline. When these pitfalls are avoided, servo-controlled sodium and fluid replacement is a reliable technique that makes it possible to study the effects of natriuretic and/or diuretic stimuli without interference from unwanted changes in extracellular volume. PMID:17693706

  19. Cystic renal tumors: new entities and novel concepts.

    PubMed

    Moch, Holger

    2010-05-01

    Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways. PMID:20418675

  20. Test Rig for Active Turbine Blade Tip Clearance Control Concepts: An Update

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn; Steinetz, Bruce; Oswald, Jay; DeCastro, Jonathan; Melcher, Kevin

    2006-01-01

    The objective is to develop and demonstrate a fast-acting active clearance control system to improve turbine engine performance, reduce emissions, and increase service life. System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA's Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  1. Physical Exercise, Fasting Glucose, and Renal Hyperfiltration in the General Population: The Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6)

    PubMed Central

    Mathisen, Ulla Dorte; Eilertsen, Britt-Ann Winther; Ingebretsen, Ole C.; Jenssen, Trond; Njølstad, Inger; Solbu, Marit D.; Toft, Ingrid; Eriksen, Bjørn O.

    2012-01-01

    Summary Background and objectives Abnormally elevated GFR, or hyperfiltration, is a proposed mechanism for kidney injury in diabetes, prediabetes, and obesity. This study investigated whether lack of physical exercise is associated with hyperfiltration and whether exercise modifies the positive association between fasting glucose and measured GFR. Design, setting, participants, & measurements The Renal Iohexol Clearance Survey in Tromsø 6 measured GFR as single-sample plasma iohexol clearance in 1506 members of the general population (age 50–62 years) without diabetes, cardiovascular disease, or kidney disease. Leisure-time physical exercise was assessed by a self-administered questionnaire. Hyperfiltration was defined as GFR above the 90th percentile after adjustment for sex, age, weight, height, and use of renin-angiotensin system inhibitors. Results High-intensity exercise was associated with lower adjusted odds of hyperfiltration in men (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.28–0.80) but not in women (OR, 1.02; 95% CI, 0.60–1.72). In both sexes, high-intensity exercise modified the association between fasting glucose and GFR. A fasting glucose level 1 mmol/L higher was associated with a GFR that was 7.3 (95% CI, 4.0–10.6) and 6.2 (95% CI, 3.4–9.0) ml/min per 1.73 m2 higher in men and women who never exercised or exercised with low intensity. There was no association between fasting glucose and GFR in men and women who exercised with high intensity (interaction, P<0.001). Conclusions High-intensity exercise was associated with lower odds of hyperfiltration in men and modified the association between glucose and GFR of both sexes in a population without diabetes. PMID:22917703

  2. High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn; Steinetz, Bruce M.; Oswald, Jay J.

    2007-01-01

    System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  3. High Temperature Investigations into an Active Turbine Blade Tip Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce; Oswald, Jay J.

    2008-01-01

    System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA s Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  4. Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans.

    PubMed

    Tisdale, J E; Rudis, M I; Padhi, I D; Svensson, C K; Webb, C R; Borzak, S; Ware, J A; Krepostman, A; Zarowitz, B J

    1995-09-01

    Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. The purpose of this randomized, two-way crossover study was to determine if para-aminobenzoic acid (PABA) inhibits N-acetylation of procainamide in healthy volunteers. Eleven (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intravenous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were collected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA concentrations were analyzed using fluorescence polarization immunoassay. Urine procainamide and NAPA concentrations were measured with high performance liquid chromatography. PABA did not significantly influence total or renal procainamide clearance, elimination rate constant, AUC0-00, amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC0-00 and t1/2 and reductions in NAPA Ke, procainamide acetylation (NAPA formation) clearance, and NAPA renal clearance. Although PABA inhibits metabolic conversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA may not be useful for optimizing the safety of efficacy of procainamide in patients. PMID:8786250

  5. Garlic Attenuates Plasma and Kidney ACE-1 and AngII Modulations in Early Streptozotocin-Induced Diabetic Rats: Renal Clearance and Blood Pressure Implications

    PubMed Central

    Al-Qattan, Khaled K.; Jayasree, Divya; Ali, Muslim

    2016-01-01

    Raw garlic aqueous extract (GE) has ameliorative actions on the renin-angiotensin system in type-1 diabetes mellitus (DM); however its effects on plasma and kidney angiotensin I converting enzyme type-1 (ACE-1) and angiotensin II (AngII) require further elucidation. This study investigated the effect of GE on plasma and kidney ACE-1 and AngII concentrations and in relation to systemic and renal clearance indicators significant to blood pressure (BP) homeostasis in early streptozotocin- (STZ-) induced type-1 DM. Normal rats (n = 10) received 0.5 mL normal saline (NR/NS), diabetic rats (n = 10) received 0.5 mL NS (DR/NS), and treated diabetic rats (n = 10) received 50 mg/0.1 mL/100 g body weight GE (DR/GE) as daily intraperitoneal injections for 8 weeks. Compared to NR/NS, DR/NS showed a significant increase in plasma ACE-1 and AngII and conversely a decrease in kidney ACE-1 and AngII. These changes were associated with an increase in BP and clearance functions. Alternatively and compared to DR/NS, DR/GE showed normalization or attenuation in plasma and kidney ACE-1 and AngII. These GE induced rectifications were associated with moderation in BP elevation and renal clearance functions. Garlic attenuates modulations in plasma and kidney ACE-1 and AngII, in addition to BP and renal clearance function in type-1 DM. PMID:27293465

  6. Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

    PubMed Central

    Bobulescu, Ion Alexandru; Moe, Orson W.

    2013-01-01

    In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible for 60–70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. In spite of tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiology, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that specifically act on individual renal urate transporters for the treatment of hyperuricemia and gout. PMID:23089270

  7. [Treatment of acute renal failure--concepts and controversies. 2. Extracorporeal renal replacement and peritoneal dialysis].

    PubMed

    Gabriel, A; Müller, E; Tarnow, J

    2001-04-01

    Therapy of prolonged acute renal failure regularly requires a renal replacement therapy. This can be achieved by different extracorporal renal replacement therapies (ERRT) or by peritoneal dialysis. ERRT are classified according to the physical principle underlying toxin elimination as hemodialysis (diffusion) and hemofiltration (convection). Another classification refers to intermittent or continuous application modes. Biocompatibility of membranes is judged according to their activation of the complement system. Prospective randomized studies did not consolidate the assumptions about the benefit of particular modalities proposed on theoretical foundations. Mortality, duration and complication rates of acute renal failure are not significantly decreased by use of biocompatible membranes. Continuous modalities are not generally preferable but optimize treatment in hemodynamically unstable patients, in whom they endorse fluid balancing and maintenance of sufficient arterial blood pressure. The use of demanding hemofiltration techniques for cytokine removal should be limited to clinical studies. The effects of ERRT-"intensity" and the best timing for initiation of ERRT have not been evaluated sufficiently. The choice of the ERRT modality is subject to clinical judgement (criterion: hemodynamic situation), practical aspects (criteria: availability of equipment and handling experience), and costs. Prior to their general use new and expensive technical modalities and membrane types should be thoroughly evaluated in studies with regard to outcome-related aspects such as patient survival and preservation of renal function. PMID:11386089

  8. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  9. Rapid Degradation and High Renal Clearance of Cu3BiS3 Nanodots for Efficient Cancer Diagnosis and Photothermal Therapy in Vivo.

    PubMed

    Liu, Jing; Wang, Pengyang; Zhang, Xiao; Wang, Liming; Wang, Dongliang; Gu, Zhanjun; Tang, Jinglong; Guo, Mengyu; Cao, Mingjing; Zhou, Huige; Liu, Ying; Chen, Chunying

    2016-04-26

    A key challenge for the use of inorganic nanomedicines in clinical applications is their long-term accumulation in internal organs, which raises the common concern of the risk of adverse effects and inflammatory responses. It is thus necessary to rationally design inorganic nanomaterials with proper accumulation and clearance mechanism in vivo. Herein, we prepared ultrasmall Cu3BiS3 nanodots (NDs) as a single-phased ternary bimetal sulfide for photothermal cancer therapy guided by multispectral optoacoustic tomography (MSOT) and X-ray computed tomography (CT) due to bismuth's excellent X-ray attenuation coefficient. We then monitored and investigated their absorption, distribution, metabolism, and excretion. We also used CT imaging to demonstrate that Cu3BiS3 NDs can be quickly removed through renal clearance, which may be related to their small size, rapid chemical transformation, and degradation in an acidic lysosomal environment as characterized by synchrotron radiation-based X-ray absorption near-edge structure spectroscopy. These results reveal that Cu3BiS3 NDs act as a simple but powerful "theranostic" nanoplatform for MSOT/CT imaging-guided tumor ablation with excellent metabolism and rapid clearance that will improve safety for clinical applications in the future. PMID:27014806

  10. Reduced methotrexate clearance and renal impairment in a boy with osteosarcoma and earlier undetected autosomal dominant polycystic kidney disease (ADPKD).

    PubMed

    Alberer, Martin; Hoefele, Julia; Bergmann, Carsten; Hartrampf, Steffen; Hilberath, Jutta; Pawlita, Ingo; Albert, Michael H; Benz, Marcus R; Weber, Lutz T; Schmid, Irene

    2010-11-01

    We report a 12-year-old boy with osteoblastic osteosarcoma of the right femur. He was started on chemotherapy according to the EURAMOS/COSS 1 protocol. Chemotherapy with doxorubicin/cisplatin resulted in reversible acute renal failure and methotrexate levels were repeatedly elevated. Family history suggested an autosomal dominant polycystic kidney disease. Genetic testing revealed a novel mutation c.10707_10712del (p.Val3569_3570del) in exon 36 of the PKD1 gene. Patients with autosomal dominant polycystic kidney disease may be at risk for acute renal failure during chemotherapy without signs of renal impairment. A careful family history is important to exclude risk factors for renal impairment before introducing high-dose chemotherapy. PMID:20921908

  11. Fast clearance of lipid droplets through MAP1S-activated autophagy suppresses clear cell renal cell carcinomas and promotes patient survival

    PubMed Central

    Liu, Xian-De; Yue, Fei; Li, Wenjiao; Li, Xun; He, Yongzhong; Jiang, Xianhan; Huang, Hai; Chen, Qi; Jonasch, Eric; Liu, Leyuan

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is composed of cells whose cytoplasm filled with lipid droplets, subcellular organelles coated with adipocyte differentiation-related protein (ADFP) for the storage of triacylglycerol converted from excess free fatty acids. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as lipid droplets. MAP1S (originally named C19ORF5) is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and promoted the survival of patients with prostate adenocarcinomas by increasing the degradation of aggregated proteins and dysfunctional mitochondria. Here we show that a suppression of MAP1S in renal cells causes an impairment of autophagic clearance of lipid droplets. In contrast, an overexpression of MAP1S causes an activation of autophagy flux and a reduction of lipid droplets so less DNA double strand breakage is induced. The levels of MAP1S in normal renal cells are dramatically higher than those in the ccRCC tissues and cell lines derived from renal cell carcinomas. High levels of MAP1S are associated with a reduced malignancy and metastasis of ccRCC and predict a better survival of ccRCC patients. Therefore, autophagy defects in the degradation of lipid droplets triggered by the MAP1S deficiency may enhance the initiation and development of ccRCC and reduce the survival of ccRCC patients. PMID:26701856

  12. Current Concepts on Diabetic Nephropathy and 2014 Data on Diabetic Renal Failure in Texas.

    PubMed

    Pazmino, Patricio A

    2016-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) in the United States and other developed countries. In 1982, diabetes accounted for 27% of patients with ESRD in the United States and rose to 36% by 1992 and to 47% in 2012. Currently, the number of prevalent cases of ESRD in the country (dialysis and transplant) exceeds more than 636,900. Primary care practitioners (PCP) provide more than 90% of the diabetic care and are well-positioned to identify, prevent, and treat initially DN. PCPs should identify DN with a urine microalbumin test, obtain a serum creatinine and glomerular filtration rate, monitor hemoglobin A1c, and treat hypertension and dyslipidemia according to current guidelines. This article reviews basic concepts and goals for DN as well as the 2014 data for diabetic renal failure in the most populous counties in Texas. The Texas counties bordering Mexico show an excessive prevalence of diabetic renal failure. PMID:27441426

  13. Challenges in Individualizing Drug Dosage for Intensive Care Unit Patients: Is Augmented Renal Clearance What We Really Want to Know? Some Suggested Management Approaches and Clinical Software Tools.

    PubMed

    Jelliffe, Roger

    2016-08-01

    Acutely ill intensive care unit (ICU) patients often have large apparent volumes of distribution of drugs and, because of this, their drug clearance (CL) is usually also increased. 'Augmented renal Cl' is a current issue in the management of drug therapy for acutely ill and unstable ICU patients; however, Cl, the product of volume and the rate constant for excretion, describes only a theoretical volume of drug cleared per unit of time. Information of the actual rate of movement of the drug itself is obscured. It is suggested that the most useful clinical information is given by describing drug volume and elimination rate constant separately. This also permits better understanding of the patient's separate issues of fluid balance and drug elimination, especially when dialysis, renal replacement therapy, or extracorporeal membrane oxygenation (ECMO) may be used, and facilitates management of these two important separate clinical issues. Optimal management of drug therapy also requires optimal methods embodied in clinical software to describe drug behavior in these highly unstable patients, and considerably more data than for ordinary patients. The interacting multiple model (IMM) clinical software facilitates management of both fluid balance and drug therapy in these unstable patients. Illustrative cases are discussed, and new monitoring and management strategies are suggested. Like other ICU skills, physicians need to learn optimal tools for managing drug therapy in the ICU. Further work should help evaluate these new approaches. PMID:26914772

  14. Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

    PubMed Central

    Level, Claude; Chauveau, Philippe; Guisset, Olivier; Cazin, Marie Cécile; Lasseur, Catherine; Gabinsky, Claude; Winnock, Stéphane; Montaudon, Danièle; Bedry, Régis; Nouts, Caroline; Pillet, Odile; Benissan, Georges Gbikpi; Favarel-Guarrigues, Jean Claude; Castaing, Yves

    2003-01-01

    Objectives To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT. Setting The medical department of intensive care. Design A prospective, observational study. Patients Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour). Measurements and main results PCT was measured with the Lumitest PCT Brahms® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH. Conclusions We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance

  15. Pharmacokinetics in renal disease.

    PubMed

    Levy, G

    1977-04-01

    The physiologic perturbations associated with renal disease can have a pronounced effect on the kinetics of elimination of drugs and their metabolites from the body. Drugs are ordinarily cleared from the body by a number of routes, each of which can be characterized by a clearance value. The sum of these clearances (renal, hepatic, etc.) is the total or body clearance which is inversely proportional to the steady-state plasma concentration produced by a given drug dosage regimen. The quantitative contribution of each route of elimination to the metabolic fate of a drug is proportional to the clearance value of that route relative to the body clearance. As a first approximation, the reduction in the renal clearance of a drug caused by renal disease is proportional to the reduction in the renal clearance of creatinine. The metabolic (biotransformation) clearance of many extensively plasma protein bound drugs is proportional to their free fraction (ratio of concentrations of free to total drug) in plasma. Since severe renal disease causes a reduction in the plasma protein binding of many drugs, the metabolic clearance of such drugs will be increased. The contribution of hemodialysis to the total clearance of a drug depends on the magnitude of the clearance obtained by hemodialysis relative to the magnitude of the body clearance of the drug on a day between dialyses. To compensate for the increased elimination of a drug during hemodialysis, the dosing rate (i.e., the dose per unit of time) must be increased by the factor (hemodialysis clearance and body clearance):body clearance, where body clearance is that during a day between dialyses. Further dosage compensation may be needed if body clearance is increased during hemodialysis due to decreased plasma protein binding of the drug. Under certain conditions, an increased accumulation of pharmacologically active drug metabolites during renal failure becomes a matter of serious concern. PMID:851113

  16. Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs.

    PubMed

    Achanta, S; Sewell, A; Ritchey, J W; Broaddus, K; Bourne, D W A; Clarke, C R; Maxwell, L K

    2016-06-01

    Cisplatin is a platinum-containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4-55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling. PMID:26440900

  17. Establishment and use of surgical rat models for assessment of organ specific in vivo clearance.

    PubMed

    Vestergaard, Bill

    2016-06-01

    Knowledge of clearance plays a key role in the development of new drug entities, especially in the development of improved analogues for treatment of chronic conditions. Improved pharmacokinetic properties can be used to increase dosing interval and thereby improve patient compliance. This will lead to improved treatment outcome or decreased risk of treatment failure when treating chronic conditions. Therefore, animal models for assessment of organ-specific clearance are of great value in preclinical drug development. These models can be used to obtain insights into the relative importance of a clearance organ and thereby guide drug design of new analogues in early drug discovery. The current PhD project was undertaken to explore surgical in vivo models, which could be used in the assessment of the relative importance of major clearance organs. It was the aim of the PhD project to establish and validate both a nephrectomy model and a hepatectomy model as tools to investigate relative importance of renal and hepatic clearance. Furthermore, the project aim was to investigate renal clearance of rFVIIa and rhGH using a nephrectomy model in rats. The thesis is composed of a short theoretical background, a literature review, two papers based on experimental work as well as experimental work not included in the papers. Chapter one is an introduction with the specific aims and hypotheses. The chapters from two to five contain theoretical background of the clearance concept, anatomical and physiological description of clearance organs and a brief overview of potential clearance models including in vivo models. Chapters six through nine highlight the experimental work with the results obtained during the PhD project. Lastly, the chapters from ten to twelve contain a general discussion, conclusion and perspectives of the current thesis. Paper I "Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics" provides a literature review of animal

  18. Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept.

    PubMed

    Maynar Moliner, J; Honore, P M; Sánchez-Izquierdo Riera, J A; Herrera Gutiérrez, M; Spapen, H D

    2012-01-01

    Continuous renal replacement therapy (CRRT) is increasingly used for the management of critically ill patients. As a consequence, the incidence of complications that accompany CRRT is also rising. However, a standardized approach for preventing or minimizing these adverse events is lacking. Dialytrauma is a newly proposed concept that encompasses all harmful adverse events related to CRRT while providing a framework for prevention or, at the least, early recognition of these events in order to attenuate the consequences. A mainstay of this approach is the utilization of a dedicated checklist for improving CRRT quality and patient safety. In this context, we discuss the most important adverse effects of CRRT and review current strategies to minimize them. PMID:23095418

  19. Cerebral Hyperperfusion after Revascularization Inhibits Development of Cerebral Ischemic Lesions Due to Artery-to-Artery Emboli during Carotid Exposure in Endarterectomy for Patients with Preoperative Cerebral Hemodynamic Insufficiency: Revisiting the “Impaired Clearance of Emboli” Concept

    PubMed Central

    Fujimoto, Kentaro; Matsumoto, Yoshiyasu; Oikawa, Kohki; Nomura, Jun-ichi; Shimada, Yasuyoshi; Fujiwara, Shunrou; Terasaki, Kazunori; Kobayashi, Masakazu; Yoshida, Kenji; Ogasawara, Kuniaki

    2016-01-01

    The purpose of the present study was to determine whether cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). In patients undergoing CEA for internal carotid artery stenosis (≥70%), cerebral blood flow (CBF) was measured using single-photon emission computed tomography (SPECT) before and immediately after CEA. Microembolic signals (MES) were identified using transcranial Doppler during carotid exposure. Diffusion-weighted magnetic resonance imaging (DWI) was performed within 24 h after surgery. Of 32 patients with a combination of reduced cerebrovascular reactivity to acetazolamide on preoperative brain perfusion SPECT and MES during carotid exposure, 14 (44%) showed cerebral hyperperfusion (defined as postoperative CBF increase ≥100% compared with preoperative values), and 16 (50%) developed DWI-characterized postoperative cerebral ischemic lesions. Postoperative cerebral hyperperfusion was significantly associated with the absence of DWI-characterized postoperative cerebral ischemic lesions (95% confidence interval, 0.001–0.179; p = 0.0009). These data suggest that cerebral hyperperfusion after revascularization inhibits development of cerebral ischemic lesions due to artery-to-artery emboli during carotid exposure in CEA, supporting the “impaired clearance of emboli” concept. Blood pressure elevation following carotid declamping would be effective when embolism not accompanied by cerebral hyperperfusion occurs during CEA. PMID:27527146

  20. Controls Considerations for Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.

    2004-01-01

    This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

  1. Fuel conservation through active control of rotor clearances

    NASA Technical Reports Server (NTRS)

    Beitler, R. S.; Saunders, A. A.; Wanger, R. P.

    1980-01-01

    Under the NASA-sponsored Energy Efficient Engine (EEE) Project, technology is being developed which will significantly reduce the fuel consumption of turbofan engines for subsonic transport aircraft. One technology concept being pursued is active control of rotor tip clearances. Attention is given to rotor tip clearance considerations and an overview of preliminary study results as well as the General Electric EEE clearance control approach is presented. Finally, potential fuel savings with active control of rotor clearances for a typical EEE mission are predicted.

  2. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

    PubMed Central

    Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

    2008-01-01

    Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

  3. The Alarmin Concept Applied to Human Renal Transplantation: Evidence for a Differential Implication of HMGB1 and IL-33

    PubMed Central

    Robin, Aurélie; Barra, Anne; Bridoux, Franck; Ameteau, Virginie; Hauet, Thierry; Girard, Jean-Philippe; Touchard, Guy; Gombert, Jean-Marc; Herbelin, André

    2014-01-01

    The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment. Moreover, both serum and urinary IL-33 (but not HMGB1) increase was positively correlated with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Finally, we postulate that leukocytes from renal recipient patients are targeted by both HMGB1 and IL-33, as suggested by increased transcription of their respective receptors (TLR2/4 and ST2L) shortly after transplantation. Consistent with this view, we found that iNKT cells, an innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1 was activated 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans. PMID:24586382

  4. Analysis and design of a uniform-clearance, pumping-ring rod seal for the Stirling engine

    NASA Technical Reports Server (NTRS)

    Etsion, I.

    1980-01-01

    A uniform clearance pumping ring, as opposed to the conventional taper clearance one, is described. The uniform clearance concept eliminates complex elastohydrodynamic problems and enables a simple analytical treatment to be made. An analytical expression is derived for the pumping rate showing the effect of various design parameters on the pumping ring's performance. An optimum clearance is found by which the pumping rate is maximized and a numerical example is presented to demonstrate the potential of the uniform clearance design.

  5. Achievements and new directions in continuous renal replacement therapies.

    PubMed

    Ronco, C; Barbacini, S; Digito, A; Zoccali, G

    1995-11-01

    The evolution of renal replacement therapy has permitted the treatment of critically ill patients with acute renal failure. In intensive care settings, continuous renal replacement therapies have been shown to be better tolerated and clinically useful. Continuous hemofiltration is now performed with blood pumps and double-lumen venous catheters, thus avoiding the complications found in previous arteriovenous treatments. The use of countercurrent dialysate flow has overcome problems related to low treatment efficiency. High clearances can now be obtained during continuous hemodialysis or hemodiafiltration, and adequate blood purification can be achieved even in severely catabolic patients. New replacement solutions allow for a more effective correction of acidosis and electrolyte imbalances. Finally, newly designed machines permit continuous therapies while minimizing staff workload. Continuous therapies are today moving toward newer indications and applications. The ability to remove proinflammatory substances by filtration and/or adsorption has opened a series of potential indications. The concept that renal support and protection take place during hemofiltration suggests that very early use of this technique is desirable, even before the onset of oliguria or azotemia. PMID:8574601

  6. Creatinine clearance test

    MedlinePlus

    ... function. In: Johnson RJ, Feehally J, Floege J. Comprehensive Clinical Nephrology . 5th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 3. Landry DW, Bazari H. Approach to the patient with renal disease. In: Goldman ...

  7. Pharmacokinetics of oral cefatrizine in patients with impaired renal function.

    PubMed

    Couet, W; Fauvel, J P; Laville, M; Pozet, N; Fourtillan, J B

    1991-06-01

    The pharmacokinetics of cefatrizine was studied in 15 patients with various degrees of renal impairment, after single oral administration of 500 mg. Cefatrizine elimination was reduced in parallel to renal function, as indicated by the significant correlations between apparent clearance (Cl/F) and creatinine clearance (Clcr), and between renal clearance (Clr) and creatinine clearance (Clcr). In patients with totally impaired renal function, the residual clearance (Cl/F) was 63 ml.min-1 per 1.73 m2. Comparisons with previously published data indicate that the apparent volume of distribution (V/F) of cefatrizine was lower in patients with impaired renal function than in young healthy volunteers, leading to increased peak concentrations (Cmax), but there was no relationship between V/F and Clcr. In patients with totally impaired renal function, the upper limit of cefatrizine elimination half-life was estimated to 5.5 h. The clinical significance of pharmacokinetic modifications observed in renal disease patients may only be realized through integration of pharmacodynamic characteristics of cefatrizine. The observed increase in Cmax and the lengthening of t1/2 could suggest a reduction of dosing frequency in patients with severe renal impairment. PMID:1869342

  8. Advanced Thermal HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    WojciechVoytek, Sak

    2006-01-01

    OBJECTIVE: Develop a fast acting HPT Active Clearance Control System to improve engine efficiency and reduce emissions CHALLENGE: Reduction of HPT blade clearance throughout engine operation System complexity, reliability and cost must remain comparable or surpass today s engines Reduced clearance may increase possibility of rubs

  9. Clearance of Tc-99m DTPA in hemodialysis and peritoneal dialysis: concise communication

    SciTech Connect

    Wainer, E.; Boner, G.; Lubin, E.; Rosenfeld, J.B.

    1981-09-01

    The clearance of Tc-99m DTPA was studied in 14 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Mean Tc-99m DTPA clearance during HD was 37.8% +/- 10.1 of creatinine clearance. Mean Tc-99m DTPA clearance in PD was 65.1% +/- 10.3 of creatinine clearance. Tc-99m DTPA, with a larger molecular weight than that of creatinine, is cleared relatively better during PD than during HD. Thus Tc-99m DTPA may be used in the assessment of the effectiveness of different dialytic treatments for substances of similar molecular weight. In addition, our study shows that clearance of DTPA both in HD and PD is sufficiently high to allow the removal of this chelating agent in patients with renal failure.

  10. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  11. The renal quantitative scintillation camera study for determination of renal function

    SciTech Connect

    Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.

    1983-03-01

    The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.

  12. The rebirth of interest in renal tubular function.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. PMID:26936872

  13. Metabolomics and Renal Disease

    PubMed Central

    Rhee, Eugene P.

    2015-01-01

    Purpose of review This review summarizes recent metabolomics studies of renal disease, outlining some of the limitations of the literature to date. Recent findings The application of metabolomics in nephrology research has expanded from initial analyses of uremia to include both cross-sectional and longitudinal studies of earlier stages of kidney disease. Although these studies have nominated several potential markers of incident CKD and CKD progression, lack of overlap in metabolite coverage has limited the ability to synthesize results across groups. Further, direct examination of renal metabolite handling has underscored the substantial impact kidney function has on these potential markers (and many other circulating metabolites). In experimental studies, metabolomics has been used to identify a signature of decreased mitochondrial function in diabetic nephropathy and a preference for aerobic glucose metabolism in PKD; in each case, these studies have outlined novel therapeutic opportunities. Finally, as a complement to the longstanding interest in renal metabolite clearance, the microbiome has been increasingly recognized as the source of many plasma metabolites, including some with potential functional relevance to CKD and its complications. Summary The high-throughput, high-resolution phenotyping enabled by metabolomics technologies has begun to provide insight on renal disease in clinical, physiologic, and experimental contexts. PMID:26050125

  14. More Power to OATP1B1: An Evaluation of Sample Size in Pharmacogenetic Studies Using a Rosuvastatin PBPK Model for Intestinal, Hepatic, and Renal Transporter-Mediated Clearances.

    PubMed

    Emami Riedmaier, Ariane; Burt, Howard; Abduljalil, Khaled; Neuhoff, Sibylle

    2016-07-01

    Rosuvastatin is a substrate of choice in clinical studies of organic anion-transporting polypeptide (OATP)1B1- and OATP1B3-associated drug interactions; thus, understanding the effect of OATP1B1 polymorphisms on the pharmacokinetics of rosuvastatin is crucial. Here, physiologically based pharmacokinetic (PBPK) modeling was coupled with a power calculation algorithm to evaluate the influence of sample size on the ability to detect an effect (80% power) of OATP1B1 phenotype on pharmacokinetics of rosuvastatin. Intestinal, hepatic, and renal transporters were mechanistically incorporated into a rosuvastatin PBPK model using permeability-limited models for intestine, liver, and kidney, respectively, nested within a full PBPK model. Simulated plasma rosuvastatin concentrations in healthy volunteers were in agreement with previously reported clinical data. Power calculations were used to determine the influence of sample size on study power while accounting for OATP1B1 haplotype frequency and abundance in addition to its correlation with OATP1B3 abundance. It was determined that 10 poor-transporter and 45 intermediate-transporter individuals are required to achieve 80% power to discriminate the AUC0-48h of rosuvastatin from that of the extensive-transporter phenotype. This number was reduced to 7 poor-transporter and 40 intermediate-transporter individuals when the reported correlation between OATP1B1 and 1B3 abundance was taken into account. The current study represents the first example in which PBPK modeling in conjunction with power analysis has been used to investigate sample size in clinical studies of OATP1B1 polymorphisms. This approach highlights the influence of interindividual variability and correlation of transporter abundance on study power and should allow more informed decision making in pharmacogenomic study design. PMID:27385171

  15. Site clearance working group

    SciTech Connect

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  16. Single-dose gentamicin clearance is a predictor of creatinine clearance in spinal man.

    PubMed

    Segal, Jack L; Gilman, Thomas A; Thompson, John F

    2010-01-01

    To identify a radionuclide-free, SCI (spinal cord injury) population-specific method for estimating renal function utilizing the total body clearance of gentamicin as a measure of creatinine clearance (CL(cr)) and glomerular filtration rate (GFR). To incorporate SCI population-specific patient variables into a predictive model for estimating CLcr and GFR. A retrolective study of gentamicin clearance as a measure of GFR in patients with SCI. Each patient had received a single, intravenous dose of gentamicin. Simultaneously, a 24-hour creatinine clearance (CL(cr-24)) was obtained. Experimentally measured total body clearance of a single intravenous administration of gentamicin (CL(gent-iv)) was estimated from PK analyses of gentamicin disposition in patients with SCI. Comparisons were made between CL(gent-iv) and predictors of GFR derived from a SCI population-specific nomogram (SCI-psn), the method of Cockcroft and Gault (C-G), CL(cr-24), and a multiplicative statistical model. A multiplicative model, calculated gentamicin clearance (CL(gent-calc)), that incorporates SCI population-specific characteristics to predict CL(cr-24) and GFR was derived from a multivariate nonlinear regression analysis, and the strengths of association between CL(gent-iv) and CL(gent-calc), and estimates of GFR derived from the method of C-G, SCI-psn, and CL(cr-24) were tested. The best predictive performance was demonstrated for CL(gent-iv) and the multiplicative model, CL(gent-calc), when tested against CL(cr-24) or the SCI-psn, supporting our premise that CL(gent-iv) can be used to estimate GFR in SCI. CL(gent-iv) and CL(gent-calc) outperformed CL(cr-24), the method of C-G, and the SCI-psn as predictors of GFR. The multiplicative model produced estimates of CL(gent-iv) which were more precise and less biased than CL(cr-24), the standard radiation-free predictor of GFR in patients with SCI, the SCI-psn, and the C-G equation. In this preliminary study, the clearance of gentamicin

  17. Propranolol disposition in renal failure.

    PubMed Central

    Wood, A J; Vestal, R E; Spannuth, C L; Stone, W J; Wilkinson, G R; Shand, D G

    1980-01-01

    1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine clearance 14.5 +/- 2.8 ml/min) but not on haemodialysis and patients on haemodialysis (creatinine clearance less than 5 ml/min). 3 The effect of haemodialysis on propranolol binding and free fraction was also examined. The percentage of propranolol unbound rose from 7.1% to 9.9%. (P less than 0.001) 20 min following heparinization and beginning haemodialysis. This was accompanied by a large rise in free fatty acids from 0.567 +/- 0.059 to 3.326 +/- 0.691 mumol/ml (P less than 0.005). 4 The blood to plasma concentration ratios of propranolol were significantly higher in patients with renal failure (P less than 0.02) and on haemodialysis (P less than 0.001) and were significantly negatively correlated (P less than 0.001) with the haematocrit. 5 Although the half-life propranolol was significantly shortened in the patients with renal failure (P less than 0.02), there was no change in the apparent liver blood flow, extraction ratio or the principal determinants of steady-state drug concentrations in blood namely oral and intravenous clearance from blood. 6 There is, therefore, no pharmacokinetic basis to adjust the dosage of propranolol in patients with renal failure. PMID:7470370

  18. Evaluation of effect of impaired renal function on lamivudine pharmacokinetics

    PubMed Central

    Bouazza, Naïm; Tréluyer, Jean-Marc; Ghosn, Jade; Hirt, Déborah; Benaboud, Sihem; Foissac, Frantz; Viard, Jean-Paul; Urien, Saik

    2014-01-01

    Aims This study aimed to describe lamivudine pharmacokinetics in patients with impaired renal function and to evaluate the consistency of current dosing recommendations. Methods A total of 244 patients, ranging in age from 18 to 79 years (median 40 years) and in bodyweight from 38 to 117 kg (median 71 kg), with 344 lamivudine plasma concentrations, were analysed using a population pharmacokinetic analysis. Serum creatinine clearance (CLCR) was calculated using the Cockcroft–Gault formula; 177 patients had normal renal function (CLCR > 90 ml min−1), 50 patients had mild renal impairment (CLCR = 60–90 ml min−1), 20 patients had moderate renal impairment (CLCR = 30–60 ml min−1), and five patients had severe renal impairment (CLCR < 30 ml min−1). Results A two-compartment model adequately described the data. Typical population estimates (percentage interindividual variability) of the apparent clearance (CL/F), central (Vc/F) and peripheral volumes of distribution (Vp/F), intercompartmental clearance (Q/F) and absorption rate constant (Ka) were 29.7 l h−1 (32%), 68.2 l, 114 l, 10.1 l h−1 (85%) and 1 h−1, respectively. Clearance increased significantly and gradually with CLCR. Our simulations showed that a dose of 300 mg day−1 in patients with mild renal impairment could overexpose them. A dose of 200 mg day−1 maintained an exposure close to that of adults with normal renal function. However, the current US Food and Drug Administration recommendations for lamivudine in other categories of patients (from severe to moderate renal impairment) provided optimal exposures. Conclusions Lamivudine elimination clearance is related to renal function. To provide optimal exposure, patients with mild renal impairment should receive 200 mg day−1 instead of 300 mg day−1. PMID:24750102

  19. Renal arteriography

    MedlinePlus

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Update Date 4/7/2014 Updated by: Jason ... Failure Kidney Tests X-Rays Browse the Encyclopedia A. ...

  20. Renal venogram

    MedlinePlus

    ... 2008:chap 6. Rankin S. Renal parenchymal disease, including renal failure, renovascular disease and transportation. In: Grainger RC, Allison D, Adam, Dixon AK, eds. Diagnostic Radiology: A Textbook of Medical Imaging . 5th ed. New York, NY: Churchill Livingstone; 2008:chap 39. Read ... arteriography Renal vein thrombosis Tumor Venogram Wilms ...

  1. Clinical application of plasma clearance of iohexol on feline patients.

    PubMed

    Miyamoto, K

    2001-09-01

    Glomerular filtration rate (GFR) was estimated by plasma clearance of iohexol (PCio) in 52 conscious cats presented for a variety of reasons to Angel Animal Hospital over a 2-year period. Cats were divided into four groups according to their clinical conditions and reasons for measuring PCio. The median PCio (ml/min/kg) was 3.68 in normal cats (NM), 2.39 in cats with suspected renal disease (SP), 1.35 in cats referred to confirm renal dysfunction (RD), and 0.84 in cats with apparent clinical signs of renal failure (RF). There was a significant difference between the results for each group. The respective medians of blood urea nitrogen (BUN) and plasma creatinine concentration (Pcr) (mg/dl) were 15 and 1.40 in NM cats, 21 and 1.71 in SP cats, 30 and 2.20 in RD cats, and 48 and 3.30 in RF cats. The reference values of BUN and Pcr were 21 +/- 7 mg/dl and 1.5 +/- 0.4 mg/dl (mean +/- SD). Diminished renal function could not be detected in SP cats by either BUN or Pcr, while a marked decrease of GFR was demonstrated before BUN and Pcr increased, indicating the insensitivity of BUN and Pcr in detecting renal dysfunction in cats. PCio can be performed non-invasively in conscious cats, which improves the veterinarian's ability to detect early stages of chronic renal disease. PMID:11876631

  2. Turbomachinery Clearance Control

    NASA Technical Reports Server (NTRS)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  3. Pharmacokinetics of brotizolam in renal failure

    PubMed Central

    Evers, J.; Renner, E.; Bechtel, W. D.

    1983-01-01

    1 Kinetics of brotizolam (0.25 mg) were studied in patients with different degrees of renal failure after single and repeated oral ingestion. Serum levels were analysed by radio-immunoassay. 2 Patients were divided into three groups according to their renal function, i.e. creatinine clearance values of 45-80, 15-45, or less than 15 ml/min. 3 The mean elimination half-life was 6.9-8.15 h, with a considerable variation of the peak concentration and elimination half-life in slight to moderate renal failure. There was no delay in elimination in severe renal failure and there was no drug accumulation. 4 No dose adjustment is necessary for brotizolam in renal failure. PMID:6661376

  4. Airway clearance in neuromuscular weakness.

    PubMed

    Gauld, Leanne Maree

    2009-05-01

    Impaired airway clearance leads to recurrent chest infections and respiratory deterioration in neuromuscular weakness. It is frequently the cause of death. Cough is the major mechanism of airway clearance. Cough has several components, and assessment tools are available to measure the different components of cough. These include measuring peak cough flow, respiratory muscle strength, and inspiratory capacity. Each is useful in assessing the ability to generate an effective cough, and can be used to guide when techniques of assisting airway clearance may be effective for the individual and which are most effective. Techniques to assist airway clearance include augmenting inspiration by air stacking, augmenting expiration by assisting the cough, and augmenting both inspiration and expiration with the mechanical insufflator-exsufflator or by direct suctioning via a tracheostomy. Physiotherapists are invaluable in assisting airway clearance, and in teaching patients and their families how to use these techniques. Use of the mechanical insufflator-exsufflator has gained popularity in recent times, but several simpler, more economical methods are available to assist airway clearance that can be used effectively alone or in combination. This review examines the literature available on the assessment and management of impaired airway clearance in neuromuscular weakness. PMID:19379290

  5. Renal handling of free sialic acid in normal humans and patients with Salla disease or renal disease.

    PubMed

    Seppala, R; Renlund, M; Bernardini, I; Tietze, F; Gahl, W A

    1990-08-01

    The renal handling of free sialic acid, a negatively charged sugar, was investigated in normal humans and in patients with impaired sialic acid metabolism or impaired renal function. A sensitive assay for sialic acid, based upon the specific degradation of free sialic acid by N-acetylneuraminic acid aldolase, was developed to measure small amounts of sialic acid in human plasma. Using this assay on plasma from patients with disorders of sialic acid metabolism, we determined that the fractional excretion of sialic acid was maintained at approximately 98% over a wide range of filtered loads, i.e., from 40 to 2617 nmoles/minute. In other patients with different degrees of renal insufficiency, free sialic acid clearance varied directly with creatinine clearance, indicating filtration of this sugar by renal glomeruli. In patients with renal Fanconi syndrome, the urinary excretion of free sialic acid was independent of the severity of the generalized tubular defect, indicating that sialic acid was not reabsorbed by renal tubular cells. These findings indicate that sialic acid is filtered but not reabsorbed by the human kidney, in contrast with the handling of other sugars known to be reabsorbed by renal tubular cells. In addition, three of eight patients with Salla disease, a storage disorder due to impaired lysosomal transport of free sialic acid, were found to have reduced creatinine clearances, but all Salla disease patients had entirely normal renal tubular function. PMID:2381164

  6. Pulmonary and urinary clearance of atrial natriuretic factor in acute congestive heart failure in dogs.

    PubMed Central

    Perrella, M A; Margulies, K B; Wei, C M; Aarhus, L L; Heublein, D M; Burnett, J C

    1991-01-01

    Atrial natriuretic factor (ANF) is a peptide hormone of cardiac origin elevated in acute congestive heart failure (CHF), which is degraded by the enzyme neutral endopeptidase 24.11 (NEP). This study was designed to investigate the pulmonary and urinary clearance of ANF before and after the initiation of acute experimental CHF in dogs, and to assess the contribution of enzymatic degradation to these clearances in CHF. This study demonstrated a significant clearance of plasma ANF across the pulmonary circulation at baseline, and a tendency for pulmonary clearance to decrease in CHF (1115 +/- 268 to 498 +/- 173 ml/min, NS). The pulmonary extraction of ANF present at baseline was not altered with acute CHF (36.0 +/- 7.8 to 34.9 +/- 12.1%, NS). NEP inhibition (NEPI) abolished both the clearance and extraction of plasma ANF across the lung in CHF. Similarly, significant urinary clearance of ANF was present at baseline, and in acute CHF the urinary clearance of ANF decreased (0.14 +/- 0.02 to 0.02 +/- 0.01 ml/min, P less than 0.05). NEPI prevented the decrease in the urinary clearance of ANF, and enhanced the renal response to endogenous ANF, independent of further increases in plasma ANF during CHF. This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF. Images PMID:1850758

  7. Dual clearance squeeze film damper

    NASA Technical Reports Server (NTRS)

    Fleming, D. P. (Inventor)

    1985-01-01

    A dual clearance hydrodynamic liquid squeeze film damper for a gas turbine engine is described. Under normal operating conditions, the device functions as a conventional squeeze film damper, using only one of its oil films. When an unbalance reaches abusive levels, as may occur with a blade loss or foreign object damage, a second, larger clearance film becomes active, controlling vibration amplitudes in a near optimum manner until the engine can be safely shut down and repaired.

  8. Method of mucociliary clearance assessment

    NASA Astrophysics Data System (ADS)

    Danilova, Tatiana V.; Manturov, Alexey O.; Ermakov, Igor Y.; Mareev, Gleb O.; Mareev, Oleg V.

    2016-04-01

    The article is devoted to the research capabilities of mucociliary clearance in the nasal cavity and paranasal sinuses using modern techniques of digital video recording and processing. We describe the setup and software for this method and the results of our research. Using microscope and digital camera we can provide a good method to study mucociliary clearance and by usage of special software we able to measure some characteristic of nasal mucosae and its main function.

  9. Pharmacokinetics, metabolism and renal clearance of flumequine in veal calves.

    PubMed

    Mevius, D J; Breukink, H J; Guelen, P J; Jansen, T; De Grève, B

    1990-06-01

    The pharmacokinetics of flumequine was studied in 1-, 5- and 18-week-old veal calves. A two-compartment model was used to fit the plasma concentration-time curve of flumequine after the intravenous injection of 10 mg/kg of a 10% solution. The elimination half-life (t1/2 beta) of the drug ranged from 6 to 7 h. The Vd beta and ClB of 1-week-old calves (1.07 l/kg, 1.78 ml/min/kg) were significantly lower than those of 5-week-old (1.89 l/kg, 3.23 ml/min/kg) and 18-week-old calves (1.57 l/kg, 3.10 ml/min/kg). After the oral administration of 10 mg/kg of a 2% flumequine formulation mixed with milk replacer, the Cmax was highest in 1-week-old (9.27 micrograms/ml) and lowest in 18-week-old calves (4.47 micrograms/ml). The absorption was rapid (Tmax of approximately 3 h) and complete. When flumequine itself and a formulation containing 2% flumequine and 20 X 10(6) iu of colistin sulphate were mixed with milk replacer and administered at the same dose rate, absorption was incomplete and Cmax was lower. The main urinary metabolite of flumequine was the glucuronide conjugate (approximately 40% recovery within 48 h of intravenous injection) and the second most important metabolite was 7-hydroxy-flumequine (approximately 3% recovery within 12 h of intravenous injection). Only 3.2-6.5% was excreted in the urine unchanged. After oral administration a 'first-pass' effect was observed, with a significant increase in the excretion of conjugated drug. For 1-week-old calves it is recommended that the 2% formulation should be administered at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h; for calves over 6 weeks old, the dose should be increased to 15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation containing colistin sulphate should be administered to 1-week-old calves at a flumequine dose of 12 mg/kg every 24 h or 6 mg/kg every 12 h. PMID:2384907

  10. Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

    PubMed Central

    Ziemniak, J A; Boppana, V K; Cyronak, M J; Beck, T R; Familiar, R G; Dubb, J W; Allison, N L; Stote, R M

    1988-01-01

    1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system. PMID:2896014

  11. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  12. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  13. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... takeoffs and landings. (c) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 23.239 can be shown with a lesser clearance. (d... airplane structure, plus any additional radial clearance necessary to prevent harmful vibration; (2)...

  14. Population pharmacokinetics of single-dose riociguat in patients with renal or hepatic impairment

    PubMed Central

    2016-01-01

    Abstract This population pharmacokinetics (PK) analysis characterized the PK of the oral soluble guanylate cyclase stimulator riociguat in patients with renal or hepatic impairment and determined whether smoking affects riociguat dosing. Two phase 1 studies were performed in patients with renal impairment (n = 72, of whom 11 were smokers), and two were performed in those with hepatic impairment (n = 64, of whom 12 were smokers). Plasma and urine samples were collected after a single oral dose of riociguat 1.0 or 0.5 mg. Nonlinear mixed-effects modeling was used to develop a combined, two-compartment population PK model for riociguat and its main metabolite, M1. Riociguat and M1 clearance was split into renal and nonrenal parts; the nonrenal part for riociguat was divided into metabolism to M1 and a metabolic (nonrenal) part. Total clearance of riociguat was 1.912 L/h. The main route of riociguat clearance is metabolism to M1 (1.2 L/h). In this model, hepatic function biomarkers or Child-Pugh classification had no significant effect on riociguat or M1 clearance. Nonrenal (nonmetabolism) riociguat clearance was similar in all groups. Renal clearance (0.242 L/h) contributed less to riociguat total clearance, mainly determined by glomerular filtration (0.174 L/h). Renal impairment reduced riociguat and M1 clearance. Hepatic or renal impairment had limited effects on total exposure to riociguat. However, individual dose adjustment of riociguat should be administered with particular care in patients with moderate hepatic or renal impairment. Riociguat is not recommended in severe hepatic or renal impairment. Smoking reduced riociguat exposure by significantly increasing metabolism to M1. PMID:27162631

  15. Effects of water immersion on renal hemodynamics in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Levinson, R.; Loutzenhiser, R.

    1976-01-01

    The present study was undertaken to delineate the effects of water immersion to the neck (NI) on renal plasma flow and glomerular filtration rate as assessed by the clearance of p-aminohippuric acid (PAH) and inulin, respectively. Nine normal male subjects were studied on two occasions, control and NI. The conditions of seated posture and time of day were identical. Immersion did not alter either clearance at a time when sodium excretion was increasing markedly. The constancy of PAH clearance during NI suggests that renal blood flow is unaltered and that the natriuresis of NI is mediated independently of alterations in overall renal perfusion. The sluggish decline of a natriuresis during recovery is consistent with the presence of a humoral factor contributing to the encountered natriuresis.

  16. Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats.

    PubMed

    Melis, M S; Rocha, S T; Augusto, A

    2009-05-01

    Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose. PMID:19675940

  17. Interspecies scaling and prediction of human clearance: comparison of small- and macro-molecule drugs

    PubMed Central

    Huh, Yeamin; Smith, David E.; Feng, Meihau Rose

    2014-01-01

    Human clearance prediction for small- and macro-molecule drugs was evaluated and compared using various scaling methods and statistical analysis.Human clearance is generally well predicted using single or multiple species simple allometry for macro- and small-molecule drugs excreted renally.The prediction error is higher for hepatically eliminated small-molecules using single or multiple species simple allometry scaling, and it appears that the prediction error is mainly associated with drugs with low hepatic extraction ratio (Eh). The error in human clearance prediction for hepatically eliminated small-molecules was reduced using scaling methods with a correction of maximum life span (MLP) or brain weight (BRW).Human clearance of both small- and macro-molecule drugs is well predicted using the monkey liver blood flow method. Predictions using liver blood flow from other species did not work as well, especially for the small-molecule drugs. PMID:21892879

  18. [Renal elastography].

    PubMed

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  19. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  20. Refrigeration system with clearance seals

    SciTech Connect

    Holland, N. J.

    1985-02-26

    In a refrigeration system such as a split Stirling system, fluid seals associated with the reciprocating displacer are virtually dragless clearance seals. Movement of the displacer relative to the pressure variations in the working volume of gas is retarded by a discrete braking element. Because it is not necessary that the brake providing any sealing action, the brake can be designed for greater durability and less dependence on ambient and operating temperatures. Similarly, the clearance seal can be formed of elements having low thermal expansion such that the seal is not temperature dependent. In the primary embodiments the braking element is a split friction brake.

  1. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  2. Shape memory alloy adaptive control of gas turbine engine compressor blade tip clearance

    NASA Astrophysics Data System (ADS)

    Schetky, Lawrence M.; Steinetz, Bruce M.

    1998-06-01

    The ambient air ingested through the inlet of a gas turbine is first compressed by an axial compressor followed by further compression in a centrifugal compressor and then fed into the combustion chamber where ignition and expansion take place to produce the engine thrust. The axial compressor typically has five or more stages which consist of revolving blades and stators and the overall performance of the turbine is strongly affected by the compressor efficiency. When the turbine is turned on, to accommodate the rapid initial increase in the compressor blade length due to centrifugal force, the cold turbine has a built in clearance between the turbine blade tip and the casing. As the turbine reached its operating temperature there is a further increase in the blade length due to thermal expansion and, at the same time, the diameter of the casing increases. The net result is that when these various components have reached their equilibrium temperatures, the initial cold build clearance is reduced, but there remains a residual clearance. The magnitude of this clearance has a direct effect on the compressor efficiency and can be stated as: Δη/Δ CLR equals 0.5 where η is efficiency and CLR is the tip clearance. The concept of adaptive tip clearance control is based on the ability of a shape memory alloy ring to shrink to a predetermined diameter when heated to the temperature of a particular stage, and thus reducing the tip clearance. The ring is fabricated from a CuAlNi shape memory alloy and is mounted in the casing so as to be coaxial with the rotating blades of the particular stage. When cold, the ring dimensions are such as to provide the required cold build clearance, but when at operating temperature the reduced diameter creates a very small tip clearance. The clearance provided by this concept is much smaller than the clearance normally obtained for a turbine of the size being studied.

  3. Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol.

    PubMed Central

    Yamamoto, T; Moriwaki, Y; Takahashi, S; Suda, M; Higashino, K

    1991-01-01

    The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 'an organic acid system' and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules. PMID:1929586

  4. Effects of Probenecid and Cimetidine on Renal Disposition of Ofloxacin in Rats

    PubMed Central

    Foote, Edward F.; Halstenson, Charles E.

    1998-01-01

    The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin’s total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems. PMID:9527807

  5. Renal tubular secretion of pramipexole.

    PubMed

    Knop, Jana; Hoier, Eva; Ebner, Thomas; Fromm, Martin F; Müller, Fabian

    2015-11-15

    The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12μM and 5.5μM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. PMID:26360835

  6. Dynamic Positron Emission Tomography Imaging of Renal Clearable Gold Nanoparticles.

    PubMed

    Chen, Feng; Goel, Shreya; Hernandez, Reinier; Graves, Stephen A; Shi, Sixiang; Nickles, Robert J; Cai, Weibo

    2016-05-01

    Optical imaging has been the primary imaging modality for nearly all of the renal clearable nanoparticles since 2007. Due to the tissue depth penetration limitation, providing accurate organ kinetics non-invasively has long been a huge challenge. Although a more quantitative imaging technique has been developed by labeling nanoparticles with single-photon emission computed tomography (SPECT) isotopes, the low temporal resolution of SPECT still limits its potential for visualizing the rapid dynamic process of renal clearable nanoparticles in vivo. The dynamic positron emission tomography (PET) imaging of renal clearable gold (Au) nanoparticles by labeling them with copper-64 ((64) Cu) to form (64) Cu-NOTA-Au-GSH is reported. Systematic nanoparticle synthesis and characterizations are performed to demonstrate the efficient renal clearance of as-prepared nanoparticles. A rapid renal clearance of (64) Cu-NOTA-Au-GSH is observed (>75%ID at 24 h post-injection) with its elimination half-life calculated to be less than 6 min, over 130 times shorter than previously reported similar nanoparticles. Dynamic PET imaging not only addresses the current challenges in accurately and non-invasively acquiring the organ kinetics, but also potentially provides a highly useful tool for studying renal clearance mechanism of other ultra-small nanoparticles, as well as the diagnosis of kidney diseases in the near future. PMID:27062146

  7. Noninvasive clearance of airway secretions.

    PubMed

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  8. Controlled Rewarming after Hypothermia: Adding a New Principle to Renal Preservation

    PubMed Central

    Schopp, Ina; Reissberg, Elmo; Lüer, Bastian; Efferz, Patrik

    2015-01-01

    Abstract Early graft dysfunction due to preservation/reperfusion injury still represents a notable issue after kidney transplantation, affecting long term prognosis of graft viability. One trigger of postischemic cell dysfunction could be recognized in the abrupt temperature shift from hypo‐ to normothermia, leading to mitochondrial dysfunction and proapoptotic signal transduction. Here we propose a technique to cope with this “rewarming injury” by interposing a period of gentle warming up by hypo‐ to subnormothermic machine perfusion of the isolated graft prior to warm reperfusion. Porcine kidneys were subjected either to 18 hours of hypothermic machine preservation (HMP) or 18 hours static cold storage + 3 hours of gentle, machine controlled oxygenated rewarming (COR). Functional integrity was evaluated in both groups by subsequent normothermic reperfusion in vitro. The functional benefit of COR was documented by an approximately twofold increase in renal clearances of creatinine as well as urea upon warm reperfusion, compared to controls. This was accompanied with a notable mitigation of postischemic mitochondrial dys‐homeostasis. COR significantly improved renal oxygen consumption and maintained total NAD tissue content upon reperfusion. Mitochondrial initiation of cellular apoptosis, as evidenced by activation of caspase 9 was also largely prevented after COR but not in controls. The concept of gentle regenerative graft rewarming could become a valuable adjunct in renal transplantation. PMID:26053383

  9. Microwave Blade Tip Clearance System: An Update

    NASA Technical Reports Server (NTRS)

    Geisheimer, Jon

    2006-01-01

    Newer engines use compressor bleed air and a model to close clearances open loop. Measuring clearances and closing the control loop can add additional efficiencies. Tip clearance control has been identified as a key technology for future engines Additional benefits in prognostics, NSMS, and condition-based maintenance. In the HPT for every 1 mil improvement in clearance: a) SFC decreases 0.1%; and b) EGT margin increases 1 C.

  10. The Dynamics of Apoptotic Cell Clearance.

    PubMed

    Elliott, Michael R; Ravichandran, Kodi S

    2016-07-25

    The phagocytic clearance of dying cells in a tissue is a highly orchestrated series of intercellular events coordinated by a complex signaling network. Recent data from genetic, biochemical, and live-imaging approaches have greatly enhanced our understanding of the dynamics of cell clearance and how the process is orchestrated at the cellular and tissue levels. We discuss how networks regulating apoptotic cell clearance are integrated to enable a rapid, efficient, and high-capacity clearance system within tissues. PMID:27459067

  11. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  12. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Underground clearance. 192.325 Section 192.325... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at least 12 inches (305 millimeters) of clearance from any other underground structure not associated...

  13. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  14. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  15. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  16. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  17. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  18. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall...

  19. 30 CFR 56.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 56.11010 Section 56.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11010 Stairstep clearance. Vertical clearance...

  20. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  1. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  2. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of at least 18 inches between each propeller and the water, unless compliance with § 25.239(a) can be shown... to prevent harmful vibration; (2) At least one-half inch longitudinal clearance between the...

  3. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  4. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  5. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  6. 33 CFR 117.47 - Clearance gauges.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Clearance gauges. 117.47 Section 117.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS General Requirements § 117.47 Clearance gauges. (a) Clearance gauges are required for drawbridges across navigable waters...

  7. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  8. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  9. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a...

  10. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  11. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  12. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor... (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall be prominently posted where the height is insufficient for vehicles and equipment....

  13. 29 CFR 1917.113 - Clearance heights.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Clearance heights. 1917.113 Section 1917.113 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) MARINE TERMINALS Terminal Facilities § 1917.113 Clearance heights. Clearance heights shall...

  14. Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency.

    PubMed

    Marescau, B; Nagels, G; Possemiers, I; De Broe, M E; Becaus, I; Billiouw, J M; Lornoy, W; De Deyn, P P

    1997-09-01

    Levels of 15 guanidino compounds and urea were determined in serum and urine of nondialyzed patients with chronic renal insufficiency subdivided according to etiology and creatinine clearances. No significantly different guanidino compound levels in serum and urine were found for the interstitial nephritis, glomerulonephritis, nephrangiosclerosis, and diabetic nephropathy subgroups. Subdividing the patients according to creatinine clearance yields the following results: (1) Serum guanidinosuccinic acid (GSA) and methylguanidine levels of patients with end-stage renal failure (creatinine clearance < 10 mL/min) are up to 100 and 35 times higher than control levels, while guanidine, creatinine, and symmetrical dimethylarginine (SDMA) are increased about 10 times. Serum levels of asymmetrical dimethylarginine (ADMA) are only doubled in end-stage renal failure. Serum levels of guanidinoacetic acid (GAA) and homoarginine are significantly decreased. (2) Urinary excretion levels of most guanidino compounds decrease with decreasing creatinine clearance except for GSA and methylguanidine. (3) Greater than 90% of patients with creatinine clearance ranging from subnormal to 40 mL/min have serum SDMA levels higher than the upper-normal limit; up to 80% have increased GSA levels. (4) The clearance rates of some of the guanidino compounds could be calculated: with the exception of arginine, they decrease with decreasing creatinine clearance. This study shows specific abnormal guanidino compound levels in serum and urine of nondialyzed patients with chronic renal insufficiency that can be used as complementary diagnostic parameters. The best correlation between serum guanidino compound levels and the degree of renal insufficiency is found for GSA, SDMA, methylguanidine, and guanidine. Urinary excretion levels of ADMA correlate best with decreasing creatinine clearance. Serum levels of GSA and especially SDMA are candidate indicators for the onset of renal failure. PMID:9284891

  15. [Renal disease].

    PubMed

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  16. Renal organogenesis

    PubMed Central

    2011-01-01

    The increasing prevalence of chronic kidney disease in the absence of new treatment modalities has become a strong driver for innovation in nephrology. An increasing understanding of stem cell biology has kindled the prospects of regenerative options for kidney disease. However, the kidney itself is not a regenerative organ, as all the nephrons are formed during embryonic development. Here, we will investigate advances in the molecular genetics of renal organogenesis, including what this can tell us about lineage relationships, and discuss how this may serve to inform us about both the normal processes of renal repair and options for regenerative therapies. PMID:22198432

  17. [Renal colic].

    PubMed

    Pinheiro, J M

    1999-01-01

    The appropriate approach to renal colic, which should be known by the family doctor, is presented. The incidence of this condition in the emergency department of a large general hospital is described as well as the physiopathology of pain, its clinical aspects and the therapeutic attitudes. Renal colic is frequent, it is often possible to diagnose the clinical aspects and general practitioners have the competence for treatment. The use of analgesic drugs, in the correct dosage, is enough to relieve pain and suffering in most of the patients. PMID:10423866

  18. The relevance of drug clearance to antibiotic dosing in critically ill patients.

    PubMed

    Roberts, Darren M

    2011-12-01

    To maximise the effect of an antibiotic it is necessary to pay careful attention to dosing. The maintenance dose is determined by antibiotic clearance which is usually determined in young healthy adults with normal physiology. Antibiotic clearance in critically ill patients may increase or decrease due to altered physiology and the treatments that are administered. Clearance may also vary significantly over time in patients with critical illness. Advancing age and comorbidities, in particular chronic kidney disease, can also decrease antibiotic clearance. Therefore, it is complicated and arguably impossible to suggest generic guidelines for the dosing of antibiotics in critically ill patients. Factors that influence clearance must be identified and accounted for in each patient for a rational approach to dose adjustment of antibiotics in patients with critical illness. The necessary changes can be predicted by understanding pharmacokinetic concepts. It is necessary to quantify organ function in patients at multiple time points because this can be used to estimate antibiotic clearance and guide dose selection. For example, creatinine clearance should be calculated but methods used in ambulatory patients may not apply to patients with critical illness. If possible, therapeutic drug monitoring should be conducted to ensure that antibiotic concentration targets are achieved and also to guide titration of subsequent doses. If blood sampling is carefully planned it may be possible to directly measure antibiotic clearance for dose adjustment. The purpose of this article is to review the concept of clearance and to highlight circumstances where antibiotic clearance may be altered in patients with critical illness. Strategies for dose modification of antibiotics in critically ill patients will be discussed. PMID:21554217

  19. Removal - An alternative to clearance

    SciTech Connect

    Feinhals, J.; Kelch, A.; Kunze, V.

    2007-07-01

    This presentation shows the differences between the application of clearance and removal, both being procedures for materials leaving radiation protection areas permanently. The differentiation will be done on the basis of the German legislation but may be also applicable for other national legislation. For clearance in Germany two basic requirements must be given, i.e. that the materials are activated or contaminated and that they result from the licensed use or can be assigned to the scope of the license. Clearance needs not to be applied to objects in Germany which are to be removed only temporarily from controlled areas with the purpose of repair or reuse in other controlled areas. In these cases only the requirements of contamination control apply. In the case of removal it must either be proved by measurements that the relevant materials are neither activated nor contaminated or that the materials result from areas where activation or contamination is impossible due to the operational history considering operational procedures and events. If the material is considered neither activated nor contaminated there is no need for a clearance procedure. Therefore, these materials can be removed from radiation protection areas and the removal is in the responsibility of the licensee. Nevertheless, the removal procedure and the measuring techniques to be applied for the different types of materials need an agreement from the competent authority. In Germany a maximum value of 10% of the clearance values has been established in different licenses as a criterion for the application of removal. As approximately 2/3 of the total mass of a nuclear power plant is not expected to be contaminated or activated there is a need for such a procedure of removal for this non contaminated material without any regulatory control especially in the case of decommissioning. A remarkable example is NPP Stade where in the last three years more than 8600 Mg were disposed of by removal and

  20. The pharmacokinetics of nortriptyline in patients with chronic renal failure.

    PubMed Central

    Dawlilng, S; Lynn, K; Rosser, R; Braithwaite, R

    1981-01-01

    1 The pharmacokinetics of single oral doses of nortriptyline were studied in twenty patients with chronic renal failure, eight of whom were receiving treatment with haemodialysis. 2 The median nortriptyline half-life was 25.2 h (range 14.5-140.0 h) and the median nortriptyline clearance was 32.3 l/h (range 8.1-122.0 l/h). 3 No differences were observed between the dialysed and non-dialysed groups. 4 Comparisons of nortriptyline half-life and clearance between the patients and groups of physically healthy subjects revealed no significant differences. 5 There was no significant linear correlation between age and either of these measurements. In the twelve patients not receiving haemodialysis there was no correlation between nortriptyline clearance and glomerular filtration rate. 6 Chronic renal failure is not associated with a significant alteration in nortriptyline metabolism as measured by its half-life or clearance, but the drug should nonetheless be used with caution, and monitored whenever possible. However, the marked inter-individual differences observed in nortriptyline half-life and clearance in patients with chronic renal failure may not be solely responsible for their unpredictable response to tricyclic antidepressant therapy, and other possible contributory factors are discussed. PMID:7248140

  1. Pharmacokinetics: metabolism and renal excretion of quinolones in man.

    PubMed

    Vree, T B; Wijnands, W J; Guelen, P J; Baars, A M; Hekster, Y A

    1986-02-21

    The quinolones are relatively poorly absorbed from the gastrointestinal tract. The elimination proceeds mainly by renal excretion. The half-life of elimination depends on the molecular structure and varies between 2 and 10 h. Impaired kidney function is expected to increase the half-life of elimination, though this effect is not always observed. Since the 4-oxo-metabolites show a higher renal clearance than the parent drug, renal impairment will result in a cumulation of the metabolites in the body. PMID:3960691

  2. Renal function recovery in chronic dialysis patients.

    PubMed

    Chu, Jay K; Folkert, Vaughn W

    2010-01-01

    Renal function recovery (RFR) from acute kidney injury requiring dialysis occurs at a high frequency. RFR from chronic dialysis, on the other hand, is an uncommon but well-recognized phenomenon, occurring at a rate of 1.0-2.4% according to data from large observational studies. The underlying etiology of renal failure is the single most important predicting factor of RFR in chronic dialysis patients. The disease types with the highest RFR rates are atheroembolic renal disease, systemic autoimmune disease, renovascular diseases, and scleroderma. The disease types with the lowest RFR rates are diabetic nephropathy and cystic kidney disease. Initial dialysis modality does not appear to influence RFR. Careful observation and history taking are needed to recognize the often nonspecific clinical and laboratory signs of RFR. When RFR is suspected in a chronic dialysis patient, a 24-hour urine urea and creatinine clearance should be measured. Based on the renal clearance, along with other clinical factors, the dialysis prescription may be gradually reduced until a complete discontinuation of dialysis. After RFR from maintenance dialysis, patients require close follow-up in an office setting for chronic kidney disease management. PMID:21166875

  3. Radiomics Analysis on FLT-PET/MRI for Characterization of Early Treatment Response in Renal Cell Carcinoma: A Proof-of-Concept Study.

    PubMed

    Antunes, Jacob; Viswanath, Satish; Rusu, Mirabela; Valls, Laia; Hoimes, Christopher; Avril, Norbert; Madabhushi, Anant

    2016-04-01

    Studying early response to cancer treatment is significant for patient treatment stratification and follow-up. Although recent advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) allow for evaluation of tumor response, a quantitative objective assessment of treatment-related effects offers localization and quantification of structural and functional changes in the tumor region. Radiomics, the process of computerized extraction of features from radiographic images, is a new strategy for capturing subtle changes in the tumor region that works by quantifying subvisual patterns which might escape human identification. The goal of this study was to demonstrate feasibility for performing radiomics analysis on integrated PET/MRI to characterize early treatment response in metastatic renal cell carcinoma (RCC) undergoing sunitinib therapy. Two patients with advanced RCC were imaged using an integrated PET/MRI scanner. [18 F] fluorothymidine (FLT) was used as the PET radiotracer, which can measure the degree of cell proliferation. Image acquisitions included test/retest scans before sunitinib treatment and one scan 3 weeks into treatment using [18 F] FLT-PET, T2-weighted (T2w), and diffusion-weighted imaging (DWI) protocols, where DWI yielded an apparent diffusion coefficient (ADC) map. Our framework to quantitatively characterize treatment-related changes involved the following analytic steps: 1) intraacquisition and interacquisition registration of protocols to allow voxel-wise comparison of changes in radiomic features, 2) correction and pseudoquantification of T2w images to remove acquisition artifacts and examine tissue-specific response, 3) characterization of information captured by T2w MRI, FLT-PET, and ADC via radiomics, and 4) combining multiparametric information to create a map of integrated changes from PET/MRI radiomic features. Standardized uptake value (from FLT-PET) and ADC textures ranked highest for reproducibility in a

  4. Radiomics Analysis on FLT-PET/MRI for Characterization of Early Treatment Response in Renal Cell Carcinoma: A Proof-of-Concept Study1

    PubMed Central

    Antunes, Jacob; Viswanath, Satish; Rusu, Mirabela; Valls, Laia; Hoimes, Christopher; Avril, Norbert; Madabhushi, Anant

    2016-01-01

    Studying early response to cancer treatment is significant for patient treatment stratification and follow-up. Although recent advances in positron emission tomography (PET) and magnetic resonance imaging (MRI) allow for evaluation of tumor response, a quantitative objective assessment of treatment-related effects offers localization and quantification of structural and functional changes in the tumor region. Radiomics, the process of computerized extraction of features from radiographic images, is a new strategy for capturing subtle changes in the tumor region that works by quantifying subvisual patterns which might escape human identification. The goal of this study was to demonstrate feasibility for performing radiomics analysis on integrated PET/MRI to characterize early treatment response in metastatic renal cell carcinoma (RCC) undergoing sunitinib therapy. Two patients with advanced RCC were imaged using an integrated PET/MRI scanner. [18 F] fluorothymidine (FLT) was used as the PET radiotracer, which can measure the degree of cell proliferation. Image acquisitions included test/retest scans before sunitinib treatment and one scan 3 weeks into treatment using [18 F] FLT-PET, T2-weighted (T2w), and diffusion-weighted imaging (DWI) protocols, where DWI yielded an apparent diffusion coefficient (ADC) map. Our framework to quantitatively characterize treatment-related changes involved the following analytic steps: 1) intraacquisition and interacquisition registration of protocols to allow voxel-wise comparison of changes in radiomic features, 2) correction and pseudoquantification of T2w images to remove acquisition artifacts and examine tissue-specific response, 3) characterization of information captured by T2w MRI, FLT-PET, and ADC via radiomics, and 4) combining multiparametric information to create a map of integrated changes from PET/MRI radiomic features. Standardized uptake value (from FLT-PET) and ADC textures ranked highest for reproducibility in a

  5. Prediction of drug clearance in children.

    PubMed

    Foissac, Frantz; Bouazza, Naïm; Valade, Elodie; De Sousa Mendes, Mailys; Fauchet, Floris; Benaboud, Sihem; Hirt, Déborah; Tréluyer, Jean-Marc; Urien, Saïk

    2015-07-01

    The pediatric population is often exposed to drugs without sufficient knowledge about pharmacokinetics. The prediction of accurate clearance values in children, especially in neonates and infants, will improve the rational in dosing decisions. Drug clearances from birth to adulthood were compiled after a systematic review of pharmacokinetic reports. The analysis was performed using NONMEM. Clearance predictions were then evaluated by external validation. Prediction errors were also compared with those obtained from weight-based allometric scaling and physiologically based clearance (PBCL) models. For the analysis, 17 and 15 drugs were used for model building and external validation, respectively. A model based on the adult drug clearance value and taking into account both weight and age was retained. Age-related maturation of clearance reached 90% of the adult value within 1.5 years of life. For children less than 2 years old, allometric scaling alone systematically overestimated clearances. Accounting for age improved the clearance prediction in the 6 months-2 years age group (prediction error < 25%). Predictions obtained from the PBCL approach were close to our results. This analysis established a single equation using the adult clearance value as well as individual age and weight to predict drug clearance in children older than 6 months. PMID:25721251

  6. Renal Fibrosis

    PubMed Central

    Zeisberg, Michael; Maeshima, Yohei; Mosterman, Barbara; Kalluri, Raghu

    2002-01-01

    During progression of chronic renal disease, qualitative and quantitative changes in the composition of tubular basement membranes (TBMs) and interstitial matrix occur. Transforming growth factor (TGF)-β1-mediated activation of tubular epithelial cells (TECs) is speculated to be a key contributor to the progression of tubulointerstitial fibrosis. To further understand the pathogenesis associated with renal fibrosis, we developed an in vitro Boyden chamber system using renal basement membranes that partially mimics in vivo conditions of TECs during health and disease. Direct stimulation of TECs with TGF-β1/epithelial growth factor results in an increased migratory capacity across bovine TBM preparations. This is associated with increased matrix metalloproteinase (MMP) production, namely MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-β1/EGF or collagen type I was insufficient in inducing migration of untreated TECs across bovine TBM preparation, suggesting that basement membrane integrity and composition play an important role in protecting TECs from interstitial fibrotic stimuli. Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases the capacity of TGF-β1-stimulated TECs to migrate through bovine TBM preparation. Collectively, these results demonstrate that basement membrane structure, integrity, and composition play an important role in determining interstitial influences on TECs and subsequent impact on potential aberrant cell-matrix interactions. PMID:12057905

  7. Renal Calculi

    PubMed Central

    Yendt, E. R.

    1970-01-01

    The pathogenesis of renal calculi is reviewed in general terms followed by the results of investigation of 439 patients with renal calculi studied by the author at Toronto General Hospital over a 13-year period. Abnormalities of probable pathogenetic significance were encountered in 76% of patients. Idiopathic hypercalciuria was encountered in 42% of patients, primary hyperparathyroidism in 11%, urinary infection in 8% and miscellaneous disorders in 8%. The incidence of uric acid stones and cystinuria was 5% and 2% respectively. In the remaining 24% of patients in whom no definite abnormalities were encountered the mean urinary magnesium excretion was less than normal. Of 180 patients with idiopathic hypercalciuria, only 24 were females. In the diagnosis of hyperparathyroidism, the importance of detecting minimal degrees of hypercalcemia is stressed; attention is also drawn to the new observation that the upper limit of normal for serum calcium is slightly lower in females than in males. The efficacy of various measures advocated for the prevention of renal calculi is also reviewed. In the author's experience the administration of thiazides has been particularly effective in the prevention of calcium stones. Thiazides cause a sustained reduction in urinary calcium excretion and increase in urinary magnesium excretion. These agents also appear to affect the skeleton by diminishing bone resorption and slowing down bone turnover. PMID:5438766

  8. Proximal renal tubular acidosis

    MedlinePlus

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  9. Management of diabetic renal disease

    PubMed Central

    Eboh, Cecil

    2015-01-01

    Diabetic nephropathy is the leading cause of end stage renal failure (ESRF) worldwide, representing over 50% of patients on renal replacement therapy in some parts of the world. The condition is common in people with type 1 and type 2 diabetes, although the incidence appears to be declining, especially in type 1 diabetes. More than 1 in 3 people with type 2 diabetes have impaired kidney function. Advances in our understanding of the pathogenesis and natural history of the condition have enabled us to consider earlier therapy aimed at renal preservation and reduction in cardiovascular morbidity. Microalbuminuria is now established as the earliest risk marker for nephropathy in type 1 diabetes and cardiovascular disease in type 2 diabetes. This review examines the current concepts in the pathogenesis and management of diabetic nephropathy. PMID:26244141

  10. Plasma clearance of rat bikunin: evidence for receptor-mediated uptake.

    PubMed Central

    Sjöberg, E M; Blom, A; Larsson, B S; Alston-Smith, J; Sjöquist, M; Fries, E

    1995-01-01

    Bikunin is a chondroitin sulphate-containing protease inhibitor with a molecular mass of 25 kDa. It is secreted into the blood by hepatocytes, and recent observations indicate that it may have an extravascular function. Here we have studied the plasma clearance of bikunin in rats and mice. On intravenous injection, radiolabelled bikunin was found to have a half-life of 10 min; in rats with ligated renal arteries, the clearance time was twice as long, implying that the kidneys account for half the uptake. As judged by gel filtration, the size of bikunin is similar to that of albumin. Autoradiographic analysis of kidneys removed 2 min after the injection of radiolabelled bikunin indicated that, despite its size, bikunin is cleared by glomerular filtration. On ligation of the renal arteries, the plasma concentration of bikunin increased linearly to at least four times normal. This finding shows that the non-renal uptake system is saturated and therefore presumably receptor-mediated. Most of the non-renal uptake of injected bikunin was found to occur in non-visceral tissues such as the skin. Analysis of skin samples by autoradiography after injection of radiolabelled bikunin suggested that bikunin had been transferred from the plasma to the interstitial space. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8948446

  11. Development of a computerised decisions support system for renal risk drugs targeting primary healthcare

    PubMed Central

    Helldén, Anders; Al-Aieshy, Fadiea; Bastholm-Rahmner, Pia; Bergman, Ulf; Gustafsson, Lars L; Höök, Hans; Sjöviker, Susanne; Söderström, Anders; Odar-Cederlöf, Ingegerd

    2015-01-01

    Objectives To assess general practitioners (GPs) experience from the implementation and use of a renal computerised decision support system (CDSS) for drug dosing, developed for primary healthcare, integrated into the patient’s electronic health record (EHR), and building on estimation of the patient's creatinine clearance (ClCG). Design Qualitative research design by a questionnaire and a focus group discussion. Setting and participants Eight GPs at two primary healthcare centres (PHCs). Interventions The GP at PHC 1, and the project group, developed and tested the technical solution of the CDSS. Proof-of-concept was tested by seven GPs at PHC 2. They also participated in a group discussion and answered a questionnaire. A web window in the EHR gave drug and dosage in relation to ClCG. Each advice was according to three principles: If? Why? Because. Outcome measures (1) The GPs’ experience of ‘easiness to use’ and ‘perceived usefulness’ at PHC 2, based on loggings of use, answers from a questionnaire using a 5-point Likert scale, and answers from a focus group discussion. (2) The number of patients aged 65 years and older with an estimation of ClCG before and after the implementation of the CDSS. Results The GPs found the CDSS fast, simple and easy to use. They appreciated the automatic presentation of the CICG status on opening the medication list, and the ability to actively look up specific drug recommendations in two steps. The CDSS scored high on the Likert scale. All GPs wanted to continue the use of the CDSS and to recommend it to others. The number of patients with an estimated ClCG increased 1.6-fold. Conclusions Acceptance of the simple graphical interface of this push and pull renal CDSS was high among the primary care physicians evaluating this proof of concept. The graphical model should be useful for further development of renal decision support systems. PMID:26150141

  12. Renal Denervation

    PubMed Central

    Persu, Alexandre; Renkin, Jean; Thijs, Lutgarde; Staessen, Jan A.

    2013-01-01

    The term “ultima ratio” has multiple, though related, meanings. The motto “ultima ratio regum,” cast on the cannons of the French army of King Louis XIV, meant that war is the last argument of kings, that is, the one to be used after all diplomatic arguments have failed. Along similar lines, we propose that, given the current evidence, renal denervation should be used as a last resort, after state-of-the-art drug treatment optimized at expert centers failed to control blood pressure. PMID:22851728

  13. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

    PubMed Central

    Yu, Mengxiao; Zheng, Jie

    2016-01-01

    A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184

  14. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE)

    PubMed Central

    Santopinto, J J; Fox, K A A; Goldberg, R J; Budaj, A; Piñero, G; Avezum, A; Gulba, D; Esteban, J; Gore, J M; Johnson, J; Gurfinkel, E P

    2003-01-01

    Objective: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). Design: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. Setting: Ninety four hospitals of varying size and capability in 14 countries across four continents. Patients: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. Main outcome measures: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30–60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). Results: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. Conclusion: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction. PMID:12923009

  15. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. ach abatement took place in a school buildin...

  16. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air-sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. Each abatement took place in a school buildi...

  17. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or taxiing... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of...

  18. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... nose wheel landing gear) or nine inches (for each airplane with tail wheel landing gear) between each propeller and the ground with the landing gear statically deflected and in the level takeoff, or taxiing... the corresponding landing gear strut bottomed. (b) Water clearance. There must be a clearance of...

  19. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  20. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  1. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  2. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.77 Clearance certificate. (a) Aircraft departing from the U.S. One... director to show that clearance is granted. (b) Scheduled aircraft. If a scheduled aircraft clears at...

  3. 30 CFR 56.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 56.11008 Section 56.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Travelways § 56.11008 Restricted clearance. Where...

  4. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  5. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  6. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at... the transmission line. If this clearance cannot be attained, the transmission line must be protected... the requirements of paragraph (a) or (b) of this section, each plastic transmission line or main...

  7. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  8. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  9. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  10. 24 CFR 35.1340 - Clearance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... abatement of lead-based paint or lead-based paint hazards shall be performed in accordance with 40 CFR 745... the steps set forth at 40 CFR 745.227(e)(8). If clearance is being performed after lead-based paint... certified to perform risk assessments or lead-based paint inspections. (b) Clearance following...

  11. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  12. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  13. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  14. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  15. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  16. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  17. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  18. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  19. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  20. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  1. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  2. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  3. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  4. 30 CFR 57.7028 - Hand clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hand clearance. 57.7028 Section 57.7028 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Drilling-Underground Only § 57.7028 Hand clearance. Persons shall not rest their hands on the chuck...

  5. 30 CFR 57.7018 - Hand clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hand clearance. 57.7018 Section 57.7018 Mineral... Drilling-Surface Only § 57.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling. Drilling—Underground Only...

  6. 30 CFR 56.7018 - Hand clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hand clearance. 56.7018 Section 56.7018 Mineral... Drilling § 56.7018 Hand clearance. Persons shall not hold the drill steel while collaring holes, or rest their hands on the chuck or centralizer while drilling....

  7. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2014-07-01 2014-07-01 false Security clearance. 154.16 Section...

  8. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2010-07-01 2010-07-01 false Security clearance. 154.16 Section...

  9. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... 32 National Defense 1 2012-07-01 2012-07-01 false Security clearance. 154.16 Section...

  10. Intelligent Engine Systems: HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

  11. Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

    PubMed

    Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

    2016-05-01

    This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. PMID:26358690

  12. Renal acid-base metabolism after ischemia.

    PubMed

    Holloway, J C; Phifer, T; Henderson, R; Welbourne, T C

    1986-05-01

    The response of the kidney to ischemia-induced cellular acidosis was followed over the immediate one hr post-ischemia reflow period. Clearance and extraction experiments as well as measurement of cortical intracellular pH (pHi) were performed on Inactin-anesthetized Sprague-Dawley rats. Arteriovenous concentration differences and para-aminohippurate extraction were obtained by cannulating the left renal vein. Base production was monitored as bicarbonate released into the renal vein and urine; net base production was related to the renal handling of glutamine and ammonia as well as to renal oxygen consumption and pHi. After a 15 min control period, the left renal artery was snared for one-half hr followed by release and four consecutive 15 min reflow periods. During the control period, cortical cell pHi measured by [14C]-5,5-Dimethyl-2,4-Oxazolidinedione distribution was 7.07 +/- 0.08, and Q-O2 was 14.1 +/- 2.2 micromoles/min; neither net glutamine utilization nor net bicarbonate generation occurred. After 30 min of ischemia, renal tissue pH fell to 6.6 +/- 0.15. However, within 45 min of reflow, cortical cell pH returned and exceeded the control value, 7.33 +/- 0.06 vs. 7.15 +/- 0.08. This increase in pHi was associated with a significant rise in cellular metabolic rate, Q-O2 increased to 20.3 +/- 6.4 micromoles/min. Corresponding with cellular alkalosis was a net production of bicarbonate and a net ammonia uptake and glutamine release; urinary acidification was abolished. These results are consistent with a nonexcretory renal metabolic base generating mechanism governing cellular acid base homeostasis following ischemia. PMID:3723929

  13. Active Piezoelectric Structures for Tip Clearance Management Assessed

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Managing blade tip clearance in turbomachinery stages is critical to developing advanced subsonic propulsion systems. Active casing structures with embedded piezoelectric actuators appear to be a promising solution. They can control static and dynamic tip clearance, compensate for uneven deflections, and accomplish electromechanical coupling at the material level. In addition, they have a compact design. To assess the feasibility of this concept and assist the development of these novel structures, the NASA Lewis Research Center developed in-house computational capabilities for composite structures with piezoelectric actuators and sensors, and subsequently used them to simulate candidate active casing structures. The simulations indicated the potential of active casings to modify the blade tip clearance enough to improve stage efficiency. They also provided valuable design information, such as preliminary actuator configurations (number and location) and the corresponding voltage patterns required to compensate for uneven casing deformations. An active ovalization of a casing with four discrete piezoceramic actuators attached on the outer surface is shown. The center figure shows the predicted radial displacements along the hoop direction that are induced when electrostatic voltage is applied at the piezoceramic actuators. This work, which has demonstrated the capabilities of in-house computational models to analyze and design active casing structures, is expected to contribute toward the development of advanced subsonic engines.

  14. Dual clearance squeeze film damper for high load conditions

    NASA Technical Reports Server (NTRS)

    Fleming, D. P.

    1984-01-01

    Squeeze film dampers are widely used to control vibrations in aircraft turbine engines and other rotating machinery. However, if shaft unbalance rises appreciably above the design value (e.g., due to a turbine blade loss), a conventional squeeze film becomes overloaded, and is no longer effective in controlling vibration amplitudes and bearing forces. A damper concept characterized by two oil films is described. Under normal conditions, only one low-clearance film is active, allowing precise location of the shaft centerline. Under high unbalance conditions, both films are active, controlling shaft vibration in a near-optimum manner, and allowing continued operation until a safe shutdown can be made.

  15. [Renal physiology].

    PubMed

    Gueutin, Victor; Deray, Gilbert; Isnard-Bagnis, Corinne

    2012-03-01

    The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, acid-base status, calcium and phosphate metabolism or erythropoiesis. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. The flow of plasma is filtered in the range of 120 mL/min, and depends on the systemic and renal hemodynamics which is subject to self-regulation. The original urine will then be modified in successive segments of the nephron. The proximal nephron is to lead the massive reabsorption of water and essential elements such as sodium, bicarbonates, amino-acids and glucose. The distal nephron includes the distal convoluted tubule, the connector tube and the collecting duct. Its role is to adapt the quality composition of urine to the needs of the body. PMID:22157516

  16. Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old

    PubMed Central

    Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio

    2012-01-01

    Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249

  17. Oral piretanide in chronic renal failure.

    PubMed Central

    Henderson, I S; Beattie, T J; Kennedy, A C; Dombey, S L

    1982-01-01

    1 The effects of high doses of piretanide, a new diuretic agent chemically related to frusemide and bumetanide were evaluated in twelve patients with severe chronic renal insufficiency (creatinine clearance below 25 ml/min). 2 Patients received either 30 mg or 60 mg piretanide orally after a water load of 11. Urine volume and the excretion of electrolytes, creatinine, urea and uric acid were measured over the subsequent 24 h. 3 Piretanide produced an effective diuresis and natriuresis in these patients, its action being broadly similar to those of bumetanide and frusemide observed in previous studies. PMID:7150461

  18. Regional evaluation of renal dynamics in post transplant kidneys with Tc-99m DTPA and scinti-camera

    SciTech Connect

    Suzuki, T.; Akuta, K.; Aoki, S.; Furunishi, H.; Yamazaki, T.; Yamazaki, T.; Nakane, Y.; Pak, K.

    1984-01-01

    The purpose of the study is to analyze the regional renal dynamic process (renal perfusion, accumulation and clearance) using Tc-99m DTPA and assess for the regional renal indices from this analysis early to detect acute tubular necrosis and acute rejection of post transplant kidneys. The subjects were 6 normal donors and 10 post renal transplant patients. Tc-99m DTPA (20 mCi) was injected into the vein by a bolus, and its activity change in the kidney was measured by a scintillation camera, and stored each 1 sec. for 20 sec. following each 15 sec. for 20 min. in the computer, to calculate the renal functional indices: the perfusion index, the blood flow mean transit time, the accumulation rate and the clearance rate in the cortex, medulla and pelvis, whose R.O.I. regions were separated in the early and late scinti-images. The accumulation ratio, a new parameter, which is the second upslope part of Tc-99m DTPA renogram, and the clearance rate were calculated from H/A method. The authors made the functional images of these indices to estimate their regional distribution. The accumulation rate and the clearance rate only in the cortex were markedly decreased in the acute tubular necrosis and the rejection, which functional images showed irregular distributions. It was possible to evaluate the renal perfusion with Tc-99m DTPA, separated from the renal accumulation and clearance process. The authors' method gave the assessment of the regional renal disorders with the functional images; the renal disorders in acute tubular necrosis and acute rejection exist mainly in the cortex.

  19. Xenon spill distribution and room clearance.

    PubMed

    Kelsey, C A; Telepak, R J

    1999-11-01

    The purpose of these studies was to investigate actual xenon gas clearance times under different exhaust conditions, to compare them with the calculated clearance times, to observe the distribution of the xenon gas while it was being exhausted from the room, and to determine the cause of a stationary xenon cloud that appeared on some clinical images. Clearance times with and without a flexible exhaust hose placed next to a simulated 133Xe gas spill were compared with clearance times measured in a room with all exhaust closed off. Two gamma cameras were used to observe the transport and exhaust of xenon following a simulated spill. Clearance times with the flexible exhaust hose were less than one minute because the xenon gas was removed before it had a chance to disperse into the room. Conventional room clearance calculations based on uniform mixing and measured exhaust rates yielded a clearance time of 22 min. The source of an artifactual stationary cloud image was discovered to be a small amount of xenon trapped between the collimator and camera face. A negative pressure and dedicated exhaust can be even more effective in exhausting spilled xenon from a room than air transfer calculations predict. The authors believe the flexible hose should always be used. PMID:10524516

  20. Renal failure in high altitude: renal functions, renal pathology and bone mineralization in rats with ablation nephropathy at 1200 m altitude.

    PubMed

    Soylu, Alper; Kavukçu, Salih; Yilmaz, Osman; Astarcioğlu, Hüseyin; Ozkal, Sermin; Türkmen, Mehmet; Sarioğlu, Sülen

    2007-01-01

    The effect of altitude on renal failure and bone mineralization is not well known. This topic is studied in a 5/6 nephrectomy rat model. After hemoglobin, creatinine clearance and proteinuria were determined in 28 Wistar rats. Two 5/6 nephrectomy (Nx1-Nx2, n=7 each) and two sham (Sh1-Sh2, n=7 each) groups were formed. The Nx1-Sh1 and Nx2-Sh2 groups were kept at sea level and at 1200 m altitude, respectively. The same analyses were performed after 3 months just before sacrifices in order to harvest kidneys and femurs for histopathologic examination. Hemoglobin, creatinine clearance, and proteinuria were similar in all groups at the onset. Final hemoglobin was higher in Nx2-Sh2, but only Sh2 vs. Sh1 was significant (p=0.001). Creatinine clearance decreased (p=0.001 for Nx1) and proteinuria increased (p=0.002 for Nx1 and p=0.005 for Nx2) after 5/6 nephrectomy, but Nx1 vs. Nx2 was similar. Histopathological changes in the remnant kidneys were prominent, but Nx1 vs. Nx2 was not different. Although the relative osteoid volume increased in Nx groups, only Nx1 vs. Sh1 was different (p=0.006). In conclusion, exposure to 1200 m altitude, compared to the sea level, preserved the creatinine clearance better in 5/6 nephrectomized rats. No change was observed in proteinuria, renal histopathology, and bone mineralization. PMID:17904299

  1. Lipoprotein lipase activity and chylomicron clearance in rats fed a high fat diet

    SciTech Connect

    Brown, C.M.; Layman, D.K.

    1988-11-01

    The relationships of tissue and plasma lipoprotein lipase (LPL) activities to tissue uptake and plasma clearance of UC-labeled chylomicron-triglyceride ( UC-CM-TG) were studied in female rats fed isoenergetic and isonitrogenous control (12% kJ from fat) or high fat diets (72% kJ from fat) for 8 wk. Animals fed the high-fat diet had higher levels of fasting plasma triglycerides and lower LPL activities in heart, renal adipose tissue and post-heparin plasma. Changes in LPL activities of skeletal muscles varied among muscles with higher values in the soleus and plantaris (32-61%) and no differences in the gastrocnemius. The lower LPL activity in renal adipose tissue was associated with lower uptake of fatty acids from UC-CM-TG by adipose. Fatty-acid uptake from labeled TG was not associated with tissue LPL activity in other tissues. Clearance of UC-CM-TG from plasma and the half-lives of UC-CM-TG were similar in both dietary groups. These data indicate that tissue and plasma LPL activities are not a direct index of uptake of fatty acids by tissues or clearance of chylomicron triglycerides.

  2. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    SciTech Connect

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion.

  3. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.; Discala, V. A.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero g or space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast 5 of the 7 remaining rats increased the fraction of the filtered sodium excreted (C sub Na/GFR, p .05) and their urinary flow rate (V, p .05). Potassium excretion increased (U sub k V, p .05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause, in rats, a decrease in distal tubular sodium, water and potassium reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis.

  4. Determination of renal blood flow by thermodilution method.

    PubMed

    Leivestad, T; Brodwall, E K; Simonsen, S

    1978-09-01

    The single bolus thermodilution method for measurement of renal vein blood flow was tested. In model experiments the thermodilution method was compared with graduated cylinder measurements over a flow range from 50 to 1050 ml/min. There was a good correlation between the two methods (r = 0.98) with a mean of differences of 5.2%. In eighteen patients measurements were performed in duplicate in thirty-one renal veins. Comparison was made between the first (x) and second (u) measurement--performed within 3 min. The correlation between the two was very good (r = 0.99; y = 1.03x - 11.48). In twelve patients bilateral renal vein blood flow measurements were performed simultaneous to blood flow measurement by PAH clearance. The correlation between total flow measured by thermodilution (y) and by the clearance method (x) was good (r = 0.98; y = 0.79x + 221). It is concluded that the thermodilution method requires catheterization of the renal veins, but is otherwise simple to perform, is inexpensive and gives reliable results. It is particularly advantageous when repeated measurements in the study of acute changes in renal haemodynamics is desirable. PMID:705231

  5. Advanced optical blade tip clearance measurement system

    NASA Technical Reports Server (NTRS)

    Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

    1978-01-01

    An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

  6. Nucleotide-mediated airway clearance.

    PubMed

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  7. Renal and Gastrointestinal Considerations in Joint Replacement Surgery

    PubMed Central

    Voss, Benjamin; Kurdi, Alexander; Skopec, Alexander; Saleh, Jasmine; El-Othmani, Mouhanad M; Lane, Joseph M; Mihalko, William M; Saleh, Khaled J

    2015-01-01

    Renal and gastrointestinal diseases affect a significant portion of the general population. The process of decision making regarding surgical clearance and pre-operative management of the various complexities and medical conditions associated with these diseases hence becomes crucial. To optimize postoperative outcomes, the considerations for the care of this patient population revolve around effective management of hemostasis and electrolyte status. This subset of conditions is uniquely important with regard to the negative impact of improper administration of medications and perioperative care on patients’ prognoses. A thorough understanding and knowledge of standards of care and treatment guidelines for patients with renal dysfunction and gastrointestinal disease assures comprehensive preoperative planning and surgical clearance. This may ultimately lead to improvement of surgical outcomes and potential decrease in postoperative morbidity and mortality. PMID:25811046

  8. High Incidence of Methotrexate Associated Renal Toxicity in Patients with Lymphoma: A Retrospective Analysis

    PubMed Central

    May, Jori; Carson, Kenneth R.; Butler, Sara; Liu, Weijian; Bartlett, Nancy L.; Wagner-Johnston, Nina D.

    2014-01-01

    High dose methotrexate (HDMTX), defined by doses of methotrexate (MTX) ≥ 1g/m2, is a widely used regimen known to cause renal toxicity. The reported incidence of renal toxicity in osteosarcoma patients is 1.8%, but the incidence in hematologic malignancies is not well characterized. In this retrospective study of 649 cycles of HDMTX in 194 patients, renal toxicity occurred in 9.1% of cycles in patients with lymphoma compared to 1.5% in patients with sarcoma. Older age, male sex, decreased baseline CrCl, and increased proton pump inhibitor use among the lymphoma population likely contributed to the observed difference. The incidence of renal toxicity was independent of the incidence of delayed MTX elimination, suggesting that kidney function is only one factor involved in MTX clearance. Renal toxicity prolonged the duration of hospitalization but severe renal insufficiency was uncommon. No significant impact on progression free or overall survival was observed. PMID:24004183

  9. Renal effects of continuous negative pressure breathing

    NASA Technical Reports Server (NTRS)

    Kinney, M. J.

    1975-01-01

    Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted and their urinary flow rate. Potassium excretion increased. End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. The adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension is confirmed.

  10. Shear joint capability versus bolt clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1992-01-01

    The results of a conservative analysis approach into the determination of shear joint strength capability for typical space-flight hardware as a function of the bolt-hole clearance specified in the design are presented. These joints are comprised of high-strength steel fasteners and abutments constructed of aluminum alloys familiar to the aerospace industry. A general analytical expression was first arrived at which relates bolt-hole clearance to the bolt shear load required to place all joint fasteners into a shear transferring position. Extension of this work allowed the analytical development of joint load capability as a function of the number of fasteners, shear strength of the bolt, bolt-hole clearance, and the desired factor of safety. Analysis results clearly indicate that a typical space-flight hardware joint can withstand significant loading when less than ideal bolt hole clearances are used in the design.

  11. Shear-Joint Capability Versus Bolt Clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1994-01-01

    NASA Technical Memorandum presents theoretical study of relationships between load-bearing capabilities of shear joints that comprise plates clamped together by multiple bolts and clearances between bolts and boltholes in those joints.

  12. Voltage-clearance recommendations for printed boards

    SciTech Connect

    Jennings, C W; Cave, G; Evans, A; Harrington, D J; Kirchenbaum, J; Martz, R E; Mierendorf, R C; Smith, G A

    1980-01-01

    Present and future trends in printed board designs point to higher circuit densities with narrower lines and closer spacings. Some designers are now laying out boards with 0.13 mm lines and spacings. The reduction of nominal spacing between conductive elements has raised questions concerning the adequacy of present voltage-clearance recommendations. The present recommendations are considered too conservative in that they are weighted with large safety factors, especially for small clearances, and are frequently disregarded by many designers. Published voltage breakdown measurements made on printed boards with comb patterns with their enhanced conductor test lengths show breakdowns occurring at much higher voltages than those specified for the clearances in existing documents. A Task Group was set up to review published breakdown measurements and to make any additional measurements necessary to provide voltage-clearance recommendations. These recommendations are reported.

  13. Compressor airfoil tip clearance optimization system

    SciTech Connect

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary. During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.

  14. Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

    PubMed Central

    Gong, Yongfeng; Himmerkus, Nina; Plain, Allein; Bleich, Markus

    2015-01-01

    The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney—claudin-14, -16, and -19—as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases. PMID:25071082

  15. Effects of renal failure on drug transport and metabolism.

    PubMed

    Sun, Hong; Frassetto, Lynda; Benet, Leslie Z

    2006-01-01

    Renal failure not only alters the renal elimination, but also the non-renal disposition of drugs that are extensively metabolized by the liver. Although reduced metabolic enzyme activity in some cases can be responsible for the reduced drug clearance, alterations in the transporter systems may also be involved in the process. With the development of renal failure, the renal secretion of organic ions mediated by organic anion transporters (OATs) and organic cation transporters (OCTs) is decreased. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and other organic anionic uremic toxins may directly inhibit the renal excretion of various drugs and endogenous organic acids by competitively inhibiting OATs. In addition, the expression of OAT1 and OCT2 was reduced in chronic renal failure (CRF) rats. Renal failure also impairs the liver uptake of drugs and organic anions, such as bromosulphophthalein (BSP), indocyanine green (ICG), and thyroxine, where organic anion transport polypeptides (OATPs) are the major transporters. Most previous studies have been done in animals or cell culture, very often in rat models, but these are presumed to reflect the presentation of advanced renal disease in humans as well. Recent studies demonstrate that the uremic toxins CMPF and indoxyl sulfate (IS) can directly inhibit rOatp2 and hOATP-C in hepatocytes. The protein content of the liver uptake transporters Oatp1, 2, and 4 were significantly decreased in CRF rats. Decreased activity of the intestinal efflux transporter, P-glycoprotein (P-gp), was also observed in CRF rats, with no significant change of protein content, suggesting that uremic toxins may suppress P-gp function. However, increased protein levels of multidrug resistance-associated protein (MRP) 2 in the kidney and MRP3 in the liver were found in CRF rats, suggesting an adaptive response that may serve as a protective mechanism. Increases in drug areas under the curve (AUCs) in subjects with advanced renal disease

  16. Prediction of glucuronidated drug clearance in pediatrics (≤5 years): An allometric approach.

    PubMed

    Mahmood, Iftekhar

    2015-03-01

    Children are not small adults. The differences between children of different age groups and adults are not merely due to body weight, but also due to physiological and biochemical differences resulting in different rates of drug metabolism or renal clearance. Glucuronidation is an important pathway of drug metabolism. Therefore, the objective of this study is to evaluate the predictive performance of several allometric exponents in children of ≤5 years for the total clearance of drugs which are mainly metabolized by glucuronidation. Four exponents (0.75, 1.0, 1.2, or 1.4) on the body weights and an allometric model developed from adults were evaluated. The four exponents and the allometric model were examined to determine the suitability of the method(s) to predict the clearances of drugs which are glucuronidated in children ≤5 years of age. Based on the analysis of ten drugs, it was noted that the combination of two allometric exponents 1.2 (for children ≤3 months) and 1.0 (for children ≥3 months ≤5 years) can be used to predict mean clearances of drugs which are mainly metabolized by glucuronidation. The suggested approach may be used to estimate a first-in-pediatric dose to initiate a pediatric clinical trial. PMID:24519316

  17. Year in review 2014: airway clearance.

    PubMed

    Strickland, Shawna L

    2015-04-01

    The respiratory therapist has had integrated adjuncts to improve mucus clearance for decades. However, there is a lack of literature describing the impact of these interventions on specific patient populations, resulting in an inability to make recommendations about the use of devices and techniques. The purpose of this article is to review recent literature regarding airway clearance therapies in a manner that is most likely to have interest to the readers of Respiratory Care. PMID:25784773

  18. Inherited renal cystic diseases.

    PubMed

    Kim, Bohyun; King, Bernard F; Vrtiska, Terri J; Irazabal, Maria V; Torres, Vicente E; Harris, Peter C

    2016-06-01

    A number of inherited renal diseases present with renal cysts and often lead to end-stage renal disease. With recent advances in genetics, increasing number of genes and mutations have been associated with cystic renal diseases. Although genetic testing can provide a definite diagnosis, it is often reserved for equivocal cases or for ongoing investigational research. Therefore, imaging findings are essential in the routine diagnosis, follow-up, and detection of complications in patients with inherited cystic renal diseases. In this article, the most recent classification, genetic analysis, clinical presentations, and imaging findings of inherited cystic renal diseases will be discussed. PMID:27167233

  19. Effects of central administration of morphine on renal function in conscious rats.

    PubMed

    Danesh, S; Walker, L A

    1988-02-01

    Systemic administration of morphine in rats produces an anti-natriuretic effect that is at least partially dependent on renal nerves. The present studies were carried out in order to assess the renal response to central administration of morphine. Male Sprague-Dawley rats were surgically prepared with arterial, venous and bladder cannulas. In addition, a guide cannula was placed into the lateral ventrical and secured to the surface of the skull. Experiments were carried out at least 3 days after surgery. Renal clearance measurements were 30 min each. After a basal period, morphine sulfate (4 micrograms/4 microliters) or vehicle was injected into the lateral cerebral ventricle. Two clearance measurements were obtained, followed by central administration of naloxone HCl (4 micrograms/4 microliters) or vehicle and two more clearance periods. Morphine administration had no effect on blood pressure or heart rate but caused a sharp reduction in sodium excretion (3200 +/- 958 vs 970 +/- 158 nEq/100 g/min in period 5; P less than .05). This response was reversed by the addition of naloxone (3280 +/- 583 nEq/100 g/min in period 5; P less than .05). Furthermore, morphine had no effect on renal plasma flow and glomerular filtration rate. Naloxone increased the renal plasma flow and glomerular filtration rate in morphine-treated rats, whereas it had no effect in controls. It is concluded that central administration of morphine in conscious rats enhances renal tubular sodium reabsorption by an opiate receptor-dependent mechanism. PMID:3346840

  20. ADAPTIVE CLEARANCE CONTROL SYSTEMS FOR TURBINE ENGINES

    NASA Technical Reports Server (NTRS)

    Blackwell, Keith M.

    2004-01-01

    The Controls and Dynamics Technology Branch at NASA Glenn Research Center primarily deals in developing controls, dynamic models, and health management technologies for air and space propulsion systems. During the summer of 2004 I was granted the privilege of working alongside professionals who were developing an active clearance control system for commercial jet engines. Clearance, the gap between the turbine blade tip and the encompassing shroud, increases as a result of wear mechanisms and rubbing of the turbine blades on shroud. Increases in clearance cause larger specific fuel consumption (SFC) and loss of efficient air flow. This occurs because, as clearances increase, the engine must run hotter and bum more fuel to achieve the same thrust. In order to maintain efficiency, reduce fuel bum, and reduce exhaust gas temperature (EGT), the clearance must be accurately controlled to gap sizes no greater than a few hundredths of an inch. To address this problem, NASA Glenn researchers have developed a basic control system with actuators and sensors on each section of the shroud. Instead of having a large uniform metal casing, there would be sections of the shroud with individual sensors attached internally that would move slightly to reform and maintain clearance. The proposed method would ultimately save the airline industry millions of dollars.

  1. Pitfalls and Limitations of Radionuclide Renal Imaging in Adults.

    PubMed

    Keramida, Georgia; James, Jacqueline M; Prescott, Mary C; Peters, Adrien Michael

    2015-09-01

    To understand pitfalls and limitations in adult renography, it is necessary to understand firstly the physiology of the kidney, especially the magnitude and control of renal blood flow, glomerular filtration rate and tubular fluid flow rate, and secondly the pharmacokinetics and renal handling of the three most often used tracers, Tc-99m-mercaptoacetyltriglycine (MAG3), Tc-99m-diethylene triamine pentaacetic acid (DTPA) and Tc-99m-dimercaptosuccinic acid (DMSA). The kidneys may be imaged dynamically with Tc-99m-MAG3 or Tc-99m-DTPA, with or without diuretic challenge, or by static imaging with Tc-99m-DMSA. Protocols are different according to whether the kidney is native or transplanted. Quantitative analysis of dynamic data includes measurement of renal vascularity (important for the transplanted kidney), absolute tracer clearance rates, differential renal function (DRF) and response to diuretic challenge. Static image reveals functional renal parenchymal damage, both focal and global, is useful in the clinical management of obstructive uropathy, renal stone disease and hypertension (under angiotensin converting enzyme inhibition), and is the preferred technique for determining DRF. Diagnosis based on morphological appearances is important in transplant management. Even though nuclear medicine is now in the era of hybrid imaging, renal imaging remains an important subspecialty in nuclear medicine and requires a sound basing in applied physiology, the classical supporting discipline of nuclear medicine. PMID:26278854

  2. Lactate clearance and metabolic aspects of continuous high-volume hemofiltration

    PubMed Central

    Cheungpasitporn, Wisit; Zand, Ladan; Dillon, John J.; Qian, Qi; Leung, Nelson

    2015-01-01

    Lactic acidosis is associated with high morbidity and mortality in hospitalized patients. Treatment of lactic acidosis is targeted on correcting the underlying causes and optimizing adequate oxygen delivery to the tissues. Even though evidence is lacking, continuous renal replacement therapy (CRRT) and dialysis have been advocated as treatments for lactic acidosis. We report a 28-year-old Caucasian male with a history of hemophagocytic lymphohistiocytosis who presented with septic shock, severe lactic acidosis and multiple organ failure. Metabolic acidosis was corrected after bicarbonate therapy and CRRT with a hemofiltration rate of 7 L/h (58 mL/kg/h). Lactate clearance was calculated to be 79 mL/min. Compared with reported rates of lactate overproduction in septic shock, the rate of lactate clearance is quite small. Our case suggests that CRRT with high-volume hemofiltration is not effective for severe lactic acidosis. Lactic acidosis alone should not be considered as a nonrenal indication for CRRT. PMID:26251702

  3. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  4. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  5. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  6. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.61 Requirements for clearance. (a) Application for clearance. A...

  7. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  8. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance...

  9. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or...

  10. Metronidazole pharmacokinetics in patients with acute renal failure.

    PubMed

    Somogyi, A A; Kong, C B; Gurr, F W; Sabto, J; Spicer, W J; McLean, A J

    1984-02-01

    The pharmacokinetics and metabolism of intravenous metronidazole were studied in six patients with acute renal failure. In two of the patients a single dose (500 mg) of metronidazole was administered, whereas in four patients the steady-state pharmacokinetics were studied after four days therapy of 500 mg twice daily. Plasma concentrations of metronidazole and its hydroxy and acetic acid metabolites were measured by a specific and sensitive HPLC method. The volume of distribution was 0.65 +/- 0.13 l/kg (mean +/- S.D.), elimination half-life was 9.9 +/- 2.5 h and total plasma clearance was 55.5 +/- 17.7 ml/min. Renal clearance was almost non-existent (1.4 +/- 1.4 ml/min), whereas non-renal clearance was 54.0 +/- 18.2 ml/min. Steady-state plasma concentrations of metronidazole were 15.3 +/- 3.8 mg/l, the hydroxy metabolite were 17.4 +/- 2.0 mg/l and the acetic acid metabolite were 1.2 +/- 0.8 mg/l. In the patients studied, a dosing regimen of 500 mg twice daily resulted in therapeutically adequate blood levels of metronidazole. PMID:6706889

  11. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.

    PubMed

    Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica

    2003-11-01

    The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and

  12. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use. PMID:25343829

  13. Renal vein thrombosis

    MedlinePlus

    ... the kidneys. Possible Complications Complications may include: Acute renal failure (especially if thrombosis occurs in a dehydrated child) ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood ... embolus Renal Tumor Update Date 5/19/2015 Updated by: ...

  14. Kidney (Renal) Failure

    MedlinePlus

    ... renal function using ureteral stenting, nephrostomy, surgery or dialysis. What is kidney (renal) failure? How is kidney ... as a urinary stent or kidney stone removal. Dialysis , including hemodialysis and peritoneal dialysis: These procedures remove ...

  15. Renal papillary necrosis

    MedlinePlus

    ... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...

  16. Renal papillary necrosis

    MedlinePlus

    ... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...

  17. Pharmacokinetics of metronidazole in patients with varying degrees of renal failure.

    PubMed Central

    Houghton, G W; Dennis, M J; Gabriel, R

    1985-01-01

    Twenty-nine patients with varying degrees of renal insufficiency were given a single intravenous dose of metronidazole (500 mg). Plasma and urinary concentrations of metronidazole and two major metabolites were determined using a specific high performance liquid chromatographic assay. The pharmacokinetic parameters of metronidazole elimination half-life, area under the metronidazole concentration against time curve, apparent volume of distribution, metronidazole clearance and predicted degree of accumulation of metronidazole on repeated dosing were not statistically significantly affected by renal inadequacy of any degree. The urinary excretion of metronidazole in patients with moderate or severe renal insufficiency was approximately half the value in healthy volunteers. The renal clearance of metronidazole was significantly greater in healthy volunteers compared to renally insufficient patients, but accounted for less than 10% of the total metronidazole clearance in all groups. The elimination half-life and predicted accumulation (on three times daily dosing) of metabolite I [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole] were significantly increased with decreasing renal function from 9.2 h and 2.3, respectively, in healthy volunteers to 34 h and 6.7, respectively, in patients with total renal failure. The degree of accumulation of this metabolite on repeated dosing is probably of limited clinical significance in all patients except those with severe or total renal failure for reasons detailed in the text. The elimination half-life and predicted accumulation on three times daily dosing of metabolite II, [2-methyl-5-nitroimidazole-1-acetic acid] increased rapidly with decreasing renal function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3986078

  18. Tenofovir-associated renal dysfunction in clinical practice: An observational cohort from western India

    PubMed Central

    Patel, Ketan K.; Patel, Atul K.; Ranjan, Rajiv R.; Patel, Apurva R.; Patel, Jagdish K.

    2010-01-01

    Background: Tenofovir (TDF) is preferred nucleoside reverse transcriptase inhibitors (NRTI) for the treatment of human immunodeficiency virus infection because of its potency and safety. Renal toxicity with TDF use is low and comparable with other NRTI in clinical trials, but there are many case studies and small case series of renal dysfunction with TDF. Materials and Methods: This is an observational longitudinal cohort of patients started on a TDF-based regimen from January 2007 to April 2010. Patients were evaluated at baseline and with every follow-up visit for serum creatinine and calculated creatinine clearance (Cockroft-Gault formula). In addition to this, the patients were also subjected to test for serum potassium, phosphorous and urine examinations as and when indicated. Renal dysfunction was defined as rise in serum creatinine to more than the upper level of normal (>1.2 mg%). Results: Of 1,271 patients started on a TDF-containing antiretroviral treatment (ART) 83 (6.53%) developed renal dysfunction, of which 79 had impaired serum creatinine and five had Fanconi’s syndrome. Renal dysfunction was more common with boosted a protease inhibitor (PI) (9.44%)-based regimen as compared to a non- nucleoside reverse transcriptase inhibitors (NNRTI) (5.01%)-based regimen (P = 0.003). The mean decline in creatinine clearance from baseline was 22.27 ml/min. The median time to develop renal dysfunction was 154 (15–935) days. Serum creatinine returned to normal in all the patients after stopping TDF. Five patients presented with features suggestive of Fanconi’s syndrome without alteration in serum creatinine. Conclusion: TDF-based treatment is associated with mild but reversible renal dysfunction. Patients receiving PI/r are at a higher risk of renal dysfunction compared to those receiving NNRTI-based ART. Clinicians should be adviced to have intensive renal monitoring, including creatinine clearance, urine examination, K+ and phosphate levels at baseline and

  19. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    PubMed Central

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  20. Cardio-renal syndrome

    PubMed Central

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  1. Renal Denervation

    PubMed Central

    Pan, Tao; Guo, Jin-he; Teng, Gao-jun

    2015-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a group of metabolic diseases of multiple etiologies. Although great progress has been made, researchers are still working on the pathogenesis of T2DM and how to best use the treatments available. Aside from several novel pharmacological approaches, catheter-based sympathetic renal denervation (RDN) has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. In this article, we will summarize herein the role sympathetic activation plays in the progression of T2DM and review the recent clinical RDN experience in glucose metabolism. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2015. Studies were included if a statistical relationship was investigated between RDN and T2DM. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did meta-regression analysis. Finally, we identified 4 eligible articles. In most studies, RDN achieved via novel catheter-based approach using radiofrequency energy has gained a significant role in resistant hypertension, as well as improvements in glycemic control in T2DM. But the DREAMS-Study showed that RDN did not change median insulin sensitivity nor systemic sympathetic activity. Firstly, the current published studies lacked a proper control group, along with the sample capacity was small. Also, data obtained in the subgroups of diabetic patients were not separately analyzed and the follow-up period was very short. In addition, a reduction in blood pressure accounts for the improvements in glucose metabolism and insulin resistance cannot be excluded. If the favorable result of better glucose metabolism is confirmed in large-scale, randomized studies

  2. Management of Ureterolithiasis in a Patient with Crossed Unfused Renal Ectopia

    PubMed Central

    2016-01-01

    Crossed renal ectopia is a rare congenital anomaly in which both kidneys are situated on one side and fused together in 85%–90% of cases. The management of urinary calculi in patients with crossed renal ectopia continues to pose challenges to urologists because the aberrant anatomy may make access and clearance of the calculi more difficult to accomplish. Here, we report a case of inferior crossed renal ectopia, without fusion, and a ureteral stone in which the patient was treated successfully by extracorporeal shock wave lithotripsy. PMID:27403369

  3. The renal response to electrical stimulation of renal efferent sympathetic nerves in the anaesthetized greyhound.

    PubMed

    Poucher, S M; Karim, F

    1991-03-01

    1. The effect of direct electrical stimulation of the renal efferent nerves upon renal haemodynamics and function was studied in greyhounds anaesthetized with chloralose and artificially ventilated. The left kidney was neurally and vascularly isolated, and perfused with blood from one of the femoral arteries at a constant pressure of 99 +/- 1 mmHg. Renal blood flow was measured with a cannulating electromagnetic flow probe placed in the perfusion circuit, glomerular filtration rate by creatinine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. Beta-Adrenergic receptor activation was blocked by the infusion of dl-propranolol (17 micrograms kg-1 min-1). The peripheral ends of the ligated renal nerves were stimulated at 0.5, 1.0, 1.5 and 2.0 Hz. 2. At 0.5 Hz frequency only osmolar excretion was significantly reduced (10.3 +/- 3.2%, P less than 0.05, n = 6). Reductions in sodium excretion (53.6 +/- 8.5%, P less than 0.01, n = 6) and water excretion (26.9 +/- 8.0%, P less than 0.05, n = 6) and further reductions of osmolar excretion (20.7 +/- 3.7%, P less than 0.01, n = 6) were observed at 1.0 Hz; however, these were observed in the absence of significant changes in renal blood flow and glomerular filtration rate. Significant reductions were observed in glomerular filtration rate at 1.5 Hz (16.3 +/- 4.1%, P less than 0.02, n = 5) and in renal blood flow at 2.0 Hz (13.1 +/- 4.0%, P less than 0.05, n = 5). Further reductions in urine flow and sodium excretion were also observed at these higher frequencies. 3. These results clearly show that significant changes in renal tubular function can occur in the absence of changes in renal blood flow and glomerular filtration rate when the renal nerves are stimulated electrically from a zero baseline activity up to a frequency of 1.5 Hz. Higher frequencies caused significant changes in both renal haemodynamics and function. PMID:2023113

  4. Renal Function Assessment During Peptide Receptor Radionuclide Therapy.

    PubMed

    Erbas, Belkis; Tuncel, Murat

    2016-09-01

    Theranostics labeled with Y-90 or Lu-177 are highly efficient therapeutic approaches for the systemic treatment of various cancers including neuroendocrine tumors and prostate cancer. Peptide receptor radionuclide therapy (PRRT) has been used for many years for metastatic or inoperable neuroendocrine tumors. However, renal and hematopoietic toxicities are the major limitations for this therapeutic approach. Kidneys have been considered as the "critical organ" because of the predominant glomerular filtration, tubular reabsorption by the proximal tubules, and interstitial retention of the tracers. Severe nephrotoxity, which has been classified as grade 4-5 based on the "Common Terminology Criteria on Adverse Events," was reported in the range from 0%-14%. There are several risk factors for renal toxicity; patient-related risk factors include older age, preexisting renal disease, hypertension, diabetes mellitus, previous nephrotoxic chemotherapy, metastatic lesions close to renal parenchyma, and single kidney. There are also treatment-related issues, such as choice of radionuclide, cumulative radiation dose to kidneys, renal radiation dose per cycle, activity administered, number of cycles, and time interval between cycles. In the literature, nephrotoxicity caused by PRRT was documented using different criteria and renal function tests, from serum creatinine level to more accurate and sophisticated methods. Generally, serum creatinine level was used as a measure of kidney function. Glomerular filtration rate (GFR) estimation based on serum creatinine was preferred by several authors. Most commonly used formulas for estimation of GFR are "Modifications of Diet in Renal Disease" (MDRD) equation and "Cockcroft-Gault" formulas. However, more precise methods than creatinine or creatinine clearance are recommended to assess renal function, such as GFR measurements using Tc-99m-diethylenetriaminepentaacetic acid (DTPA), Cr-51-ethylenediaminetetraacetic acid (EDTA), or

  5. The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats.

    PubMed

    Chia, Tan Y; Sattar, Munavvar A; Abdulla, Mohammed H; Rathore, Hassaan A; Ahmad, Fiaz ud Din; Kaur, Gurjeet; Abdullah, Nor A; Johns, Edward J

    2013-08-01

    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p < 0.05), respectively. Tempol treatment in TCs or TLCs prevented the increase in blood pressure and improved creatinine clearance and sodium excretion compared to untreated Cs. The renal vasoconstriction in Cs or LCs to NA, PE and Ang II were lower than control by ∼35-48% (all p < 0.05). In TCs or TLCs, there was enhanced renal vasoconstriction to all agonist by ∼39-114% compared to Cs. SOD is important to counterbalance the hypertensive effect of a defective NO system and to allow the normal vasoconstrictor response of the renal vasculature to adrenergic agonists and Ang II in a model of CsA-induced renal insufficiency. PMID:23822648

  6. Anemia in pediatric renal transplant recipients.

    PubMed

    Kausman, Joshua Yehuda; Powell, Harley Robert; Jones, Colin Lindsay

    2004-05-01

    The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses

  7. Effect of renal insufficiency on stone recurrence in patients with urolithiasis.

    PubMed

    Kang, Ho Won; Seo, Sung Phil; Kim, Won Tae; Kim, Yong-June; Yun, Seok-Joong; Lee, Sang-Cheol; Kim, Wun-Jae

    2014-08-01

    The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence. PMID:25120325

  8. Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis

    PubMed Central

    He, Yongzhong; Li, Xun; Zhao, Haibo; Su, Zhengming; Jiang, Xianhan; Li, Wenjiao; Zou, Jing; Chen, Qi; Liu, Leyuan

    2016-01-01

    Excessive deposition of extracellular matrix proteins in renal tissues causes renal fibrosis and renal function failure. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles. MAP1S is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and predicts a better prognosis in patients suffering from clear cell renal cell carcinomas. Furthermore, we have characterized that MAP1S enhances the turnover of fibronectin, and mice overexpressing LC3 but with MAP1S deleted accumulate fibronectin and develop liver fibrosis because of the synergistic impact of LC3-induced over-synthesis of fibronectin and MAP1S depletion-caused impairment of fibronectin degradation. Here we show that a suppression of MAP1S in renal cells caused an impairment of autophagy clearance of fibronectin and an activation of pyroptosis. Depletion of MAP1S in mice leads to an accumulation of fibrosis-related proteins and the development of renal fibrosis in aged mice. The levels of MAP1S were dramatically reduced and levels of fibronectin were greatly elevated in renal fibrotic tissues from patients diagnosed as renal atrophy and renal failure. Therefore, MAP1S deficiency may cause the accumulation of fibronectin and the development of renal fibrosis. PMID:27236336

  9. Necessary Clearance to Prevent Side Flashes

    NASA Astrophysics Data System (ADS)

    Shindo, Takatoshi; Asakawa, Akira; Honda, Hideki; Sakae, Maki; Tanaka, Shuusaku

    Side flashes often occur when lightning strikes a tree and cause injury or death of human beings staying nearby the tree. Necessary clearance to prevent the side flash has been said to be 2 m, but the physical meaning of the value is unclear. In this paper, we have proposed a model of side flashes based on the physics of discharges and necessary clearance has been calculated. Furthermore, we have carried out model experiments of the side flash using real trees of a heights of 3.5 m and a naturally growing tree of a height of more than 10 m. The results of the model experiments have verified the proposed theory and it is concluded that clearance of more than 3 m from a tree is necessary to prevent side flashes from the tree.

  10. Glycerol clearance in alcoholic liver disease.

    PubMed Central

    Johnston, D G; Alberti, K G; Wright, R; Blain, P G

    1982-01-01

    Glycerol clearance was studied by a primed dose-constant infusion technique in 14 patients with alcoholic liver disease and six normal control subjects. Fasting blood glycerol concentrations were raised in the alcoholic subjects (0.09 +/- 0.01 vs 0.06 +/- 0.01 mumol/l, p less than 0.05) and glycerol clearance was impaired (24.5 +/- 1.9 vs 37.5 +/- 3.2 ml/kg/min, p less than 0.005). Endogenous production rate of glycerol and distribution space at steady state were similar in alcoholic and control subjects. The metabolic clearance rate of glycerol correlated negatively with basal glycerol concentrations. Thus tissue uptake of glycerol is impaired in liver disease. As glycerol is metabolised primarily in the liver by conversion to glucose, these data suggest a defect of gluconeogenesis in alcoholic liver disease. PMID:7076002

  11. Oral and dental aspects of chronic renal failure.

    PubMed

    Proctor, R; Kumar, N; Stein, A; Moles, D; Porter, S

    2005-03-01

    The present article reviews, in detail, the current knowledge of the oral and dental aspects of chronic renal failure (CRF). Worldwide, increasing numbers of persons have CRF; thus, oral health care staffs are increasingly likely to provide care for patients with such disease. Chronic renal failure can give rise to a wide spectrum of oral manifestations, affecting the hard or soft tissues of the mouth. The majority of affected individuals have disease that does not complicate oral health care; nevertheless, the dental management of such individuals does require that the clinician understand the multiple systems that can be affected. The clinician should also consider the adverse side-effects of drug therapy and appropriate prescribing, in view of compromised renal clearance. PMID:15723858

  12. Endocrine and Metabolic Regulation of Renal Drug Transporters

    PubMed Central

    Yacovino, Lindsay L.; Aleksunes, Lauren M.

    2012-01-01

    Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function. PMID:22933250

  13. Hydrogen Sulfide Inhibits High-Salt Diet-Induced Renal Oxidative Stress and Kidney Injury in Dahl Rats.

    PubMed

    Huang, Pan; Shen, Zhizhou; Liu, Jia; Huang, Yaqian; Chen, Siyao; Yu, Wen; Wang, Suxia; Ren, Yali; Li, Xiaohui; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

    2016-01-01

    BACKGROUND. The study was designed to investigate if H2S could inhibit high-salt diet-induced renal excessive oxidative stress and kidney injury in Dahl rats. METHODS. Male salt-sensitive Dahl and SD rats were used. Blood pressure (BP), serum creatinine, urea, creatinine clearance rate, and 24-hour urine protein were measured. Renal ultra- and microstructures were observed. Collagen-I and -III contents the oxidants and antioxidants levels in renal tissue were detected. Keap1/Nrf2 association and Keap1 s-sulfhydration were detected. RESULTS. After 8 weeks of high-salt diet, BP was significantly increased, renal function and structure were impaired, and collagen deposition was abundant in renal tissues with increased renal MPO activity, H2O2, MDA, GSSG, and (•)OH contents, reduced renal T-AOC and GSH contents, CAT, GSH-PX and SOD activity, and SOD expressions in Dahl rats. Furthermore, endogenous H2S in renal tissues was decreased in Dahl rats. H2S donor, however, decreased BP, improved renal function and structure, and inhibited collagen excessive deposition in kidney, in association with increased antioxidative activity and reduced oxidative stress in renal tissues. H2S activated Nrf2 by inducing Keap1 s-sulfhydration and subsequent Keap1/Nrf2 disassociation. CONCLUSIONS. H2S protected against high-salt diet-induced renal injury associated with enhanced antioxidant capacity and inhibited renal oxidative stress. PMID:26823949

  14. Pharmacologic agents for mucus clearance in bronchiectasis.

    PubMed

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  15. Contrast enhanced ultrasound of renal masses

    PubMed Central

    Ignee, Andre; Straub, Bernd; Schuessler, Gudrun; Dietrich, Christoph Frank

    2010-01-01

    Contrast enhanced ultrasound (CEUS) has gained clinical importance over the last years for the characterization of hepatic masses. Its role in extrahepatic indications has been investigated repeatedly but has been less comprehensively studied. Currently more than 50% of renal masses are incidentally diagnosed, mostly by B-mode ultrasound. The method of choice for characterization of renal lesions is contrast enhanced computed tomography (CECT). In the case of cystic lesions CECT refers to the Bosniak classification for cystic lesions to assess the risk of malignant behavior. The majority of masses are renal cell carcinoma, but the exact proportion is controversial. Disadvantages of CECT are a significant risk for patients with impaired renal function, allergic reactions and hyperthyroidism due to iodinated contrast agents. Several studies concerning CEUS for the characterization of both solid and cystic renal lesions have been published, but prospective multicenter studies are missing, the presented data being mainly descriptive. The aim of the this manuscript is to review the current literature for CEUS in renal masses, to summarize the available data and focus on possible concepts for studies in the future. PMID:21160736

  16. Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs.

    PubMed

    Nikolic, Katarina; Agababa, Danica

    2009-10-01

    Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL'(int)) and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relationship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2)>0.808 and cross-validation parameter q(pre)(2)>0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL'(int) and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data. PMID:19713138

  17. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  18. Recurrent renal giant leiomyosarcoma

    PubMed Central

    Öziş, Salih Erpulat; Gülpınar, Kamil; Şahlı, Zafer; Konak, Baha Burak; Keskin, Mete; Özdemir, Süleyman; Ataoğlu, Ömür

    2016-01-01

    Primary renal leiomyosarcomas are rare, aggressive tumors. They constitute 1–2% of adult malignant renal tumors. Although leiomyosarcomas are the most common histological type (50–60%) of renal sarcomas, information on renal leiomyosarcoma is limited. Local or systemic recurrences are common. The radiological appearance of renal leiomyosarcomas is not specific, therefore renal leiomyosarcoma cannot be distinguished from renal cell carcinoma by imaging methods in all patients. A 74-year-old female patient presented to our clinic complaining of a palpable mass on the right side of her abdomen in November 2012. The abdominal magnetic resonance imaging revealed a mass, 25 × 24 × 23 cm in size. Her past medical history revealed that she has undergone right radical nephrectomy in 2007, due to a 11 × 12 × 13 cm renal mass that was then reported as renal cell carcinoma on abdominal magnetic resonance imaging, but the pathological diagnosis was low-grade renal leiomyosarcoma. The most recent follow-up of the patient was in 2011, with no signs of local recurrence or distant metastases within this four-year period. The patient underwent laparotomy on November 2012, and a 35 cm retroperitoneal mass was excised. The pathological examination of the mass was reported as high-grade leiomyosarcoma. The formation of this giant retroperitoneal mass in 1 year can be explained by the transformation of the lesion’s pathology from low-grade to a high-grade tumor.

  19. Radial Clearance Found To Play a Key Role in the Performance of Compliant Foil Air Bearings

    NASA Technical Reports Server (NTRS)

    Radil, Kevin C.

    2003-01-01

    Compliant foil air bearings are at the forefront of the Oil-Free turbomachinery revolution, which supports gas turbine engines with hydrodynamic bearings that use air instead of oil as the working fluid. These types of bearings have been around for almost 50 years and have found a home in several commercial applications, such as in air cycle machines, turbocompressors, and microturbines, but are now being aggressively pursued for use in small and midrange aircraft gas turbine engines. Benefits include higher operating speeds and temperatures, lower maintenance costs, and greater reliability. The Oil-Free Turbomachinery team at the NASA Glenn Research Center is working to foster the transition of Oil-Free technology into gas turbine engines by performing in-house experiments on foil air bearings in order to gain a greater insight into their complex operating principles. A research program recently undertaken at Glenn focused on the concept of radial clearance and its influence on bearing performance. The tests were conducted on foil bearings with different radial clearances. As defined for a foil bearing, radial clearance is a measure of the small amount of shaft radial motion that is present from play that exists in the elastic support structure, such as between the top and bump foils and the bump foils and bearing shell (see the drawing). With an insufficient amount of radial clearance, the bearing imparts a high preload on the shaft, which when excessive, can reduce the loadcarrying capability of the bearing. On the other hand, systems using foil bearings with excessive radial clearance may experience rotordynamic instabilities because of low bearing preload. Therefore, without a more thorough understanding of radial clearance, it is difficult to accurately predict the performance of a given bearing design. The test program demonstrated that there is a direct correlation between radial clearance and the performance of foil air bearings. As shown in the graph, an

  20. Simultaneous study of the metabolic turnover and renal excretion of salivary amylase-125I and pancreatic amylase-131I in the baboon

    PubMed Central

    Duane, William C.; Frerichs, Roger; Levitt, Michael D.

    1972-01-01

    The metabolic turnover of salivary and pancreatic amylase was studied in the baboon, an animal with a serum amylase level and renal clearance of amylase similar to man. Purified amylase was electrolytically iodinated. Although iodinated and uniodinated amylase had similar gel filtration, electrophoretic, enzymatic, glycogen precipitation characteristics, the labeled enzyme was cleared less rapidly by the kidney than was the unlabeled material. However, urinary iodinated amylase which had been biologically screened by the kidney had a renal clearance and serum disappearance rate indistinguishable from unlabeled amylase and thus can serve as a tracer in metabolic turnover studies. Administration of a mixture of salivary amylase-125I and pancreatic amylase-131I made it possible to simultaneously measure the serum disappearance and renal clearance of these two isoenzymes. The metabolic clearance of both isoenzymes was extremely rapid with half-times of about 130 min. This rapid turnover of serum amylase probably accounts for the transient nature of serum amylase elevation which frequently occurs in pancreatitis. Pancreatic amylase-131I was consistently cleared more rapidly (mean clearance ratio: 1.8) by the kidney than was salivary amylase-125I. This more rapid renal clearance of pancreatic amylase may help to explain the disproportionate elevation of urinary amylase relative to serum amylase observed in pancreatitis. PMID:5024043

  1. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... security personnel who have no access to classified information. (11) To drivers, chauffeurs and...

  2. 32 CFR 154.16 - Security clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be processed for a security clearance in accordance with 32 CFR part 353 and the provisions of this... shall be accomplished in accordance with 32 CFR part 159. The investigative requirement shall be the... security personnel who have no access to classified information. (11) To drivers, chauffeurs and...

  3. Mediators and mucociliary clearance in asthma.

    PubMed

    Pavia, D; Lopez-Vidriero, M T; Clarke, S W

    1987-01-01

    Lung mucociliary clearance is significantly reduced in asthmatic patients compared to healthy controls even during clinical remission. Further retardation in mucous clearance occurs during sleep per se and this may be a contributing factor to nocturnal asthma. Chemical mediators of anaphylaxis appear to have various and, sometimes opposing effects on the two essential components for mucociliary clearance, namely cilia and mucus. Some mediators such as leukotrienes C4 and D4 are potent secretagogues and histamine increases the water flux into the lumen of the airways from the mucosa. Slow-reacting substance of anaphylaxis (SRS-A) reduces mucus transport whereas histamine enhances it. Ciliostimulation has been reported following allergen challenge and this contrasts with the cilioinhibitory effect of asthmatics' sputa. It appears however, that the net effect of the various chemicals of anaphylaxis is one of impairment of mucus clearance. Some pharmacological agents, used for the relief of bronchospasm and control of asthma, also stimulate mucociliary transport, a desirable additional effect. PMID:3311245

  4. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524.74 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INMATE ADMISSION, CLASSIFICATION, AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74...

  5. 30 CFR 57.11008 - Restricted clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Restricted clearance. 57.11008 Section 57.11008 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground §...

  6. 30 CFR 57.11010 - Stairstep clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stairstep clearance. 57.11010 Section 57.11010 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Travelways and Escapeways Travelways-Surface and Underground...

  7. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... accordance with requirements of the Foreign Trade Statistics Regulations (15 CFR part 30) and § 758.1 of the... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  8. Acute psychological stress reduces plasma triglyceride clearance.

    PubMed

    Stoney, Catherine M; West, Sheila G; Hughes, Joel W; Lentino, Lisa M; Finney, Montenique L; Falko, James; Bausserman, Linda

    2002-01-01

    Acute stress elevates blood lipids, with the largest increases among men and postmenopausal women. The mechanisms for the effect are unknown, but may be due to altered lipid metabolism. This study investigated if acute stress induces transient reductions in triglyceride clearance in middle-aged men and women, and determined if gender and menopause affect triglyceride metabolism. Of the 35 women, half were premenopausal, and half were naturally postmenopausal; men (n = 35) were age matched. Clearance of an intravenously administered fat emulsion was assessed twice: once during a nonstress session, and again during a stress-testing session. During the stress session, a battery of behavioral stressors (serial subtraction, speech, mirror tracing, and Stroop) were performed for 40 min. The clearance rate of exogenous fat was significantly diminished during the stress, relative to the nonstress session. Women had more efficient clearance, relative to men, but there were no effects of menopausal status. The diminished ability to clear an intravenous fat emulsion during stress suggests one mechanism for stress-induced elevations in lipids. PMID:12206298

  9. 49 CFR 192.325 - Underground clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Underground clearance. 192.325 Section 192.325 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM...

  10. Renal Artery Embolization

    PubMed Central

    Sauk, Steven; Zuckerman, Darryl A.

    2011-01-01

    Renal artery embolization (RAE) is an effective minimally invasive alternative procedure for the treatment of a variety of conditions. Since the 1970s when RAE was first developed, technical advances and growing experience have expanded the indications to not only include treatment of conditions such as symptomatic hematuria and palliation for metastatic renal cancer, but also preoperative infarction of renal tumors, treatment of angiomyolipomas, vascular malformations, medical renal disease, and complications following renal transplantation. With the drastically improved morbidity associated with this technique in part due to the introduction of more precise embolic agents and smaller delivery catheters, RAE continues to gain popularity for various urologic conditions. The indications and techniques for renal artery embolization are reviewed in the following sections. PMID:23204638

  11. Mechanisms of viral clearance and persistence.

    PubMed

    Borrow, P

    1997-01-01

    Using examples predominantly drawn from study of the lymphocytic choriomeningitis virus (LCMV) model system, this review describes the mechanisms involved in control of virus infections by the cell-mediated immune response, and some of the different strategies viruses have evolved to evade such immune clearance so that they can persist in their hosts. The important role played by the CD8+ cytotoxic lymphocyte (CTL) response in clearance of many systemic virus infections is discussed; and it is emphasized that although CD8+ CTL are classically thought of as lymphocytes which mediate lysis of virus-infected target cells, the principal mechanism by which CD8+ T cells effect clearance of persistent and many acute virus infections via production of antiviral cytokines such as tumour necrosis factor-alpha and interferon-gamma, not via destruction of virus-producing cells. To avoid immune-mediated clearance, viruses frequently use a combination of several different strategies. These can be grouped into mechanisms for avoiding recognition by the immune response (such as establishing latent infections, replicating in immune-privileged sites, down-regulating the expression of immune recognition signals on the surface of infected cells, or undergoing antigenic variation); and mechanisms for suppressing the immune response. The latter include generalized immune suppression mechanisms, and strategies for more precisely disabling the specific immune response such as inducing tolerance or exhaustion of virus-specific CTL. The value of understanding both immune clearance mechanisms and viral evasion strategies in the rational design of immune-based therapies to combat persistent virus infections is discussed. PMID:9429206

  12. 75 FR 70341 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security..._Submission@omb.eop.gov . (SSA), Social Security Administration, DCBFM, Attn: Reports Clearance Officer,...

  13. 19 CFR 122.26 - Entry and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  14. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  15. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  16. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  17. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All U.S. entry and clearance requirements for aircraft, passengers, crews,...

  18. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance. (a... pertinent laws, and the nature of international security and information exchange agreements. The...

  19. 77 FR 44641 - Critical Infrastructure Private Sector Clearance Program Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... Programs Directorate (NPPD), Office of Infrastructure Protection (IP) will submit the following Information... Infrastructure Private Sector Clearance Program (PSCP). DHS previously published this ICR in the Federal...

  20. 77 FR 21989 - Critical Infrastructure Private Sector Clearance Program Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... SECURITY Critical Infrastructure Private Sector Clearance Program Request AGENCY: National Protection and... Programs Directorate (NPPD), Office of Infrastructure Protection (IP) will submit the following Information... information provided. SUPPLEMENTARY INFORMATION: The Critical Infrastructure Private Sector Clearance...

  1. Renal cystic disease

    SciTech Connect

    Hartman, D.S.

    1988-01-01

    The book begins with an overview of renal cystic disease and a presentation of simple renal cysts. Subsequent chapters cover cystic disease in association with renal neoplasms and medullary sponge kidney. The chapters addressing autosomal-dominant and autosomal-recessive polycystic kidney disease discuss and differentiate the infantile and adult forms of the disease. There are also separate discussions of medullary cystic disease, multicystic dysplastic kidney, and cysts of the renarenal sinus.

  2. Calcified renal oncocytoma

    SciTech Connect

    Wasserman, N.F.; Ewing, S.L.

    1983-10-01

    Renal oncocytoma, a neoplasm thought to derive from cells of the proximal convoluted tubules, exhibits benign clinical features. Its preoperative distinction from typical renal cell carcinoma would enable the surgeon to perform a more limited procedure. In a patient who is a poor operative candidate, surgery might be deferred. However, preoperative diagnosis has been elusive. A rare case of bilateral renal oncocytoma is reported. One of these tumors represents the first reported oncocytoma showing radiologically demonstrable calcification.

  3. Cross-sectional analysis of erythropoietin use in CPD: its relation to azotemic index clearances.

    PubMed

    Fox, L; Tzamaloukas, A H; Antoniou, S; Katsoudas, S; Tzouganatou, A; Chisam, G; Goldman, R S; Kakavas, J; Dimitriadis, A; Nicolopoulou, N

    1995-01-01

    The association between the use of erythropoietin and urea or creatinine clearance was studied in two populations on continuous peritoneal dialysis (CPD) residing either at an altitude of 1600 m (n = 194) or at sea level (n = 108). Among peritoneal and total KT/V urea and creatinine clearance (CCr) indices, only total CCr was lower in the high altitude group receiving erythropoietin than in the corresponding group not receiving erythropoietin (68.0 +/- 34.9 vs 82.9 +/- 40.9 L/1.73 m2 weekly, p < 0.01). However, 24-hour urine volume and urinary KT/V urea and CCr were consistently lower in the groups receiving erythropoietin than in those not receiving erythropoietin. Total weekly KT/V urea < or = 1.70 and CCr < or = 52 L/1.73 m2 were considered indicators of inadequate CPD. Although the percent of patients receiving erythropoietin did not differ overall between groups with adequate and those with inadequate CPD, a trend towards more frequent use of erythropoietin was found in the sea level group with inadequate CCr versus the group with adequate CCr (28.2% vs 16.9%, p = 0.084). In CPD decreased renal function is associated with more frequent use of erythropoietin. Whether inadequate total urea or creatinine clearance is also associated with more frequent erythropoietin use requires further study. PMID:8534715

  4. Leptospirosis: an ignored cause of acute renal failure in Taiwan.

    PubMed

    Yang, C W; Pan, M J; Wu, M S; Chen, Y M; Tsen, Y T; Lin, C L; Wu, C H; Huang, C C

    1997-12-01

    Leptospirosis, caused by a spirochete, is the most common zoonosis in domestic or wild animals. Animals excrete infected urine in soil or water and may cause human infections through abrased wound, mucosa, conjunctiva, or by swallowing contaminated water. Clinical presentations of leptospirosis are mostly subclinical. Five to ten percent of leptospirosis are fatal, causing fever, hemorrhage, jaundice, and acute renal failure (Weil's syndrome). Leptospirosis has been ignored as a cause of acute renal failure in Taiwan. We report two patients with leptospirosis who presented with high fever, abdominal pain, jaundice, and acute renal failure. Patient 1 died on day 12 of admission of multiple organ failure associated with pancytopenia, hypogammaglobulinemia, and reactive hemophagocytosis. Leptospirosis was recognized after death. Patient 2 was admitted with similar presentations 2 weeks later. Penicillin and doxycycline were given early in the course, and azotemia, jaundice, respiratory failure, and aseptic meningitis gradually improved. Renal biopsy showed interstitial nephritis. Several tubular clearance tests showed proximal tubular defect with severe bicarbonate wasting (FeHCO3- 20.9%) and incomplete type II renal tubular acidosis without affecting the distal nephron. After 80 days of treatment, this patient was discharged with recovery of conscious level and renal function. This is the first leptospirosis patient with detailed tubular functional and morphological studies of the kidney. Diagnosis of leptospirosis was made by microscopic agglutination test (MAT) for antibody to leptospira and by polymerase chain reaction (PCR) for leptospira DNA in blood and urine (interrogans serogroup australis in case 1 and Leptospira borgpetersenii serogroup ballum in case 2). Because active surveillance has resulted in 13 cases diagnosed as leptospirosis islandwide thereafter, underestimation and ignorance of leptospirosis as a cause of acute renal failure may occur in Taiwan

  5. [Hereditary renal cell carcinomas].

    PubMed

    Hartmann, A; Stöhr, C G; Junker, K

    2010-10-01

    Renal cell carcinomas occur in several hereditary tumor syndromes. These renal tumors frequently have a specific histopathological appearance which can be a sign for a hereditary cause of the disease. The genetic alterations responsible for most of these tumor syndromes were identified in recent years. Interestingly, renal cell carcinomas show specific histopathological features in each of the hereditary renal cancer syndromes. Clear cell and often cystic renal cell carcinomas occur in von Hippel-Lindau syndrome (VHL), while oncocytomas and chromophobe renal cell carcinomas are found in the Birt-Hugg-Dube syndrome, often also as hybrid tumors. Well differentiated papillary carcinomas (Type 1 according to the WHO) are found in the hereditary papillary renal cell carcinoma (HPRC). In contrast, poorly diffentiated papillary renal cell carcinomas (Type 2 according to the WHO) occur in combination with leiomyomas and leiomyosarcomas of the skin and uterus in hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The various genetic causes for these hereditary tumor syndromes open up new therapeutic possibilities, some of which are already being investigated in clinical studies. PMID:20960197

  6. Mast cell stabilizers obviate high fat diet-induced renal dysfunction in rats.

    PubMed

    Reena; Kaur, Tajpreet; Kaur, Anudeep; Singh, Manjinder; Buttar, Harpal Singh; Pathak, Devendra; Singh, Amrit Pal

    2016-04-15

    The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats. PMID:26944217

  7. Relationship between pharmacokinetics and bioavailability of cefroxadine (CGP 9000) and renal function.

    PubMed

    Bergan, T; Brodwall, E K; Larsen, E W

    1983-01-01

    The pharmacokinetics and bioavailability of cefroxadine were studied in 15 patients with different renal functions after administration of 0.5 g as oral capsules and as intravenous infusions. Microbiological assays by agar diffusion and high-pressure liquid chromatography may both be used for this agent since no metabolite can be found. The bioavailability is near 100% of the oral dose regardless of renal function. Urinary recovery varied from about 50% in renal glomerular filtration rates (GFR) of less than 7 ml/min to nearly 100% in normal renal function. The serum concentrations, serum elimination half-life and total body clearance were significantly influenced by reduced renal function. Nonrenal elimination occurred in reduced renal function; the maximum serum elimination half-life was 24.6 h. Dose modifications according to renal function are suggested with from three doses/24 in normal renal function to one dose/24 h in patients with GFR of 10 ml/min. The relative distribution volume corresponded to approximately 30% of the body weight. Tubular secretion of cefroxadine took place. The concentrations in urine remained above 32 mg/l for 12 h in all subjects regardless of renal function. PMID:6872614

  8. WWW-based data entry for document clearance requests

    SciTech Connect

    Stasiak, D.M.

    1997-10-08

    All documents created at Argonne must be cleared before being published. The clearance process is coordinated by the Publications and Record Services. The Electronic Document Review and Clearance System (EDRC) consists of a Web-based system for submission of clearance requests, an electronic staging area for document awaiting review, and Web-based review and clearance of documents. This report covers the document clearing process, the EDRC system, expected benefits/costs, and a demonstration.

  9. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

    PubMed Central

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  10. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  11. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  12. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  13. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  14. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  15. 23 CFR Appendix B to Part 1327 - OMB Clearance

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false OMB Clearance B Appendix B to Part 1327 Highways NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURES FOR PARTICIPATING..., App. B Appendix B to Part 1327—OMB Clearance The OMB clearance number of this regulation is OMB...

  16. 61 FR 11709 - Real Estate Title Clearance and Loan Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    1996-03-22

    ... 0575-AB52 Real Estate Title Clearance and Loan Closing AGENCIES: Rural Housing Service, Rural Business... ``agency,'' amend the Real Estate Title Clearance and Loan Closing regulation. This action makes loan.... The proposed rule discussed the need to make real estate title clearance and loan closing...

  17. 59 FR- Real Estate Title Clearance and Loan Closing

    Federal Register 2010, 2011, 2012, 2013, 2014

    1994-05-11

    .... SUMMARY: The Farmers Home Administration (FmHA) proposes to amend its Real Estate Title Clearance and Loan... changes affect FmHA processing, real estate title clearance, and loan closing. Paperwork Reduction Act The... EO. Discussion FmHA recognizes the need to make Real Estate Title Clearance and Loan...

  18. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  19. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  20. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  1. 14 CFR § 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Customs clearance and visas. § 1260.63 Section § 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance...

  2. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  3. Wear analysis of revolute joints with clearance in multibody systems

    NASA Astrophysics Data System (ADS)

    Bai, ZhengFeng; Zhao, Yang; Wang, XingGui

    2013-08-01

    In this work, the prediction of wear for revolute joint with clearance in multibody systems is investigated using a computational methodology. The contact model in clearance joint is established using a new hybrid nonlinear contact force model and the friction effect is considered by using a modified Coulomb friction model. The dynamics model of multibody system with clearance is established using dynamic segmentation modeling method and the computational process for wear analysis of clearance joint in multibody systems is presented. The main computational process for wear analysis of clearance joint includes two steps, which are dynamics analysis and wear analysis. The dynamics simulation of multibody system with revolute clearance joint is carried out and the contact forces are drawn and used to calculate the wear amount of revolute clearance joint based on the Archard's wear model. Finally, a four-bar multibody mechanical system with revolute clearance joint is used as numerical example application to perform the simulation and show the dynamics responses and wear characteristics of multibody systems with revolute clearance joint. The main results of this work indicate that the contact between the joint elements is wider and more frequent in some specific regions and the wear phenomenon is not regular around the joint surface, which causes the clearance size increase non-regularly after clearance joint wear. This work presents an effective method to predict wear of revolute joint with clearance in multibody systems.

  4. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Processing facility clearance. 95.17 Section 95.17 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance. (a) Following the receipt of an acceptable...

  5. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  6. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... contracting officer shall assume all responsibilities of the plant clearance officer identified in 48 CFR 45... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function....

  7. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... contracting officer shall assume all responsibilities of the plant clearance officer identified in 48 CFR 45... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function....

  8. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  9. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  10. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case....

  11. 33 CFR 157.455 - Minimum under-keel clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  12. 33 CFR 157.455 - Minimum under-keel clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  13. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  14. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  15. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  16. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  17. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  18. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  19. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be...

  20. 30 CFR 56.9330 - Clearance for surface equipment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance for surface equipment. 56.9330... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Loading... Dumping Sites § 56.9330 Clearance for surface equipment. Continuous clearance of at least 30 inches...

  1. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... clearances (PCLs); and (4) Appointing a U.S. citizen employee as the facility security officer. (b) An... NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance....

  2. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  3. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  4. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main...

  5. 10 CFR 95.23 - Termination of facility clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.23 Termination of facility clearance. (a... determination that continued facility clearance is not in the interest of national security. (b) When...

  6. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  7. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  8. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  9. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  10. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  11. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  12. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  13. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  14. 14 CFR 27.661 - Rotor blade clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  15. 14 CFR 29.661 - Rotor blade clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  16. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  17. Tuberous Sclerosis Complex Renal Disease

    PubMed Central

    Dixon, Bradley P.; Hulbert, John C.; Bissler, John J.

    2010-01-01

    Although not as common as other genetic renal diseases such as autosomal dominant polycystic kidney disease, patients with tuberous sclerosis complex frequently have significant renal involvement. Recent revelations in the cell biology of these renal disease manifestations as well as effective therapies for tuberous sclerosis complex-related renal issues have heralded hope of improved renal survival and improved quality of life for the TSC patient. This review specifically addresses some of the major renal manifestations of this disease. PMID:21071977

  18. Renal cell carcinoma: Evolving and emerging subtypes.

    PubMed

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-12-16

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  19. Renal cell carcinoma: Evolving and emerging subtypes

    PubMed Central

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-01-01

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  20. Renal tubular secretion of glutathione (GSH)

    SciTech Connect

    Scott, R.D.; Curthoys, N.P.

    1986-05-01

    The rapid turnover of renal GSH may require its secretion into the tubular lumen. Renal clearance of plasma GSH was measured in rats anesthetized with Inactin and infused with (/sup 3/H)inulin. Renal ..gamma..-glutamyltranspeptidase (..gamma..GT) was then inactivated (> 97%) by infusion of acivicin and samples were collected for 6-7 h. By 4.5 h arterial and urinary GSH increased from 5..mu..M and 1.3 n mol/h to 23 ..mu..M and 2400-7000 nmol/h, respectively. The ratio of urinary GSH to filtered load increased from < 0.01 to 0.7-2.6. When renal GSH was decreased to 30% of normal by pretreating rats with buthionine sulfoximine (BSO), the subsequent inactivation of ..gamma..GT caused only a slight increase in arterial GSH and urinary GSH increased to only 400-600 nmol/h (60-70% of filtered load). The amount of GSH filtered by the kidney was reduced by initially treating a rat with acivicin and 3 h later infusing purified ..gamma..GT (0.2 mg/h) to degrade plasma GSH. Just before infusion of ..gamma..GT, arterial GSH was 23 ..mu..M and urinary GSH was equal to 90% of the filtered load. At 1 h after infusion of ..gamma..GT, arterial GSH decreased to 0.3 ..mu..M, whereas urinary GSH remained elevated (1200-1800 nmol/h) and now equalled 10-20 times the filtered load. When similar experiments were carried out in BSO treated rats, maximal urinary GSH was reduced to 200 nmol/h, a value that was still 10 times the filtered load. Therefore, secreted GSH constitutes a significant portion of the GSH that is normally catabolized within the tubular lumen.

  1. The interstitial expression of alpha-smooth muscle actin in glomerulonephritis is associated with renal function

    PubMed Central

    Novakovic, Zana Saratlija; Durdov, Merica Glavina; Puljak, Livia; Saraga, Marijan; Ljutic, Dragan; Filipovic, Tomislav; Pastar, Zvonimir; Bendic, Antonia; Vukojevic, Katarina

    2012-01-01

    Summary Background In a healthy kidney, contractile protein alpha-smooth muscle actin (ASMA) is immunohistochemically strongly expressed only in the blood vessels, while in pathological conditions it can be visualized in glomerular mesangial cells and interstitial myofibroblasts. The aim of this study was to explore the possible correlation between expression of ASMA in glomerulonephritis (GN) and indicators of renal function. Material/Methods We analyzed expression of ASMA in percutaneous renal biopsy of 142 adult and pediatric patients with GN and its correlation with blood pressure, serum creatinine, creatinine clearance and 24-hour urine protein at the time of biopsy. Immunoexpression of ASMA was analyzed quantitatively using computer-assisted morphometric analysis. Relative surface of ASMA expression in all glomeruli and interstitium was calculated for each patient. Results In adults and children, greater expression of ASMA in interstitium was associated with higher serum creatinine and reduced creatinine clearance. Conversely, greater ASMA expression in glomeruli was associated with normal or decreased serum creatinine in adults and increased creatinine clearance in children. In children, correlation was found between high blood pressure and ASMA expression in interstitium. Conclusions We confirmed that interstitial expression of ASMA is associated with reduced renal function at time of biopsy. The connection of ASMA expression in glomeruli with lower serum creatinine and normal or increased creatinine clearance suggests a favorable role of this phenotypic change in glomerular filtration rate; further investigation is needed. PMID:22460095

  2. Lower bound of optimization in radiological protection system taking account of practical implementation of clearance

    SciTech Connect

    Hattori, Takatoshi

    2007-07-01

    The dose criterion used to derive clearance and exemption levels is of the order of 0.01 mSv/y based on the Basic Safety Standard (BSS) of the International Atomic Energy Agency (IAEA), the use of which has been agreed upon by many countries. It is important for human beings, who are facing the fact that global resources for risk reduction are limited, to carefully consider the practical implementation of radiological protection systems, particularly for low-radiation-dose regions. For example, in direct gamma ray monitoring, to achieve clearance level compliance, difficult issues on how the uncertainty (error) of gamma measurement should be handled and also how the uncertainty (scattering) of the estimation of non-gamma emitters should be treated in clearance must be resolved. To resolve these issues, a new probabilistic approach has been proposed to establish an appropriate safety factor for compliance with the clearance level in Japan. This approach is based on the fundamental concept that 0.1 mSv/y should be complied with the 97.5. percentile of the probability distribution for the uncertainties of both the measurement and estimation of non-gamma emitters. The International Commission on Radiological Protection, ICRP published a new concept of the representative person in Publication 101 Part I. The representative person is a hypothetical person exposed to a dose that is representative of those of highly exposed persons in a population. In a probabilistic dose assessment, the ICRP recommends that the representative person should be defined such that the probability of exposure occurrence is lower than about 5% that of a person randomly selected from the population receiving a high dose. From the new concept of the ICRP, it is reasonable to consider that the 95. percentile of the dose distribution for the representative person is theoretically always lower than the dose constraint. Using this established relationship, it can be concluded that the minimum dose

  3. Heparanase mediates renal dysfunction during early sepsis in mice

    PubMed Central

    Lygizos, Melissa I; Yang, Yimu; Altmann, Christopher J; Okamura, Kayo; Hernando, Ana Andres; Perez, Mario J; Smith, Lynelle P; Koyanagi, Daniel E; Gandjeva, Aneta; Bhargava, Rhea; Tuder, Rubin M; Faubel, Sarah; Schmidt, Eric P

    2013-01-01

    Heparanase, a heparan sulfate-specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N-desulfated re-N-acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP-treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P < 0.05) in comparison to sham mice. Administration of heparanase inhibitors 2 h prior to CLP attenuated sepsis-induced loss of glomerular filtration rate, demonstrating that heparanase activation contributes to early septic renal dysfunction. Glomerular heparanase activation was not associated with renal neutrophil influx or altered vascular permeability, in marked contrast to previously described effects of pulmonary heparanase on neutrophilic lung injury during sepsis. CLP induction of renal inflammatory gene (IL-6, TNF-α, IL-1β) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-α, IL-1β) were not impacted by NAH pretreatment, heparanase inhibition attenuated the CLP-induced increase in serum IL-10. These findings demonstrate that glomerular heparanase is active during sepsis and contributes to septic renal dysfunction via mechanisms disparate from heparanase-mediated lung injury. PMID:24400155

  4. Impaired renal function and bleeding in elderly treated with dabigatran.

    PubMed

    Berthelot, Emmanuelle; Lavenu-Bombled, Cecile; Orostegui-Giron, Lupe; Desconclois, Céline; Assayag, Patrick

    2014-09-01

    Advantages of dabigatran, a thrombin inhibitor, for stroke prevention in patients with atrial fibrillation are numerous. Elderly patients with impaired renal function are at high risk of bleeding. Recommendations about the renal monitoring in elderly patients are not precise enough. The hemoclot direct thrombin inhibitor (HTI) assay measures accurately the dabigatran activity. Both could help managing serious bleeding events in selected populations. Four elderly patients recently treated with appropriate doses of dabigatran were hospitalized for major bleeding. Three patients were very elderly (> 80 years) and three had impaired renal function (clearance < 50 ml/min) before treatment initiation. Serious bleeding events occurred shortly after dabigatran initiation (< 2 months). In all cases, there was a documented dabigatran plasma overdose associated with a renal function impairment concomitant with the bleeding. Why should physicians be aware of this finding?: A close follow-up of the renal function in clinically fragile elderly patient, before and during the weeks following dabigatran initiation, could help to detect the risk of major bleeding event. The HTI dosage could help managing the treatment in case of severe bleeding event. PMID:24509332

  5. Gas turbine engine active clearance control

    NASA Technical Reports Server (NTRS)

    Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

    1985-01-01

    Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

  6. Autophagy promotes DNA-protein crosslink clearance.

    PubMed

    Mu, Haibo; Liu, Qianjin; Niu, Hong; Wang, Dongdong; Tang, Jiangjiang; Duan, Jinyou

    2016-02-01

    Toxic DNA-protein crosslinks (DPCs) can result from exposure to radiation or chemotherapeutic agents. DPCs can also accumulate during aging or stress. However, the cellular mechanisms underlying clearance of DPCs remain largely unknown. Here, we have identified an important role of autophagy in the processing of DPCs induced by three representative agents: formaldehyde, a chemical used widely in industry; UV light; and camptothecin, a cytotoxic anticancer drug. Autophagy inhibitors, 3-methyladenine (3-MA) or chloroquine (CQ), promoted the accumulation of DPCs in damaged cells and injured organs. siRNA-mediated silencing of Atg5 or Atg7, two essential components for the formation of the autophagosome, gave similar results. In contrast, the autophagy inducer rapamycin (RAP) attenuated DPCs in vitro and in vivo. Our findings reveal the importance of autophagy in controlling the level of DPCs, and may open up a new avenue for understanding the formation and clearance of this detrimental DNA adduct. PMID:26921017

  7. High-Clearance Six-Wheel Suspension

    NASA Technical Reports Server (NTRS)

    Bickler, Donald B.

    1992-01-01

    Multilevered suspension system gives body of vehicle high clearance and allows wheels to be steered independently. Suspension linkages above wheels enable body to skim over obstacles as high as wheel. Levers and independently steered wheels enable vehicle to climb steps 1 1/2 wheel diameters high and cross gaps 1 3/4 wide. Adaptable to off-the-road recreational vehicles, military scout vehicles, and robotic emergency vehicles.

  8. Instrument for Measuring Engine Clearance Volumes

    NASA Technical Reports Server (NTRS)

    Sparrow, S W

    1920-01-01

    With the advent of the V type engine, a new method to measure the clearance volume in cylinders was needed. It was suggested that this measurement could be made by a process which consisted essentially of simultaneously changing both a known and unknown volume of gas by a known amount and then calculating the magnitude of the unknown from the resulting difference in pressure between the two. An instrument based on this design is described.

  9. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1976-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as determined principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of convenient approximations of the respiratory tract to predict tractional deposition according to fundamental physical processes of impaction, sedimentation, and diffusion. These theoretical models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with experimental studies of inhaled dusts in humans or experimental animals that have been performed in many laboratories over several decades. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior of very fine (less than 0.01 mum) particles requires further refinement.Properties of particle shape, charge, and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns and further experimental work is urgently needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of such techniques with selected inhaled particle size holds promise in possible diagnostic aid in diagnosis of normal versus disease conditions. Mechanisms of conducting airway and alveolar clearance processes involving mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic clearance are discussed. The roles of the pulmonary macrophage in airway and alveolar clearance are described, and the applicability of recent solubility models for translocation or deposited materials to liver, skeleton, or other systemic organs is discussed. PMID:797567

  10. Localization of Tubular Adaptation to Renal Sodium Loss in Gitelman Syndrome

    PubMed Central

    Nau, Valérie; Kolb, Isabelle; Vargas-Poussou, Rosa; Hannedouche, Thierry; Moulin, Bruno

    2012-01-01

    Summary Background and objectives Gitelman syndrome (GS) is a salt-wasting tubulopathy that results from the inactivation of the human thiazide–sensitive sodium chloride cotransporter located in the distal convoluted tubule. Tubular adaptation to renal sodium loss has been described and localized in the distal tubule in experimental models of GS but not in humans with GS. Design, setting, participants, & measurements The tubular adaptation to renal sodium loss is described. Osmole-free water clearance and endogenous lithium clearance with furosemide infusion are used to compare 7 patients with genetically confirmed GS and 13 control participants. Results Neither endogenous lithium clearance nor osmole-free water clearance disclosed enhanced proximal fluid reabsorption in patients with GS. These patients displayed significantly lower osmole-free water clearance factored by inulin clearance (7.1±1.9 versus 10.1±2.2; P<0.01) and significantly lower fractional sodium reabsorption in the diluting nephron (73.2%±7.1% versus 86.1%±4.7%; P<0.005), consistent with the inactivation of the thiazide-sensitive sodium chloride cotransporter. The furosemide-induced reduction rate of fractional sodium reabsorption in the diluting segment was higher in patients with GS (75.6%±6.1% versus 69.9%±3.2%; P<0.039), suggesting that sodium reabsorption would be enhanced in the cortical part of the thick ascending limb of the loop of Henle in patients with GS. Conclusions These findings suggest that tubular adaptation to renal sodium loss in GS would be devoted to the cortical part of the thick ascending limb of the loop of Henle in humans. PMID:22241817

  11. Impact of glycation on antibody clearance.

    PubMed

    Yang, Jane; Primack, Ronya; Frohn, Mike; Wang, Wei; Luan, Peng; Retter, Marc W; Flynn, Gregory C

    2015-01-01

    Glycation of therapeutic proteins occurs during mammalian cell culture expression and upon administration to patients. Since the chemical attachment of mannose or other sugars via a chemical linker has been shown to increase a protein's clearance rate in mice through the mannose receptor, we explored the effect of mannose glycation on the clearance of an IgG in mice. An IgG decorated with high levels of mannose (~18 mol/mol protein) through glycation did not clear faster in mice than the underivatized protein, whereas the same IgG decorated with mannose attached in a way to maintain the normal glycosidic bond (2-imino-2-methoxyethyl-1-thiomannoside, or IMT-mannose) at similar derivatization levels cleared significantly faster. Surface plasmon resonance studies revealed that the IgG derivatized with IMT-mannose bound tightly to the mannose receptor (KD = 20 nM) but the IgG glycated with mannose did not bind. These results indicate that glycation, even at unnaturally elevated levels, does not appear to be a clearance concern for therapeutic proteins. PMID:25413724

  12. Pathophysiology of protracted acute renal failure in man

    SciTech Connect

    Moran, S.M.; Myers, B.D.

    1985-10-01

    Postischemic acute renal failure (ARF) induced by cardiac surgery is commonly prolonged and may be irreversible. To examine whether persistence of postischemic, tubular cell injury accounts for delayed recovery from ARF, we studied 10 patients developing protracted (36 +/- 4 d) ARF after cardiac surgery. The differential clearance and excretion dynamics of probe solutes of graded size were determined. Inulin clearance was depressed (5.0 +/- 1.7 ml/min), while the fractional urinary clearance of dextrans (radii 17-30 A) were elevated above unity. Employing a model of conservation of mass, we calculated that 44% of filtered inulin was lost via transtubular backleak. The clearance and fractional backleak of technetium-labeled DTPA ((/sup 99m/Tc)DTPA, radius = 4 A) were identical to those of inulin (radius 15 A). The time at which inulin or DTPA excretion reached a maximum after an intravenous bolus injection was markedly delayed when compared with control subjects with ARF of brief duration, 102 vs. 11 min. Applying a three-compartment model of inulin/DTPA kinetics (which takes backleak into account) revealed the residence time of intravenously administered inulin/DTPA in the compartment occupied by tubular fluid and urine to be markedly prolonged, 20 vs. 6 min in controls, suggesting reduced velocity of tubular fluid flow.

  13. Similarity analysis of compressor tip clearance flow structure

    NASA Technical Reports Server (NTRS)

    Chen, G. T.; Greitzer, E. M.; Tan, C. S.; Marble, F. E.

    1991-01-01

    A new approach is presented for analyzing compressor tip clearance flow. The basic idea is that the clearance velocity field can be (approximately) decomposed into independent throughflow and crossflow, since chordwise pressure gradients are much smaller than normal pressure gradients in the clearance region. As in the slender body approximation in external aerodynamics, this description implies that the three-dimensional steady clearance flow can be viewed as a two-dimensional, unsteady flow. Using this approach, a similarity scaling for the crossflow in the clearance region is developed and a generalized description of the clearance vortex is derived. Calculations based on the similarity scaling agree well with a wide range of experimental data in regard to flow features such as crossflow velocity field, static pressure field, and tip clearance vortex trajectory.

  14. Analysis and experimental study of the spherical joint clearance

    NASA Astrophysics Data System (ADS)

    Zhao, Peng; Hu, Penghao; Bao, Xinxin; Li, Shuaipeng

    2013-10-01

    The spherical joint clearance is a key error factor, which influenced and restricted the application of parallel mechanism in high precision field. This paper discusses the regularity of the spherical joint clearance in the parallel mechanism and its influence on the accuracy of the parallel mechanism in both theoretical and experimental aspects. A spherical joint clearance measuring instrument is introduced and used to measure the joint clearance. And the relationship between the clearance and its work pose is revealed. Based on the theoretical and experimental analysis, it is concluded that the clearance of the spherical joint is near-linear proportional to the applied load as well as the clearances in different poses obey the Rayleigh distribution approximately under the same load.

  15. Renal Response to Chronic Centrifugation in Rats

    NASA Technical Reports Server (NTRS)

    Ortiz, Rudy M.; Wang, T. J.; Corbin, B. J.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

  16. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice.

    PubMed

    Arai, Satoko; Kitada, Kento; Yamazaki, Tomoko; Takai, Ryosuke; Zhang, Xizhong; Tsugawa, Yoji; Sugisawa, Ryoichi; Matsumoto, Ayaka; Mori, Mayumi; Yoshihara, Yasunori; Doi, Kent; Maehara, Natsumi; Kusunoki, Shunsuke; Takahata, Akiko; Noiri, Eisei; Suzuki, Yusuke; Yahagi, Naoki; Nishiyama, Akira; Gunaratnam, Lakshman; Takano, Tomoko; Miyazaki, Toru

    2016-02-01

    Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI. PMID:26726878

  17. Progress on Shape Memory Alloy Actuator Development for Active Clearance Control

    NASA Technical Reports Server (NTRS)

    DeCastro, Jonathan; Melcher, Kevin; Noebe, Ronald

    2006-01-01

    Results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine has been conducted. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 in. Design results show that an actuator comprised of 10 wires 2 in. in length is adequate for control at critical engine operating points and still exhibit acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

  18. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  19. Assessment of the effects of renal impairment and smoking on the pharmacokinetics of a single oral dose of the soluble guanylate cyclase stimulator riociguat (BAY 63-2521)

    PubMed Central

    Becker, Corina; Unger, Sigrun; Schmidt, Anja; Wensing, Georg; Mück, Wolfgang

    2016-01-01

    Abstract Renal impairment is a common comborbidity in patients with pulmonary hypertension. The breakdown of riociguat, an oral soluble guanylate cyclase stimulator used to treat pulmonary hypertension, may be affected by smoking because polycyclic aromatic hydrocarbons in tobacco smoke induce expression of one of the metabolizing enzymes, CYP1A1. Two nonrandomized, nonblinded studies were therefore performed to investigate the pharmacokinetics and safety of a single oral dose of riociguat 1.0 mg in individuals with mild, moderate, or severe renal impairment compared with age-, weight-, and sex-matched healthy controls, including either smokers and nonsmokers (study I) or nonsmokers alone (study II). Pharmacokinetic analyses focused on the integrated per-protocol data set of both studies (N = 63). In patients with renal impairment, the renal clearance of riociguat was reduced and its terminal half-life prolonged compared with those in healthy controls. There was a monotonic relationship between creatinine clearance on treatment day and riociguat renal clearance (R2 = 0.62). However, increased riociguat exposure with decreasing renal function was not strictly proportional. Riociguat exposure appeared to be greater in nonsmokers than in the combined population of smokers and nonsmokers, irrespective of renal function. Adverse events were mild to moderate and in line with the mode of action of riociguat. No serious adverse events occurred. In conclusion, renal impairment was associated with reduced riociguat clearance compared with that in controls; however, riociguat exposure in patients with renal impairment was highly variable, and ranges overlapped with those observed in healthy controls. PMID:27162624

  20. Pharmacokinetics of iothalamate in endstage renal disease

    SciTech Connect

    Evans, J.R.; Cutler, R.E.; Forland, S.C.

    1988-09-01

    Some nephrologists make alterations in routine peritoneal and hemodialysis schedules after diagnostic studies that use radiographic contrast agents. A study to determine the pharmacokinetics of one contrast agent, iothalamate, is reported. The plasma (total body) clearance of iothalamate was measured in seven patients who had endstage renal disease (ESRD) and who received maintenance hemodialysis. During an interdialytic period, plasma clearance of iothalamate varied from 0.7 to 5.2 mL/min (3.1 +/- 1.8 mL/min, mean +/- SD) with an elimination rate constant (beta) of 0.0164 +/- 0.01 hr-1, a terminal half-life of 61 +/- 42 hours, and an estimated distribution volume of 11 +/- 3.9 L. Hemodialysis clearance of iothalamate was 104 +/- 54 mL/min. With the assumption that iothalamate is mainly distributed in the extracellular fluid (ECF) compartment, the theoretical fluid shift from the intracellular fluid (ICF) compartment to the ECF compartment was 323 mL after administration of the largest dose (2.1 mL/kg or 1.6 mmol/kg of body weight) of 60% meglumine iothalamate solution. The average maximum serum osmolarity change was less than expected, suggesting some type of internal buffering of meglumine iothalamate. In the first few hours after radiocontrast administration in four patients, the average change in serum osmolarity was 5 mmol/L; the average change in serum sodium concentration during this same time was a decrease of 0.5 mmol/L. The minor increase in ECF volume induced by hyperosmolar contrast agents does not require immediate dialysis in most patients. When needed, however, for contrast-related adverse effects, hemodialysis is efficient in rapidly removing iothalamate.

  1. Renal glucose release during hypoglycemia is partly controlled by sympathetic nerves - a study in pigs with unilateral surgically denervated kidneys.

    PubMed

    Bischoff, Sabine J; Schmidt, Martin; Lehmann, Thomas; Schwab, Matthias; Matziolis, Georg; Saemann, Alexander; Schiffner, René

    2015-11-01

    Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 ± 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 ± 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients. PMID:26564063

  2. Complex Disease–, Gene–, and Drug–Drug Interactions: Impacts of Renal Function, CYP2D6 Phenotype, and OCT2 Activity on Veliparib Pharmacokinetics

    PubMed Central

    Li, Jing; Kim, Seongho; Sha, Xianyi; Wiegand, Richard; Wu, Jianmei; LoRusso, Patricia

    2014-01-01

    Purpose Veliparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, undergoes renal excretion and liver metabolism. This study quantitatively assessed the interactions of veliparib with metabolizing enzyme (CYP2D6) and transporter (OCT2) in disease settings (renal impairment). Experimental Design Veliparib in vitro metabolism was examined in human liver microsomes and recombinant enzymes carrying wild-type CYP2D6 or functional defect variants (CYP2D6*10 and *4). Plasma pharmacokinetics were evaluated in 27 patients with cancer. A parent–metabolite joint population model was developed to characterize veliparib and metabolite (M8) pharmacokinetics and to identify patient factors influencing veliparib disposition. A physiologically based pharmacokinetic model integrated with a mechanistic kidney module was developed to quantitatively predict the individual and combined effects of renal function, CYP2D6 phenotype, and OCT2 activity on veliparib pharmacokinetics. Results In vitro intrinsic clearance of CYP2D6.1 and CYP2D6.10 for veliparib metabolism were 0.055 and 0.017 μL/min/pmol CYP, respectively. Population mean values for veliparib oral clearance and M8 clearance were 13.3 and 8.6 L/h, respectively. Creatinine clearance was identified as the significant covariate on veliparib oral clearance. Moderate renal impairment, CYP2D6 poor metabolizer, and co-administration of OCT2 inhibitor (cimetidine) increased veliparib steady-state exposure by 80%, 20%, and 30%, respectively. These factors collectively led to >2-fold increase in veliparib exposure. Conclusions Renal function (creatinine clearance) is a significant predictor for veliparib exposure in patients with cancer. Although a single factor (i.e., renal impairment, CYP2D6 deficiency, and reduced OCT2 activity) shows a moderate impact, they collectively could result in a significant and potentially clinically relevant increase in veliparib exposure. PMID:24947923

  3. Analysis and preliminary design of an optical digital tip clearance sensor for propulsion control

    NASA Technical Reports Server (NTRS)

    Poppel, G. L.

    1978-01-01

    Following the generation of several concepts for passive, digital compatible, optical sensors for propulsion control systems, a tip clearance sensor was chosen for further analysis and preliminary design. Emphasis was placed on application to the TF34 engine compressor section. Laboratory experiments were performed to investigate several optical aspects of the concept. Preliminary design included an assessment of all sensor elements and recommendations for development programs. Quantitative predictions were made of sensor performance. A test plan was written to demonstrate sensor feasibility and that the performance goals can be met. A continuing experimental and design effort was suggested.

  4. Renal function and plasma volume following ultramarathon cycling.

    PubMed

    Neumayr, G; Pfister, R; Hoertnagl, H; Mitterbauer, G; Prokop, W; Joannidis, M

    2005-01-01

    In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training. PMID:15643528

  5. Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease.

    PubMed

    Iwama, Ryosuke; Sato, Tsubasa; Katayama, Masaaki; Shimamura, Shunsuke; Satoh, Hiroshi; Ichijo, Toshihiro; Furuhama, Kazuhisa

    2015-08-01

    We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1-3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD. PMID:25864431

  6. Relationships between Serum Levels of Atazanavir and Renal Toxicity or Lithiasis

    PubMed Central

    Marinescu, C. I.; Leyes, M.; Ribas, M. A.; Peñaranda, M.; Murillas, J.; Campins, A. A.; Martin-Pena, L.; Barcelo, B.; Barceló-Campomar, C.; Grases, F.; Frontera, G.; Riera Jaume, Melchor

    2015-01-01

    The main aim of this study is to describe the relationship between serum levels of atazanavir, renal toxicity, and lithiasis. This is a prospective observational study of patients being treated with atazanavir (ATV) at Son Espases Teaching Hospital, Palma de Mallorca, between 2011 and 2013. The study includes 98 patients. Sixteen were found to have a history of urolithiasis. During a median monitoring period of 23 months, nine patients suffered renal colic, in three of whom ATV crystals were evidenced in urine. Cumulative incidence of renal colic was 9.2 per 100 patients. The variables related to having renal colic were the presence of alkaline urine pH and lower basal creatinine clearance. The mean serum level of ATV was slightly higher in patients with renal colic—1,303 μg/L versus 1,161 μg/L—but did not reach statistical significance. Neither were any significant differences detected by analysing the levels according to the timetable for ATV dosage. Cumulative incidence of renal colic was high in patients being treated with ATV, in 33% of whom the presence of ATV crystals was evidenced in urine. We were unable to demonstrate a relationship between ATV serum levels and renal colic or progression towards renal failure. PMID:26064679

  7. Managing new-onset gout in pediatric renal transplant recipients: when, how, to what extent.

    PubMed

    Assadi, Farahnak

    2013-01-01

    Hyperuricemia and gout are common among adult renal transplant recipients, but it is rarely reported following pediatric renal transplantations. Treating gout in pediatric kidney transplant recipients presents clinical challenges to the management of both immunosuppressive regimen and hyperuricemia for their effects on serum uric acid levels, renal function and drug interactions. Most renal transplant recipients have a relative impairment of renal clearance of urate due to abnormalities in renal transport, explaining the association of hyperuricemia and decreased glomerular filtration rate. Risk factors for the development of gout include impaired renal function, hypertension, heart failure and diabetes mellitus. Calcineurin inhibitors, particularly cyclosporine, are the most important risk factor for gout in transplant recipients and should not be used in pediatric renal transplant recipients. Diuretic therapy increases the risk of gout by causing extracellular volume contraction with consequent enhancement of proximal tubular reabsorption. Corticosteroids are increasingly replacing nonsteroidal antiinflammatory drugs and colchicine for the treatment of acute gout flares because they have little effect on kidney function. Proper management is aimed at lowering serum uric acid level below 6.0 mg/dL with xanthine oxidase inhibitors such as allopurinol or febuxostat. Allopurinol and mycophenolate mofetil are safer to use in combination than are allopurinol and azathioprine. Febuxostat is an alternative to allopurinol in patients with allopurinol intolerance or hypersensitivity. Pegloticase is indicated for patients with severe gout in whom allopurinol and febuxostat have not been effective or tolerated. PMID:22941874

  8. [Atherosclerotic renal artery stenosis].

    PubMed

    Sauguet, A; Honton, B

    2014-12-01

    Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. Renal artery stenosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Many patients with RAS may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the cardiovascular outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of RAS for cardiologists in the context of recent randomized clinical trials. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary edema, rapidly declining renal function and severe resistant hypertension. PMID:25450992

  9. [Renal osteodystrophy (2): its treatment in renal insufficiency before dialysis].

    PubMed

    Hottelart, C; Bako, G; Oprisiu, R; Georgita, A; Presne, C; Sarraj, A; Morinière, P; el Esper, N; Fournier, A

    2000-01-01

    1. In the patient with renal insufficiency before dialysis, the phosphocalcic disorders appear insidiously. They are dominated by hyperparathyroidism which will be diagnosed on the initially yearly determination of plasma intact PTH as soon as creatinine clearance decreases below 60 ml/min, eventhough there is still no modification in plasma concentrations of calcium and phosphate. Its diagnosis should lead to initiate the therapeutic measures in order to prevent the irreversible thining of the corticals by endosteal resorption and later the occurrence of histological and radiological osteitis fibrosa favoring fractures. 2. Hyperparathyroidism prevention relies on two main measures: prevention of phosphate retention and hypocalcemia is implemented by progressive phosphate and protein restriction (from 1 g/kg/day when Ccr < 60 ml/min to 0.6 g/kg/day when Ccr < 20 ml/min) and administration of CaCO3 (1.5 g at lunch and dinner to better complex the phosphate) as soon as PTH is above normal; optimal vitamin D repeletion will be implemented by systematic supplementation of native vitamin D or 25OH vitamin D3 in order to bring P25OHD between 30-60 ng/ml (75-150 nmol/l) or more generally around the upper limit of the epidemiologic range of the laboratory; these measures should aim at maintaining plasma intact PTH in its optimal range variable with the degree of renal insufficiency: 0.5-1; 1-2.5 and 2-3 folds the upper limit of normal for creatinine clearance respectively at 60-30; 30-10 and < 10 ml/min. 3. Because of their hyperphosphatemic and hypercalcemic effect, 1 alpha-hydroxylated vitamin D derivatives will be regularly efficient and safe only when non-calcemic non-aluminic phosphate binder will be available and proven to be without side-effects. 4. Instrumental (surgical or by alcohol injection) parathyroidectomy should be considered when plasma intact PTH is > 5 to 7 times the upper limit of normal in the presence of hypercalcemia (> 2.60 mmol/l) and

  10. Cadmium and renal cancer

    SciTech Connect

    Il'yasova, Dora; Schwartz, Gary G. . E-mail: gschwart@wfubmc.edu

    2005-09-01

    Background: Rates of renal cancer have increased steadily during the past two decades, and these increases are not explicable solely by advances in imaging modalities. Cadmium, a widespread environmental pollutant, is a carcinogen that accumulates in the kidney cortex and is a cause of end-stage renal disease. Several observations suggest that cadmium may be a cause of renal cancer. Methods: We performed a systematic review of the literature on cadmium and renal cancer using MEDLINE for the years 1966-2003. We reviewed seven epidemiological and eleven clinical studies. Results: Despite different methodologies, three large epidemiologic studies indicate that occupational exposure to cadmium is associated with increased risk renal cancer, with odds ratios varying from 1.2 to 5.0. Six of seven studies that compared the cadmium content of kidneys from patients with kidney cancer to that of patients without kidney cancer found lower concentrations of cadmium in renal cancer tissues. Conclusions: Exposure to cadmium appears to be associated with renal cancer, although this conclusion is tempered by the inability of studies to assess cumulative cadmium exposure from all sources including smoking and diet. The paradoxical findings of lower cadmium content in kidney tissues from patients with renal cancer may be caused by dilution of cadmium in rapidly dividing cells. This and other methodological problems limit the interpretation of studies of cadmium in clinical samples. Whether cadmium is a cause of renal cancer may be answered more definitively by future studies that employ biomarkers of cadmium exposure, such as cadmium levels in blood and urine.

  11. Predictive factors for renal failure and a control and treatment algorithm

    PubMed Central

    Cerqueira, Denise de Paula; Tavares, José Roberto; Machado, Regimar Carla

    2014-01-01

    Objectives to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease. Method exploratory, descriptive, prospective study with a quantitative approach. Results a total of 30 patients (75.0%) were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6%) showed a reduction in creatinine clearance in the first 24 hours of hospitalization. Conclusion a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way. PMID:26107827

  12. Clinical efficacy of 99m-technetium mercaptoacetylglycine kit formulation in routine renal scintigraphy

    SciTech Connect

    duCret, R.P.; Boudreau, R.J.; Gonzalez, R.; Carpenter, R.; Tennison, J.; Kuni, C.C.

    1989-07-01

    99m-Technetium mercaptoacetylglycine is a promising new renal radiopharmaceutical undergoing phase III trials in the United States. In a preliminary investigation of the efficacy and safety of mercaptoacetylglycine in 30 adult patients with suspected renal disease we used simultaneous imaging with orthoiodohippurate as the physiological ''gold standard''. Of these patients 11 had undergone renal transplantation. Factors, such as time to peak renal activity, clearance half-life and regional functional comparison, were similar by orthoiodohippurate and mercaptoacetylglycine imaging. Visual and quantitative analysis of angiograms and renograms was markedly facilitated with the use of mercaptoacetylglycine. Several morphological abnormalities were apparent only during mercaptoacetylglycine evaluation. No adverse effects, changes in vital signs or significant changes in clinical laboratory status were encountered. Since mercaptoacetylglycine combined an excellent technetium image with the pharmacokinetics of orthoiodohippurate, mercaptoacetylglycine may supplant all other agents for routine clinical use.

  13. Stem cell technology for the treatment of acute and chronic renal failure

    PubMed Central

    Pino, Christopher J.; Humes, H. David

    2010-01-01

    Acute and chronic renal failure are disorders with high rates of morbidity and mortality. Current treatment is based upon conventional dialysis to provide volume regulation and small solute clearance. There is growing recognition that renal failure is a complex disease state requiring a multifactorial therapy to address the short-comings of the conventional monofactorial approach. Kidney transplantation remains the most effective treatment, however, organ availability lags far behind demand. Many key kidney functions including gluconeogenesis, ammoniagenesis, metabolism of glutathione, catabolism of important peptide hormones, growth factors, and cytokines critical to multiorgan homeostasis and immunomodulation are provided by renal tubule cells. Therefore, cell-based therapies are promising multifactorial treatment approaches. In this review, current stem cell technologies including adult stem cells, embryonic stem cells and induced pluripotent stem cells will be discussed as cell sources for the treatment of acute and chronic renal failure. PMID:20801413

  14. Multicystic renal dysplasia.

    PubMed

    Nagaraj, V P; Ratnakar, K S

    2001-07-01

    Multicystic renal dysplasia, the most common form of cystic renal disease in the newborn period, is a clinically important consequence of abnormal nephrogenesis. It usually presents as an abdominal mass. The dysplasias are usually unilateral, but it can be bilateral, segmental or focal. The clinical presentation usually depends on the extent of the dysplastic involvement and the degree of the associated urinary obstruction. Here, we present a case of histologically multicystic renal dysplasia, which is ?bilateral. The left kidney showed typical radiological, gross and histopathological features of multicystic dysplasia, but the right kidney showed only radiological features of dysplastic cystic kidney. PMID:11479648

  15. Renal Replacement Therapy.

    PubMed

    Villa, Gianluca; Ricci, Zaccaria; Ronco, Claudio

    2015-10-01

    Renal replacement therapy (RRT) is a cornerstone in the clinical management of patients with acute kidney injury. Results from different studies agree that early renal support therapy (aimed to support the residual kidney function during early phases of organ dysfunction) may reduce mortality with respect to late RRT (aimed to substitute the complete loss of function during the advanced kidney insufficiency). Although it seems plausible that a timely initiation of RRT may be associated with improved renal and nonrenal outcomes in these patients, there is scarce evidence in literature to exactly identify the most adequate onset timing for RRT. PMID:26410148

  16. Impaired Clearance of Methotrexate in Organic Anion Transporter 3 (Slc22a8) Knockout Mice: A Gender Specific Impact of Reduced Folates

    PubMed Central

    VanWert, Adam L.; Sweet, Douglas H.

    2010-01-01

    Purpose To elucidate the role of the renal basolateral transporter, Oat3, in the disposition of methotrexate. Materials and Methods Chinese hamster ovary cells expressing mouse Oat3 were used to determine kinetics and specificity of inhibition of methotrexate transport. Methotrexate clearance was then examined in vivo in wildtype and Oat3 knockout mice. Results NSAIDs, ß-lactams, and uremic toxins inhibited mOat3-mediated methotrexate uptake by 70–100%, while folate, leucovorin, and 5-methyltetrahydrofolate inhibited transport by 25–50%. A Km of 60.6±9.3 μM for methotrexate transport was determined. Oat3 knockout mice exhibited reduced methotrexate-to-inulin clearance ratios versus wildtype. Male wildtype mice, but not knockouts or females, demonstrated significantly accelerated methotrexate clearance in response to reduced folates. Reduced folates also markedly inhibited hepatic methotrexate accumulation in males, but not females, and the response was independent of Oat3 function. Conclusions Oat3 contributes to methotrexate clearance, but represents only one component responsible for methotrexate's elimination. Therefore, in patients, dysfunctional hOAT3 polymorphisms or drug competition for hOAT3 transport may severely impact methotrexate elimination only when redundant means of methotrexate removal are also compromised. Furthermore, the present findings suggest that reduced-folate administration only influences methotrexate disposition in males, with the renal reduced-folate response influenced by OAT3 function. PMID:17660957

  17. Cyclosporin-erythromycin interaction in renal transplant patients.

    PubMed Central

    Gupta, S K; Bakran, A; Johnson, R W; Rowland, M

    1989-01-01

    1. The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA. 2. Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c. 3. Erythromycin produced almost a two-fold increase in bioavailability, from 36% to 60%; with a small (13%) decrease in clearance of CyA. 4. The metabolite 17 data further support the postulate that erythromycin increases the absorption of CyA rather than inhibits its metabolism, as generally believed. PMID:2655690

  18. Dialysis disequilibrium syndrome occurring during continuous renal replacement therapy

    PubMed Central

    Tuchman, Shamir; Khademian, Zarir P.; Mistry, Kirtida

    2013-01-01

    The dialysis disequilibrium syndrome (DDS) is characterized by progressive neurological symptoms and signs attributable to cerebral edema that occurs due to fluid shifts into the brain following a relatively rapid decrease in serum osmolality during hemodialysis (HD). Since continuous renal replacement therapy (CRRT) is less efficient at solute clearance than intermittent HD, it seems logical that this mode of therapy is less likely to cause DDS. This entity has not been previously reported to occur with this modality. Here, we report two cases of DDS associated with CRRT that provide insights into its pathophysiological mechanisms and suggest strategies for its prevention. PMID:26120445

  19. We use Continuous Renal Replacement Therapy for Overdoses and Intoxications.

    PubMed

    Cabrera, Valerie Jorge; Shirali, Anushree C

    2016-07-01

    Extracorporeal modalities for the removal of drugs and toxins are indicated for the treatment of overdoses and intoxications. Well-established modalities include hemodialysis (HD), high-flux HD (HfD), and charcoal hemoperfusion (HP). Recently, there have been increasing reports on the use of continuous renal replacement therapy (CRRT), such as continuous veno-venous hemodialysis (CVVHD), continuous veno-venous hemofiltration (CVVH) or CVVH combined with dialysis (CVVHDF). In the present article, we will discuss the various factors that determine the clearance of drugs and toxins and accordingly, we will propose that with few exceptions, CRRT does not have a role in the routine management of intoxications. PMID:27126739

  20. Pharmacokinetics of serelaxin in patients with severe renal impairment or end-stage renal disease requiring hemodialysis: A single-dose, open-label, parallel-group study.

    PubMed

    Dahlke, Marion; Halabi, Atef; Canadi, Jasna; Tsubouchi, Chiaki; Machineni, Surendra; Pang, Yinuo

    2016-04-01

    Serelaxin, a recombinant human relaxin-2 hormone, is in clinical development for treating acute heart failure. This open-label, parallel-group study investigated serelaxin pharmacokinetics (PK) after a single 4-hour intravenous infusion (10 µg/kg) in patients with severe renal impairment (n = 6) or end-stage renal disease (ESRD) requiring hemodialysis (PK on the day of dialysis [n = 6] or during dialysis-free interval [n = 6]), compared with matched healthy subjects (n = 18). In all participants, serum serelaxin concentration peaked at the end of infusion and subsequently declined with mean terminal elimination half-life of 6.5-8.8 hours. Compared with healthy subjects, a moderate decrease in serelaxin systemic clearance (37%-52%) and increase in its exposure (30%-115%) were observed in all patients. During the 4-hour hemodialysis in ESRD patients, 30% serelaxin was removed, with hemodialysis clearance constituting approximately 52% of total systemic clearance. Serelaxin was well tolerated with no deaths, serious adverse events (AE), or AE-related discontinuations. Antiserelaxin antibodies were not detected in any participant. Given the shallow dose-response relationship observed with serelaxin in clinical studies and its wide therapeutic window, the observed PK differences in patients with severe renal impairment compared with healthy subjects are unlikely to pose a safety risk and do not warrant a predefined dosage adjustment in such patients. PMID:26239266

  1. Mechanism of Effect of Prostaglandin E1 on Renal Water Excretion

    PubMed Central

    Berl, T.; Schrier, R. W.

    1973-01-01

    The present study examined the effect of prostaglandin E1 (PGE1) on renal water excretion in the anesthetized dog. Renal perfusion pressure was kept constant by adjustment of a suprarenal aortic clamp. In seven experiments the intravenous administration of PGE1 (7 μg/min) significantly increased urinary osmolality from 76 to 381 mosmol (P < 0.001) and decreased free water clearance from 2.2 to - 0.02 ml/min (P < 0.001). These effects promptly were reversed with cessation of the infusion. This antidiuretic effect occurred both in innervated and denervated kidneys and was not associated with changes in glomerular filtration rate, renal vascular resistance, or solute excretion rate. In 10 experiments in hypophysectomized dogs no effect of intravenous PGE1 on free water clearance and urinary osmolality was observed. The intrarenal administration of PGE1 (1 μg/min) to six water-loaded and two hypophysectomized dogs caused no systemic vascular changes and increased rather than decreased free water clearance (2.83 to 4.08 ml/min, P < 0.001). No significant change in urinary osmolality occurred. Glomerular filtration rate was not altered by the intrarenal infusion, but reversible changes in solute excretion rate and renal vascular resistance occurred. These results thus indicate that the antidiuresis associated with intravenous PGE1 is mediated primarily by the release of vasopressin rather than alterations in renal hemodynamics or solute excretion. The diuretic effect of intrarenal PGE1 occurs in the absence of vasopressin and is most likely mediated primarily by increased distal delivery of tubular fluid to the diluting segment of the nephron rather than changes in water permeability of the renal tubular epithelium. PMID:4683884

  2. Does previous open renal surgery or percutaneous nephrolithotomy affect the outcomes and complications of percutaneous nephrolithotomy.

    PubMed

    Ozgor, Faruk; Kucuktopcu, Onur; Sarılar, Omer; Toptas, Mehmet; Simsek, Abdulmuttalip; Gurbuz, Zafer Gokhan; Akbulut, Mehmet Fatih; Muslumanoglu, Ahmet Yaser; Binbay, Murat

    2015-11-01

    In this study, we aim to evaluate the effectiveness and safety of PNL in patients with a history of open renal surgery or PNL by comparing with primary patients and to compare impact of previous open renal surgery and PNL on the success and complications of subsequent PNL. Charts of patients, who underwent PNL at our institute, were analyzed retrospectively. Patients were divided into three groups according to history of renal stone surgery. Patients without history of renal surgery were enrolled into Group 1. Other patients with previous PNL and previous open surgery were categorized as Group 2 and Group 3. Preoperative characteristic, perioperative data, stone-free status, and complication rates were compared between the groups. Stone-free status was accepted as completing clearance of stone and residual fragment smaller than 4 mm. Eventually, 2070 patients were enrolled into the study. Open renal surgery and PNL had been done in 410 (Group 2) and 131 (Group 3) patients, retrospectively. The mean operation time was longer (71.3 ± 33.5 min) in Group 2 and the mean fluoroscopy time was longer (8.6 ± 5.0) in Group 3 but there was no statistically significant difference between the groups. Highest stone clearance was achieved in primary PNL patients (81.62%) compared to the other groups (77.10% in Group 2 and 75.61% in Group 3). Stone-free rate was not significantly different between Group 2 and Group 3. Fever, pulmonary complications, and blood transfusion requirement were not statically different between groups but angioembolization was significantly higher in Group 2. Percutaneous nephrolithotomy is a safe and effective treatment modality for patients with renal stones regardless history of previous PNL or open renal surgery. However, history of open renal surgery but not PNL significantly reduced PNL success. PMID:26141983

  3. Effects of passive smoking on theophylline clearance.

    PubMed

    Matsunga, S K; Plezia, P M; Karol, M D; Katz, M D; Camilli, A E; Benowitz, N L

    1989-10-01

    Theophylline disposition was examined in seven passive smokers, defined as nonsmokers with long-term exposure to cigarette smoke, and seven age-matched nonsmokers with minimal smoke exposure. Subjects were given an intravenous infusion of aminophylline (6 mg/kg) and blood samples were drawn before and during the 48-hour postinfusion period. Clearance for passive smokers was 6.01 x 10(-2) L/hr.kg and for nonsmokers, clearance was 4.09 x 10(-2) L/hr.kg (p less than 0.025). Terminal elimination half-life for passive smokers was 6.93 hours versus 8.69 hours for nonsmokers (p less than 0.05). The mean residence time for passive smokers was 9.89 hours. For nonsmokers, the mean residence time was 13.11 hours (p less than 0.05). These measurements were statistically different, whereas there was no difference in volume of distribution between the groups, suggesting that passive smokers metabolize theophylline more rapidly than nonsmokers. Plasma and urine cotinine and nicotine concentrations were measured in all subjects. There was a significant difference between the subject groups in plasma (p less than 0.004) and urine (p less than 0.002) cotinine concentrations. Theophylline clearance correlated with both plasma (r = 0.73, p less than 0.01) and urine (r = 0.79, p less than 0.01) cotinine concentrations. Additional studies should be conducted to further define the pharmacokinetic characteristics of passive smokers and to assess the effects of passive smoking on drugs metabolized by the mixed function oxidase system. PMID:2791443

  4. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

    NASA Astrophysics Data System (ADS)

    Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

    2014-10-01

    Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal

  5. Renal Mitochondrial Cytopathies

    PubMed Central

    Emma, Francesco; Montini, Giovanni; Salviati, Leonardo; Dionisi-Vici, Carlo

    2011-01-01

    Renal diseases in mitochondrial cytopathies are a group of rare diseases that are characterized by frequent multisystemic involvement and extreme variability of phenotype. Most frequently patients present a tubular defect that is consistent with complete De Toni-Debré-Fanconi syndrome in most severe forms. More rarely, patients present with chronic tubulointerstitial nephritis, cystic renal diseases, or primary glomerular involvement. In recent years, two clearly defined entities, namely 3243 A > G tRNALEU mutations and coenzyme Q10 biosynthesis defects, have been described. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this paper, the physiopathologic bases of mitochondrial cytopathies, the diagnostic approaches, and main characteristics of related renal diseases are summarized. PMID:21811680

  6. Statistical Tolerance and Clearance Analysis for Assembly

    NASA Technical Reports Server (NTRS)

    Lee, S.; Yi, C.

    1996-01-01

    Tolerance is inevitable because manufacturing exactly equal parts is known to be impossible. Furthermore, the specification of tolerances is an integral part of product design since tolerances directly affect the assemblability, functionality, manufacturability, and cost effectiveness of a product. In this paper, we present statistical tolerance and clearance analysis for the assembly. Our proposed work is expected to make the following contributions: (i) to help the designers to evaluate products for assemblability, (ii) to provide a new perspective to tolerance problems, and (iii) to provide a tolerance analysis tool which can be incorporated into a CAD or solid modeling system.

  7. Assessment of renal function in workers previously exposed to cadmium.

    PubMed Central

    Elinder, C G; Edling, C; Lindberg, E; Kågedal, B; Vesterberg, O

    1985-01-01

    Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate. PMID:3904816

  8. 'Transcollateral' Renal Angioplasty for a Completely Occluded Renal Artery

    SciTech Connect

    Chandra, Subash; Chadha, Davinder S. Swamy, Ajay

    2011-02-15

    Percutaneous transluminal renal angioplasty with stenting has been effective in the control of hypertension, renal function, and pulmonary edema caused by atherosclerotic renal artery stenosis. However, the role of the procedure has not been fully established in the context of chronic total occlusion of renal artery. We report the successful use of this procedure in 57-year-old male patient who reported for evaluation of a recent episode of accelerated hypertension. A renal angiogram in this patient showed ostial stenosis of the right renal artery, which was filling by way of the collateral artery. Renal angioplasty for chronic total occlusion of right renal artery was successfully performed in a retrograde fashion through a collateral artery, thereby leading to improvement of renal function and blood pressure control.

  9. Clearance of extractables and leachables from single-use technologies via ultrafiltration/diafiltration operations.

    PubMed

    Magarian, Nicholas; Lee, Kate; Nagpal, Kunal; Skidmore, Ken; Mahajan, Ekta

    2016-05-01

    Quantifying the clearance of extractables and leachables (E/L) throughout ultrafiltration/diafiltration (UFDF) operations allows for greater flexibility in the implementation of single-use technologies in steps upstream of the UFDF process. A proof-of-concept study was completed in which the clearance of 7 E/L from single-use technologies (trimethylsilanol, hexanoic acid, butyrolactone, t-butyl alcohol, caprolactam, acetonitrile, and benzyl alcohol) in four representative proteins were measured and monitored during the UFDF process using quantitative NMR. This study demonstrated that the defined E/L spiked into a variety of protein solutions can be cleared to <1 ppm by 9 diavolumes from a maximum initial load concentration of 1,000 ppm. However, in some cases a rebound effect was observed in the recovered pool to >1 ppm, which is explained in detail. The overall clearance trend observed for both buffer control and protein-containing solutions resembled the ideal clearance trend where no apparent interactions were observed between E/L with the protein, UFDF system, or with other defined E/L which may be present in the system. Additionally, the UFDF system is capable of clearing these potential E/L from single-use technologies below 1 ppm irrespective of initial concentrations in the load (1,000 or 100 ppm), independently from the type of protein. In general, mass recoveries were within ±15% of each spiked compound in protein solutions and their respective buffer controls, suggesting spiked E/L do not interact strongly with protein. By demonstrating the product independent clearance trends of the spiked E/L across UFDF, these results will contribute to the simplification of the E/L toxicology assessment and allow modular manufacturing approach for single-use technologies in biopharmaceutical manufacturing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:718-724, 2016. PMID:27071939

  10. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a bench top calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  11. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high-temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short-range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a benchtop calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  12. Disappearing renal calculus

    PubMed Central

    Cui, Helen; Thomas, Johanna; Kumar, Sunil

    2013-01-01

    We present a case of a renal calculus treated solely with antibiotics which has not been previously reported in the literature. A man with a 17 mm lower pole renal calculus and concurrent Escherichia coli urine infection was being worked up to undergo percutaneous nephrolithotomy. However, after a course of preoperative antibiotics the stone was no longer seen on retrograde pyelography or CT imaging. PMID:23580676

  13. Lipoprotein X Causes Renal Disease in LCAT Deficiency

    PubMed Central

    Thacker, Seth G.; Vaisman, Boris; Pryor, Milton; Freeman, Lita A.; Brantner, Christine A.; Baranova, Irina; Francone, Nicolás O.; Demosky, Stephen J.; Vitali, Cecilia; Locatelli, Monica; Abbate, Mauro; Zoja, Carlamaria; Franceschini, Guido; Calabresi, Laura; Remaley, Alan T.

    2016-01-01

    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis. PMID:26919698

  14. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    PubMed

    Ossoli, Alice; Neufeld, Edward B; Thacker, Seth G; Vaisman, Boris; Pryor, Milton; Freeman, Lita A; Brantner, Christine A; Baranova, Irina; Francone, Nicolás O; Demosky, Stephen J; Vitali, Cecilia; Locatelli, Monica; Abbate, Mauro; Zoja, Carlamaria; Franceschini, Guido; Calabresi, Laura; Remaley, Alan T

    2016-01-01

    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis. PMID:26919698

  15. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    PubMed Central

    Ndisang, Joseph Fomusi; Tiwari, Shuchita

    2014-01-01

    Obesity and excessive inflammation/oxidative stress are pathophysiological forces associated with kidney dysfunction. Although we recently showed that heme-oxygenase (HO) improves renal functions, the mechanisms are largely unclear. Moreover, the effects of the HO-system on podocyte cytoskeletal proteins like podocin, podocalyxin, CD2-associated-protein (CD2AP) and proteins of regeneration/repair like beta-catenin, Oct3/4, WT1 and Pax2 in renal tissue from normoglycemic obese Zucker-fatty rats (ZFs) have not been reported. Treatment with hemin reduced renal histo-pathological lesions including glomerular-hypertrophy, tubular-cast, tubular-atrophy and mononuclear cell-infiltration in ZFs. These were associated with enhanced expression of beta-catenin, Oct3/4, WT1, Pax2 and nephrin, an essential transmembrane protein required for the formation of the scaffoldings of the podocyte slit-diaphragm, permitting the filtration of small ions, but not massive excretion of proteins, hence proteinuria. Besides nephrin, hemin also enhanced other important podocyte-regulators including, podocalyxin, podocin and CD2AP. Correspondingly, important markers of renal dysfunction such as albuminuria and proteinuria were reduced, while creatinine clearance increased, suggesting improved renal function in hemin-treated ZFs. The renoprotection by hemin was accompanied by the reduction of inflammatory/oxidative mediators including, macrophage-inflammatory-protein-1α, macrophage-chemoattractant-protein-1 and 8-isoprostane, whereas HO-1, HO-activity and the total-anti-oxidant-capacity increased. Contrarily, the HO-inhibitor, stannous-mesoporphyrin nullified the reno-protection by hemin. Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with

  16. Study of blade clearance effects on centrifugal pumps

    NASA Technical Reports Server (NTRS)

    Hoshide, R. K.; Nielson, C. E.

    1972-01-01

    A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

  17. Dynamics analysis of space robot manipulator with joint clearance

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Bai, Zheng Feng

    2011-04-01

    A computational methodology for analysis of space robot manipulator systems, considering the effects of the clearances in the joint, is presented. The contact dynamics model in joint clearance is established using the nonlinear equivalent spring-damp model and the friction effect is considered using the Coulomb friction model. The space robot system dynamic equation of manipulator with clearance is established. Then the dynamics simulation is presented and the dynamics characteristics of robot manipulator with clearance are analyzed. This work provides a practical method to analyze the dynamics characteristics of space robot manipulator with joint clearance and improves the engineering application. The computational methodology can predict the effects of clearance on space robot manipulator preferably, which is the basis of space robot manipulator design, precision analysis and ground test.

  18. Concept Formation.

    ERIC Educational Resources Information Center

    Vaidya, Narendera

    This document, published in India by the Regional College of Education, deals with 13 subjects: the tough context (thinking), definitions of concept, functions of concept, the process of concept formation, discriminant learning, mediation process, second signalling system, factors affecting concept formation, studies in concept formation, the…

  19. Hereditary Renal Cancer Syndromes

    PubMed Central

    Haas, Naomi B.

    2013-01-01

    Inherited susceptibility to kidney cancer is a fascinating and complex topic. Our knowledge about types of genetic syndromes associated with an increased risk of disease is continually expanding. Currently, there are 10 syndromes associated with an increased risk of all types of renal cancer, which are reviewed herein. Clear cell renal cancer is associated with von Hippel Lindau disease, chromosome 3 translocations, PTEN hamartomatous syndrome and mutations in BAP1, as well as several of the genes encoding the proteins comprising the succinate dehydrogenase complex (SDHB/C/D). Type 1 papillary renal cancers arise in conjunction with germline mutations in MET and type 2 as part of Hereditary Leiomyomatosis and Renal Cell Cancer (FH mutations). Chromophone and oncocytic renal cancers are predominantly associated with Birt Hogg Dubé syndrome. Angiomyolipomas are commonly and their malignant counterpart epitheliod angiomyolipomas rarely are found in patients with Tuberous Sclerosis Complex. The targeted therapeutic options for the renal cancer associated with these diseases are just starting to expand, and are an area of active clinical research. PMID:24359990

  20. [Falls and renal function: a dangerous association].

    PubMed

    De Giorgi, Alfredo; Fabbian, Fabio; Pala, Marco; Mallozzi Menegatti, Alessandra; Misurati, Elisa; Manfredini, Roberto

    2012-01-01

    Falls are an important health problem and the risk of falling increases with age. The costs due to falls are related to the progressive decline of patients' clinical conditions, with functional inability inducing increasing social costs, morbidity and mortality. Renal dysfunction is mostly present in elderly people who often have several comorbidities. Risk factors for falls have been classified as intrinsic and extrinsic, and renal dysfunction is included among the former. Chronic kidney disease per se is an important risk factor for falls, and the risk correlates negatively with creatinine clearance. Vitamin D deficiency, dysfunction of muscles and bones, nerve degeneration, cognitive decline, electrolyte imbalance, anemia, and metabolic acidosis have been reported to be associated with falls. Falls seem to be very frequent in dialysis patients: 44% of subjects on hemodialysis fall at least once a year with a 1-year mortality due to fractures of 64%. Male sex, comorbidities, predialysis hypotension, and a history of previous falls are the main risk factors, together with events directly related to renal replacement therapy such as biocompatibility of the dialysis membrane, arrhythmias, fluid overload and length of dialysis treatment. Peripheral nerve degeneration and demyelination as well as altered nerve conduction resulting in muscular weakness and loss of peripheral sensitivity are frequent when the glomerular filtration rate is less than 12 mL/min. Moreover, depression and sleep disorders can also increase the risk of falls. Kidney function is an important parameter to consider when evaluating the risk of falls in the elderly, and the development of specific guidelines for preventing falls in the uremic population should be considered. PMID:22718453

  1. Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

    SciTech Connect

    Welz, Stefan Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

    2007-12-01

    Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m{sup 2}), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m{sup 2}/24 h). A dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m{sup 2} in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of {<=}12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m{sup 2} administered before and after simultaneous 5-FU and radiotherapy.

  2. Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats.

    PubMed

    Jaikumkao, Krit; Pongchaidecha, Anchalee; Chattipakorn, Nipon; Chatsudthipong, Varanuj; Promsan, Sasivimon; Arjinajarn, Phatchawan; Lungkaphin, Anusorn

    2016-06-01

    What is the central question of this study? This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity through modulating the Nrf2 pathway by decreasing the oxidative stress. What is the main finding and its importance? Atorvastatin exerts a nephroprotective effect by attenuating oxidative stress, protecting renal function and renal organic anion transporter 3 function from the effects of gentamicin. Atorvastatin might protect the tissues via its antioxidant property and by modulating the antioxidant enzymes through the Nrf2 signalling pathway, which may be the underlying mechanisms of these protective effects. Recent evidence demonstrates that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exert not only lipid-lowering effects but also antioxidant, anti-inflammatory and anti-apoptotic effects. Nephrotoxicity, a serious side-effect of gentamicin, is related to an increase in reactive oxygen species in the kidney. This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were used. Nephrotocixity was induced by i.p. injection of gentamicin, 100 mg kg(-1)  day(-1) , for 15 days. Atorvastatin, 10 mg kg(-1)  day(-1) , was administered by gavage 30 min before gentamicin injection (pretreatment) for 15 days or only on days 10-15 (post-treatment). Renal function and renal organic anion transporter 3 (Oat3) function and expression were examined. Gentamicin-treated rats demonstrated impaired renal function by attenuation of creatinine clearance and increased oxidative stress. Gentamicin treatment also decreased renal Oat3 function and expression as shown by decreased [(3) H]estrone sulfate uptake into renal cortical slices and decreased expression. The protein expressions of protein kinase C, Nrf2, NAD(P)H:quinone oxidoreductase 1

  3. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1984-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as governed principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of approximations of the respiratory tract to predict fractional deposition caused by fundamental physical processes of particle impaction, sedimentation, and diffusion. These models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with early and recent experimental studies. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior in the respiratory tract of very fine (less than 0.1 micron) particles requires further investigation. Properties of particle shape, charge and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns; definitive experimental work is needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of differing ventilation techniques with selected inhaled particle sizes holds promise in diagnosis of respiratory tract diseases. Mechanisms of conducting airway and alveolar clearance processes involving the pulmonary macrophage, mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic vessels are discussed. PMID:6376108

  4. ESR measurement of radical clearance in lung of whole mouse

    SciTech Connect

    Takeshita, K.; Utsumi, H.; Hamada, A. )

    1991-06-14

    Clearance of the nitroxide radicals, hydroxy-TEMPO and carboxy-PROxYL, in whole-mouse lung was directly measured by in vivo ESR. After injecting a nitroxide radical, distribution of the nitroxide radical all over the lung was confirmed by ESR imaging. The ESR signal of hydroxy-TEMPO was reduced in the lung and the clearance obeyed first-order kinetics, whereas the signal of carboxy-PROxYL remained constant. Comparison of the clearance rates of live and dead mice indicated the presence of 2 different clearance systems in the lung: loss of its paramagnetism in the lung, and transfer from alveolar to the blood circulation system.

  5. Elimination kinetics of labetalol in severe renal failure

    PubMed Central

    Wood, A. J.; Ferry, D. G.; Bailey, R. R.

    1982-01-01

    1 The pharmacokinetics of intravenously administered labetalol were studied in four patients with severe renal failure and in three normal subjects. 2 A new and sensitive method for the assay of plasma labetalol concentrations using high performance liquid chromatography is described. 3 Labetalol has a relatively large apparent volume of distribution (3.3-7.9 l/kg, two-compartment open model) and a relatively high plasma clearance (0.3-1.6 1 h-1 kg-1). 4 There were no significant differences between the patients with severe renal failure and the controls for any of the pharmacokinetic parameters measured. 5 In the presence of renal functional impairment, no modification of labetalol dosage is required. 6 In another study of 31 patients, glomerular filtration rate was measured at 3-month intervals for 3-18 months. In ten patients there was no change, in ten there was an improvement and in 11 there was deterioration, but in only three was this attributable to treatment. 7 In our experience with over 300 patients, we conclude that labetalol plus diuretic treatment is efficacious and safe in all grades of hypertension including those with all degrees of renal insufficiency. PMID:7093103

  6. 4D MRI of renal function in the developing mouse

    PubMed Central

    Xie, Luke; Subashi, Ergys; Qi, Yi; Knepper, Mark A.; Johnson, G. Allan

    2014-01-01

    The major roles of filtration, metabolism, and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (4D) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full 3D image (125-micron isotropic resolution) every 7.7 seconds over a 50-minute scan. This time course permitted demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13, and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts for segmenting the 4 regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM, and inner medulla (IM). Local volumes, time-to-peak (TTP) values, and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. PMID:25066408

  7. Morphofunctional renal alterations in rats induced by intrauterine hyperglycemic environment

    PubMed Central

    França-Silva, Nathane; Oliveira, Natácia Dreyce Gonçalves

    2015-01-01

    Introduction The renal development of rats begins in intrauterine life, finishing by 15 days after birth. Diabetes and other diseases during pregnancy can cause systemic changes in the offspring. We evaluated the structural and functional renal alterations of the offspring from diabetic mothers. Material and methods Pregnant rats were separated and 1, 7, 30 and 90 days-old (DO) pups were divided into groups according to the treatment that the mothers received: G1: control, G2: untreated diabetic and G3: insulin-treated diabetic. The kidneys from offspring at 1, 7 and 30 DO were removed for immunohistochemical and histological studies. Furthermore, blood and urine samples were collected from animals at 30 DO to determine the glomerular filtration rate (GFR) by creatinine clearance, and the animals at 90 DO were subjected to blood pressure measurement by plethysmography. Results Our results show an increase of PCNA+ glomerular cells at 7 DO and a reduction in 30 DO animals as well as increased α-smooth muscle actin (α-SMA) tubulointerstitial expression at 1 and 7 DO in animals from G2, when compared with controls. The adult offspring from G2 showed reduced GFR and increased blood pressure. Conclusions Maternal diabetes may have induced programming of renal damage in offspring of hyperglycemic mothers, which may have contributed to the impairment of renal function. PMID:27186167

  8. Influence of severe renal impairment on the pharmacokinetics of clazosentan.

    PubMed

    Bruderer, Shirin; Sasu, Boris; Tsvitbaum, Nahum; Dingemanse, Jasper

    2011-03-01

    The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of 6 hours in 9 subjects with severe renal impairment (group A) and 8 healthy subjects (group B) (creatinine clearance <30 mL/min and >80 mL/min, respectively). The subjects in both groups were well matched for sex, body mass index, and age (±10 years). The PK parameters of clazosentan were calculated by both model-independent and model-dependent methods. The differences in the PK parameters between the subjects with severe renal impairment and healthy subjects were minor. The geometric means for area under the curve (AUC) during the infusion, AUC(0-t), (AUC from zero to time t of the last measured concentration above the limit of quantification) AUC(0-∞) (AUC from zero to infinity), and concentration at steady state were 7%, 8%, 8%, and 8%, respectively, higher in group A than in group B. The results obtained after 2-compartmental modeling were in agreement with those obtained after noncompartmental analysis. Administration of clazosentan was well tolerated in both groups. The data suggest that there is no need for dose adjustment of clazosentan in patients with renal impairment. PMID:20926750

  9. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study.

    PubMed

    Zürcher, R M; Bock, H A; Thiel, G

    1994-01-01

    Patients on cyclosporin A (CsA) often develop hyperuricaemia and gout. In transplant patients the use of uricosuric drugs for treating hyperuricaemia may be preferable to allopurinol because of the known interaction of the latter with azathioprine. We therefore prospectively studied the uricosuric efficacy of 100 mg benzbromarone (Bbr;Desuric) daily in 25 CsA-treated renal transplant patients with stable graft function and hyperuricaemia (> 359 mumol/l for females, > 491 mumol/l for males). Benzbromarone decreased plasma uric acid from 579 + 18 mumol/l to 313 +/- 24 mumol/l (mean +/- SEM; P < 0.0001) and thereby normalized plasma uric acid in 21 of 25 patients. The remaining four patients had creatinine clearances between 21 and 25 ml/min, the lowest of the entire study group. Mean fractional clearance of uric acid increased from 5.4 +/- 0.4% to 17.2 +/- 1.0% (P < 0.001). The relative decrease of plasma uric acid closely correlated with baseline creatinine clearance (r = 0.67; P < 0.001). CsA trough values were not influenced. None of the patients experienced any significant side-effects. As an unexpected find-ing, urinary uric acid excretion increased from 2082 +/- 175 mumol/24 h to 3233 +/- 232 mumol/24 h after 4 weeks' treatment with benzbromarone. In conclusion, benzbromarone normalized plasma uric acid in all CsA-treated renal transplant recipients with a creatinine clearance > 25 ml/min. Due to its excellent efficacy and lack of significant side-effects, benzbromarone appears to be preferable to allopurinol in CsA-treated renal transplant recipients with a creatinine clearance over 25 ml/min. PMID:8090336

  10. Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

    SciTech Connect

    Yang, Gary Y.; May, Kilian Salerno; Iyer, Renuka V.; Chandrasekhar, Rameela M.A.; Wilding, Gregory E.; McCloskey, Susan A.; Khushalani, Nikhil I.; Yendamuri, Saikrishna S.; Gibbs, John F.; Fakih, Marwan; Thomas, Charles R.

    2010-10-01

    Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

  11. Ureteroscopic treatment of larger renal calculi (>2 cm)

    PubMed Central

    Bagley, Demetrius H.; Healy, Kelly A.; Kleinmann, Nir

    2012-01-01

    Objectives To evaluate the current status of ureteroscopic lithotripsy (UL) for treating renal calculi of >2 cm, as advances in flexible ureteroscope design, accessory instrumentation and lithotrites have revolutionised the treatment of urinary calculi. While previously reserved for ureteric and small renal calculi, UL has gained an increasing role in the selective management of larger renal stone burdens. Methods We searched the available databases, including PubMed, Google Scholar, and Scopus, for relevant reports in English, and the article bibliographies to identify additional relevant articles. Keywords included ureteroscopy, lithotripsy, renal calculi, and calculi >2 cm. Retrieved articles were reviewed to consider the number of patients, mean stone size, success rates, indications and complications. Results In all, nine studies (417 patients) were eligible for inclusion. After one, two or three procedures the mean (range) success rates were 68.2 (23–84)%, 87.1 (79–91)% and 94.4 (90.1–96.7)%, respectively. Overall, the success rate was >90% with a mean of 1.2–2.3 procedures per patient. The overall complication rate was 10.3%, including six (1.4%) intraoperative and 37 (8.9%) postoperative complications, most of which were minor. The most common indications for UL were a failed previous treatment (46%), comorbidities (18.2%), and technical and anatomical factors (12.3%). Conclusions UL is safe and effective for treating large renal calculi. While several procedures might be required for total stone clearance, UL should be considered a standard approach in the urologist’s options treating renal calculi of >2 cm. PMID:26558040

  12. [Hereditary renal cancer].

    PubMed

    Sanz-Ortega, Julián; Olivier, Carlos; Pérez Segura, Pedro; Galante Romo, Isabel; San José Mansó, Luis; Saez, Mamen

    2009-02-01

    Kidney cancer is the tenth most common cause of cancer death. There are a growing number of genes known to be associated with an increased risk of specific types of kidney cancer. People with Von Hippel-Lindau syndrome have about a 40% risk of developing multiple bilateral clear cell kidney cancers. They can also develop retinal and brain hemangioblastoma, kidneys or pancreas cysts, pheochromocytoma and endolymphatic sac tumor. Four phenotypes with different renal cancer and pheocromocitoma risk have been described depending on the germline mutation. Hereditary papillary renal cell carcinoma syndrome has type 1 papillary renal cell carcinomas associated with protooncogene c-MET germline mutations. Birt-Hogg-Dubé syndrome has FLCN gene mutations associated with fibrofolliculomas, lung cysts with a high risk for spontaneous pneumothorax, and a 15% to 30% risk of kidney cancer (most classified as chromophobe carcinoma, oncocytoma or oncocytic hybrid, but clear cell and papillary kidney cancers have also been reported). Histopathological findings such as oncocytosis and oncocytic hybrids are very unusual outside the syndrome. Hereditary leiomyomatosis and renal cell cancer syndrome shows mutations of Fumarate hydratase gene and cutaneous leiomyomata in 76% of affected individuals, uterine leiomyomata in 100% of females, and unilateral, solitary, and aggressive papillary renal cancer in 10 to 16% of patients. A specific histopathological change is eosinophilic prominent nucleoli with a perinucleolar halo. Tuberous sclerosis complex is one of the most prevalent (1/5.800) hereditary syndromes where renal disease is the second leading cause of death, associated with angiomyolipomas (70%), renal cysts, oncocytomas or clear cell cancer. PMID:19418834

  13. Resveratrol ameliorates renal injury in spontaneously hypertensive rats by inhibiting renal micro-inflammation.

    PubMed

    Xue, Hai-Yan; Yuan, Li; Cao, Ying-Jie; Fan, Ya-Ping; Chen, Xiao-Lan; Huang, Xin-Zhong

    2016-07-01

    Micro-inflammation plays an important role in the pathogenesis of spontaneously hypertensive rat (SHR). In the present study, we investigated the therapeutic potential of resveratrol (RSV), a polyphenol with anti-fibrosis activity in hypertensive renal damage model. In SHR renal damage model, RSV treatment blunted the increase in urine albumin excretion, urinary β2-microglobulin (β2-MG), attenuated the decrease in creatinine clearance rate (CCR). The glomerular sclerosis index (1.54±0.33 compared with 0.36±0.07) and tubulointerstitial fibrosis (1.57±0.31 compared with 0.19±0.04) were significantly higher in SHRs compared with Wistar Kyoto rats (WKYs), which were significantly lower by RSV treatment. The increases in mesangium accumulation and the expression of renal collagen type I (Col I), fibronectin (Fn), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) in SHR were also reduced by RSV treatment. Nuclear factor κB (NF-κB) expression was increased in the cytoplasm and nuclei of the SHR kidneys, which was significantly decreased by RSV treatment. Furthermore, the protein level of IκB-α significantly decreased in the kidneys of the SHR when compared with the WKYs. RSV treatment partially restored the decreased IκB-α level. In SHR kidney, increased expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) were observed. These changes were attenuated by RSV treatment. No changes in blood pressure were detected between SHR group and SHR + RSV group. Taken together, the present study demonstrated that RSV treatment may significantly attenuate renal damage in the SHR model of chronic kidney disease (CKD). The renal protective effect is associated with inhibition of IL-6, ICAM-1 and MCP-1 expression via the regulation of the nuclear translocation of NF-κB, which suggesting that micro-inflammation may be a potential therapeutic target of hypertensive

  14. Hepatitis C virus related lymphoproliferative disorder in a renal transplant recipient.

    PubMed

    Aravindan, A N; Moger, Venkatesh; Sakhuja, Vinay; Kohli, Harbir S; Varma, Neelam; Jha, Vivekanand

    2006-01-01

    Posttransplant lymphoproliferative disorders (PTLD) are commonly caused by Ebstein-Barr Virus infection. The role of hepatitis C virus (HCV) in the genesis of lymphomas has been recognized recently. We report a HCV infected renal transplant recipient who developed PTLD 11 months after transplantation. Reduction of immunosuppression led to disappearance of viremia and clearance of PTLD. This is the first such report in the world literature. PMID:16868710

  15. Plasma D dimer: a useful marker of fibrin breakdown in renal failure.

    PubMed

    Gordge, M P; Faint, R W; Rylance, P B; Ireland, H; Lane, D A; Neild, G H

    1989-06-30

    D dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 +/- 31 ng/ml) (mean +/- SEM) and diabetic nephropathy (308 +/- 74 ng/ml), when compared with healthy controls (96 +/- 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 +/- 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure. PMID:2799764

  16. Renal blood flow distribution during E. coli endotoxin shock in dog.

    PubMed

    Kirkebø, A; Tyssebotn, I

    1980-04-01

    The effect of endotoxin on renal blood flow distribution was studied in anesthetized dogs. Renal blood flow was measured as hydrogen clearance by platinum electrodes placed in outer and in inner halves of cortex and by electromagnetic flowmeter. Intravenous injection of E. coli endotoxin, 3-5 mg/kg b. wt., promptly reduced arterial blood pressure (AP) and renal blood flow. After a transient increase for 45 min AP and renal blood flow declined to about 50% of the control 2 1/2-3 h after injection. The reduction in outer cortical blood flow (OCF) was not significantly different from the reduction in inner cortical blood flow (ICF). The hematocrit (Hct) increased from 40.1 +/- 3.8% to 54.6 +/- 8%, but mean renal vascular resistance did not change. Total plasma protein concentration was not significantly elevated. A marked local flow variability was observed in some periods during the phase of shock with declining AP and total renal blood flow at high Hct. Thus renal blood flow showed phasic changes, but the OCF/ICF ratio was not changed during endotoxin shock. Local blood flow instability was observed periodically at high Hct. PMID:6998257

  17. Modelling acute renal failure using blood and breath biomarkers in rats.

    PubMed

    Moorhead, Katherine T; Hill, Jonathan V; Chase, J Geoffrey; Hann, Christopher E; Scotter, Jennifer M; Storer, Malina K; Endre, Zoltan H

    2011-02-01

    This paper compares three methods for estimating renal function, as tested in rats. Acute renal failure (ARF) was induced via a 60-min bilateral renal artery clamp in 8 Sprague-Dawley rats and renal function was monitored for 1 week post-surgery. A two-compartment model was developed for estimating glomerular filtration via a bolus injection of a radio-labelled inulin tracer, and was compared with an estimated creatinine clearance method, modified using the Cockcroft-Gault equation for rats. These two methods were compared with selected ion flow tube-mass spectrometry (SIFT-MS) monitoring of breath analytes. Determination of renal function via SIFT-MS is desirable since results are available non-invasively and in real time. Relative decreases in renal function show very good correlation between all 3 methods (R²=0.84, 0.91 and 0.72 for breath-inulin, inulin-creatinine, and breath-creatinine correlations, respectively), and indicate good promise for fast, non-invasive determination of renal function via breath testing. PMID:20728235

  18. Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms

    SciTech Connect

    Slotkin, T.A.; Kavlock, R.J.; Cowdery, T.; Orband, L.; Bartolome, M.

    1986-01-01

    The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

  19. Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis.

    PubMed Central

    Bugert, P.; Kovacs, G.

    1996-01-01

    Recent application of molecular cytogenetic techniques has resulted in a new type of genetic classification of renal cell tumors. The key aspect of the novel diagnostic concept is reflected by biologically distinct entities, each characterized by a specific combination of genetic changes. To work out a diagnostic/prognostic approach, we have applied polymorphic microsatellite markers for a quick analysis, based on polymerase chain reaction, of 82 tumor specimens. We compared the results to previously evaluated cytogenetic and histological data. All nonpapillary and chromophobe renal cell carcinomas, which make up approximately 90% of all malignant renal cell tumors, and a subset of renal oncocytomas were correctly diagnosed by detection of loss of heterozygosity at chromosomal sites 1, 2, and 3p. Allelic losses at chromosomal regions 8p, 9p, and 14q are associated with an advanced pathological stage of nonpapillary renal cell carcinomas. A loss of heterozygosity at chromosomes 6, 10, 13, 17, and 21, in addition to those at chromosomes 1 and 2, confirm the diagnosis of chromophobe renal cell tumors. Using this approach, the differential diagnosis of renal cell tumors could be carried out within 1 or 2 days. Images Figure 2 PMID:8952540

  20. Investigation on the Dynamic Performance of the Tripod-Ball Sliding Joint with Clearance in a CRANK-SLIDER Mechanism. Part 1. Theoretical and Experimental Results

    NASA Astrophysics Data System (ADS)

    JIA, X.; JIN, D.; JI, L.; ZHANG, J.

    2002-05-01

    Clearance is inevitable in the kinematic joints of mechanisms. In this paper, the dynamic behavior of a crank-slider mechanism with clearance in its tripod-ball sliding joint is investigated theoretically and experimentally. The mathematical model of this new-type of joint is established, and the new concepts of basal system and active system are put forward. Based on the mode-change criterion established in this paper, the consistent equations of motion in full-scale are derived by using Kane method. The experimental rig was set up to measure the effects of the clearance on the dynamic response. The dynamic responses including additional motion, input torque and acceleration have been obtained, and the effects of the clearance size and driving speed have also been investigated by both analytical and experimental means. Corresponding experimental studies verify the theoretical results satisfactorily.

  1. Continuous renal replacement therapy amino acid, trace metal and folate clearance in critically ill children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesized that continuous veno-venous hemodialysis (CVVHD) results in amino acid, trace metals, and folate losses, thereby adversely impacting nutrient balance. Critically ill children receiving CVVHD were studied prospectively for 5 days. Blood concentrations, amino acids, copper, zinc, man...

  2. A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance.

    PubMed

    Resch, Gregory; Moreillon, Philippe; Fischetti, Vincent A

    2011-12-01

    Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer. PMID:21982146

  3. The Clearance of Creatinine, Inulin, Para-aminohippurate and Phenosulphothalein in the Cat

    PubMed Central

    Osbaldiston, G. W.; Fuhrman, W.

    1970-01-01

    Endogenous creatinine, inulin, para-amino-hippurate and phenolsulphothalein clearances for healthy cats are presented. The values for inulin and para-aminohippurate clearances (ml/kg/min) are similar to those for the dog. Creatinine clearance was less than inulin clearance values. Pnenolsulphothalein clearance may be a better index of glomerular rather than tubular function in the cat. PMID:4246836

  4. Renal sympathetic denervation for the treatment of refractory hypertension.

    PubMed

    Leong, Kui Toh Gerard; Walton, Antony; Krum, Henry

    2014-01-01

    Resistant hypertension poses significant health concerns. There are strong demands for new and safe therapies to control resistant hypertension while addressing its common causes, specifically poor compliance to lifelong polypharmacy, lifestyle modifications, and physician inertia. The sympathetic nervous system plays a significant pathophysiological role in hypertension. Surgical sympathectomy for blood pressure reduction is an old but extremely efficacious therapeutic concept, now abandoned with the dawn of a safer contemporary pharmacology era. Recently, clinical studies have revealed promising results for safe and sustained blood pressure reduction with percutaneous renal sympathetic denervation. This is a novel, minimally invasive, device-based therapy, specifically targeting and ablating the renal artery nerves with radiofrequency waves without permanent implantation. There are also reported additional benefits in related comorbidities, such as impaired glucose metabolism, renal impairment, left ventricular hypertrophy, heart failure, and others. This review focuses on how selective renal sympathetic denervation works, its present and potential therapeutic indications, and its future directions. PMID:24422574

  5. Renal disease in Colombia.

    PubMed

    Gómez, Rafael Alberto

    2006-01-01

    Chronic renal disease represents a problem of public health in Colombia. Its prevalence has increased in last decade, with a prevalence of 44.7 patients per million (ppm) in 1993 to 294.6 ppm in 2004, considering that only 56.2% of the population has access to the health. This increase complies with the implementation of Law 100 of 1993, offering greater coverage of health services to the Colombian population. The cost of these pathologies is equivalent to the 2.49% of the budget for health of the nation. The three most common causes of renal failure are diabetes mellitus (DM; 30%), arterial hypertension (30%), and glomerulonephritis (7.85%). In incident patients, the DM accounts for 32.9%. The rate of global mortality is 15.8%, 17.4% in hemodialysis and 15.1% in peritoneal dialysis. In 2004, 467 renal transplants were made, 381 of deceased donor with an incidence of 10.3 ppm. The excessive cost of these pathologies can cause the nation's health care system to collapse if preventative steps are not taken. In December of 2004, the Colombian Association of Nephrology with the participation of the Latin American Society of Nephrology and Arterial Hypertension wrote the "Declaration of Bogotá," committing the state's scientific societies and promotional health companies to develop a model of attention for renal health that, in addition to implementing national registries, continues to manage renal disease. PMID:17162422

  6. Renal consequences of obesity.

    PubMed

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  7. Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufficiency.

    PubMed Central

    Patel, I H; Bornemann, L D; Brocks, V M; Fang, L S; Tolkoff-Rubin, N E; Rubin, R H

    1985-01-01

    Five healthy volunteers and 31 patients with various degrees of renal impairment received a 10-mg/kg intravenous dose of amdinocillin by infusion over 15 min to establish the disposition profile of the drug in plasma and urine. Both clearance from plasma and elimination rate constant showed a linear relationship with creatinine clearance. It was noted that in subjects with creatinine clearances of greater than 50 ml/min, the elimination half-life remained relatively constant; however, as the creatinine clearance decreased from 50 to 5 ml/min, there was a progressive rise in the elimination half-life. Despite the removal of the drug by hemodialysis (32 to 72% of the dose), concentrations of amdinocillin in plasma remained in the therapeutic range. In patients undergoing peritoneal dialysis, less than 4.0% of the infused dose was removed by dialysis during the hourly exchanges over a 14- to 18-h period. Although the clearance from plasma and the half-life of amdinocillin were altered up to fourfold in patients with creatinine clearances of less than 15 ml/min, the amdinocillin dosage per se may not need to be reduced for these patients if the frequency of dosing is reduced from six to three or four times daily. This is based on drug accumulation estimates of 56% from a regimen of 10 mg/kg every 8 h in these patients as compared with less than 10% from a regimen of 10 mg/kg every 4 h in subjects with normal renal function. In addition, supplemental doses may not be necessary during or at the end of hemodialysis for patients undergoing hemodialysis. PMID:4037777

  8. A Microwave Blade Tip Clearance Sensor for Propulsion Health Monitoring

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Abdul-Aziz, Ali; Bencic, Timothy J.

    2010-01-01

    Microwave sensor technology is being investigated by the NASA Glenn Research Center as a means of making non-contact structural health measurements in the hot sections of gas turbine engines. This type of sensor technology is beneficial in that it is accurate, it has the ability to operate at extremely high temperatures, and is unaffected by contaminants that are present in turbine engines. It is specifically being targeted for use in the High Pressure Turbine (HPT) and High Pressure Compressor (HPC) sections to monitor the structural health of the rotating components. It is intended to use blade tip clearance to monitor blade growth and wear and blade tip timing to monitor blade vibration and deflection. The use of microwave sensors for this application is an emerging concept. Techniques on their use and calibration needed to be developed. As a means of better understanding the issues associated with the microwave sensors, a series of experiments have been conducted to evaluate their performance for aero engine applications. This paper presents the results of these experiments.

  9. Effect of short-term treatment with meloxicam and pimobendan on the renal function in healthy beagle dogs.

    PubMed

    Fusellier, M; Desfontis, J-C; Le Roux, A; Madec, S; Gautier, F; Thuleau, A; Gogny, M

    2008-04-01

    The aim of the study was to investigate the renal function in clinically normal dogs receiving meloxicam and pimobendan alone or in combination. Ten adult female beagle dogs were administered the treatment for 7 days in a randomized crossover trial (control/meloxicam/pimobendan/meloxicam and pimobendan). Renal function was assessed by blood urea, creatinine, sodium, potassium and chloride concentrations and by glomerular filtration rate, measured by means of renal scintigraphy [renal uptake of (99m)Tc-diethylenetriaminepentacetic acid (DTPA)] and plasma clearance of (99m)Tc-DTPA. As compared with the control group, renal uptake and plasma clearance of (99m)Tc-DTPA were not significantly modified after a 7-day period of treatment with meloxicam or pimobendan alone, or meloxicam and pimobendan in combination. Furthermore, urea, creatinine, sodium, potassium and chloride levels in the serum of the dogs during the 7-day period treatment were not significantly modified in relation to the treatments. It was therefore concluded that meloxicam and pimobendan alone or in combination did not alter renal function in healthy dogs. PMID:18307507

  10. Urinary N-acetyl-beta-D-glucosaminidase and malondialdehyde as a markers of renal damage in burned patients.

    PubMed Central

    Kang, H. K.; Kim, D. K.; Lee, B. H.; Om, A. S.; Hong, J. H.; Koh, H. C.; Lee, C. H.; Shin, I. C.; Kang, J. S.

    2001-01-01

    This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns. PMID:11641529

  11. A meta-analysis of renal outcomes in living kidney donors

    PubMed Central

    Li, Sha-Sha; Huang, Yan-Mei; Wang, Min; Shen, Jian; Lin, Bing-Jie; Sui, Yi; Zhao, Hai-Lu

    2016-01-01

    Abstract Given the increased burden of end-stage renal disease (ESRD), renal outcomes of kidney donation by living donors are of particular interest. PubMed, ProQuest, MEDLINE, EMBASE, Chinese national knowledge infrastructure, and Wanfang databases were searched for clinical outcomes of living kidney donors (LKDs) including renal death, ESRD, proteinuria/albuminuria, and renal function after donation. We included 62 studies from 19 countries involving 114,783 kidney donors and nondonors to evaluate the renal consequences less than 6 months, 6 months to 5 years, 5 to 10 years, and 10 years onward after donation. The pooled data showed that uninephrectomy significantly decreased glomerular filtration rate and creatinine clearance rate in parallel with increased serum creatinine concentration (all P < 0.05). The drastic changes in renal function occurred within 6 months rather than 5 to 10 years after donation. Ten years and onward, rate of proteinuria/albuminuria increased gradually: microalbuminuria from 5.3% to 20.9%, proteinuria from 4.7% to 18.9%, and overt proteinuria from 2.4% to 5.7% (all P < 0.05). Prevalence of ESRD was 1.1%. All-cause mortality was 3.8% and all the renal deaths on average occurred 10 years postnephrectomy. LKDs might have aggravated glomerular filtration and creatinine clearance within 6 months after donation. Five years and onward, albuminuria, proteinuria, ESRD, and death might be the major concerns of LKDs. Long-term studies may clarify the survival time after donation. PMID:27310964

  12. Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function

    PubMed Central

    Kunz, Christina; Luedtke, Doreen; Unseld, Anna; Hamilton, Alan; Halabi, Atef; Wein, Martina; Formella, Stephan

    2016-01-01

    Purpose In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated. Subjects and methods The first trial included eight subjects with mild hepatic function impairment (Child–Pugh A), eight subjects with moderate impairment (Child–Pugh B), and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL·min−1) and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 μg olodaterol administered with the Respimat Soft Mist inhaler. Results Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0–4) for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%–125%) and 105% (79%–140%), respectively. Corresponding values for dose-normalized maximum concentration (Cmax) were 112% (84%–151%) (mild impairment) and 99% (73%–135%) (moderate impairment). The geometric mean ratio (90% confidence interval) of AUC0–4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%–195%), and for Cmax was 137% (84%–222%). There was no significant relationship between creatinine clearance and AUC0–4 or Cmax. Renal clearance of olodaterol was reduced to 20% of normal in severe renal impairment. Conclusion Mild to moderate hepatic function impairment or severe renal function impairment did not result in a clinically relevant increase of olodaterol systemic exposure after a single inhaled dose. PMID:27051282

  13. Improved Flight Test Procedures for Flutter Clearance

    NASA Technical Reports Server (NTRS)

    Lind, Rick C.; Brenner, Martin J.; Freudinger, Lawrence C.

    1997-01-01

    Flight flutter testing is an integral part of flight envelope clearance. This paper discusses advancements in several areas that are being investigated to improve efficiency and safety of flight test programs. Results are presented from recent flight testing of the F/A-18 Systems Research Aircraft. A wingtip excitation system was used to generate aeroelastic response data. This system worked well for many flight conditions but still displayed some anomalies. Wavelet processing is used to analyze the flight data. Filtered transfer functions are generated that greatly improve system identification. A flutter margin is formulated that accounts for errors between a model and flight data. Worst-case flutter margins are computed to demonstrate the flutter boundary may lie closer to the flight envelope than previously estimated. This paper concludes with developments for a distributed flight analysis environment and on-line health monitoring.

  14. Validation of Dose Calculation Codes for Clearance

    SciTech Connect

    Menon, S.; Wirendal, B.; Bjerler, J.; Studsvik; Teunckens, L.

    2003-02-27

    Various international and national bodies such as the International Atomic Energy Agency, the European Commission, the US Nuclear Regulatory Commission have put forward proposals or guidance documents to regulate the ''clearance'' from regulatory control of very low level radioactive material, in order to allow its recycling as a material management practice. All these proposals are based on predicted scenarios for subsequent utilization of the released materials. The calculation models used in these scenarios tend to utilize conservative data regarding exposure times and dose uptake as well as other assumptions as a safeguard against uncertainties. None of these models has ever been validated by comparison with the actual real life practice of recycling. An international project was organized in order to validate some of the assumptions made in these calculation models, and, thereby, better assess the radiological consequences of recycling on a practical large scale.

  15. Allometric scaling for predicting human clearance of bisphenol A

    SciTech Connect

    Collet, Séverine H. Picard-Hagen, Nicole Lacroix, Marlène Z. Puel, Sylvie Viguié, Catherine Bousquet-Melou, Alain Toutain, Pierre-Louis Gayrard, Véronique

    2015-05-01

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

  16. 10 CFR 95.17 - Processing facility clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... concerning the foreign intelligence threat, risk of unauthorized technology transfer, type and sensitivity of... SECURITY INFORMATION AND RESTRICTED DATA Physical Security § 95.17 Processing facility clearance. (a... related classified information, or process the facility for a facility clearance. Processing will...

  17. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  18. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  19. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  20. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  1. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated...

  2. 48 CFR 245.7203 - Assigning plant clearance case numbers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Assigning plant clearance case numbers. 245.7203 Section 245.7203 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT GOVERNMENT PROPERTY Special Instructions 245.7203 Assigning plant clearance case...

  3. Study of global operational needs for mine clearance equipment

    NASA Astrophysics Data System (ADS)

    Blagden, Paddy M.

    2003-09-01

    The Geneva International Centre for Humanitarian Demining studied the needs of landmine clearance groups for equipment to carry out specific functions of mine clearance. This was done on a global level, and useful results were obtained, which will provide the basis for further analysis.

  4. 48 CFR 245.7202 - Establishing a plant clearance case.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Establishing a plant clearance case. 245.7202 Section 245.7202 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT GOVERNMENT PROPERTY Special Instructions 245.7202 Establishing a plant clearance case....

  5. Benefits of Improved HP Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

    2007-01-01

    As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

  6. Mechanistic evaluation of virus clearance by depth filtration.

    PubMed

    Venkiteshwaran, Adith; Fogle, Jace; Patnaik, Purbasa; Kowle, Ron; Chen, Dayue

    2015-01-01

    Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance. PMID:25683459

  7. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  8. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  9. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  10. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  11. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Recording Statements of Clearance. 644.527 Section 644.527 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  12. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Recording Statements of Clearance. 644.527 Section 644.527 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from...

  13. 14 CFR 375.24 - Entry and clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Entry and clearance. 375.24 Section 375.24 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS NAVIGATION OF FOREIGN CIVIL AIRCRAFT WITHIN THE UNITED STATES Rules Generally Applicable § 375.24 Entry and clearance. All...

  14. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Plant clearance function. 945.603-70 Section 945.603-70 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CONTRACT MANAGEMENT GOVERNMENT PROPERTY Reporting, Redistribution, and Disposal of Contractor Inventory 945.603-70 Plant clearance function. If the...

  15. 76 FR 17978 - Agency Information Collection Activities: Emergency Clearance Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... From the Federal Register Online via the Government Publishing Office SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Emergency Clearance Request The Social Security Administration (SSA) publishes a list of information collection packages requiring clearance by the Office of Management and Budget (OMB) in compliance...

  16. 5 CFR 720.307 - Interagency report clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Interagency report clearance. 720.307 Section 720.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) AFFIRMATIVE EMPLOYMENT PROGRAMS Disabled Veterans Affirmative Action Program § 720.307 Interagency report clearance. The...

  17. 33 CFR 160.115 - Withholding of clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Withholding of clearance. 160.115 Section 160.115 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY PORTS AND WATERWAYS SAFETY-GENERAL Control of Vessel and Facility Operations § 160.115 Withholding of clearance....

  18. 30 CFR 57.19104 - Clearance at shaft stations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance at shaft stations. 57.19104 Section 57.19104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Personnel Hoisting Shafts § 57.19104 Clearance at...

  19. 30 CFR 56.19104 - Clearance at shaft stations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance at shaft stations. 56.19104 Section 56.19104 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personnel Hoisting Shafts § 56.19104 Clearance at...

  20. 19 CFR 122.158 - Other entry and clearance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Other entry and clearance requirements. 122.158 Section 122.158 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Flights to and From Cuba § 122.158 Other entry and clearance requirements. All other provisions...

  1. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  2. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  3. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  4. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  5. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  6. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  7. Clearance systems in the brain-implications for Alzheimer disease.

    PubMed

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

  8. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  9. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  10. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  11. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  12. 49 CFR 229.71 - Clearance above top of rail.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Clearance above top of rail. 229.71 Section 229.71....71 Clearance above top of rail. No part or appliance of a locomotive except the wheels, flexible nonmetallic sand pipe extension tips, and trip cock arms may be less than 21/2 inches above the top of rail....

  13. 33 CFR 118.160 - Vertical clearance gauges.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Vertical clearance gauges. 118.160 Section 118.160 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LIGHTING AND OTHER SIGNALS § 118.160 Vertical clearance gauges. (a) When necessary for reasons of safety of navigation, the...

  14. Radioaerosol delivery and clearance in patients with respiratory failure

    SciTech Connect

    Jacobs, M.P.; Tennenberg, S.D.; Baughman, R.P.

    1987-12-01

    A technique for radioaerosol delivery to patients requiring mechanical ventilation is described. Ventilation images and pulmonary radioaerosol clearance rates were successfully obtained in 35 patients regardless of ventilator type or level of positive end-expiratory pressure (PEEP). Those patients with noncardiogenic pulmonary edema (NPE) had significantly increased clearance rates relative to those patients in whom NPE was not present.

  15. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  16. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  17. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false Clearance of Air Force lands. 644.516 Section... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  18. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Clearance of Air Force lands. 644.516 Section... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  19. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological...

  20. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...