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Sample records for accelerated blood clearance

  1. Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.

    PubMed

    Rao, Lang; Bu, Lin-Lin; Xu, Jun-Hua; Cai, Bo; Yu, Guang-Tao; Yu, Xiaolei; He, Zhaobo; Huang, Qinqin; Li, Andrew; Guo, Shi-Shang; Zhang, Wen-Feng; Liu, Wei; Sun, Zhi-Jun; Wang, Hao; Wang, Tza-Huei; Zhao, Xing-Zhong

    2015-12-01

    For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance. PMID:26488923

  2. Influence of dose and animal species on accelerated blood clearance of PEGylated liposomal doxorubicin.

    PubMed

    Suzuki, Takuya; Ichihara, Masako; Hyodo, Kenji; Yamamoto, Eiichi; Ishida, Tatsuhiro; Kiwada, Hiroshi; Kikuchi, Hiroshi; Ishihara, Hiroshi

    2014-12-10

    We recently demonstrated that Doxil loses its long-circulating properties when injected repeatedly at doses below 2 mg/m(2) in dogs. In studies using other animal species, PEGylated liposomal doxorubicin has been reported not to induce the accelerated blood clearance (ABC) phenomenon. We investigated the issue of whether Doxil can elicit the ABC phenomenon in several species. In minipigs, the ABC phenomenon was induced at 2 mg/m(2). In other animal species, the ABC phenomenon was not observed at higher doses (>2 mg/m(2)), but was observed at much lower doses (0.2 mg/m(2)). The pharmacokinetic profile of a second dose of Doxil reflected the circulating anti-PEG IgM level induced by the first dose. The ABC phenomenon was not observed at the clinically recommended DXR dose (20 mg/m(2)) in any animal species. These results indicate that Doxil can cause the ABC phenomenon in all animals tested, the extent of induction was dependent on the first dose of Doxil, and a higher Doxil dose lessened the ABC phenomenon. The current study results suggest that a careful study design including selection of animal species is important for preclinical studies using PEGylated liposomal formulations even if they contain anticancer drugs that suppress the host immune response. PMID:25280884

  3. Accelerated Blood Clearance Phenomenon Reduces the Passive Targeting of PEGylated Nanoparticles in Peripheral Arterial Disease.

    PubMed

    Im, Hyung-Jun; England, Christopher G; Feng, Liangzhu; Graves, Stephen A; Hernandez, Reinier; Nickles, Robert J; Liu, Zhuang; Lee, Dong Soo; Cho, Steve Y; Cai, Weibo

    2016-07-20

    Peripheral arterial disease (PAD) is a leading global health concern. Due to limited imaging and therapeutic options, PAD and other ischemia-related diseases may benefit from the use of long circulating nanoparticles as imaging probes and/or drug delivery vehicles. Polyethylene glycol (PEG)-conjugated nanoparticles have shown shortened circulation half-lives in vivo when injected multiple times into a single subject. This phenomenon has become known as the accelerated blood clearance (ABC) effect. The phenomenon is of concern for clinical translation of nanomaterials as it limits the passive accumulation of nanoparticles in many diseases, yet it has not been evaluated using inorganic or organic-inorganic hybrid nanoparticles. Herein, we found that the ABC phenomenon was induced by reinjection of PEGylated long circulating organic-inorganic hybrid nanoparticles, which significantly reduced the passive targeting of (64)Cu-labeled PEGylated reduced graphene oxide-iron oxide nanoparticles ((64)Cu-RGO-IONP-PEG) in a murine model of PAD. Positron emission tomography (PET) imaging was performed at 3, 10, and 17 days postsurgical induction of hindlimb ischemia. At day 3 postsurgery, the nanoparticles displayed a long circulation half-life with enhanced accumulation in the ischemic hindlimb. At days 10 and 17 postsurgery, reinjected mice displayed a short circulation half-life and lower accumulation of the nanoparticles in the ischemic hindlimb, in comparison to the naïve group. Also, reinjected mice showed significantly higher liver uptake than the naïve group, indicating that the nanoparticles experienced higher sequestration by the liver in the reinjected group. Furthermore, photoacoustic (PA) imaging and Prussian blue staining confirmed the enhanced accumulation of the nanoparticles in the liver tissue of reinjected mice. These findings validate the ABC phenomenon using long circulating organic-inorganic hybrid nanoparticles upon multiple administrations to the same

  4. Impact of Large Aggregated Uricases and PEG Diol on Accelerated Blood Clearance of PEGylated Canine Uricase

    PubMed Central

    Zhang, Chun; Fan, Kai; Ma, Xuefeng; Wei, Dongzhi

    2012-01-01

    Background Uricase has proven therapeutic value in treating hyperuricemia but sufficient reduction of its immunogenicity may be the largest obstacle to its chronic use. In this study, canine uricase was modified with 5 kDa mPEG-SPA and the impact of large aggregated uricases and cross-linked conjugates induced by difunctional PEG diol on immunogenicity was investigated. Methods and Findings Recombinant canine uricase was first expressed and purified to homogeneity. Source 15Q anion-exchange chromatography was used to separate tetrameric and aggregated uricase prior to pegylation, while DEAE anion-exchange chromatography was used to remove Di-acid PEG (precursor of PEG diol) from unfractionated 5 kDa mPEG-propionic acid. Tetrameric and aggregated uricases were separately modified with the purified mPEG-SPA. In addition, tetrameric uricases was modified with unfractionated mPEG-SPA, resulting in three types of 5 kDa mPEG-SPA modified uricase. The conjugate size was evaluated by dynamic light scattering and transmission electron microscope. The influence of differently PEGylated uricases on pharmacokinetics and immunogenicity were evaluated in vivo. The accelerated blood clearance (ABC) phenomenon previously identified for PEGylated liposomes occurred in rats injected with PEGylated uricase aggregates. Anti-PEG IgM antibodies, rather than neutralizing antibodies, were found to mediate the ABC. Conclusions The size of conjugates is important for triggering such phenomena and we speculate that 40–60 nm is the lower size limit that can trigger ABC. Removal of the uricase aggregates and the PEG diol contaminant and modifying with small PEG reagents enabled ABC to be successfully avoided and sufficient reduction in the immunogenicity of 5 kDa mPEG-modified tetrameric canine uricase. PMID:22745806

  5. Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs

    PubMed Central

    Wang, Chunling; Cheng, Xiaobo; Su, Yuqing; Pei, Ying; Song, Yanzhi; Jiao, Jiao; Huang, Zhenjun; Ma, Yanfei; Dong, Yinming; Yao, Ying; Fan, Jingjing; Ta, Han; Liu, Xinrong; Xu, Hui; Deng, Yihui

    2015-01-01

    The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors. PMID:25999716

  6. Zwitterionic Poly(carboxybetaine)-based Cationic Liposomes for Effective Delivery of Small Interfering RNA Therapeutics without Accelerated Blood Clearance Phenomenon

    PubMed Central

    Li, Yan; Liu, Ruiyuan; Shi, Yuanjie; Zhang, Zhenzhong; Zhang, Xin

    2015-01-01

    For efficient delivery of small interfering RNA (siRNA) to the target diseased site in vivo, it is important to design suitable vehicles to control the blood circulation of siRNA. It has been shown that surface modification of cationic liposome/siRNA complexes (lipoplexes) with polyethylene glycol (PEG) could enhance the circulation time of lipoplexes. However, the first injection of PEGylated lipoplexes in vivo induces accelerated blood clearance and enhances hepatic accumulation of the following injected PEGylated lipoplexes, which is known as the accelerated blood clearance (ABC) phenomenon. Herein, we developed zwitterionic poly(carboxybetaine) (PCB) modified lipoplexes for the delivery of siRNA therapeutics, which could avoid protein adsorption and enhance the stability of lipoplexes as that for PEG. Quite different from the PEGylation, the PCBylated lipoplexes could avoid ABC phenomenon, which extended the blood circulation time and enhanced the tumor accumulation of lipoplexes in vivo. After accumulation in tumor site, the PCBylation could promote the cellular uptake and endosomal/lysosomal escape of lipoplexes due to its unique chemical structure and pH-sensitive ability. With excellent tumor accumulation, cellular uptake and endosomal/lysosomal escape abilities, the PCBylated lipoplexes significantly inhibited tumor growth and induced tumor cell apoptosis. PMID:25825598

  7. Zwitterionic poly(carboxybetaine)-based cationic liposomes for effective delivery of small interfering RNA therapeutics without accelerated blood clearance phenomenon.

    PubMed

    Li, Yan; Liu, Ruiyuan; Shi, Yuanjie; Zhang, Zhenzhong; Zhang, Xin

    2015-01-01

    For efficient delivery of small interfering RNA (siRNA) to the target diseased site in vivo, it is important to design suitable vehicles to control the blood circulation of siRNA. It has been shown that surface modification of cationic liposome/siRNA complexes (lipoplexes) with polyethylene glycol (PEG) could enhance the circulation time of lipoplexes. However, the first injection of PEGylated lipoplexes in vivo induces accelerated blood clearance and enhances hepatic accumulation of the following injected PEGylated lipoplexes, which is known as the accelerated blood clearance (ABC) phenomenon. Herein, we developed zwitterionic poly(carboxybetaine) (PCB) modified lipoplexes for the delivery of siRNA therapeutics, which could avoid protein adsorption and enhance the stability of lipoplexes as that for PEG. Quite different from the PEGylation, the PCBylated lipoplexes could avoid ABC phenomenon, which extended the blood circulation time and enhanced the tumor accumulation of lipoplexes in vivo. After accumulation in tumor site, the PCBylation could promote the cellular uptake and endosomal/lysosomal escape of lipoplexes due to its unique chemical structure and pH-sensitive ability. With excellent tumor accumulation, cellular uptake and endosomal/lysosomal escape abilities, the PCBylated lipoplexes significantly inhibited tumor growth and induced tumor cell apoptosis. PMID:25825598

  8. Exploring the relationship between anti-PEG IgM behaviors and PEGylated nanoparticles and its significance for accelerated blood clearance.

    PubMed

    Shiraishi, Kouichi; Kawano, Kumi; Maitani, Yoshie; Aoshi, Taiki; Ishii, Ken J; Sanada, Yusuke; Mochizuki, Shinichi; Sakurai, Kazuo; Yokoyama, Masayuki

    2016-07-28

    Surface PEGylation on nanoparticles has greatly helped prolong their blood circulation half-lives. However, The injection of PEGylated nanoparticles into mice induced poly(ethylene glycol) (PEG)-specific IgM antibodies (anti-PEG IgMs), significantly changing PEG-liposomes' pharmacokinetics. In this study, we used various PEG-conjugates to conduct a mechanistic study of anti-PEG IgMs' binding behavior. The conventional belief has been that anti-PEG IgMs bind to PEG main chains; however, our findings reveal that anti-PEG IgMs did not bind to PEG main chains, whereas anti-PEG IgMs did bind to PEG-hydrophobic polymer blocks. The insertion of a hydrophilic polymer between each PEG chain and each hydrophobic polymer block suppressed anti-PEG IgMs' binding. We prove here that hydrophobic blocks are essential to anti-PEG IgMs' binding, and also that anti-PEG IgMs do not bind to intact PEGs without hydrophobic moiety. These results support our conclusion that anti-PEG IgMs exhibit specificity to PEG; however, the presence of a hydrophobic block at a proximity position from each PEG chain is essential for the binding. Also in the present study, we elucidate relations between anti-PEG IgMs and PEGylated nanoparticles. In one of our previous studies, anti-PEG IgMs scarcely affected the pharmacokinetics of PEG-b-poly(β-benzyl l-aspartate) block copolymer (PEG-PBLA) micelles, whereas anti-PEG IgMs significantly decreased PEG-liposomes' blood circulation half-life. Finally, we found that the ratio of anti-PEG IgM molecules to PEG-liposome particles is critical to these pharmacokinetic changes, and that a 10-fold increase in the number of anti-PEG IgM molecules permitted them to capture the PEG-liposome particles, thus leading to the aforementioned changes. PMID:27164541

  9. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance.

    PubMed

    Zhao, Zhen; Sagare, Abhay P; Ma, Qingyi; Halliday, Matthew R; Kong, Pan; Kisler, Kassandra; Winkler, Ethan A; Ramanathan, Anita; Kanekiyo, Takahisa; Bu, Guojun; Owens, Nelly Chuqui; Rege, Sanket V; Si, Gabriel; Ahuja, Ashim; Zhu, Donghui; Miller, Carol A; Schneider, Julie A; Maeda, Manami; Maeda, Takahiro; Sugawara, Tohru; Ichida, Justin K; Zlokovic, Berislav V

    2015-07-01

    PICALM is a highly validated genetic risk factor for Alzheimer's disease (AD). We found that reduced expression of PICALM in AD and murine brain endothelium correlated with amyloid-β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminished Aβ clearance across the murine blood-brain barrier (BBB) and accelerated Aβ pathology in a manner that was reversible by endothelial PICALM re-expression. Using human brain endothelial monolayers, we found that PICALM regulated PICALM/clathrin-dependent internalization of Aβ bound to the low density lipoprotein receptor related protein-1, a key Aβ clearance receptor, and guided Aβ trafficking to Rab5 and Rab11, leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD-derived endothelial monolayers, which was reversible by adenoviral-mediated PICALM transfer. Inducible pluripotent stem cell-derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance, which has implications for Aβ brain homeostasis and clearance therapy. PMID:26005850

  10. GPU-accelerated minimum distance and clearance queries.

    PubMed

    Krishnamurthy, Adarsh; McMains, Sara; Haller, Kirk

    2011-06-01

    We present practical algorithms for accelerating distance queries on models made of trimmed NURBS surfaces using programmable Graphics Processing Units (GPUs). We provide a generalized framework for using GPUs as coprocessors in accelerating CAD operations. By supplementing surface data with a surface bounding-box hierarchy on the GPU, we answer distance queries such as finding the closest point on a curved NURBS surface given any point in space and evaluating the clearance between two solid models constructed using multiple NURBS surfaces. We simultaneously output the parameter values corresponding to the solution of these queries along with the model space values. Though our algorithms make use of the programmable fragment processor, the accuracy is based on the model space precision, unlike earlier graphics algorithms that were based only on image space precision. In addition, we provide theoretical bounds for both the computed minimum distance values as well as the location of the closest point. Our algorithms are at least an order of magnitude faster and about two orders of magnitude more accurate than the commercial solid modeling kernel ACIS. PMID:21474862

  11. Mechanisms tagging senescent red blood cells for clearance in healthy humans

    PubMed Central

    Lutz, Hans U.; Bogdanova, Anna

    2013-01-01

    This review focuses on the analysis and evaluation of the diverse senescence markers suggested to prime red blood cells (RBC) for clearance in humans. These tags develop in the course of biochemical and structural alterations accompanying RBC aging, as the decrease of activities of multiple enzymes, the gradual accumulation of oxidative damage, the loss of membrane in form of microvesicles, the redistribution of ions and alterations in cell volume, density, and deformability. The actual tags represent the penultimate galactosyl residues, revealed by desialylation of glycophorins, or the aggregates of the anion exchanger (band 3 protein) to which anti-galactose antibodies bind in the first and anti-band 3 naturally occurring antibodies (NAbs) in the second case. While anti-band 3 NAbs bind to the carbohydrate-free portion of band 3 aggregates in healthy humans, induced anti-lactoferrin antibodies bind to the carbohydrate-containing portion of band 3 and along with anti-band 3 NAbs may accelerated clearance of senescent RBC in patients with anti-neutrophil cytoplasmic antibodies (ANCA). Exoplasmically accessible phosphatidylserine (PS) and the alterations in the interplay between CD47 on RBC and its receptor on macrophages, signal regulatory protein alpha (SIRPalpha protein), were also reported to induce erythrocyte clearance. We discuss the relevance of each mechanism and analyze the strength of the data. PMID:24399969

  12. Interest of ICG blood clearance monitoring for reproducible 810-nm diode laser coagulation of blood vessels

    NASA Astrophysics Data System (ADS)

    Desmettre, Thomas; Soulie-Begu, Sylvie; Devoisselle, Jean-Marie; Mordon, Serge R.

    1999-02-01

    Purpose: To evaluate a method of control of diode laser fluence leading to a reproducible ICG-enhanced selective photocoagulation of blood vessels. This method would use the chromophore clearance, i.e. ICG blood concentration decay to adapt the laser fluence. Materials and Methods: A skin flap window was used on hamsters. After a 15 mg/kg ICG solution injection, photocoagulation of vessels were performed. Results: Selective photocoagulation of blood vessels was obtained only during the first 10 minutes. The fluence required to obtain a selective photocoagulation of vessels (F) was modelized using a one compartment phamacokinetic equation: F equals Of(1-e-t/(tau )). The best fit was obtained for a time constant (tau) equals 4.8 min and Of equals 300 J/cm2 (correlation coefficient r2 equals 0.996). During the first 10 minutes, the fluence required for selective photocoagulation of vessels was increased by a factor 4.5. Conclusion: Fluence required for a selective photocoagulation of vessels was correlated to ICG blood concentration decay. The time constant was equivalent to ICG half-life time in human blood. These results demonstrate that diode laser ICG-enhanced photocoagulation can be controlled by monitoring the ICG blood clearance.

  13. Estimation of error limits for cerebral blood flow values obtained from xenon-133 clearance curves

    SciTech Connect

    Ryding, E.

    1989-02-01

    I provide the theoretical basis for an error calculus for measurements of cerebral blood flow using a freely diffusible tracer substance such as xenon-133. The use of the error calculus is exemplified by a study of the effect on the error margins in measurements of gray matter blood flow from flow level, relative weight of the gray matter compartment, and use of the earliest parts of the clearance curves. The clinical value of the error calculus is illustrated by its ability to separate different sources of measurement error. As a consequence, it is possible to optimize the method for blood flow calculation from the clearance curves, depending on the type of cerebral blood flow measurement. I show that if a true picture of the regional gray matter blood flow distribution is sought, the earliest part of the clearance curves should be used. This does, however, increase the error in the estimate of the average cerebral blood flow value.

  14. Transplacental clearance and blood flows of bovine gravid uterus at several stages of gestation

    SciTech Connect

    Reynolds, L.P.; Ferrell, C.L.

    1987-11-01

    Rates of uterine and umbilical blood flows and transplacental clearance of deuterium oxide (D/sub 2/O) were determined for cows on 137 +/- 1.0 (SE, n = 9), 180 +/- 0.5 (n = 8), 226 +/- 0.4 (n = 9), and 250 +/- 1.8 (n = 5) days of gestation. From days 137 to 250, rates increased 4.5-fold for uterine blood flow, 21-fold for umbilical blood flow, and 14-fold for clearance of D/sub 2/O. Changes in rates of umbilical blood flow and D/sub 2/O clearance paralleled increased rates of fetal growth and metabolism, which have previously been reported to occur during the last half of gestation. The regressions of D/sub 2/O clearance on uterine and umbilical blood flows were significant (P less than 0.01) and explained 94-99% of the variation in placental clearance of D/sub 2/O. Because the rate of D/sub 2/O clearance was always less than that of uterine and umbilical blood flows, and because a relatively simple statistical model explained most of the variation in clearance, it was suggested that a concurrent or countercurrent arrangement of maternal and fetal placental microvasculatures is not adequate to explain clearance of highly diffusable substances across the bovine placenta. In addition, a placental exchange diagram of the data showed the existence of severe uneven distribution of maternal and fetal placental blood flows and/or significant shunting of maternal and fetal placental flows away from areas of exchange. Taken together, these data indicate that the placenta of the cow, like those of the sheep and goat, represents a relatively inefficient system of transplacental exchange.

  15. Endoscopic measurements of canine colonic mucosal blood flow using hydrogen gas clearance

    SciTech Connect

    Soybel, D.I.; Wan, Y.L.; Ashley, S.W.; Yan, Z.Y.; Ordway, F.S.; Cheung, L.Y.

    1987-04-01

    We have examined the feasibility of hydrogen (H/sub 2/) clearance for endoscopic measurements of colonic mucosal blood flow in anesthetized dogs. In 6 animals, measurements of H2 clearance did not differ significantly in different regions of the sigmoid colon and they were highly reproducible on different days. In a total of 12 dogs, measurements of H2 clearance correlated closely with those obtained using radioactive microspheres under resting conditions and, in 4 dogs, during infusion of vasopressin. In 8 dogs, ligation of the major arteries supplying the sigmoid colon resulted in an acute 60% decrease in sigmoid mucosal blood flow; however, in 5 animals that survived the procedure, mucosal blood flow returned nearly to control levels as early as 3 days after operation. Endoscopic H/sub 2/ clearance thus appears to be feasible for measuring mucosal blood flow in the colon. Serial measurements of H/sub 2/ clearance may prove useful in characterizing the role of mucosal blood flow in the pathogenesis of various forms of human colonic disease.

  16. Hydrogen clearance: Assessment of technique for measurement of skin-flap blood flow in pigs

    SciTech Connect

    Thomson, J.G.; Kerrigan, C.L. )

    1991-10-01

    The hydrogen clearance technique has been used for many years by investigators to determine brain blood flow and has been partially validated in this setting using other methods of blood flow measurement. The method has been modified to allow blood flow measurements in skin, but the accuracy of H2 clearance for measuring skin blood flow has not been determined. Multiple blood flow measurements were performed using H2 clearance and radioactive microspheres on skin flaps and control skin in pigs. On 12 pigs, a total of 117 flap and 42 control skin measurements were available for analysis. There was no significant difference between the two techniques in measuring mean control skin blood flow. In skin flaps, H2 clearance was significantly correlated to microsphere-measured blood flow, but it consistently gave an overestimate. Sources of error may include injury to the tissues by insertion of electrodes, consumption of H2 by the electrodes, or diffusion of H2 from the relatively ischemic flap to its well-vascularized bed. Further studies are necessary to determine the cause of this error and to measure the technique's accuracy in skeletal muscle and other flaps.

  17. Numerical analysis of blood flow in the clearance regions of a continuous flow artificial heart pump.

    PubMed

    Anderson, J; Wood, H G; Allaire, P E; Olsen, D B

    2000-06-01

    The CFVAD3 is the third prototype of a continuous flow ventricular assist device being developed for implantation in humans. The pump consists of a fully shrouded 4-blade impeller supported by magnetic bearings. On either side of this suspended rotating impeller is a small clearance region through which the blood flows. The spacing and geometry of these clearance regions are very important to the successful operation of this blood pump. Computational fluid dynamics (CFD) solutions for this flow were obtained using TascFlow, a software package available from AEA Technology, U.K. Flow in these clearance regions was studied parametrically by varying the size of the clearance, the blood flow rate into the pump, and the rotational speed of the pump. The numerical solutions yield the direction and magnitude of the flow and the dynamic pressure. Experimentally measured pump flow rates are compared to the numerical study. The results of the study provide guidance for improving pump efficiency. It is determined that current clearances can be significantly reduced to improve pump efficiency without negative impacts. PMID:10886072

  18. Comparison of thermal clearance measurement of regional cerebral blood flow with radiolabelled microspheres

    SciTech Connect

    Hoehner, P.J.; Dean, J.M.; Rogers, M.C.; Traystman, R.J.

    1987-05-01

    A thermal clearance technique for measuring cerebral blood flow is described and compared with the radiolabelled microsphere technique. The thermal technique involves measurement of the rewarming curve generated after bolus infusion of 4-5 ml of ice-cold saline into the common carotid artery with a subdural thermistor placed on the parietal cortex. Evaluation of the biexponential decay curves obtained with this technique demonstrated a close correlation with total hemispheric, parietal, and parietal gray blood flow determined by simultaneous microsphere measurement. Despite significant correlations (p less than 0.001), scatter in the data produced a broad 95% confidence interval, thus making interpretation of blood flow with the thermal clearance technique impossible. Furthermore, instrumentation with the thermal probe, which required opening of the dura, blunted the cerebral blood flow response to hypercapnia. We conclude that the major limitations of the thermal clearance technique include: nonhomogeneous clearance function, significant variability, and depression of CO/sub 2/ reactivity. These limitations must be addressed before this technique can be used reliably in the laboratory.

  19. Robust Foot Clearance Estimation Based on the Integration of Foot-Mounted IMU Acceleration Data

    PubMed Central

    Benoussaad, Mourad; Sijobert, Benoît; Mombaur, Katja; Azevedo Coste, Christine

    2015-01-01

    This paper introduces a method for the robust estimation of foot clearance during walking, using a single inertial measurement unit (IMU) placed on the subject’s foot. The proposed solution is based on double integration and drift cancellation of foot acceleration signals. The method is insensitive to misalignment of IMU axes with respect to foot axes. Details are provided regarding calibration and signal processing procedures. Experimental validation was performed on 10 healthy subjects under three walking conditions: normal, fast and with obstacles. Foot clearance estimation results were compared to measurements from an optical motion capture system. The mean error between them is significantly less than 15% under the various walking conditions. PMID:26703622

  20. Rapid blood clearance of biotinylated IgG after infusion of avidin

    SciTech Connect

    Sinitsyn, V.V.; Mamontova, A.G.; Checkneva, Y.Y.; Shnyra, A.A.; Domogatsky, S.P.

    1989-01-01

    The techniques of immunotherapy and radioimmunoimaging suffer from the problem of background: intravenously injected antibodies remain in the circulation much longer than it is necessary for effective binding to the target. Various approaches, including the postinjection of second antibodies, were explored to overcome the problem with some success. The phenomenon of a 100-fold more rapid blood clearance of biotinylated immunoglobulins after postinjection of an equivalent dose of avidin is described. The concentration of /sup 125/I-labeled biotinylated IgG in the circulation of rats slowly decreased to 20% of initial in 24 hr. Avidin injection at any interval during this period induced 90-95% reduction of radioactivity in blood in 15 min. Up to 70% of the radioactivity was recovered in the liver. Avidin-induced blood clearance of biotinylated immunoglobulins may find applications in immunotherapy and radio- or nuclear magnetic resonance immunoimaging.

  1. Comparison of gas clearance and radioactive microspheres for pancreatic blood flow measurement

    SciTech Connect

    DeMar, A.R.; Graham, L.S.; Lake, R.; Fink, A.S. )

    1989-01-01

    Measurement of pancreatic blood flow (PBF) is technically demanding. Although radiolabeled microspheres are considered the gold standard for PBF assessment, they have practical limitations. In the current study, H{sub 2} and xenon-133 gas clearance techniques were adapted to PBF measurement and compared to radiolabeled microsphere techniques. Simultaneous measurements of PBF were made using either hydrogen or xenon gas washout and radiolabeled microspheres. Measurements were made under basal, vasoconstricted (vasopressin 2U i.v. or nicotine 4 micrograms/kg/h) and stimulated (secretin 125 ng/kg/h or 2 U/kg i.v.) conditions (random order). Mean PBF was 26.9 +/- 5.3, 50.5 +/- 2.3 and 27.6 +/- 5.2 ml/min/100 g basally, 36.9 +/- 8.0, 90.1 +/- 18.9, and 81.7 +/- 14.5 ml/min/100 g in the stimulated state, and 24.2 +/- 7.8, 25.0 +/- 3.5, and 14.9 +/- 7.5 ml/min/100 g in the vasoconstricted state for hydrogen gas clearance, xenon gas clearance, and radiolabeled microspheres, respectively. The H{sub 2} clearance technique resulted in tissue trauma, was complicated by frequent electrode displacement, and correlated poorly (r2 = 0.36, p greater than 0.05) with microsphere values. In contrast, xenon clearance measurement had no apparent effect on the pancreas and correlated well (r2 = 0.83, p less than 0.01) with microsphere data. We conclude that xenon clearance offers an attractive, validated alternative to radiolabeled microspheres for measuring pancreatic blood flow.

  2. The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia.

    PubMed

    Li, Xiaoyang; Zhu, Hongming; Zhang, Yunxiang; Zhao, Weili; Mi, Jianqing; Hu, Jiong; Li, Junmin

    2016-01-01

    The value of clearance of peripheral blood blasts (PBB) as a predictor of outcomes in acute myeloid leukemia (AML) is controversial. To investigate the prognostic significance of the time to clearance of PBB after induction in Chinese patients with AML, a retrospective analysis of 146 patients with newly diagnosed AML at Shanghai Ruijin Hospital was performed. Patients were categorized into early blast clearance (EBC; ≤5 days) and delayed blast clearance (DBC; >5 days) groups based on a receiver operating characteristic analysis. Complete remission (CR) after induction chemotherapy was related to the time to clearance of PBB (p < 0.001). Relapse-free survival (RFS; p = 0.003) and overall survival (p < 0.001) were longer in the EBC group. Multivariate analysis demonstrated that the time to clearance of PBB and cytogenetic risk independently predicted CR and RFS. Early clearance of PBB after induction chemotherapy can be a significant predictor of survival outcomes in AML patients. PMID:26967450

  3. Microhaemodynamics within the blade tip clearance of a centrifugal turbodynamic blood pump.

    PubMed

    Antaki, J F; Diao, C-G; Shu, F-J; Wu, J-C; Zhao, R; Kameneva, M V

    2008-05-01

    A persistent challenge facing the quantitative design of turbodynamic blood pumps is the great disparity of spatial scales between the primary and auxiliary flow paths. Fluid passages within journals and adjacent to the blade tips are often on the scale of several blood cells, confounding the application of macroscopic continuum models. Yet, precisely in these regions there exists the highest shear stress, which is most likely to cause cellular trauma. This disparity has motivated these microscopic studies to visualize the kinematics of the blood cells within the small clearances of a miniature turbodynamic blood pump. A transparent model of a miniature centrifugal pump having an adjustable tip clearance (50-200 microm) was prepared for direct optical visualization of the region between the impeller blade tip and the stationary housing. Synchronized images of the blood cells were obtained by a microscopic visualization system, consisting of an inverted microscope fitted with long-working-distance objective lens (40x), mercury lamp, and high-resolution charge-coupled device camera electronically triggered by the rotation of the impeller. Experiments with 7 microm fluorescent particles revealed the influence of the gap dimension on the trajectory across the blade thickness. The lateral component of velocity (perpendicular to the blade) was dramatically enhanced in the 50 microm gap compared with the 200 microm gap, thereby reducing the exposure time. Studies with diluted bovine blood (Ht = 0.5 per cent) showed that the concentration of cells traversing the gap is also reduced dramatically (30 per cent) as the blade tip clearance is reduced from 200 microm to 50 microm. These results motivate further investigation into the microfluidic phenomena responsible for cellular trauma within turbodynamic blood pumps. PMID:18595366

  4. [Evaluation on blood clearance and hepatic uptake of 99mTc-GSA in rats with blood flow conversion].

    PubMed

    Ohno, K

    1997-05-01

    This study was aimed to clarify a contribution of the hepatic blood flow in hepatic accumulation of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA). The experiment was performed in rats by the blood flow conversion with an external scintillation gamma camera and laser doppler flowmeter. Rats were divided into 4 groups: hepatic artery ligation (HAL, n = 10), portal vein ligation (PVL, n = 8), both hepatic artery and portal vein ligation (HAL+PVL, n = 9), and control (CONT, n = 10) groups. The scintigraphic data were obtained in each group for 10 minutes after intravenous injection of 99mTc-GSA (50 micrograms/100 g B.W). The regions of interest were assigned over the heart and whole liver and the time activity curves (TAC) were generated. Five parameters of HH 4, LHL 4, KH1, KH2, KL, were calculated as blood clearance and hepatic accumulation from TAC in each rat. HH4 as blood clearance index in CONT, HAL, PVL and HAL+PVL was 0.58 +/- 0.04 (mean +/- SE), 0.63 +/- 0.04, 0.85 +/- 0.04, 0.97 +/- 0.001, respectively. HH 4 between CONT vs PVL, HAL+PVL was statistically significant (p < 0.05). LHL 4 as hepatic uptake index in CONT, HAL, PVL and HAL+PVL was 0.96 +/- 0.001, 0.93 +/- 0.01, 0.71 +/- 0.07, 0.41 +/- 0.04, respectively. This parameter was also statistically significant between CONT vs PVL and HAL+PVL groups. Another parameter of KH1 for blood clearance and KL for hepatic uptake were also significant between CONT vs PVL and HAL+PVL groups. All parameters obtained in 99mTc-GSA study correlated well with the hepatic flow rate which was measured with a laser doppler flowmeter and reflected the reduction rate of the hepatic tissue blood flow 4 minutes after the ligation of target vessels. These result suggest that blood clearance and hepatic uptake of 99mTc-GSA are significantly affected by hepatic blood inflow. 99mTc-GSA scintigraphy may be useful in evaluating hepatic tissue blood flow. PMID:9226469

  5. Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier

    PubMed Central

    Keaney, James; Walsh, Dominic M.; O’Malley, Tiernan; Hudson, Natalie; Crosbie, Darragh E.; Loftus, Teresa; Sheehan, Florike; McDaid, Jacqueline; Humphries, Marian M.; Callanan, John J.; Brett, Francesca M.; Farrell, Michael A.; Humphries, Peter; Campbell, Matthew

    2015-01-01

    The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting neural tissue from damaging blood-borne agents. The barrier is characterized by endothelial tight junctions that limit passive paracellular diffusion of polar solutes and macromolecules from blood to brain. Decreased brain clearance of the neurotoxic amyloid-β (Aβ) peptide is a central event in the pathogenesis of Alzheimer’s disease (AD). Whereas transport of Aβ across the BBB can occur via transcellular endothelial receptors, the paracellular movement of Aβ has not been described. We show that soluble human Aβ(1–40) monomers can diffuse across the paracellular pathway of the BBB in tandem with a decrease in the tight junction proteins claudin-5 and occludin in the cerebral vascular endothelium. In a murine model of AD (Tg2576), plasma Aβ(1–40) levels were significantly increased, brain Aβ(1–40) levels were decreased, and cognitive function was enhanced when both claudin-5 and occludin were suppressed. Furthermore, Aβ can cause a transient down-regulation of claudin-5 and occludin, allowing for its own paracellular clearance across the BBB. Our results show, for the first time, the involvement of the paracellular pathway in autoregulated Aβ movement across the BBB and identify both claudin-5 and occludin as potential therapeutic targets for AD. These findings also indicate that controlled modulation of tight junction components at the BBB can enhance the clearance of Aβ from the brain. PMID:26491725

  6. Parametric study of blade tip clearance, flow rate, and impeller speed on blood damage in rotary blood pump.

    PubMed

    Kim, Nahn Ju; Diao, Chenguang; Ahn, Kyung Hyun; Lee, Seung Jong; Kameneva, Marina V; Antaki, James F

    2009-06-01

    Phenomenological studies on mechanical hemolysis in rotary blood pumps have provided empirical relationships that predict hemoglobin release as an exponential function of shear rate and time. However, these relations are not universally valid in all flow circumstances, particularly in small gap clearances. The experiments in this study were conducted at multiple operating points based on flow rate, impeller speed, and tip gap clearance. Fresh bovine red blood cells were resuspended in phosphate-buffered saline at about 30% hematocrit, and circulated for 30 min in a centrifugal blood pump with a variable tip gap, designed specifically for these studies. Blood damage indices were found to increase with increased impeller speed or decreased flow rate. The hemolysis index for 50-microm tip gap was found to be less than 200-microm gap, despite increased shear rate. This is explained by a cell screening effect that prevents cells from entering the smaller gap. It is suggested that these parameters should be reflected in the hemolysis model not only for the design, but for the practical use of rotary blood pumps, and that further investigation is needed to explore other possible factors contributing to hemolysis. PMID:19473143

  7. Blood pressure and creatinine clearance in lead-exposed children: the effect of treatment

    SciTech Connect

    Friedlander, M.A.; Brooks, C.T.; Sheehe, P.R.

    1981-01-01

    The authors speculated that normal growth might cause the release of stored lead in children, providing an endogenous source of exposure for years after the acute toxic episode had resolved. The purpose of this study was to answer the following two questions: (1) is a chelation-responsive lead burden present 2 to 5 yr after therapy for acute poisoning; and (2) does blood pressure or creatinine clearance correlate with body lead burden, as demonstrated by chelation. Thirty-eight children who had undergone ethylene diamine tetraacetic acid mobilization testing at least one time during the course of treatment in a lead clinic returned for follow-up care within 2-5 yr. All were asymptomatic. To determine the current level of body lead burden, a single-dose oral chelation with penicillamine was performed. Blood pressure and creatinine clearences were measured. From the data obtained for each child, we generated a geometric ''area'' representing the magnitude of lead burden integrated over the length of carriage of this burden. Multiple regression analysis indicated that after adjustment for the background variables of age, sex, height, and weight, none of the three parameters-mobilization ratio ''area,'' blood lead level, or FEP level-was a significant contributor to the variation observed in the blood pressures or creatinine clearances of the 38 lead-exposed children (P>.05).

  8. Lipoprotein-based nanoparticles rescue the memory loss of mice with Alzheimer's disease by accelerating the clearance of amyloid-beta.

    PubMed

    Song, Qingxiang; Huang, Meng; Yao, Lei; Wang, Xiaolin; Gu, Xiao; Chen, Juan; Chen, Jun; Huang, Jialin; Hu, Quanyin; Kang, Ting; Rong, Zhengxing; Qi, Hong; Zheng, Gang; Chen, Hongzhuan; Gao, Xiaoling

    2014-03-25

    Amyloid-beta (Aβ) accumulation in the brain is believed to play a central role in Alzheimer's disease (AD) pathogenesis, and the common late-onset form of AD is characterized by an overall impairment in Aβ clearance. Therefore, development of nanomedicine that can facilitate Aβ clearance represents a promising strategy for AD intervention. However, previous work of this kind was concentrated at the molecular level, and the disease-modifying effectiveness of such nanomedicine has not been investigated in clinically relevant biological systems. Here, we hypothesized that a biologically inspired nanostructure, apolipoprotein E3-reconstituted high density lipoprotein (ApoE3-rHDL), which presents high binding affinity to Aβ, might serve as a novel nanomedicine for disease modification in AD by acceleratingclearance. Surface plasmon resonance, transmission electron microscopy, and co-immunoprecipitation analysis showed that ApoE3-rHDL demonstrated high binding affinity to both Aβ monomer and oligomer. It also accelerated the microglial, astroglial, and liver cell degradation of Aβ by facilitating the lysosomal transport. One hour after intravenous administration, about 0.4% ID/g of ApoE3-rHDL gained access to the brain. Four-week daily treatment with ApoE3-rHDL decreased Aβ deposition, attenuated microgliosis, ameliorated neurologic changes, and rescued memory deficits in an AD animal model. The findings here provided the direct evidence of a biomimetic nanostructure crossing the blood-brain barrier, capturing Aβ and facilitating its degradation by glial cells, indicating that ApoE3-rHDL might serve as a novel nanomedicine for disease modification in AD by acceleratingclearance, which also justified the concept that nanostructures with Aβ-binding affinity might provide a novel nanoplatform for AD therapy. PMID:24527692

  9. Clearance of lead-212 ions from rabbit bronchial epithelium to blood.

    PubMed

    James, A C; Greenhalgh, J R; Smith, H

    1977-09-01

    The absorption of 212Pb ions from bronchial epithelium to blood has been investigated in anaesthetized rabbits. The 212Pb ions were introduced by intubation either into the trachea or into smaller, more distal bronchi. Removal from lung was followed by external gamma-counting. Mucociliary clearance to the GI tract was blocked by tracheostomy. Two distinct phases of clearance from bronchial epithelium to blood were observed. Approximately 20% of deposited 212Pb is rapidly absorbed with a half-time of about 4 min, the remainder with a biological half-time of about 9 h, irrespective of the site of instillation in the bronchial tree. Two hours after deposition, the 212Pb remaining in lung was found to be partitioned between mucus and the bronchial epithelium, with a substantial but minor fraction in the epithelium. Uptake of 212Pb in the skeleton was estimated to be about 20% of the 212Pb entering the blood circulation. Removal by the kidneys, at 25%, was comparable with skeletal uptake. These results are compared with previously published work using rodents, dogs and man which demonstrated either rapid or slow absorption but not both phases occuring together. PMID:909929

  10. Multicompartmental analysis of tracer clearance and its application to cerebral blood flow measurement

    SciTech Connect

    Rusinek, H.

    1986-10-01

    A new algorithm for computing cerebral blood flow is shown to overcome compartmental slippage and unstability problems associated with the conventional bicompartmental analysis. The tracer clearance curve is decomposed into a nonnegative linear combination of predetermined flow components. A weighted average of flows above (below) a fixed threshold yields the gray (white) matter flow. The accuracy and the stability of the new algorithm are analyzed by Monte-Carlo simulations, determining the effect of factors such as random error in tracer concentration, gray-white flow difference, tissue content of gray matter, and end-fit time. While the new algorithm requires 50-100% more CPU time and memory space than the bicompartmental method, its accuracy and stability is superior, especially as the conditions of the measurement deteriorate. The results suggest that more than twofold error reduction in measuring the blood flow in pathological brain tissue is possible.

  11. Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity.

    PubMed

    Broadley, Steven P; Plaumann, Ann; Coletti, Raffaele; Lehmann, Christin; Wanisch, Andreas; Seidlmeier, Amelie; Esser, Knud; Luo, Shanshan; Rämer, Patrick C; Massberg, Steffen; Busch, Dirk H; van Lookeren Campagne, Menno; Verschoor, Admar

    2016-07-13

    Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeria monocytogenes, we show that bacterial clearance is not a uniform process but a "dual-track" mechanism consisting of parallel "fast" and "slow" pathways. "Slow clearance" is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from "fast clearance" and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8α(+) dendritic cells. We consistently find "fast" and "slow" clearance patterns for a broad panel of other Gram+ and Gram- bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity. PMID:27345696

  12. The role of blood lactate clearance as a predictor of mortality in children undergoing surgery for tetralogy of Fallot

    PubMed Central

    Ladha, Suruchi; Kapoor, Poonam Malhotra; Singh, Sarvesh Pal; Kiran, Usha; Chowdhury, Ujjwal Kumar

    2016-01-01

    Background: The identification of biomarkers for predicting morbidity and mortality, particularly in pediatric population undergoing cardiac surgery will contribute toward improving the patient outcome. There is an increasing body of literature establishing the clinical utility of hyperlactatemia and lactate clearance as prognostic indicator in adult cardiac surgical patients. However, the relationship between lactate clearance and mortality risk in the pediatric population remains to be established. Objective: To assess the role of lactate clearance in determining the outcome in children undergoing corrective surgery for tetralogy of Fallot (TOF). Methods and Study Design: A prospective, observational study. Setting: A tertiary care center. Study Population: Two hundred children undergoing elective surgery for TOF. Study Method: Blood lactate levels were obtained as baseline before operation (T0), postoperatively at admission to the cardiac intensive care unit after surgery (T1), and then at every 6 h for the first 24 h of Intensive Care Unit (ICU) stay (T6, T12, T18, and T24, respectively). The lactate clearance in the study is defined by the equation ([lactate initial – lactate delayed]/lactate initial) ×100%. Lactate clearance was determined at T1–T6, T1–T12, T1–T18, and T1–T24 time interval, respectively. The primary outcome measured was mortality. Secondary outcomes measured were the duration of mechanical ventilation, duration of inotropic requirement, and duration of ICU stay. Results: Eleven out of the two hundred patients enrolled in the study died. Nonsurvivors had higher postoperative lactate concentration (P < 0.05) and low-blood lactate clearance rate during 24 h (P < 0.05) in comparison to the survivors. Lactate clearance was significantly higher in survivors than in nonsurvivors for the T1–T6 period (19.55 ± 14.28 vs. 5.24 ± 27.79%, P = 0.009) and remained significantly higher for each studied interval in first 24 h. Multivariate

  13. Cerebral blood flow in the newborn infant: comparison of Doppler ultrasound and /sup 133/xenon clearance

    SciTech Connect

    Greisen, G.; Johansen, K.; Ellison, P.H.; Fredriksen, P.S.; Mali, J.; Friis-Hansen, B.

    1984-03-01

    Two techniques of Doppler ultrasound examination, continuous-wave and range-gated, applied to the anterior cerebral artery and to the internal carotid artery, were compared with /sup 133/xenon clearance after intravenous injection. Thirty-two sets of measurements were obtained in 16 newborn infants. The pulsatility index, the mean flow velocity, and the end-diastolic flow velocity were read from the Doppler recordings. Mean cerebral blood flow was estimated from the /sup 133/Xe clearance curves. The correlation coefficients between the Doppler and the /sup 133/Xe measurements ranged from 0.41 to 0.82. In the subset of 16 first measurements in each infant, there were no statistically significant differences between the correlation coefficients of the various Doppler ultrasound variables, but the correlation coefficients were consistently lower for the pulsatility index than for mean flow velocity or end-diastolic flow velocity, and they were consistently higher for the range-gated than for the continuous-wave Doppler technique.

  14. Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers

    NASA Astrophysics Data System (ADS)

    Singh, Ravi; Pantarotto, Davide; Lacerda, Lara; Pastorin, Giorgia; Klumpp, Cédric; Prato, Maurizio; Bianco, Alberto; Kostarelos, Kostas

    2006-02-01

    Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium (111In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications. nanomedicine | blood circulation half-life | drug delivery | pharmacokinetics | nanotoxicology

  15. Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

    PubMed Central

    Schallner, Nils; Pandit, Rambhau; LeBlanc, Robert; Thomas, Ajith J.; Ogilvy, Christopher S.; Zuckerbraun, Brian S.; Gallo, David; Otterbein, Leo E.; Hanafy, Khalid A.

    2015-01-01

    Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms. PMID:26011640

  16. Simultaneous recording of fingertip skin blood flow changes by multiprobe laser Doppler flowmetry and frequency-corrected thermal clearance.

    PubMed

    Raamat, Rein; Jagomägi, Kersti; Kingisepp, Peet

    2002-09-01

    We compared the results of skin blood flow (SBF) measurements, obtained simultaneously in adjacent fingertips by laser Doppler flowmetry (LDF) and thermal clearance (TC) probes, having approximately the same spatial and temporal characteristics. Experiments were performed in nine healthy volunteers during rest at room temperature (26-28 degrees C). A time resolution equal to about a second was achieved by speeding up the response of the thermal measurement circuit by applying the computer simulation software of the MATLAB package. The comparison revealed that the frequency-corrected TC signal correlated well with the multiprobe LDF signal (median correlation coefficient = 0.90, range = 0.84 to 0.96). At the same time the individual slope values of the regression equation ranged from 0.58 to 1.61, revealing the difficulties encountered in obtaining the invariant scaling factor between the TC and LDF measurements. The relationship between the frequency-corrected TC signal and the multiprobe LDF signal was found to be linear in the range of SBF changes of about three- to fourfold. In the case of larger fluctuations in SBF, excessive acceleration at high SBF rates was noted. PMID:12204645

  17. Pneumocystis pneumonia increases the clearance rate of inhaled /sup 99m/Tc DTPA from lung to blood

    SciTech Connect

    Jones, D.K.; Higenbottam, T.W.

    1985-10-01

    Despite no radiographic change, a patient with Pneumocystis pneumonia showed increased clearance of inhaled /sup 99m/Tc DTPA from lung to blood. Gas transfer for carbon monoxide was also reduced, but improved with treatment. This was paralleled by serial increase in the t1/2 LB.

  18. NOTE: Blood irradiation with accelerator produced electron beams

    NASA Astrophysics Data System (ADS)

    Butson, M. J.; Cheung, T.; Yu, P. K. N.; Stokes, M. J.

    2000-11-01

    Blood and blood products are irradiated with gamma rays to reduce the risk of graft versus host disease (GVHD). A simple technique using electron beams produced by a medical linear accelerator has been studied to evaluate irradiation of blood and blood products. Variations in applied doses for a single field 20 MeV electron beam are measured in a phantom study. Doses have been verified with ionization chambers and commercial diode detectors. Results show that the blood product volume can be given a relatively homogeneous dose to within 6% using 20 MeV electrons without the need to rotate the blood bags or the beam entry point. The irradiation process takes approximately 6.5 minutes for 30 Gy applied dose to complete as opposed to 12 minutes for a dual field x-ray field irradiation at our centre. Electron beams can be used to satisfactorily irradiate blood and blood products in a minimal amount of time.

  19. Computational Fluid Dynamics Analysis of Blade Tip Clearances on Hemodynamic Performance and Blood Damage in a Centrifugal Ventricular Assist Device

    PubMed Central

    Wu, Jingchun; Paden, Bradley E.; Borovetz, Harvey S.; Antaki, James F.

    2011-01-01

    An important challenge facing the design of turbodynamic ventricular assist devices (VADs) intended for long-term support is the optimization of the flow path geometry to maximize hydraulic performance while minimizing shear-stress-induced hemolysis and thrombosis. For unshrouded centrifugal, mixed-flow and axial-flow blood pumps, the complex flow patterns within the blade tip clearance between the lengthwise upper surface of the rotating impeller blades and the stationary pump housing have a dramatic effect on both the hydrodynamic performance and the blood damage production. Detailed computational fluid dynamics (CFD) analyses were performed in this study to investigate such flow behavior in blade tip clearance region for a centrifugal blood pump representing a scaled-up version of a prototype pediatric VAD. Nominal flow conditions were analyzed at a flow rate of 2.5 L/min and rotor speed of 3000 rpm with three blade tip clearances of 50, 100, and 200 μm. CFD simulations predicted a decrease in the averaged tip leakage flow rate and an increase in pump head and axial thrust with decreasing blade tip clearances from 200 to 50 μm. The predicted hemolysis, however, exhibited a unimodal relationship, having a minimum at 100 μm compared to 50 μm and 200 μm. Experimental data corroborate these predictions. Detailed flow patterns observed in this study revealed interesting fluid dynamic features associated with the blade tip clearances, such as the generation and dissipation of tip leakage vortex and its interaction with the primary flow in the blade-blade passages. Quantitative calculations suggested the existence of an optimal blade tip clearance by which hydraulic efficiency can be maximized and hemolysis minimized. PMID:19832736

  20. Computational fluid dynamics analysis of blade tip clearances on hemodynamic performance and blood damage in a centrifugal ventricular assist device.

    PubMed

    Wu, Jingchun; Paden, Bradley E; Borovetz, Harvey S; Antaki, James F

    2010-05-01

    An important challenge facing the design of turbodynamic ventricular assist devices (VADs) intended for long-term support is the optimization of the flow path geometry to maximize hydraulic performance while minimizing shear-stress-induced hemolysis and thrombosis. For unshrouded centrifugal, mixed-flow and axial-flow blood pumps, the complex flow patterns within the blade tip clearance between the lengthwise upper surface of the rotating impeller blades and the stationary pump housing have a dramatic effect on both the hydrodynamic performance and the blood damage production. Detailed computational fluid dynamics (CFD) analyses were performed in this study to investigate such flow behavior in blade tip clearance region for a centrifugal blood pump representing a scaled-up version of a prototype pediatric VAD. Nominal flow conditions were analyzed at a flow rate of 2.5 L/min and rotor speed of 3000 rpm with three blade tip clearances of 50, 100, and 200 microm. CFD simulations predicted a decrease in the averaged tip leakage flow rate and an increase in pump head and axial thrust with decreasing blade tip clearances from 200 to 50 microm. The predicted hemolysis, however, exhibited a unimodal relationship, having a minimum at 100 microm compared to 50 microm and 200 microm. Experimental data corroborate these predictions. Detailed flow patterns observed in this study revealed interesting fluid dynamic features associated with the blade tip clearances, such as the generation and dissipation of tip leakage vortex and its interaction with the primary flow in the blade-blade passages. Quantitative calculations suggested the existence of an optimal blade tip clearance by which hydraulic efficiency can be maximized and hemolysis minimized. PMID:19832736

  1. Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats.

    PubMed

    Ying, Changjiang; Zhou, Xiaoyan; Chang, Zhenzhen; Ling, Hongwei; Cheng, Xingbo; Li, Wei

    2016-07-01

    Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism. Diabetes in the rats was induced by a high sugar, high-fat diet, and a single dose of STZ (35 mg/kg)-injected intraperitoneally. Unstable blood sugar models were induced by subcutaneous insulin injection and intravenous glucose injection alternately. Body weight, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and Creatinine clearance (Ccr) were assessed. T-SOD activity and MDA level were measured by assay kit. Change in renal tissue ultrastructure was observed by light microscopy and electron microscopy. Phosphorylated ser/thr protein kinase (p-AKT) (phosphor-Ser473), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) (phosphor-Ser9), Bcl-2-associated X protein (BAX), B cell lymphoma/leukemia 2 (BCL-2), and cleaved-cysteinyl aspartate-specific proteinase-3 (caspase-3) levels were detected by immunohistochemistry and Western blot. We observed that BUN and Scr were increased in diabetic rats, and Ccr was decreased. Furthermore, blood glucose fluctuations could exacerbate the Ccr changes. Renal tissue ultrastructure was also seriously injured by glucose variability in diabetic rats. In addition, glucose fluctuation increased the oxidative stress of renal tissue. Moreover, fluctuating blood glucose decreased p-AKT level and BCL-2, and increased p-GSK-3β, BAX, cleaved-caspase-3 levels, and ratio of BAX/BCL-2 in the kidneys of diabetic rats. In conclusion, these results suggest that blood glucose fluctuation accelerated renal injury is due, at least in part to its oxidative stress promoting and inhibiting the AKT signaling pathway in diabetic rats. PMID:26860515

  2. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

    PubMed Central

    Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

    2014-01-01

    Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes A

  3. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

    PubMed

    Qosa, Hisham; Abuasal, Bilal S; Romero, Ignacio A; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N; Kaddoumi, Amal

    2014-04-01

    Alzheimer's disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected (125)I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of (125)I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of (125)I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in (125)I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes

  4. Nanoformulated alpha-mangostin ameliorates Alzheimer's disease neuropathology by elevating LDLR expression and accelerating amyloid-beta clearance.

    PubMed

    Yao, Lei; Gu, Xiao; Song, Qingxiang; Wang, Xiaolin; Huang, Meng; Hu, Meng; Hou, Lina; Kang, Ting; Chen, Jun; Chen, Hongzhuan; Gao, Xiaoling

    2016-03-28

    Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest global healthcare challenges. However, an effective therapy is still lacking. Accumulation of amyloid-beta (Aβ) in the brain is supposed to trigger pathogenic cascades that eventually lead to AD. Therefore, Aβ clearance strategy is being actively pursued as a promising disease modifying therapy. Here, we found that α-mangostin (α-M), a polyphenolic xanthone derivative from mangosteen, up-regulated low density lipoprotein receptor (LDLR) expression in microglia and liver cells, and efficiently facilitated Aβ clearance. However, the in vivo application of α-M is limited due to its hydrophobic nature, poor aqueous solubility and stability, and thus low bioavailability and accumulation in the target organs. To overcome this limitation, α-M was encapsulated into the core of poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles [NP(α-M)]. Such nanoencapsulation improved the biodistribution of α-M in both the brain and liver, enhanced the brain clearance of (125)I-radiolabeled Aβ1-42 in an LDLR-dependent manner, reduced Aβ deposition, attenuated neuroinflammatory responses, ameliorated neurologic changes and reversed behavioral deficits in AD model mice. These findings justified the concept that polyphenol-mediated modulation of LDLR expression might serve as a safe and efficient disease-modifying therapy for AD by acceleratingclearance. It also demonstrated the powerful capacity of nanotechnology in modulating the biodistribution behavior of drug to improve its therapeutic efficacy in AD. PMID:26836197

  5. Monoexponential analysis of /sup 133/Xe clearance curves for regional cerebral blood flow measurements

    SciTech Connect

    Ryding, E.

    1984-06-01

    The theoretical properties of a monoexponential flow index, analogous to the one used earlier by other investigators for regional CBF (rCBF) measured after intraarterial injection, were investigated after the administration of /sup 133/Xe intraarterially, intravenously, and by inhalation under high and low flow conditions. The sensitivity of the flow index to changes in fast flow components or changes in the weight ratio between the fast and the slow flow compartments was found to be dependent on whichever part of the /sup 133/Xe clearance curve was used for the flow calculation and on the shape of the input function for /sup 133/Xe. Since biexponential analysis of the clearance curves includes a monoexponential approximation for each of the two components of the clearance curve corresponding to the high and the low flow ''families'' in the brain, the limitations of the monoexponential flow index observed are in principle also valid for the results of biexponential analysis of the clearance curves.

  6. Rapid Treponema pallidum Clearance from Blood and Ulcer Samples following Single Dose Benzathine Penicillin Treatment of Early Syphilis

    PubMed Central

    Tipple, Craig; Jones, Rachael; McClure, Myra; Taylor, Graham

    2015-01-01

    Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08x107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20–56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies. PMID:25700164

  7. Rapid Treponema pallidum clearance from blood and ulcer samples following single dose benzathine penicillin treatment of early syphilis.

    PubMed

    Tipple, Craig; Jones, Rachael; McClure, Myra; Taylor, Graham

    2015-02-01

    Currently, the efficacy of syphilis treatment is measured with anti-lipid antibody tests. These can take months to indicate cure and, as a result, syphilis treatment trials require long periods of follow-up. The causative organism, Treponema pallidum (T. pallidum), is detectable in the infectious lesions of early syphilis using DNA amplification. Bacteraemia can likewise be identified, typically in more active disease. We hypothesise that bacterial clearance from blood and ulcers will predict early the standard serology-measured treatment response and have developed a qPCR assay that could monitor this clearance directly in patients with infectious syphilis. Patients with early syphilis were given an intramuscular dose of benzathine penicillin. To investigate the appropriate sampling timeframe samples of blood and ulcer exudate were collected intensively for T. pallidum DNA (tpp047 gene) and RNA (16S rRNA) quantification. Sampling ended when two consecutive PCRs were negative. Four males were recruited. The mean peak level of T. pallidum DNA was 1626 copies/ml whole blood and the mean clearance half-life was 5.7 hours (std. dev. 0.53). The mean peak of 16S rRNA was 8879 copies/ml whole blood with a clearance half-life of 3.9 hours (std. dev. 0.84). From an ulcer, pre-treatment, 67,400 T. pallidum DNA copies and 7.08 x 107 16S rRNA copies were detected per absorbance strip and the clearance half-lives were 3.2 and 4.1 hours, respectively. Overall, T. pallidum nucleic acids were not detected in any sample collected more than 56 hours (range 20-56) after treatment. All patients achieved serologic cure. In patients with active early syphilis, measuring T. pallidum levels in blood and ulcer exudate may be a useful measure of treatment success in therapeutic trials. These laboratory findings need confirmation on a larger scale and in patients receiving different therapies. PMID:25700164

  8. Splanchnic blood flow and plus or minus Gx acceleration.

    NASA Technical Reports Server (NTRS)

    Stone, H. L.; Erickson, H.; Sandler, H.

    1972-01-01

    Experimental data show that there is a neurogenic response to acceleration stress in the front to back direction and that this response is intensified during higher accelerative forces. The afferent limb of this response is unknown but possibilities are suggested. The integrated response at high acceleration levels might serve to conserve oxygen during the stress time. The effector limb is the constriction of less critical vascular beds to preserve blood flow to the heart and brain. The concomitant increase in vagal activity causes a slowing down of the heart.

  9. Strongly Accelerated Margination of Active Particles in Blood Flow.

    PubMed

    Gekle, Stephan

    2016-01-19

    Synthetic nanoparticles and other stiff objects injected into a blood vessel filled with red blood cells are known to marginate toward the vessel walls. By means of hydrodynamic lattice-Boltzmann simulations, we show that active particles can strongly accelerate their margination by moving against the flow direction: particles located initially in the channel center migrate much faster to their final position near the wall than in the nonactive case. We explain our findings by an enhanced rate of collisions between the stiff particles and the deformable red blood cells. Our results imply that a significantly faster margination can be achieved either technically by the application of an external magnetic field (if the particles are magnetic) or biologically by self-propulsion (if the particles are, e.g., swimming bacteria). PMID:26789773

  10. Comparison of quantitative autoradiographic and xenon-133 clearance methods: correlation of gray and white matter cerebral blood flow with compartmental blood flow indices

    SciTech Connect

    Tuor, U.I.; Fitch, W.; Graham, D.I.; Mendelow, A.D.

    1986-08-01

    The relationships between CBF in gray and white matter to those of the fast and slow components of xenon-133 clearance curves remain uncertain. CBF was measured in 13 anaesthetized baboons under a variety of conditions, using both the xenon-133 clearance technique and (14C)iodoantipyrine quantitative autoradiography. There was a linear relationship between CBF, as determined by the stochastic (height/area) analysis of the clearance curve, and mean CBF determined from the autoradiograms (r = 0.94, p less than 0.001, slope = 0.86 +/- 0.09). There was also a linear correlation between the fast-flow component (measured with xenon-133) and blood flow in the cerebral gray matter (measured with (14C)iodoantipyrine) (r = 0.92, p less than 0.001, slope = 0.69 +/- 0.15) and between the slow-flow component (with xenon-133) and blood flow in white matter (with (14C)iodoantipyrine) (r = 0.79, p less than 0.01, slope = 0.81 +/- 0.10). In the primate brain, the fast- and slow-flow indices therefore appear to be representative of CBF in gray matter and white matter, respectively, whereas the stochastic analysis provides a stable measure of mean CBF within the tissue monitored.

  11. The Comparative Effects of Sports Massage, Active Recovery, and Rest in Promoting Blood Lactate Clearance After Supramaximal Leg Exercise

    PubMed Central

    Martin, Nancy A.; Zoeller, Robert F.; Robertson, Robert J.; Lephart, Scott M.

    1998-01-01

    Objective: To determine the comparative effect of sports massage, active recovery, and rest on promoting blood lactate clearance after maximal anaerobic (supramaximal) leg exercise. Design and Setting: A counterbalanced experimental design with repeated measures was used. The repeated measures were the three treatment conditions. The order of the conditions was determined by random assignment to a counterbalanced test sequence. All data were collected in the Human Energy Research Laboratory at the University of Pittsburgh. Subjects: Ten male competitive cyclists volunteered for this investigation. Measurements: Serial venous blood samples were drawn and analyzed for blood lactate concentration for each test condition. Results: There were significant main effects for both absolute and relative values of blood lactate concentration between the three treatment groups and across time within groups. Conclusions: After supramaximal leg exercise, active recovery produced significant decreases in both absolute and relative measures of blood lactate concentration when compared with the sports massage and rest conditions. No significant difference was found between sports massage and rest for either absolute or relative changes in blood lactate concentration. PMID:16558481

  12. Blocking the association of HDAC4 with MAP1S accelerates autophagy clearance of mutant Huntingtin

    PubMed Central

    Yue, Fei; Li, Wenjiao; Zou, Jing; Chen, Qi; Xu, Guibin; Huang, Hai; Xu, Zhen; Zhang, Sheng; Gallinari, Paola; Wang, Fen; McKeehan, Wallace L.; Liu, Leyuan

    2015-01-01

    Autophagy controls and executes the turnover of abnormally aggregated proteins. MAP1S interacts with the autophagy marker LC3 and positively regulates autophagy flux. HDAC4 associates with the aggregation-prone mutant huntingtin protein (mHTT) that causes Huntington's disease, and colocalizes with it in cytosolic inclusions. It was suggested HDAC4 interacts with MAP1S in a yeast two-hybrid screening. Here, we found that MAP1S interacts with HDAC4 via a HDAC4-binding domain (HBD). HDAC4 destabilizes MAP1S, suppresses autophagy flux and promotes the accumulation of mHTT aggregates. This occurs by an increase in the deacetylation of the acetylated MAP1S. Either suppression of HDAC4 with siRNA or overexpression of the MAP1S HBD leads to stabilization of MAP1S, activation of autophagy flux and clearance of mHTT aggregates. Therefore, specific interruption of the HDAC4-MAP1S interaction with short peptides or small molecules to enhance autophagy flux may relieve the toxicity of mHTT associated with Huntington's disease and improve symptoms of HD patients. PMID:26540094

  13. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation.

    PubMed

    Yamashita, Takuma; Takahashi, Yuki; Nishikawa, Makiya; Takakura, Yoshinobu

    2016-01-01

    Exosomes, which are expected to be delivery systems for biomolecules such as nucleic acids, are collected by several methods. However, the effect of exosome isolation methods on the characteristics of exosomes as drug carriers, such as recovery efficiency after sterile filtration and pharmacokinetics, has not been investigated despite the importance of these characteristics for the development of exosome-based delivery systems. In the present study, exosomes collected from murine melanoma B16-BL6 cells by several methods were compared with respect to dispersibility, recovery rate after filtering, and clearance from the blood circulation in mice. The exosomes were collected by three ultracentrifugation-based methods: simple ultracentrifugation/pelleting (pelleting method), ultracentrifugation with an iodixanol cushion (cushion method), and ultracentrifugation on an iodixanol density gradient (gradient method). The isolation methods had little effect on the particle number of exosomes. In contrast, transmission electron microscopy observation and size distribution measurement using tunable resistive pulse sensing indicated that the exosomes of the gradient method were more dispersed than the others. The exosomes were labeled with Gaussia luciferase and intravenously injected into mice. Clearance of injected exosomes from the blood circulation did not significantly change with isolation methods. When the exosomes were filtered using a 0.2-μm filter, the recovery rate was 82% for the exosomes of the gradient method, whereas it was less than 50% for the others. These results indicate that the exosome isolation method markedly affects the dispersibility and filtration efficiency of the exosomes. PMID:26545617

  14. Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice.

    PubMed

    Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L; Jerome, Jacob A; Madsen, Daniel H; Christofidou-Solomidou, Melpo; Speicher, David W; Bachovchin, William W; Feghali-Bostwick, Carol; Puré, Ellen

    2016-04-01

    Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. PMID:26663085

  15. Endometrial blood flow measured by xenon 133 clearance in women with normal menstrual cycles and dysfunctional uterine bleeding

    SciTech Connect

    Fraser, I.S.; McCarron, G.; Hutton, B.; Macey, D.

    1987-01-01

    Endometrial blood flow was measured through the menstrual cycle in nonpregnant women (28 studies of 17 women with normal menstrual cycles and 32 studies of 20 women with dysfunctional uterine bleeding) with use of a clearance technique in which 100 to 400 microCi of the gamma-emitting isotope, xenon 133 in saline solution was instilled into the uterine cavity. The mean (+/- SEM) endometrial blood flow in normal cycles was 27.7 +/- 2.6 ml/100 gm/min, with a significant elevation in the middle to late follicular phase, followed by a substantial fall and a secondary slow luteal phase rise that was maintained until the onset of menstruation. There was a significant correlation between plasma estradiol levels and endometrial blood flow in the follicular but not the luteal phase. Blood flow patterns in women with ovulatory dysfunctional bleeding were similar to normal, except for a significantly lower middle follicular rate. Women with anovulatory dysfunctional bleeding exhibited exceedingly variable flow rates.

  16. Blood clearance of radiolabeled antibody: enhancement by lactosamination and treatment with biotin-avidin or anti-mouse IgG antibodies

    SciTech Connect

    Klibanov, A.L.; Martynov, A.V.; Slinkin, M.A.; Sakharov, I.Yu.; Smirnov, M.D.; Muzykantov, V.R.; Danilov, S.M.; Torchilin, V.P.

    1988-12-01

    Methods of rapid blood clearance of In-labeled mouse monoclonal antibody 9B9 against angiotensin-converting enzyme were studied. Indium-111-9B9 is specifically accumulated in rat lung, but its blood clearance is relatively slow and target-to-blood radioactivity ratio/g tissue (localization ratio) increases from 11 to 30 only 48 hr postinjection. Injection of second (anti-mouse immunoglobulin) antibodies results in slight (1.8-fold) increase of 9B9 localization ratio. Chemical modification of 9B9 aminogroups with lactose results in enhanced liver uptake and rapid blood clearance of antibody. Blood radioactivity level decreases tenfold, and as a result localization ratio increases threefold (up to 38 in 30 min). Injection of avidin following the injection of biotinylated 9B9 results in rapid clearance of blood radioactivity with increased uptake in liver and spleen. Lung uptake is not changed. Localization ratio increases fivefold over the avidin-untreated animal value. Implications of these approaches for various applications in immunoimaging are discussed.

  17. Numerical investigation of the effects of the clearance gap between the inducer and impeller of an axial blood pump.

    PubMed

    Chan, Weng-Kong; Wong, Yew-Wah; Ong, Wendy; Koh, Sy-Yuan; Chong, Victor

    2005-03-01

    A series of numerical models are generated to investigate the flow characteristics and performance of an axial blood pump. The pump model includes a straightener, an inducer-impeller, and diffuser. Numerical studies of the effects of angular alignment of the inducer and impeller blades and the axial clearance gap between the inducer and impeller are presented in this article. The pump characteristics derived from numerical simulation are validated with experimental data. Numerically simulated results showed a sinusoidal variation in the pressure generated across the pump with changes in angular alignment between the inducer and impeller. This is attributed to additional losses when flow is forced or diverted from the trailing edge of the inducer to either the pressure or suction side of the impeller blade when the alignment between the two sets of blades is not optimal. The pressure generated is a maximum when the impeller blades are at 0 or 30 degrees with respect to the inducer. The effect of rotating the impeller with respect to the inducer causes the sinusoidal pressure variation. In addition, it was observed that when the clearance gap between the inducer and impeller is reduced to 1 mm, the pressure generated is a minimum when compared to the other models. This is attributed to the interference between the inducer and impeller when the gap separating them is too small. The location of the maximum pressure on the pressure side of the impeller blade shifts upstream while its magnitude decreases for small clearance gap between the inducer and the impeller. There was no flow separation in the inducer while small regions of backflow are observed at the impeller trailing edge. Recommendations for future modifications and improvements to the pump design and model simulation are also given. PMID:15725228

  18. Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia.

    PubMed

    Grosskopf, I; Shaish, A; Charach, G; Harats, D; Kamari, Y

    2016-04-01

    Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARγ. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288±798 vs. 501±260 mg·dl(-1)·h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0±26.5 vs. 23.4±10.6 mg·l(-1)·h, p<0.05) and chylomicron remnant (15.2±5.4 vs. 11.7±4.7 mg·l(-1)·h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients. PMID:26849821

  19. Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

    PubMed

    Vandermeulen, Eva; De Sadeleer, Carlos; Piepsz, Amy; Ham, Hamphrey R; Dobbeleir, André A; Vermeire, Simon T; Van Hoek, Ingrid M; Daminet, Sylvie; Slegers, Guido; Peremans, Kathelijne Y

    2010-08-01

    Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies. PMID:20452793

  20. Intestinal absorption and blood clearance of L-histidine-related compounds after ingestion of anserine in humans and comparison to anserine-containing diets.

    PubMed

    Kubomura, Daiki; Matahira, Yoshiharu; Masui, Ayano; Matsuda, Hideki

    2009-03-11

    Anserine is a bioactive dipeptide found in muscles and brains of vertebrates, but little is known about the kinetics of its absorption into blood and the clearance after the ingestion of anserine or anserine-containing diets. This study investigated time-dependent changes in the concentrations of l-histidine-related compounds from deproteinized blood. The concentration of anserine peaked and then decreased to zero, whereas the concentration of pi-methylhistidine gradually increased, at which point anserine was not detected. Thus, ingested anserine is absorbed intact in human blood and is hydrolyzed to pi-methylhistidine and beta-alanine by serum and tissue carnosinases. Moreover, the crossover study suggests that there was no significant difference in absorption under curves of anserine between anserine alone and anserine-containing diet, whereas there was significant difference in the peak concentration of anserine. This is the first study to demonstrate intestinal absorption and blood clearance of anserine. PMID:19256552

  1. Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice.

    PubMed

    Tang, Huan; Yang, Sheng-Tao; Yang, Yi-Fan; Ke, Da-Ming; Liu, Jia-Hui; Chen, Xing; Wang, Haifang; Liu, Yuanfang

    2016-07-20

    As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 μmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future. PMID:27351208

  2. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    SciTech Connect

    Chen, Min; Wang, Yanru; Qu, Aijuan

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  3. Mechanisms and pathways for the clearance of bacteria from blood circulation in health and disease.

    PubMed

    Minasyan, Hayk

    2016-06-01

    Available data do not support the concept that leukocytes engulf and kill bacteria in the bloodstream. Leukocytes cannot recognize or engulf bacteria in flowing blood; therefore, phagocytosis is impossible in the bloodstream and occurs instead outside of the bloodstream in the body tissues. Erythrocytes capture bacteria in the circulation using an electric charge and kill them using oxidation. The dead bacteria are then disintegrated and digested by the reticuloendothelial system (RES), particularly in the liver and the spleen. PMID:26971017

  4. Hemolytic performance of a MagLev disposable rotary blood pump (MedTech Dispo): effects of MagLev gap clearance and surface roughness.

    PubMed

    Hoshi, Hideo; Asama, Junichi; Hijikata, Wataru; Hara, Chikara; Shinshi, Tadahiko; Yasuda, Toshitaka; Ohuchi, Katsuhiro; Shimokohbe, Akira; Takatani, Setsuo

    2006-12-01

    Mechanical shaft seal bearing incorporated in the centrifugal blood pumps contributes to hemolysis and thrombus formation. In addition, the problem of durability and corrosion of mechanical shaft seal bearing has been recently reported from the safety point of view. To amend the shortcomings of the blood-immersed mechanical bearings, a magnetic levitated centrifugal rotary blood pump (MedTech Dispo Model 1; Tokyo Medical and Dental University, Tokyo, Japan) has been developed for extracorporeal disposable application. In this study, the hemolytic performance of the MedTech Dispo Model 1 centrifugal blood pump system was evaluated, with special focus on the narrow blood path clearance at the magnetic bearing between rotor and stator, and on the pump housing surface roughness. A pump flow of 5 L/min against the head pressure of 100 mm Hg for 4 h was included in the hemolytic test conditions. Anticoagulated fresh porcine blood was used as a working fluid. The clearance of blood path at the magnetic bearing was in the range of 100-250 micro m. Pump housing surface roughness was controlled to be around Ra = 0.1-1.5 micro m. The lowest hemolytic results were obtained at the clearance of 250 micro m and with the polished surface (Ra = 0.1 micro m) yielding the normalized index of hemolysis (NIH) of less than 0.001 g/100 L, which was 1/5 of the Biopump BP-80 (Medtronic Inc., Minneapolis, MN, USA, and 1/4 of the BPX-80. In spite of rough surface and narrow blood path, NIH levels were less than clinically acceptable level of 0.005 g/100 L. The noncontact, levitated impeller system is useful to improve pump performance in blood environment. PMID:17181835

  5. ICP-MS analysis of lanthanide-doped nanoparticles: A quantitative and multiplexing approach to investigate biodistribution, blood clearance, and targeting

    NASA Astrophysics Data System (ADS)

    Crayton, Samuel

    The rapidly progressing field of nanotechnology promises to revolutionize healthcare in the 21st century, with applications in the prevention, diagnosis, and treatment of a wide range of diseases. However, before nanoparticulate agents can be brought into clinical use, they must first be developed, optimized, and evaluated in animal models. In the typical pre-clinical paradigm, almost all of the optimization is done at the in vitro level, with only a few select agents reaching the level of animal studies. Since only one experimental nanoparticle formulation can be investigated in a single animal, and in vivo experiments have relatively higher complexity, cost, and time requirements, it is not feasible to evaluate a very large number of agents at the in vivo stage. A major drawback of this approach, however, is that in vitro assays do not always accurately predict how a nanoparticle will perform in animal studies. Therefore, a method that allows many agents to be evaluated in a single animal subject would allow for much more efficient and predictive optimization of nanoparticles. We have found that by incorporating lanthanide tracer metals into nanoparticle formulations, we are successfully able to use inductively coupled plasma mass spectrometry (ICP-MS) to quantitatively determine a nanoparticle's blood clearance kinetics, biodistribution, and tumor delivery. This approach was applied to evaluate both passive and active tumor targeting, as well as metabolically directed targeting of nanoparticles to low pH tumor microenvironments. Importantly, we found that these in vivo measurements could be made for many nanoparticle formulations simultaneously, in single animals, due to the high-order multiplexing capability of mass spectrometry. This approach allowed for efficient and reproducible comparison of performance between different nanoparticle formulations, by eliminating the effects of subject-to-subject variability. In the future, we envision that this "higher

  6. Homer proteins accelerate Ca2+ clearance mediated by the plasma membrane Ca2+ pump in hippocampal neurons.

    PubMed

    Salm, Elizabeth J; Thayer, Stanley A

    2012-07-20

    The plasma membrane Ca(2+) ATPase (PMCA) is responsible for maintaining basal intracellular Ca(2+) concentration ([Ca(2+)](i)) and returning small increases in [Ca(2+)](i) back to resting levels. The carboxyl terminus of some PMCA splice variants bind Homer proteins; how binding affects PMCA function is unknown. Here, we examined the effects of altered expression of Homer proteins on PMCA-mediated Ca(2+) clearance from rat hippocampal neurons in culture. The kinetics of PMCA-mediated recovery from the [Ca(2+)](i) increase evoked by a brief train of action potentials was determined in the soma of single neurons using indo-1-based photometry. Exogenous expression of Homer 1a, Homer 1c or Homer 2a did not affect PMCA function. However, shRNA mediated knockdown of Homer 1 slowed PMCA mediated Ca(2+) clearance by 28% relative to cells expressing non-silencing shRNA. The slowed recovery rate in cells expressing Homer 1 shRNA was reversed by expression of a short Homer 2 truncation mutant. These results indicate that constitutively expressed Homer proteins tonically stimulate PMCA function in hippocampal neurons. We propose a model in which binding of short or long Homer proteins to the carboxyl terminus of the PMCA stimulates Ca(2+) clearance rate. PMCA-mediated Ca(2+) clearance may be stimulated following incorporation of the pump into Homer organized signaling domains and following induction of the Homer 1a immediate early gene. PMID:22732411

  7. Blood-brain barrier changes and cell invasion differ between therapeutic immune clearance of neurotrophic virus and CNS autoimmunity.

    PubMed

    Fabis, Marzena J; Phares, Timothy W; Kean, Rhonda B; Koprowski, Hilary; Hooper, D Craig

    2008-10-01

    CNS tissues are protected from circulating cells and factors by the blood-brain barrier (BBB), a specialization of the neurovasculature. Outcomes of the loss of BBB integrity and cell infiltration into CNS tissues can differ vastly. For example, elevated BBB permeability is closely associated with the development of neurological disease in experimental allergic encephalomyelitis (EAE) but not during clearance of the attenuated rabies virus CVS-F3 from the CNS tissues. To probe whether differences in the nature of BBB permeability changes may contribute to the pathogenesis of acute neuroinflammatory disease, we compared the characteristics of BBB permeability changes in mice with EAE and in mice clearing CVS-F3. BBB permeability changes are largely restricted to the cerebellum and spinal cord in both models but differ in the extent of leakage of markers of different size and in the nature of cell accumulation in the CNS tissues. The accumulation in the CNS tissues of CD4 T cells expressing mRNAs specific for IFN-gamma and IL-17 is common to both, but iNOS-positive cells invade into the CNS parenchyma only in EAE. Mice that have been immunized with myelin basic protein (MBP) and infected exhibit the features of EAE. Treatment with the peroxynitrite-dependent radical scavenger urate inhibits the invasion of iNOS-positive cells into the CNS tissues and the development of clinical signs of EAE without preventing the loss of BBB integrity in immunized/infected animals. These findings indicate that BBB permeability changes can occur in the absence of neuropathology provided that cell invasion is restricted. PMID:18829442

  8. Radioactive microsphere study of cerebral blood flow under acceleration. Technical report

    SciTech Connect

    Greenlees, K.J.; Yoder, J.E.; Toth, D.M.; Oloff, C.M.; Karl, A.

    1980-11-01

    A study using radioactive microspheres for the investigation of cerebral blood flow during acceleration is described. Details of a technique for the blunt dissection of cerebral tissues are included. Results of flow studies at 3 and 5 G sub z acceleration stress indicate there is no selective regional preservation of cerebral tissue. (Author)

  9. Measurement of gastric mucosal blood flow in dogs by the /sup 99m/Tc 4-methylaminophenazone clearance technique

    SciTech Connect

    Doebroente, Z.; Lang, J.; Sagi, I.; Varro, V.

    1982-07-01

    In anesthetized dogs, correlation was found between the /sup 99m/Tc 4-methylaminophenazone and aminopyrine clearance measured in the same animal after administration of the gastric secretory stimulants vasopressin or glucagon. Similar correlation was observed between the /sup 99m/Tc 4-methylaminophenazone and /sup 14/C aminopyrine clearance during histamine administration. The clearance values were always corrected by the actual degree of dissociation of the radioactive molecules. The results suggest that /sup 99m/Tc 4-methylaminophenazone is suitable to study circulatory changes in human gastric mucosa. Advantages of this compound include a much lower dose of radiation absorbed by the patient and his surroundings, a simplified measurement technique, and considerably reduced expenses.

  10. Skin blood flow during histamine flare using the clearance of epicutaneous applied Xenon-133 in diabetic and non-diabetic subjects

    SciTech Connect

    Hutchison, K.J.; Overton, T.R.; Biltek, K.B.; Nixon, R.; Williams, H.T.

    1983-04-01

    The increase in skin blood flow produced by both reactive hyperemia and histamine was examined in 8 normal, 8 diabetic and 3 cancer patients using the epicutaneous Xenon-133 clearance method. The histamine flare response in both diabetic and cancer groups was reduced compared to that in the normal group. There was no significant difference in the reactive hyperemia responses. It is concluded that the reduction in the histamine flare response is due to a defect in the sensory nerves mediating the axon reflex and not due to a change in the vascular response.

  11. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo

    PubMed Central

    SHELAT, S. G.; SMITH, P.; AI, J.; ZHENG, X. L.

    2008-01-01

    Summary Background Many patients with acquired thrombotic thrombocytopenic purpura (TTP) harbor autoantibodies that may bind and/or inhibit ADAMTS-13 proteolytic activity and accelerate its clearance in vivo. Methods To test this hypothesis, we determined ADAMTS-13 activity and antigen levels in parallel plasma samples from patients clinically diagnosed with TTP. Collagen binding, GST-VWF73 and FRETS-VWF73 assays were used to determine ADAMTS-13 activity and to detect inhibitory autoantibodies. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation plus Western blotting (IP/WB) were used to detect total anti-ADAMTS-13 IgG (inhibitory and non-inhibitory). Results Among 40 patients with TTP (21 idiopathic and 19 non-idiopathic), inhibitory autoantibodies were detected (by FRETS-VWF73) in 52% of idiopathic and 0% of non-idiopathic TTP patients. In contrast, non-inhibitory IgG autoantibodies were detected in 29% of idiopathic and 50% of non-idiopathic TTP patients. The concentration of inhibitory IgG autoantibody in idiopathic TTP patients was significantly higher than that of non-inhibitory IgG in either idiopathic or non-idiopathic TTP patients. Idiopathic TTP patients demonstrated significantly reduced ADAMTS-13 activity compared with non-idiopathic patients, but only slightly lower ADAMTS-13 antigen levels. Interestingly, patients with inhibitory autoantibodies exhibited significantly lower ADAMTS-13 antigen levels than those with only non-inhibitory IgG autoantibodies or no autoantibody. Serial plasma exchanges increased levels of ADAMTS-13 activity and antigen concurrently in patients with inhibitory autoantibodies. Conclusion The identification of severe ADAMTS-13 deficiency and autoantibodies or inhibitors appears to be assay-dependent; the inhibitory IgG autoantibodies, in addition to binding and inhibiting ADAMTS-13 proteolytic activity, may accelerate ADAMTS-13 clearance in vivo. PMID:16879212

  12. 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

  13. Global distribution of polymorphisms associated with delayed Plasmodium falciparum parasite clearance following artemisinin treatment: genotyping of archive blood samples.

    PubMed

    Murai, Kenji; Culleton, Richard; Hisaoka, Teruhiko; Endo, Hiroyoshi; Mita, Toshihiro

    2015-06-01

    The recent emergence and spread of artemisinin-resistant Plasmodium falciparum isolates is a growing concern for global malaria-control efforts. A recent genome-wide analysis study identified two SNPs at genomic positions MAL10-688956 and MAL13-1718319, which are linked to delayed clearance of parasites following artemisinin combination therapy (ACT). It is expected that continuous artemisinin pressure will affect the distribution of these SNPs. Here, we investigate the worldwide distribution of these SNPs using a large number of archived samples in order to generate baseline data from the period before the emergence of ACT resistance. The presence of SNPs in MAL10-688956 and MAL13-1718319 was assessed by nested PCR RFLP and direct DNA sequencing using 653 global P. falciparum samples obtained before the reported emergence of ACT resistance. SNPs at MAL10-688956 and MAL13-1718319 associated with delayed parasite clearance following ACT administration were observed in 8% and 3% of parasites, respectively, mostly in Cambodia and Thailand. Parasites harbouring both SNPs were found in only eight (1%) isolates, all of which were from Cambodia and Thailand. Linkage disequilibrium was detected between MAL10-688956 and MAL13-1718319, suggesting that this SNP combination may have been selected by ACT drug pressure. Neither of the SNPs associated with delayed parasite clearance were observed in samples from Africa or South America. Baseline information of the geographical difference of MAL10-688956 and MAL13-1718319 SNPs provides a solid basis for assessing whether these SNPs are selected by artemisinin-based combination therapies. PMID:25449286

  14. Evaluation of the effectiveness of packed red blood cell irradiation by a linear accelerator

    PubMed Central

    Olivo, Ricardo Aparecido; da Silva, Marcus Vinícius; Garcia, Fernanda Bernadelli; Soares, Sheila; Rodrigues Junior, Virmondes; Moraes-Souza, Helio

    2015-01-01

    Irradiation of blood components with ionizing radiation generated by a specific device is recommended to prevent transfusion-associated graft-versus-host disease. However, a linear accelerator can also be used in the absence of such a device, which is the case of the blood bank facility studied herein. In order to evaluate the quality of the irradiated packed red blood cells, this study aimed to determine whether the procedure currently employed in the facility is effective in inhibiting the proliferation of T lymphocytes without damaging blood components. The proliferation of T lymphocytes, plasma potassium levels, and the degree of hemolysis were evaluated and compared to blood bags that received no irradiation. Packed red blood cell bags were irradiated at a dose of 25 Gy in a linear accelerator. For this purpose, a container was designed to hold the bags and to ensure even distribution of irradiation as evaluated by computed tomography and dose-volume histogram. Irradiation was observed to inhibit the proliferation of lymphocytes. The percentage of hemolysis in irradiated bags was slightly higher than in non-irradiated bags (p-value >0.05), but it was always less than 0.4% of the red cell mass. Although potassium increased in both groups, it was more pronounced in irradiated red blood cells, especially after seven days of storage, with a linear increase over storage time. The findings showed that, at an appropriate dosage and under validated conditions, the irradiation of packed red blood cells in a linear accelerator is effective, inhibiting lymphocyte proliferation but without compromising the viability of the red cells. PMID:26041416

  15. Regional differences in blood-brain barrier permeability changes and inflammation in the apathogenic clearance of virus from the central nervous system.

    PubMed

    Phares, Timothy W; Kean, Rhonda B; Mikheeva, Tatiana; Hooper, D Craig

    2006-06-15

    The loss of blood-brain barrier (BBB) integrity in CNS inflammatory responses triggered by infection and autoimmunity has generally been associated with the development of neurological signs. In the present study, we demonstrate that the clearance of the attenuated rabies virus CVS-F3 from the CNS is an exception; increased BBB permeability and CNS inflammation occurs in the absence of neurological sequelae. We speculate that regionalization of the CNS inflammatory response contributes to its lack of pathogenicity. Despite virus replication and the expression of several chemokines and IL-6 in both regions being similar, the up-regulation of MIP-1beta, TNF-alpha, IFN-gamma, and ICAM-1 and the loss of BBB integrity was more extensive in the cerebellum than in the cerebral cortex. The accumulation of CD4- and CD19-positive cells was higher in the cerebellum than the cerebral cortex. Elevated CD19 levels were paralleled by kappa-L chain expression levels. The timing of BBB permeability changes, kappa-L chain expression in CNS tissues, and Ab production in the periphery suggest that the in situ production of virus-neutralizing Ab may be more important in virus clearance than the infiltration of circulating Ab. The data indicate that, with the possible exception of CD8 T cells, the effectors of rabies virus clearance are more commonly targeted to the cerebellum. This is likely the result of differences in the capacity of the tissues of the cerebellum and cerebral cortex to mediate the events required for BBB permeability changes and cell invasion during virus infection. PMID:16751414

  16. Ultrasonic observation of blood disturbance in a stenosed tube: effects of flow acceleration and turbulence downstream.

    PubMed

    Nam, Kweon-Ho; Paeng, Dong-Guk; Choi, Min Joo; Shung, K Kirk

    2008-01-01

    Red blood cell (RBC) aggregation is known to be highly dependent on hemodynamic parameters such as shear rate, flow turbulence and flow acceleration under pulsatile flow. The effects of all three hemodynamic parameters on RBC aggregation and echogenicity of porcine whole blood were investigated downstream of an eccentric stenosis in a mock flow loop using B-mode images with Doppler spectrograms of a commercial ultrasonic system. A hyperechoic parabolic profile appeared downstream during flow acceleration, yielding another piece of evidence suggesting that the enhancement of rouleaux formation may be caused by flow acceleration. It was also found that echogenicity increased locally at a distance of three tube diameters downstream from the stenosis. The local increase of echogenicity is thought to be mainly due to flow turbulence. The hypoechoic "black hole" was also seen at the center of the tube downstream of the stenosis where blood flow was disturbed, and this may be caused by the compound effect of flow turbulence and shear rate. PMID:17900794

  17. Measurement of ischemic changes in cerebral blood flow by the hydrogen clearance technique and brain cortical temperature. Influence of flunarizine.

    PubMed

    Marrannes, R; Edmonds, H L; Wauquier, A; Melis, W; Van Loon, J

    1986-06-01

    In dogs global cerebral ischemia was produced by clamping reversibly the left subclavian and brachiocephalic arteries, supplying the head. The intercostal arteries were ligated permanently. Cerebral blood flow (CBF) was measured discontinuously using a hydrogen saturation-desaturation technique. Clamping of the former two vessels caused an increase in systemic blood pressure. When this increase was not blunted by previous splenectomy and blood withdrawal a still important CBF remained during the clamp. However, if this rise in blood pressure was impaired, CBF decreased to 9 +/- 8% (mean +/- S.D., n = 14) of the pre-ischemic value. Flunarizine is known to have anti-hypoxic/ischemic properties. The influence of this drug (0.1 mg/kg i.v.), injected 10 min after the beginning of a 30-min ischemia period, on the post-ischemic CBF was investigated. Two-three hour after ischemia CBF was significantly lower in the solvent-treated animals than in the flunarizine-treated group, in which CBF approached the preischemic values. Changes in CBF were also followed continuously by measurement of the variations of brain versus aortic temperature. It was analyzed what information this can provide on CBF. PMID:3753102

  18. ICP-MS Analysis of Lanthanide-Doped Nanoparticles as a Non-Radiative, Multiplex Approach to Quantify Biodistribution and Blood Clearance

    PubMed Central

    Crayton, Samuel H.; Elias, Andrew; Al-Zaki, Ajlan; Cheng, Zhiliang; Tsourkas, Andrew

    2011-01-01

    Recent advances in material science and chemistry have led to the development of nanoparticles with diverse physicochemical properties, e.g. size, charge, shape, and surface chemistry. Evaluating which physicochemical properties are best for imaging and therapeutic studies is challenging not only because of the multitude of samples to evaluate, but also because of the large experimental variability associated with in vivo studies (e.g. differences in tumor size, injected dose, subject weight, etc.). To address this issue, we have developed a lanthanide-doped nanoparticle system and analytical method that allows for the quantitative comparison of multiple nanoparticle compositions simultaneously. Specifically, superparamagnetic iron oxide (SPIO) with a range of different sizes and charges were synthesized, each with a unique lanthanide dopant. Following the simultaneous injection of the various SPIO compositions into tumor-bearing mice, inductively coupled plasma mass spectroscopy (ICP-MS) was used to quantitatively and orthogonally assess the concentration of each SPIO composition in serial blood samples and the resected tumor and organs. The method proved generalizable to other nanoparticle platforms, including dendrimers, liposomes, and polymersomes. This approach provides a simple, cost-effective, and non-radiative method to quantitatively compare tumor localization, biodistribution, and blood clearance of more than 10 nanoparticle compositions simultaneously, removing subject-to-subject variability. PMID:22100983

  19. Potential use of blood bank platelet concentrates to accelerate wound healing of diabetic ulcers.

    PubMed

    Han, Seung-Kyu; Kim, Deok-Woo; Jeong, Seong-Ho; Hong, Yong-Taek; Woo, Hong-Suh; Kim, Woo-Kyung; Gottrup, Finn

    2007-11-01

    Many clinical trials have shown the effectiveness of platelet releasates on diabetic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. This study was undertaken to investigate the potential of blood bank platelet concentrate (BBPC) for accelerating diabetic wound healing. Platelet-derived growth factor-BB (PDGF-BB) contents in BBPC were determined by enzyme-linked immunosorbent assay in vitro, and the in vivo study involved comparing extents of wound healing in BBPC-treated and control groups using diabetic mouse wound models. In the in vitro study, 5.2 +/- 1.2 pg of PDGF-BB was found to be released by 1 million platelets in fresh BBPC, and adding thrombin to BBPC significantly increased the levels of PDGF-BB released. Our in vivo study in diabetic mice revealed that BBPC treatment greatly accelerated wound healing. Our results suggest that BBPC has potential to accelerate the healing of diabetic ulcers. PMID:17992147

  20. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    NASA Technical Reports Server (NTRS)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (<10 µg/dL) have indicated associations of blood lead level with lower cognitive test scores in children, later onset of puberty in girls, and increased blood pressure and cardiovascular mortality rates in adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  1. Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood-cerebrospinal fluid barrier in human brain.

    PubMed

    Matsumoto, Koichi; Chiba, Yoichi; Fujihara, Ryuji; Kubo, Hiroyuki; Sakamoto, Haruhiko; Ueno, Masaki

    2015-12-01

    A large number of previous reports have focused on the transport of amyloid-β peptides through cerebral endothelial cells via the blood-brain barrier, while fewer reports have mentioned the transport through the choroid plexus epithelium via the blood-cerebrospinal fluid barrier. Concrete roles of these two pathways remain to be clarified. In this study, we immunohistochemically examined the expression of transporters/receptors that are supposed to be related to the clearance of amyloid-β peptides in the choroid plexus epithelium, the ventricular ependymal cells and the brain microvessels, using seven autopsied human brains. In the choroid plexus epithelium, immunoreactivity for low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), LRP2, formylpeptide receptor-like 1 (FPRL1), ATP-binding cassette (ABC) transporter-A1 (ABCA1), ABCC1 and ABCG4 was seen in 7 of 7 brains, while that for ABCB1, ABCG2, RAGE and CD36 was seen in 0-2 brains. In the ventricular ependymal cells, immunoreactivity for CD36, LDLR, LRP1, LRP2, FPRL1, ABCA1, ABCC1 and ABCG4 was seen in 6-7 brains, while that for ABCB1, ABCG2 and RAGE was seen in 0-1 brain. Immunoreactivity for insulin-degrading enzyme (IDE) was seen in three and four brains in the choroid plexus epithelium and the ventricular ependymal cells, respectively. In addition, immunoreactivity for LDLR, ABCB1 and ABCG2 was seen in over 40 % of the microvessels (all seven brains), and that for FPRL1, ABCA1, ABCC1 and RAGE was seen in over 5 % of the microvessels (4-6 brains), while that for CD36, IDE, LRP1, LRP2 and ABCG4 was seen in less than 5 % of the microvessels (0-2 brains). These findings may suggest that these multiple transporters/receptors and IDE expressed on the choroid plexus epithelium, ventricular ependymal cells and brain microvessels complementarily or cooperatively contribute to the clearance of amyloid-β peptides from the brain. PMID:26449856

  2. Impact of Multiple Negative Charges on Blood Clearance and Biodistribution Characteristics of 99mTc-Labeled Dimeric Cyclic RGD Peptides

    PubMed Central

    2015-01-01

    This study sought to evaluate the impact of multiple negative charges on blood clearance kinetics and biodistribution properties of 99mTc-labeled RGD peptide dimers. Bioconjugates HYNIC-P6G-RGD2 and HYNIC-P6D-RGD2 were prepared by reacting P6G-RGD2 and P6D-RGD2, respectively, with excess HYNIC-OSu in the presence of diisopropylethylamine. Their IC50 values were determined to be 31 ± 5 and 41 ± 6 nM, respectively, against 125I-echistatin bound to U87MG glioma cells in a whole-cell displacement assay. Complexes [99mTc(HYNIC-P6G-RGD2)(tricine)(TPPTS)] (99mTc-P6G-RGD2) and [99mTc(HYNIC-P6D-RGD2)(tricine)(TPPTS)] (99mTc-P6D-RGD2) were prepared in high radiochemical purity (RCP > 95%) and specific activity (37–110 GBq/μmol). They were evaluated in athymic nude mice bearing U87MG glioma xenografts for their biodistribution. The most significant difference between 99mTc-P6D-RGD2 and 99mTc-P6G-RGD2 was their blood radioactivity levels and tumor uptake. The initial blood radioactivity level for 99mTc-P6D-RGD2 (4.71 ± 1.00%ID/g) was ∼5× higher than that of 99mTc-P6G-RGD2 (0.88 ± 0.05%ID/g), but this difference disappeared at 60 min p.i. 99mTc-P6D-RGD2 had much lower tumor uptake (2.20–3.11%ID/g) than 99mTc-P6G-RGD2 (7.82–9.27%ID/g) over a 2 h period. Since HYNIC-P6D-RGD2 and HYNIC-P6G-RGD2 shared a similar integrin αvβ3 binding affinity (41 ± 6 nM versus 31 ± 5 nM), the difference in their blood activity and tumor uptake is most likely related to the nine negative charges and high protein binding of 99mTc-P6D-RGD2. Despite its low uptake in U87MG tumors, the tumor uptake of 99mTc-P6D-RGD2 was integrin αvβ3-specific. SPECT/CT studies were performed using 99mTc-P6G-RGD2 in athymic nude mice bearing U87MG glioma and MDA-MB-231 breast cancer xenografts. The SPECT/CT data demonstrated the tumor-targeting capability of 99mTc-P6G-RGD2, and its tumor uptake depends on the integrin αvβ3 expression levels on tumor cells and neovasculature. It was concluded that

  3. Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method.

    PubMed

    Duez, J; Holleran, J P; Ndour, P A; Pionneau, C; Diakité, S; Roussel, C; Dussiot, M; Amireault, P; Avery, V M; Buffet, P A

    2015-08-01

    During their lifespan, circulating RBC are frequently checked for their deformability. This mechanical quality control operates essentially in the human spleen. RBC unable to squeeze though narrow splenic slits are retained and cleared from the blood circulation. Under physiological conditions this prevents microvessels from being clogged by senescent, rigid RBC. Retention of poorly deformable RBC is an important determinant of pathogenesis in malaria and may also impact the clinical benefit of transfusion. Modulating the splenic retention of RBC has already been proposed to support therapeutic approaches in these research fields. To this aim, the development of microplates for high throughput filtration of RBC through microsphere layers (microplate-based microsphiltration) has been undertaken. This review focuses on potential therapeutic applications provided by this technology in malaria chemotherapy and transfusion. PMID:26138907

  4. Cerebral blood flow velocity and cranial fluid volume decrease during +Gz acceleration

    NASA Technical Reports Server (NTRS)

    Kawai, Y.; Puma, S. C.; Hargens, A. R.; Murthy, G.; Warkander, D.; Lundgren, C. E.

    1997-01-01

    Cerebral blood flow (CBF) velocity and cranial fluid volume, which is defined as the total volume of intra- and extracranial fluid, were measured using transcranial Doppler ultrasonography and rheoencephalography, respectively, in humans during graded increase of +Gz acceleration (onset rate: 0.1 G/s) without straining maneuvers. Gz acceleration was terminated when subjects' vision decreased to an angle of less than or equal to 60 degrees, which was defined as the physiological end point. In five subjects, mean CBF velocity decreased 48% from a baseline value of 59.4 +/- 11.2 cm/s to 31.0 +/- 5.6 cm/s (p<0.01) with initial loss of peripheral vision at 5.7 +/- 0.9 Gz. On the other hand, systolic CBF velocity did not change significantly during increasing +Gz acceleration. Cranial impedance, which is proportional to loss of cranial fluid volume, increased by 2.0 +/- 0.8% above the baseline value at the physiological end point (p<0.05). Both the decrease of CBF velocity and the increase of cranial impedance correlated significantly with Gz. These results suggest that +Gz acceleration without straining maneuvers decreases CBF velocity to half normal and probably causes a caudal fluid shift from both intra- and extracranial tissues.

  5. A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD-positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and FcgammaIIIA genes.

    PubMed

    Miescher, Sylvia; Spycher, Martin O; Amstutz, Hanspeter; De Haas, Masja; Kleijer, Marion; Kalus, Ulrich J; Radtke, Hartmut; Hubsch, Alphonse; Andresen, Irmgard; Martin, Roland M; Bichler, Johann

    2004-06-01

    A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase 1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC) clearance, and prevention of RhD immunization in RhD-negative men challenged with 15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD effectively cleared RhD-positive RBCs after intravenous and intramuscular injection. The recombinant anti-RhD demonstrated a slower clearance rate compared with the polyclonal anti-RhD. There was no dose response, and there was considerable variation among subjects who received the same dose of recombinant anti-RhD. Interestingly, RhD-positive RBC clearance rates were strongly associated with Fcgamma receptor IIA (FcgammaRIIA) and FcgammaIIIA but not with FcgammaIIIB polymorphisms. Subjects homozygous for FcgammaRIIA-131H or FcgammaRIIIA-158V allotypes showed a faster clearance rate compared with both the heterozygote and the corresponding alternative homozygote allotypes. A similar but less marked trend was seen for the polyclonal anti-RhD. Despite the variation in clearance rates there was no evidence of anti-RhD alloantibodies in any of the subjects at +6 months after the RBC challenge. PMID:14976055

  6. In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

    PubMed Central

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M.; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D’Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-01-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

  7. CD36 and Proteoglycan-Mediated Pathways for (n-3) Fatty Acid–Enriched Triglyceride-Rich Particle Blood Clearance in Mouse Models In Vivo and in Peritoneal Macrophages In Vitro1,2

    PubMed Central

    Densupsoontorn, Narumon; Carpentier, Yvon A.; Racine, Radjini; Murray, Faith M.; Seo, Toru; Ramakrishnan, Rajasekhar; Deckelbaum, Richard J.

    2008-01-01

    Because the mechanisms of (n-3) fatty acid–enriched triglyceride-rich particle [(n-3)-TGRP] uptake are not well characterized, we questioned whether (n-3)-TGRP are removed via “nonclassical” pathways, e.g., pathways other than an LDL receptor and/or involving apolipoprotein E (apoE). Chylomicron-sized model (n-3)-TGRP labeled with [3H]cholesteryl ether were injected into wild-type (WT) and CD36 knockout (CD36−/−) mice at low, nonsaturating and high, saturating doses. Blood clearance of (n-3)-TGRP was determined by calculating fractional catabolic rates. At saturating doses, blood clearance of (n-3)-TGRP was slower in CD36−/− mice relative to WT mice, suggesting that in part CD36 contributes to (n-3)-TGRP uptake. To further examine the potential nonclassical clearance pathways, peritoneal-elicited macrophages from WT and CD36−/− mice were incubated with (n-3)-TGRP in the presence of apoE, lactoferrin, and/or sodium chlorate. Cellular (n-3)-TGRP uptake was measured to test the roles of apoE-mediated pathways and/or proteoglycans. ApoE-mediated pathways compensated in part for defective (n-3)-TGRP uptake in CD36−/− cells. Lactoferrin decreased (n-3)-TGRP uptake in the presence of apoE. Inhibition of cell proteoglycan synthesis by chlorate reduced (n-3)-TGRP uptake in both groups of macrophages, and chlorate effects were independent of apoE. We conclude that although CD36 is involved, it is not the primary contributor to the blood clearance of (n-3)-TGRP. The removal of (n-3)-TGRP likely relies more on nonclassical pathways, such as proteoglycan-mediated pathways. PMID:18203888

  8. Manual blood exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals with imported severe Plasmodium falciparum malaria

    PubMed Central

    2013-01-01

    Background Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or to artesunate were compared with patients treated with parenteral treatment with quinine or artesunate but who did not receive ET. ET was executed using a standardized manual isovolumetric exchange protocol. Methods All patients in the Rotterdam Malaria Cohort treated for severe P. falciparum malaria at the Institute for Tropical Diseases of the Harbour Hospital between 1999 and 2011 were included in this retrospective follow-up study. Both a two-stage approach and a log-linear mixed model approach were used to estimate parasite clearance times (PCTs) in patients with imported malaria. Severe malaria was defined according to WHO criteria. Results A total of 87 patients with severe malaria was included; 61 received intravenous quinine, whereas 26 patients received intravenous artesunate. Thirty-nine patients received ET as an adjunct treatment to either quinine (n = 23) or artesunate (n = 16). Data from 84 of 87 patients were suitable for estimation of parasite clearance rates. PCTs were significantly shorter after administration of artesunate as compared with quinine. In both models, ET did not contribute significantly to overall parasite clearance. Conclusion Manual exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals. There may be a small effect of ET on parasite clearance under quinine treatment. Institution of ET to promote parasite clearance in settings where artesunate is available is not recommended, at least not with manually executed exchange procedures. PMID:23537187

  9. Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration.

    PubMed

    Convertino, V A

    2001-04-01

    The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation. PMID:11247814

  10. Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.

    2001-01-01

    The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

  11. Evaluation of the effect of blood contamination on the compressive strength of MTA modified with hydration accelerators

    PubMed Central

    Oloomi, Kaveh; Saberi, Eshaghali; Mokhtari, Hadi; Mokhtari Zonouzi, Hamid Reza; Nosrat, Ali; Dummer, Paul Michael Howell

    2013-01-01

    Objectives This study was performed to evaluate the effect of blood contamination on the compressive strength (CS) of Root MTA (RMTA) modified with Calcium chloride (CaCl2) and Disodium hydrogen phosphate (Na2HPO4) as setting accelerators over time. Materials and Methods A total of 110 cylindrical specimens of RMTA were divided into 6 experimental groups as follows: Group1, RMTA; Group 2, RMTA modified with CaCl2 (RMTA-C); Group 3, RMTA modified with Na2HPO4 (RMTA-N); Group 4, RMTA contaminated with blood; Group 5, RMTA-C contaminated with blood; Group 6, RMTA-N contaminated with blood. The CS of specimens in all groups was evaluated after 3 hr, 24 hr, and 1 wk. In the modified groups (groups 2, 3, 5, and 6) the CS of five specimens per group was also evaluated after 1 hr. Results Blood contamination significantly reduced the CS of all materials at all time intervals (p < 0.05). After 3 hr, the CS of specimens in the RMTA groups (with and without blood contamination) was significantly lower than those in the RMTA-C and RMTA-N groups (p < 0.05). The CS values were not significantly different at the other time intervals. In all groups, the CS of specimens significantly increased over time (p < 0.05). Conclusions Blood contamination decreased the CS of both original and accelerated RMTA. PMID:24010078

  12. Graphics processing unit accelerated one-dimensional blood flow computation in the human arterial tree.

    PubMed

    Itu, Lucian; Sharma, Puneet; Kamen, Ali; Suciu, Constantin; Comaniciu, Dorin

    2013-12-01

    One-dimensional blood flow models have been used extensively for computing pressure and flow waveforms in the human arterial circulation. We propose an improved numerical implementation based on a graphics processing unit (GPU) for the acceleration of the execution time of one-dimensional model. A novel parallel hybrid CPU-GPU algorithm with compact copy operations (PHCGCC) and a parallel GPU only (PGO) algorithm are developed, which are compared against previously introduced PHCG versions, a single-threaded CPU only algorithm and a multi-threaded CPU only algorithm. Different second-order numerical schemes (Lax-Wendroff and Taylor series) are evaluated for the numerical solution of one-dimensional model, and the computational setups include physiologically motivated non-periodic (Windkessel) and periodic boundary conditions (BC) (structured tree) and elastic and viscoelastic wall laws. Both the PHCGCC and the PGO implementations improved the execution time significantly. The speed-up values over the single-threaded CPU only implementation range from 5.26 to 8.10 × , whereas the speed-up values over the multi-threaded CPU only implementation range from 1.84 to 4.02 × . The PHCGCC algorithm performs best for an elastic wall law with non-periodic BC and for viscoelastic wall laws, whereas the PGO algorithm performs best for an elastic wall law with periodic BC. PMID:24009129

  13. Delayed nerve stimulation promotes axon-protective neurofilament phosphorylation, accelerates immune cell clearance and enhances remyelination in vivo in focally demyelinated nerves.

    PubMed

    McLean, Nikki A; Popescu, Bogdan F; Gordon, Tessa; Zochodne, Douglas W; Verge, Valerie M K

    2014-01-01

    Rapid and efficient axon remyelination aids in restoring strong electrochemical communication with end organs and in preventing axonal degeneration often observed in demyelinating neuropathies. The signals from axons that can trigger more effective remyelination in vivo are still being elucidated. Here we report the remarkable effect of delayed brief electrical nerve stimulation (ES; 1 hour @ 20 Hz 5 days post-demyelination) on ensuing reparative events in a focally demyelinated adult rat peripheral nerve. ES impacted many parameters underlying successful remyelination. It effected increased neurofilament expression and phosphorylation, both implicated in axon protection. ES increased expression of myelin basic protein (MBP) and promoted node of Ranvier re-organization, both of which coincided with the early reappearance of remyelinated axons, effects not observed at the same time points in non-stimulated demyelinated nerves. The improved ES-associated remyelination was accompanied by enhanced clearance of ED-1 positive macrophages and attenuation of glial fibrillary acidic protein expression in accompanying Schwann cells, suggesting a more rapid clearance of myelin debris and return of Schwann cells to a nonreactive myelinating state. These benefits of ES correlated with increased levels of brain derived neurotrophic factor (BDNF) in the acute demyelination zone, a key molecule in the initiation of the myelination program. In conclusion, the tremendous impact of delayed brief nerve stimulation on enhancement of the innate capacity of a focally demyelinated nerve to successfully remyelinate identifies manipulation of this axis as a novel therapeutic target for demyelinating pathologies. PMID:25310564

  14. Blood

    MedlinePlus

    ... solid part of your blood contains red blood cells, white blood cells, and platelets. Red blood cells (RBC) deliver oxygen from your lungs to your tissues and organs. White blood cells (WBC) fight infection and are part of your ...

  15. A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609

    PubMed Central

    Zhang, Rou; Suwanarusk, Rossarin; Malleret, Benoit; Cooke, Brian M.; Nosten, Francois; Lau, Yee-Ling; Dao, Ming; Lim, Chwee Teck; Renia, Laurent; Tan, Kevin Shyong Wei; Russell, Bruce

    2016-01-01

    Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite–infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax– and Plasmodium falciparum–infected RBCs. PMID:26136472

  16. Accelerated RBC senescence as a novel pathologic mechanism of blood stasis syndrome in traditional East Asian medicine

    PubMed Central

    You, Sooseong; Park, Bongki; Lee, Myeong Soo

    2015-01-01

    Blood stasis syndrome (BSS) is an important pathologic condition in traditional East Asian medicine, characterized by multiple signs and symptoms, including sublingual varicosis, angiotelectasis, slow and choppy pulse, local fixed pain, nyctalgia, menstrual cramps, dark-purple tongue and infra-orbital darkness. However, recent studies have been restricted to the circulatory disorder and could not suggest the pathologic core to explain all of the characteristics of BSS. Here, we review the current research on the senescence of red blood cells (RBCs), focusing on the correlation between the pathologic properties of senescent RBCs and BSS-specific manifestations. The accumulation of senescent RBCs and their products induce pathological conditions that affect blood flow resistance and cause thrombosis, vasoconstriction and methemoglobinemia. These pathological alterations are identical to the characteristics of BSS, therefore supporting the hypothesis that accelerated RBC aging could be considered as a novel pathologic mechanism of BSS. PMID:26045884

  17. Some experimental errors in calculating regional cerebral blood flow from the intracarotid 133Xe clearance curve. A quantitative evaluation employing a digital model.

    PubMed

    Kanno, I; Uemura, K

    1975-01-01

    A digital model study has been developed for quantitative assessment of experimental errors in the analysis of 133Xe clearance curve from the brain. A small computer synthesized a model of the clearance curve, varying combinations of fast and slow components. The curves were convoluted with Poisson random digits to simulate statistical fluctuations. Identical curves were overlapped with varying intervals to study the influence of remaining activity. The height over area method to ten minutes was confirmed to overestimate CBF by 10% to 15% with a slow component of 20 ml/100 gm per minute, and the overstimation was increased with a lower slow flow component. The initial slope value was shown to have a close relationship with the fast flow component when the latter was less than 100 ml/100 gm per minute. Errors due to statistical fluctuations were determined only by the initial height (Ho cps), as the percent standard deviation was deltaHo/Ho in the height over area method and 2 deltaHo/HologHo in the initial slope method, where deltaHo equals square rootHo. Remaining activity caused errors of 1% to 3% in the initial slope method with an injection interval of 15 minutes. The influence of remaining activity can be eliminated with an injection interval of more than 25 to 30 minutes in the initial slope method and more than 40 minutes in the height over area method. PMID:1154473

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . PMID:26371170

  19. Blood

    MedlinePlus

    ... fight infection and are part of your body's defense system. Platelets help blood to clot when you have a cut or wound. Bone marrow, the spongy material inside your bones, makes new blood cells. Blood cells ...

  20. Accelerated apoptosis of peripheral blood monocytes in Cebpb-deficient mice.

    PubMed

    Tamura, Akihiro; Hirai, Hideyo; Yokota, Asumi; Sato, Atsushi; Shoji, Tsukimi; Kashiwagi, Takahiro; Iwasa, Masaki; Fujishiro, Aya; Miura, Yasuo; Maekawa, Taira

    2015-08-21

    The CCAAT/enhancer-binding protein β (C/EBPβ) transcription factor is required for granulopoiesis under stress conditions. However, little is known about its roles in steady state hematopoiesis. Here, we analyzed the peripheral blood and bone marrow of Cebpb(-/-) mice at steady state by flow cytometry and unexpectedly found that the number of peripheral blood monocytes was severely reduced, while the number of bone marrow monocytes was maintained. The ability of Cebpb(-/-) bone marrow cells to give rise to macrophages/monocytes in vitro was comparable to that of wild-type bone marrow cells. Apoptosis of monocytes was enhanced in the peripheral blood, but not in the bone marrow of Cebpb(-/-) mice. These results indicate that C/EBPβ is required for the survival of monocytes in peripheral blood. PMID:26168729

  1. The effects of accelerated growth rates and estrogen implants in prepubertal Holstein heifers on growth, feed efficiency, and blood parameters.

    PubMed

    Lammers, B P; Heinrichs, A J; Kensinger, R S

    1999-08-01

    Sixty-eight Holstein heifers were used to determine the effects of accelerated growth rates by increased nutrient intake and estrogen implants on feed efficiency, structural growth, and blood parameters in heifers between 19 and 39 wk of age. At the beginning of the treatment period, the heifers were assigned to one of four treatment groups by using a randomized complete block design in a 2 x 2 factorial arrangement. The treatments were standard growth rate (700 g/d), accelerated growth rate (1000 g/d), standard growth rate with an estradiol implant, and accelerated growth rate with an estradiol implant. All heifers received the same diet, but dry matter intake was adjusted weekly to achieve the target rate of gain. Accelerating heifer growth rates from 705 to 1007 g/d improved feed efficiency 5.1%, increased the rate of withers height, heart girth, and hip width growth 12, 27, and 27%, respectively, and body condition scores 0.25 points. Estradiol implants improved feed efficiency 2.4% and decreased the rate of withers height 6% and heart girth growth 3.5%. Increased nutrient intake and average daily gain depressed mean plasma growth hormone and urea nitrogen content 17 and 7%, respectively, while elevating insulin-like growth factor-1 levels by 10%. Estradiol implants increased mean plasma growth hormone content by 29% and insulin-like growth factor-1 levels by 17%, but decreased urea nitrogen content by 11%. Feeding prepubertal heifers for accelerated growth rates increased structural growth with a small increase in body condition, whereas estradiol implants improved feed efficiency and decreased the growth rate of withers height and heart girth without affecting the rate of hip width growth. PMID:10480101

  2. Influence of unlabeled monoclonal anti-mouse antibody on the clearance rate of radiolabeled mouse monoclonal antibody

    SciTech Connect

    Wahl, R.L.; Laino, L.; Jackson, G.; Fisher, S.; Beierwaltes, W.H.

    1985-05-01

    High blood background levels of intact radiolabeled monoclonal antibody (MoAb) after intravenous (iv) injection are problematic. The injection of unlabeled polyclonal antimouse Abs following injection with labeled MoAbs produces accelerated MoAb clearance. This study evaluates a Mo antimouse Ab for efficacy of accelerating radio MoAb clearance. HB-58 is a rat/mouse MoAb which binds strongly to mouse kappa light chains present in 95% of murine monoclonals. It is unreactive with rat, rabbit or human kappa chains. Six rats were injected iv with 30 ..mu..Ci (approximately 6 ..mu..g) of I-125 UPC-10, a non-specific IgG2ak MoAb that is bound to well by HB-58. No alteration was seen in the clearance of UPC-10 in any of the animals, regardless of the injection type or amount on the second day. In addition, no increase in liver or spleen activity was seen in those rats that received HB-58. The lack of change in rate of clearance and biodistribution of UPC-10 after the iv injection of a purified, specific, anti-mouse MoAb is in marked contrast to the accelerated clearance reported following polyclonal anti-mouse antibody administration. This may be due to the inability of MoAbs to cross link. These preliminary studies suggest that Mo anti-mouse Abs, at these dose levels, are not useful in achieving increased rates of radiolabeled murine MoAb clearance.

  3. 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

  4. Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency).

    PubMed

    Reid, M E; Mallinson, G; Sim, R B; Poole, J; Pausch, V; Merry, A H; Liew, Y W; Tanner, M J

    1991-12-15

    A 38-year-old Russian woman (KZ) has been identified as the fourth proposita with the Inab blood group phenotype. Like the first two propositi, she has a chronic intestinal disorder and, as shown for the third proposita, her Inab phenotype is demonstrably inherited. KZ's serum contained anti-IFC, which reacted with a red blood cell (RBC) membrane component with an Mr of 70,000, which is decay accelerating factor (DAF). Her RBCs lacked all Cromer-related blood group antigens and DAF. Her RBCs were no more susceptible than normal control RBCs to lysis in acid lysis or in rabbit or human antibody-initiated complement lysis tests. Northern blots of total RNA isolated from KZ's Epstein-Barr virus-transformed lymphoblasts showed a marked reduction of DAF mRNA when compared with normal. Polymerase chain reaction (PCR) amplification of cDNA confirmed this reduced level of DAF mRNA. Sequencing of the PCR product showed a 44-nucleotide deletion in the mRNA close to the short consensus repeats IIIa/IIIb intron/exon boundary. This deletion results in a change in the reading frame that places a termination codon six amino acids after the deletion. The putative translation product would lack a glycosyl phosphatidyl-inositol linkage site and, therefore, would not be membrane-bound in the RBC. PMID:1720702

  5. 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.

  6. Stage I/II follicular lymphoma: spread of bcl-2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy.

    PubMed

    Pulsoni, Alessandro; Starza, Irene Della; Frattarelli, Natalia; Ghia, Emanuela; Carlotti, Emanuela; Cavalieri, Elena; Matturro, Angela; Tempera, Settimio; Rambaldi, Alessandro; Foà, Robin

    2007-05-01

    Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl-2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66.6%). After treatment, in 9/15 Bcl-2/IgH positive evaluable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 43.5 months (range 11-70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl-2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR. PMID:17408460

  7. A Single Mutation in the Glycophorin A Binding Site of Hepatitis A Virus Enhances Virus Clearance from the Blood and Results in a Lower Fitness Variant

    PubMed Central

    Costafreda, M. Isabel; Ribes, Enric; Franch, Àngels; Bosch, Albert

    2012-01-01

    Hepatitis A virus (HAV) has previously been reported to bind to human red blood cells through interaction with glycophorin A. Residue K221 of VP1 and the surrounding VP3 residues are involved in such an interaction. This capsid region is specifically recognized by the monoclonal antibody H7C27. A monoclonal antibody-resistant mutant with the mutation G1217D has been isolated. In the present study, the G1217D mutant was characterized physically and biologically in comparison with the parental HM175 43c strain. The G1217D mutant is more sensitive to acid pH and binds more efficiently to human and rat erythrocytes than the parental 43c strain. In a rat model, it is eliminated from serum more rapidly and consequently reaches the liver with a certain delay compared to the parental 43c strain. In competition experiments performed in vivo in the rat model, the G1217D mutant was efficiently outcompeted by the parental 43c strain. Only in the presence of antibodies reacting specifically with the parental 43c strain could the G1217D mutant outcompete the parental 43c strain in serum, although the latter still showed a remarkable ability to reach the liver. Altogether, these results indicate that the G1217D mutation induces a low fitness phenotype which could explain the lack of natural antigenic variants of the glycophorin A binding site. PMID:22593170

  8. Quantification of hepatic blood flow using a high-resolution phase-contrast MRI sequence with compressed sensing acceleration.

    PubMed

    Dyvorne, Hadrien A; Knight-Greenfield, Ashley; Besa, Cecilia; Cooper, Nancy; Garcia-Flores, Julio; Schiano, Thomas D; Markl, Michael; Taouli, Bachir

    2015-03-01

    OBJECTIVE. The objective of our study was to evaluate the performance of a high-spatial-resolution 2D phase-contrast (PC) MRI technique accelerated with compressed sensing for portal vein (PV) and hepatic artery (HA) flow quantification in comparison with a standard PC MRI sequence. SUBJECTS AND METHODS. In this prospective study, two PC MRI sequences were compared, one with parallel imaging acceleration and low spatial resolution (generalized autocalibrating partial parallel acquisition [GRAPPA]) and one with compressed sensing acceleration and high spatial resolution (sparse). Seventy-six patients were assessed, including 37 patients with cirrhosis. Two observers evaluated PC image quality. Quantitative analyses yielded a mean velocity, flow, and vessel area for the PV and HA and an arterial fraction. The PC techniques were compared using the paired Wilcoxon test and Bland-Altman statistics. The sensitivity of the flow parameters to the severity of cirrhosis was also assessed. RESULTS. Vessel delineation was significantly improved using the PC sparse sequence (p < 0.034). For both in vitro and in vivo measurements, PC sparse yielded lower estimates for vessel area and flow, and larger differences between PC GRAPPA and PC sparse were observed in the HA. PV velocity and flow were significantly lower in patients with cirrhosis on both PC sparse (p < 0.001 and p = 0.042, respectively) and PC GRAPPA (p < 0.001 and p = 0.005, respectively). PV velocity correlated negatively with Child-Pugh class (r = -0.50, p < 0.001), whereas the arterial fraction measured with PC sparse was higher in patients with Child-Pugh class B or C disease than in those with Child-Pugh class A disease, with a trend toward significance (p = 0.055). CONCLUSION. A high-spatial-resolution highly accelerated compressed sensing technique (PC sparse) allows total hepatic blood flow measurements obtained in 1 breath-hold, provides improved delineation of the hepatic vessels compared with a standard PC

  9. 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

  10. 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.

  11. Influence of posture and positive end-tidal expiratory pressure (PEEP) on clearance of Tc99m-DTPA from the lungs

    SciTech Connect

    Mason, G.R.; Maublant, J.; Sietsema, K.; Effros, R.M.; Mena, I.

    1984-01-01

    The clearance of Tc99m-DTPA aerosols from the lung has been used to detect and quantitate alterations in the permeability of the pulmonary epithelium. Clearance of the radionuclide is accelerated by both chronic and acute injuries to the lung and by smoking. Several laboratories have reported that Tc99m-DTPA clearance from upper lobes exceeded that from lower lobes in upright subjects. To investigate this phenomenon further the authors studied subjects with simultaneous anterior and posterior cameras in upright and supine positions. In the upright position, clearance from both the anterior and posterior upper regions of interest (ROI's) exceeded the lower regions (-1.64 +- .42 S.D. vs. -0.75 +- .41, anterior, p < .05, n=6), -1.04 +- .23 vs. -0.50 +- .36, posterior. All units = %/min. This difference was not observed in the supine subjects. Clearance from the anterior chest exceeded that from the posterior chest in the supine subjects (-1.28 +- .45 vs. -0.05 +- 1.08) and a small increase in radio-activity was observed in at least one ROI of 5 of 6 subjects from the posterior camera. An increase in activity is likely to be secondary to labeling of blood pool, which would have greatest affect where pulmonary blood volume is largest. Computer processing of the entire lung without observer bias in ROI placement showed similar effects of posture over non-peripheral ROI's. Five subjects breathed on PEEP to cause airspace distention, causing clearance to double. Both dependency and airspace distention appear to influence clearance of aerosolized DTPA, the latter may occur by stretching of epithelial pores.

  12. Accelerated removal of antibody-coated red blood cells from the circulation is accurately tracked by a biotin label

    PubMed Central

    Mock, Donald M.; Lankford, Gary L.; Matthews, Nell I.; Burmeister, Leon F.; Kahn, Daniel; Widness, John A.; Strauss, Ronald G.

    2013-01-01

    BACKGROUND Safe, accurate methods to reliably measure circulating red blood cell (RBC) kinetics are critical tools to investigate pathophysiology and therapy of anemia, including hemolytic anemias. This study documents the ability of a method using biotin-labeled RBCs (BioRBCs) to measure RBC survival (RCS) shortened by coating with a highly purified monomeric immunoglobulin G antibody to D antigen. STUDY DESIGN AND METHODS Autologous RBCs from 10 healthy D+ subjects were labeled with either biotin or 51Cr (reference method), coated (opsonized) either lightly (n = 4) or heavily (n = 6) with anti-D, and transfused. RCS was determined for BioRBCs and for 51Cr independently as assessed by three variables: 1) posttransfusion recovery at 24 hours (PTR24) for short-term RCS; 2) time to 50% decrease of the label (T50), and 3) mean potential life span (MPL) for long-term RCS. RESULTS BioRBCs tracked both normal and shortened RCS accurately relative to 51Cr. For lightly coated RBCs, mean PTR24, T50, and MPL results were not different between BioRBCs and 51Cr. For heavily coated RBCs, both short-term and long-term RCS were shortened by approximately 17 and 50%, respectively. Mean PTR24 by BioRBCs (84 ± 18%) was not different from 51Cr (81 ± 10%); mean T50 by BioRBCs (23 ± 17 days) was not different from 51Cr (22 ± 18 days). CONCLUSION RCS shortened by coating with anti-D can be accurately measured by BioRBCs. We speculate that BioRBCs will be useful for studying RCS in conditions involving accelerated removal of RBCs including allo- and autoimmune hemolytic anemias. PMID:22023312

  13. 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

  14. 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

  15. 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

  16. 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

  17. Increased Clearance of Antipyrine and d-Propranolol after Phenobarbital Treatment in the Monkey

    PubMed Central

    Branch, Robert A.; Shand, David G.; Wilkinson, Grant R.; Nies, Alan S.

    1974-01-01

    The effects of phenobarbital treatment for 12 days on the regional distribution of blood flow and on the disposition of two model drugs, antipyrine and d-propranolol, have been determined in six unanesthetized rhesus monkeys. Phenobarbital significantly increased total hepatic blood flow from 179±15 to 239±27 ml/min. Liver weight was increased to a similar degree (34%) in phenobarbital-treated animals as compared to control monkeys. The clearance of both antipyrine and d-propranolol was increased and the half-life decreased significantly by phenobarbital. Analysis of the data by a perfusion-limited pharmacokinetic model showed that the changes in antipyrine clearance were due almost entirely to enzyme induction. On the other hand, with d-propranolol, the increase in liver blood flow contributed as much to the enhanced clearance as did the stimulation of drug metabolism. The mechanism by which phenobarbital produces the frequently observed increase in drug clearance, therefore, depends upon the initial clearance value of the drug. For low clearance drugs like antipyrine, clearance changes occur largely as a result of enzyme induction. With higher clearance drugs, the effects of increased hepatic blood flow become progressively more important the greater the initial clearance value. PMID:4205524

  18. 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.

  19. 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.

  20. Pulmonary function and clearance after prolonged sulfuric acid aerosol exposure

    SciTech Connect

    Ives, P.J. ); Gerrity, T.R.; DeWitt, P.; Folinsbee, L.J. )

    1991-03-15

    The authors studied pulmonary function and clearance responses after a 4 H exposure to 75-100 {mu}g/m{sup 3} sulfuric acid aerosol (SAA). Healthy subjects, who exercised for 30 min/H at ventilation of about 25 L/min, were exposed once to clean air and once to SAA. Oral hygiene and acidic juice gargle were used to minimize oral ammonia. Lung function tests, including spirometry, plethysmography, and partial flow-volume (PEFV) curves were performed before and after exposure. Clearance of 99m-Technetium labeled iron oxide was assessed after each exposure. The first moment of fractional tracheobronchial retention (M1TBR), after correcting for 24 H retention and normalizing to time zero, was used as an index of clearance. There were no significant changes in lung volumes, airways resistance, or maximum expiratory flows after SAA exposure. Flow at 40% of total lung capacity on PEFV curves decreased 17% (NS) after SAA exposure. Tracheobronchial clearance was accelerated after a single exposure to SAA; M1TBR decreased from 73 {plus minus} 5 min (air) to 69 {plus minus} 5 min (SAA). These results suggest that acute prolonged exposure to low levels of SAA has minimal effects on lung mechanics in healthy subjects but does produce a modest acceleration of particle clearance.

  1. Allometric scaling for predicting human clearance of bisphenol A.

    PubMed

    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. PMID:25759244

  2. 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

  3. 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.

  4. 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.

  5. 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)...

  6. 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)...

  7. 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)...

  8. [Effect of accelerated heavy ions of carbon 12C, neon 20Ne and iron 56Fe on the chromosomal apparatus of human blood lymphocytes in vitro].

    PubMed

    Repina, L A

    2011-01-01

    Cytogenetic assay of the chromosomal apparatus of human blood lymphocytes was carried out after in vitro irradiation by heavy charged particles with high LET values. Blood plasm samples enriched with lymphocytes were irradiated by accelerated ions of carbon 12C (290 MeV/nucleon and LET = 70 keV/microm), neon 20Ne (400 MeV/nucleon and LET = 70 keV/microm), and iron 56Fe (500 MeV/nucleon and LET = 200 keV/microm) in the dose range from 0.25 to 1 Gy. Rate of chromosome aberrations showed a linear dependence on doses from the densely ionizing radiations with high LET values. Frequency of dicentrics and centric rings in human lymphocytes irradiated by 12C with the energy of 290 MeV/nucleon was maximal at 1 Gy (p < 0.05) relative to the other heavy particles. It was found that relative biological effectiveness of heavy nuclei is several times higher than of 60Co gamma-radiation throughout the range of doses in this investigation. PMID:22312859

  9. Inhalation of Shin-I essential oil enhances lactate clearance in treadmill exercise

    PubMed Central

    Chen, Hsuan-Ying; Wang, Ming-Fu; Lin, Jun-Ying; Tsai, Ying-Chieh; Cheng, Fu-Chou

    2014-01-01

    Objective To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise. Methods : Adult male Sprague Dawley rats (n=12) were randomly divided into the control or the Shin-I group. Rats were subjected to a treadmill exercise program (15 m/min for 30 min). After exercise, rats were exposed to 200 µL of water or Shin-I essential oil, respectively, using a nebulizer for 180 min during the recovery period. Blood samples were collected every 15 min. Blood glucose and lactate concentrations were determined in a CMA 600 analyzer. Results : The basal glucose and lactate levels were no significantly different between two groups. After exercise, glucose levels were slightly increased to about 110%-120% of the basal level in both groups. Lactate levels of both groups reached to 110%-140% of basal levels during exercise. In the recovery period, lactate levels further increased to 180% of the basal level and were maintained at a plateau in the control group. However, lactate levels gradually decreased to 60%-65% of the basal level in the Shin-I group. Lactate clearance was significantly enhanced after Shin-I essential oil inhalation. Conclusions : Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats. PMID:25182288

  10. 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

  11. An evaluation of hepatic extraction and clearance of doxorubicin.

    PubMed Central

    August, D. A.; Verma, N.; Vaertan, M. A.; Shah, R.; Brenner, D. E.

    1995-01-01

    A swine model was developed to study quantitatively the pharmacokinetics of hepatic extraction and clearance of doxorubicin (DOX). Systemic and hepatic artery infusions of DOX (0.5-9 mg kg-1) were administered to 34 pigs. Pharmacokinetic analysis was simplified by use of a double-balloon catheter in the inferior vena cava to collect hepatic venous effluent. During hepatic artery infusion only, DOX in hepatic venous blood was extracted using activated carbon filters to prevent drug recirculation. Hepatic extraction and clearance of DOX were independent of dose and route of administration. Extraction ratios varied from 0.75 to 0.91 during hepatic artery infusion and from 0.50 to 0.72 during systemic infusion. Clearance results were analogous. After cessation of drug infusions, hepatic extraction and clearance of DOX was negative, suggesting that the liver serves as a drug reservoir during DOX infusion and subsequently is a net source of unmetabolised drug. Liver extraction and clearance of DOX in pigs are substantial. During either systemic or hepatic artery infusion of DOX, the liver serves as a drug reservoir. Subsequent mobilisation of this hepatic pool of DOX may cause prolonged systemic exposure to drug. PMID:7599068

  12. 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

  13. 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.

  14. 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

  15. Density increment and decreased survival of rat red blood cells induced by cadmium

    SciTech Connect

    Kunimoto, M.; Miura, T.

    1986-01-01

    Male Wistar rats were injected with CdCl/sub 2/ subcutaneously to examine in vivo effects of Cd on density and survival of red blood cells. During the 7 days after administration of 1.0 mg Cd/kg, the following sequence of events occurred: (1) a progressive increase in the amount of more dense red blood cells concomitant with a decrease in that of light red blood cells from the first to the third day; (2) an increase in the spleen weight at the third day; (3) a decrease in the hematocrit value and an increase in the amount of light red blood cells at the fifth day; and (4) a recovery of the hematocrit value at the seventh day. Five days after administration, the hematocrit value decreased in a dose-dependent mode and the decrease was significant at the 1% level at 1.0 and 1.5 mg Cd/kg. A highly significant splenomegaly was also observed at 0.5 to 1.5 mg Cd/kg. In order to label red blood cells in vivo, (/sup 3/H) diisopropylfluorophosphate ((/sup 3/H)DFP) was injected into rats. At Day 11, Cd at either 0.5 or 1.0 mg/kg was administered to (/sup 3/H)DFP-prelabeled animals. Cd administration accelerated /sup 3/H-labeled red cell clearance from the blood. Six days after Cd administration, the radioactivity of red blood cells was 76 and 68% of the control at 0.5 and 1.0 mg Cd/kg, respectively. In vitro treatment of rat red density and accelerated in vivo clearance of red blood cells from the recipient circulation. These results show that Cd at low dose can cause anemia by increasing red cell density and by accelerating red cell sequestration, presumably in the spleen.

  16. Clearance of circulating radio-antibodies using streptavidin or second antibodies in a xenograft model.

    PubMed Central

    Marshall, D.; Pedley, R. B.; Boden, J. A.; Boden, R.; Begent, R. H.

    1994-01-01

    The improved tumour to non-tumour ratios needed for effective tumour targeting with antibodies requires that blood background radioactivity is reduced. We investigated the effect of streptavidin as a clearing agent for 125I-labelled biotinylated anti-CEA antibodies in a human colon carcinoma xenograft model. By comparing the biodistribution of the monoclonal antibody A5B7 with four, nine or 22 biotins per antibody molecule, we investigated how the degree of biotinylation of the primary radiolabelled antibody affects its clearance with streptavidin. Limiting the degree of biotinylation limited blood clearance, whereas nine or 22 biotins per antibody molecule resulted in a 13- to 14-fold reduction in blood radioactivity, the streptavidin-biotinylated antibody complexes clearing rapidly via the liver and spleen. Although a reduction in tumour activity was also seen, a 6.6-fold improvement in the tumour to blood ratio was achieved. A comparative study of streptavidin versus second antibody clearance was carried out using the polyclonal antibody PK4S biotinylated with 12 biotins per antibody molecule. This study indicated that second antibody was superior for clearance of the polyclonal antibody, resulting in a larger and faster reduction in blood radioactivity and improved tumour to blood ratios. In this case the primary antibody was polyclonal, and therefore non-uniformity of biotinylation may affect complexation with streptavidin. Therefore, the degree of biotinylation and type of antibody must be carefully considered before the use of streptavidin clearance. PMID:8123481

  17. Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep.

    PubMed Central

    Berthiaume, Y; Staub, N C; Matthay, M A

    1987-01-01

    We did experiments to determine whether beta-adrenergic agonists increase lung liquid clearance in anesthetized ventilated adult sheep and, if so, whether the increase is mediated by beta receptors and what mechanism is involved. We instilled 100 ml of autologous serum either alone or with a beta-adrenergic agonist (terbutaline, 10(-5) M, or epinephrine, 5.5 X 10(-6) M) into one lower lobe. After 4 h both terbutaline and epinephrine increased lung liquid clearance. The increase in lung liquid clearance was inhibited when propranolol (a beta blocker) or amiloride (a sodium channel blocker) was added to the terbutaline. Increased clearance was not explained by changes in pulmonary hemodynamics, pulmonary blood flow, or lung lymph flow. We conclude that beta-adrenergic agonists increase lung liquid clearance in anesthetized intact adult sheep. This increase is mediated through beta receptors and probably depends on increased active transport of sodium across the alveolar barrier. Images PMID:2879851

  18. 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

  19. Comparison of blood velocity measurements between ultrasound Doppler and accelerated phase-contrast MR angiography in small arteries with disturbed flow

    NASA Astrophysics Data System (ADS)

    Jiang, Jingfeng; Strother, Charles; Johnson, Kevin; Baker, Sara; Consigny, Dan; Wieben, Oliver; Zagzebski, James

    2011-03-01

    Ultrasound Doppler (UD) velocity measurements are commonly used to quantify blood flow velocities in vivo. The aim of our work was to investigate the accuracy of in vivo spectral Doppler measurements of velocity waveforms. Waveforms were derived from spectral Doppler signals and corrected for intrinsic spectral broadening errors by applying a previously published algorithm. The method was tested in a canine aneurysm model by determining velocities in small arteries (3-4 mm diameter) near the aneurysm where there was moderately disturbed flow. Doppler results were compared to velocity measurements in the same arteries acquired with a rapid volumetric phase contrast MR angiography technique named phase contrast vastly undersampled isotropic projection reconstruction magnetic resonance angiography (PC-VIPR MRA). After correcting for intrinsic spectral broadening, there was a high degree of correlation between velocities obtained by the real-time UD and the accelerated PC-MRA technique. The peak systolic velocity yielded a linear correlation coefficient of r = 0.83, end diastolic velocity resulted in r = 0.81, and temporally averaged mean velocity resulted in r = 0.76. The overall velocity waveforms obtained by the two techniques were also highly correlated (r = 0.89 ± 0.06). There were, however, only weak correlations for the pulsatility index (PI: 0.25) and resistive index (RI: 0.14) derived from the two techniques. Results demonstrate that to avoid overestimations of peak systolic velocities, the results for UD must be carefully corrected to compensate for errors caused by intrinsic spectral broadening.

  20. 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

  1. 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.

  2. 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

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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....

  3. 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....

  4. 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....

  5. 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...

  6. How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?

    PubMed

    Hastings, Ian M; Kay, Katherine; Hodel, Eva Maria

    2015-10-01

    Artemisinin-based combination therapies (ACTs) are currently the first-line drugs for treating uncomplicated falciparum malaria, the most deadly of the human malarias. Malaria parasite clearance rates estimated from patients' blood following ACT treatment have been widely adopted as a measure of drug effectiveness and as surveillance tools for detecting the presence of potential artemisinin resistance. This metric has not been investigated in detail, nor have its properties or potential shortcomings been identified. Herein, the pharmacology of drug treatment, parasite biology, and human immunity are combined to investigate the dynamics of parasite clearance following ACT. This approach parsimoniously recovers the principal clinical features and dynamics of clearance. Human immunity is the primary determinant of clearance rates, unless or until artemisinin killing has fallen to near-ineffective levels. Clearance rates are therefore highly insensitive metrics for surveillance that may lead to overconfidence, as even quite substantial reductions in drug sensitivity may not be detected as lower clearance rates. Equally serious is the use of clearance rates to quantify the impact of ACT regimen changes, as this strategy will plausibly miss even very substantial increases in drug effectiveness. In particular, the malaria community may be missing the opportunity to dramatically increase ACT effectiveness through regimen changes, particularly through a switch to twice-daily regimens and/or increases in artemisinin dosing levels. The malaria community therefore appears overreliant on a single metric of drug effectiveness, the parasite clearance rate, that has significant and serious shortcomings. PMID:26239987

  7. How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?

    PubMed Central

    Kay, Katherine; Hodel, Eva Maria

    2015-01-01

    Artemisinin-based combination therapies (ACTs) are currently the first-line drugs for treating uncomplicated falciparum malaria, the most deadly of the human malarias. Malaria parasite clearance rates estimated from patients' blood following ACT treatment have been widely adopted as a measure of drug effectiveness and as surveillance tools for detecting the presence of potential artemisinin resistance. This metric has not been investigated in detail, nor have its properties or potential shortcomings been identified. Herein, the pharmacology of drug treatment, parasite biology, and human immunity are combined to investigate the dynamics of parasite clearance following ACT. This approach parsimoniously recovers the principal clinical features and dynamics of clearance. Human immunity is the primary determinant of clearance rates, unless or until artemisinin killing has fallen to near-ineffective levels. Clearance rates are therefore highly insensitive metrics for surveillance that may lead to overconfidence, as even quite substantial reductions in drug sensitivity may not be detected as lower clearance rates. Equally serious is the use of clearance rates to quantify the impact of ACT regimen changes, as this strategy will plausibly miss even very substantial increases in drug effectiveness. In particular, the malaria community may be missing the opportunity to dramatically increase ACT effectiveness through regimen changes, particularly through a switch to twice-daily regimens and/or increases in artemisinin dosing levels. The malaria community therefore appears overreliant on a single metric of drug effectiveness, the parasite clearance rate, that has significant and serious shortcomings. PMID:26239987

  8. 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

  9. RGS21, A Regulator of Taste and Mucociliary Clearance?

    PubMed Central

    Kimple, Adam J.; Garland, Alaina L.; Cohen, Staci P.; Setola, Vincent; Willard, Francis S.; Zielinski, Thomas; Lowery, Robert G.; Tarran, Robert; Siderovski, David P.

    2014-01-01

    Objectives/Hypothesis: Motile cilia of airway epithelial cells help to expel harmful inhaled material. Activation of bitterant-responsive G protein-coupled receptors (GPCRs) is believed to potentiate cilia beat frequency and mucociliary clearance. In this study, we investigated whether regulator of G protein signaling-21 (RGS21) has the potential to modulate signaling pathways connected to airway mucociliary clearance, given that RGS proteins modulate GPCR signaling by acting as GTPase-accelerating proteins (GAPs) for the Gα subunits of heterotrimeric G proteins. Study Design: This is a pilot investigation to determine if RGS21, a potential tastant specific RGS gene, is expressed in sinonasal mucosa, and to determine its specific Gα substrate using in vitro biochemical assays with purified proteins. Methods: Rgs21 expression in sinonasal mucosa was determined using quantitative, real-time PCR and a transgenic mouse expressing RFP from the Rgs21 promoter. Rgs21 was cloned, over-expressed, and purified using multistep protein chromatography. Biochemical and biophysical assays were used to determine if RGS21 could bind and accelerate the hydrolysis of GTP on heterotrimeric Gα subunits. Results: Rgs21 was expressed in sinonasal mucosa and lingual epithelium. Purified recombinant protein directly bound and accelerated GTP hydrolysis on Gα subunits. Conclusions: Rgs21 is expressed in sinonasal mucosa, is amenable to purification as a recombinant protein, and can bind to Gαi/o/q subunits. Furthermore, RGS21 can accelerate the hydrolysis rate of GTP on Gαi subunits. This provides evidence that RGS21 may be a negative regulator of bitterant responses. Future studies will be needed to determine the physiological role of this protein in mucociliary clearance. PMID:23908053

  10. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    NASA Astrophysics Data System (ADS)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  11. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves

    PubMed Central

    Gomez-Sanchez, Jose A.; Carty, Lucy; Iruarrizaga-Lejarreta, Marta; Palomo-Irigoyen, Marta; Varela-Rey, Marta; Griffith, Megan; Hantke, Janina; Macias-Camara, Nuria; Azkargorta, Mikel; Aurrekoetxea, Igor; De Juan, Virginia Gutiérrez; Jefferies, Harold B.J.; Aspichueta, Patricia; Elortza, Félix; Aransay, Ana M.; Martínez-Chantar, María L.; Baas, Frank; Mato, José M.; Mirsky, Rhona

    2015-01-01

    Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease. PMID:26150392

  12. Central role for PICALM in amyloid–β blood–brain barrier transcytosis and clearance

    PubMed Central

    Zhao, Zhen; Sagare, Abhay P.; Ma, Qingyi; Halliday, Matthew R.; Kong, Pan; Kisler, Kassandra; Winkler, Ethan A.; Ramanathan, Anita; Kanekiyo, Takahisa; Bu, Guojun; Owens, Nelly Chuqui; Rege, Sanket V.; Si, Gabriel; Ahuja, Ashim; Zhu, Donghui; Miller, Carol A.; Schneider, Julie A.; Maeda, Manami; Maeda, Takahiro; Sugawara, Tohru; Ichida, Justin K.; Zlokovic, Berislav V.

    2015-01-01

    PICALM is highly validated genetic risk factor for Alzheimer’s disease (AD). Here, we report that PICALM reductions in AD and murine brain endothelium correlate with amyloid–β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminishes Aβ clearance across the murine blood–brain barrier (BBB) and accelerates Aβ pathology that is reversible by endothelial PICALM re–expression. Using human brain endothelial monolayer, we show that PICALM regulates PICALM/clathrin–dependent internalization of Aβ bound to the low density lipoprotein receptor related protein–1, a key Aβ clearance receptor, and guides Aβ trafficking to Rab5 and Rab11 leading to Aβ endothelial transcytosis and clearance. PICALM levels and Aβ clearance were reduced in AD–derived endothelial monolayers, which was reversible by adenoviral–mediated PICALM transfer. iPSC–derived human endothelial cells carrying the rs3851179 protective allele exhibited higher PICALM levels and enhanced Aβ clearance. Thus, PICALM regulates Aβ BBB transcytosis and clearance that has implications for Aβ brain homeostasis and clearance therapy. PMID:26005850

  13. 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

  14. 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

  15. Reduction in slow intercompartmental clearance of urea during dialysis

    SciTech Connect

    Bowsher, D.J.; Krejcie, T.C.; Avram, M.J.; Chow, M.J.; Del Greco, F.; Atkinson, A.J. Jr.

    1985-04-01

    The kinetics of urea and inulin were analyzed in five anesthetized dogs during sequential 2-hour periods before, during, and after hemodialysis. The distribution of both compounds after simultaneous intravenous injection was characterized by three-compartment models, and the total volumes of urea (0.66 +/- 0.05 L/kg) and inulin (0.19 +/- 0.01 L/kg) distribution were similar to expected values for total body water and extravascular space, respectively. Intercompartmental clearances calculated before dialysis were used to estimate blood flows to the fast and slow equilibrating compartments. In agreement with previous results, the sum of these flows was similar to cardiac output, averaging 101% of cardiac output measured before dialysis (range 72% to 135%). Dialysis was accompanied by reductions in the slow intercompartmental clearances of urea (81%) and inulin (47%), which reflected a 90% attenuation in blood flow supplying the slow equilibrating compartments. This was estimated to result in a 10% average reduction in the efficiency with which urea was removed by dialysis (range 2.0% to 16.4%). Mean arterial pressure fell by less than 5% during dialysis, but total peripheral resistance increased by 47% and cardiac output fell by 35%. In the postdialysis period, total peripheral resistance and cardiac output returned toward predialysis values, but blood flow to the slow equilibrating peripheral compartment was still reduced by 80%. These changes parallel activation of the renin-angiotensin system, but further studies are required to establish causality.

  16. Respiratory tract clearance model for dosimetry and bioassay of inhaled radionuclides

    SciTech Connect

    Bailey, M.R.; Birchall, A. ); Cuddihy, R.G. ); James, A.C. ); Roy, M. . Inst. de Protection et de Surete Nucleaire)

    1990-07-01

    The ICRP Task Group on Respiratory Tract Models is developing a model to describe the retention and clearance of deposited radionuclides for dose-intake calculations and interpretation of bioassay data. Clearance from each region is treated as competition between mechanical transport, which moves particles to the gastro-intestinal tract and lymph nodes, and the translocation of material to blood. It is assumed that mechanical transport rates are the same for all materials, and that rates of translocation to blood are the same in all regions. Time-dependent clearance is represented by combinations of compartments. Representative values of parameters to describe mechanical transport from the human respiratory tract have been estimated, and guidance is given on the determination of translocation rates. It is emphasized that the current version of the model described here is still provisional. 30 refs.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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;...

  14. 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....

  15. 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....

  16. 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....

  17. 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....

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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....

  9. 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...

  10. 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...

  11. 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...

  12. 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.

  13. Transient Response of Rotor on Rolling-Element Bearings with Clearance

    NASA Technical Reports Server (NTRS)

    Fleming, David P.; Murphy, Brian T.; Sawicki, Jerzy T.; Poplawski, J. V.

    2006-01-01

    Internal clearance in rolling element bearings is usually present to allow for radial and axial growth of the rotor-bearing system and to accommodate bearing fit-up. The presence of this clearance also introduces a "dead band" into the load-deflection behavior of the bearing. Previous studies demonstrated that the presence of dead band clearance might have a significant effect on synchronous rotor response. In this work, the authors investigate transient response of a rotor supported on rolling element bearings with internal clearance. In addition, the stiffness of the bearings varies nonlinearly with bearing deflection and with speed. Bearing properties were accurately calculated with a state of the art rolling bearing analysis code. The subsequent rotordynamics analysis shows that for rapid acceleration rates the maximum response amplitude may be less than predicted by steady-state analysis. The presence of clearance may shift the critical speed location to lower speed values. The rotor vibration response exhibits subharmonic components which are more prominent with bearing clearance.

  14. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  15. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  16. Gastric mucosal blood flow during pentagastrin- and histamine-stimulated acid secretion in the rat

    PubMed Central

    Main, I. H. M.; Whittle, B. J. R.

    1973-01-01

    1. Gastric mucosal blood flow was studied in the rat by means of a [14C]-aniline clearance technique. 2. There was a significant correlation between clearance and stimulated acid secretion. 3. No significant difference was found in the relationship between clearance and acid secretion during submaximal stimulation with either pentagastrin or histamine. 4. Estimates of mucosal blood flow per unit acid secretion by [14C]-aniline clearance in the rat were similar to those reported with aminopyrine clearance in the dog and cat. PMID:4777713

  17. Protein Clearance Mechanisms of Alpha-Synuclein and Amyloid-Beta in Lewy Body Disorders

    PubMed Central

    Deleidi, Michela; Maetzler, Walter

    2012-01-01

    Protein clearance is critical for the maintenance of the integrity of neuronal cells, and there is accumulating evidence that in most—if not all—neurodegenerative disorders, impaired protein clearance fundamentally contributes to functional and structural alterations eventually leading to clinical symptoms. Dysfunction of protein clearance leads to intra- and extraneuronal accumulation of misfolded proteins and aggregates. The pathological hallmark of Lewy body disorders (LBDs) is the abnormal accumulation of misfolded proteins such as alpha-synuclein (Asyn) and amyloid-beta (Abeta) in a specific subset of neurons, which in turn has been related to deficits in protein clearance. In this paper we will highlight common intraneuronal (including autophagy and unfolded protein stress response) and extraneuronal (including interaction of neurons with astrocytes and microglia, phagocytic clearance, autoimmunity, cerebrospinal fluid transport, and transport across the blood-brain barrier) protein clearance mechanisms, which may be altered across the spectrum of LBDs. A better understanding of the pathways underlying protein clearance—in particular of Asyn and Abeta—in LBDs may result in the identification of novel biomarkers for disease onset and progression and of new therapeutic targets. PMID:23133788

  18. Effects of sustained exercise on pulmonary clearance of aerosolized sup 99m Tc-DTPA

    SciTech Connect

    Lorino, A.M.; Meignan, M.; Bouissou, P.; Atlan, G. )

    1989-11-01

    The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized {sup 99m}Tc-labeled diethylenetriaminepentaacetate ({sup 99m}Tc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. {sup 99m}Tc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O{sub 2} uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency.

  19. Pulmonary clearance of radiotracers after positive end-expiratory pressure or acute lung injury

    SciTech Connect

    Barrowcliffe, M.P.; Zanelli, G.D.; Jones, J.G.

    1989-01-01

    In anesthetized rabbits we measured clearance from lung to blood of eight aerosolized technetium-99m-labeled compounds: diethylenetriaminepentaacetate (99mTc-DTPA); cytochrome c; myoglobin; a myoglobin polymer; albumin; and anionic, cationic, and neutral dextrans of equivalent molecular size. We investigated the effect of applying positive end-expiratory pressure (PEEP) and, on a subsequent occasion, of injecting oleic acid intravenously to produce acute lung injury on the pulmonary clearance rate. Base-line clearance rates were monoexponential and varied with the molecular weights of the radiotracers. For each tracer the rate of clearance was increased a similar degree by either PEEP or oleic acid. However, with PEEP, clearance remained monoexponential, whereas after oleic acid, smaller molecular-weight radiotracers had multiexponential clearance curves. This suggests that after oleic acid the alveolar epithelium breaks down in a nonuniform fashion. We conclude that differentiation of the effect of PEEP from that of severe lung injury caused by oleic acid is not readily accomplished by either increasing the size of the tracer molecule or by varying the molecular charge.

  20. 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

  1. Clearance Deficiency and Cell Death Pathways: A Model for the Pathogenesis of SLE

    PubMed Central

    Mahajan, Aparna; Herrmann, Martin; Muñoz, Luis E.

    2016-01-01

    Alterations of cell death pathways, including apoptosis and the neutrophil specific kind of death called NETosis, can represent a potential source of autoantigens. Defects in the clearance of apoptotic cells may be responsible for the initiation of systemic autoimmunity in several chronic inflammatory diseases, including systemic lupus erythematosus (SLE). Autoantigens are released mainly from secondary necrotic cells because of a defective clearance of apoptotic cells or an inefficient degradation of DNA-containing neutrophil extracellular traps (NETs). These modified autoantigens are presented by follicular dendritic cells to autoreactive B cells in germinal centers of secondary lymphoid organs. This results in the loss of self-tolerance and production of autoantibodies, a unifying feature of SLE. Immune complexes (IC) are formed from autoantibodies bound to uncleared cellular debris in blood or tissues. Clearance of IC by blood phagocytes, macrophages, and dendritic cells leads to proinflammatory cytokine secretion. In particular, plasmacytoid dendritic cells produce high amounts of interferon-α upon IC uptake, thereby contributing to the interferon signature of patients with SLE. The clearance of antinuclear IC via Fc-gamma receptors is considered a central event in amplifying inflammatory immune responses in SLE. Along with this, the accumulation of cell remnants represents an initiating event of the etiology, while the subsequent generation of autoantibodies against nuclear antigens (including NETs) results in the perpetuation of inflammation and tissue damage in patients with SLE. Here, we discuss the implications of defective clearance of apoptotic cells and NETs in the development of clinical manifestations in SLE. PMID:26904025

  2. Tissue distribution, metabolism, and clearance of the convulsant trimethylolpropane phosphate in rats.

    PubMed

    Rossi, J; Jung, A E; Ritchie, G D; Lindsey, J W; Nordholm, A F

    1998-11-01

    The distribution, metabolism, and clearance of trimethylolpropane phosphate (TMPP), a potent, bicyclophosphate, gamma-aminobutyric acid-ergic convulsant, were studied in male Fischer-344 rats. Intraperitoneal administration of TMPP was compared with oral gavage with respect to rates of absorption, distribution, and clearance. Distribution of TMPP to major body tissues was evaluated for the first 24 hr after administration or, in the case of regional brain distribution, immediately after the first TMPP-induced clinical seizure. Samples purified from the urine, feces, and bile of rats exposed to TMPP, as well as from rat liver microsomes incubated with TMPP in vitro, were analyzed for possible phase I and phase II metabolism, using HPLC. The disposition and clearance of TMPP in the blood and major body tissues were measured. TMPP was found to be well distributed to highly vascularized tissue compartments, with little retention >24 hr after administration. TMPP was eliminated through the urine and feces as the parent compound, with no evidence of phase I or phase II metabolism. TMPP was rapidly cleared from the blood during the first 30 min after exposure, with slower clearance of >87% of the drug during the following 8-hr period and >99.5% clearance by 100 hr after injection. Repeated daily exposure to TMPP for up to 5 successive days resulted in no measurable accumulation in the brain or other major tissue compartments. Possible mechanisms for TMPP-induced, short- and long-term, neurobehavioral modulation are discussed. PMID:9806946

  3. IgM Promotes the Clearance of Small Particles and Apoptotic Microparticles by Macrophages

    PubMed Central

    Litvack, Michael L.; Post, Martin; Palaniyar, Nades

    2011-01-01

    Background Antibodies are often involved in enhancing particle clearance by macrophages. Although the mechanisms of antibody-dependent phagocytosis have been studied for IgG in greater detail, very little is known about IgM-mediated clearance. It has been generally considered that IgM does not support phagocytosis. Recent studies indicate that natural IgM is important to clear microbes and other bioparticles, and that shape is critical to particle uptake by macrophages; however, the relevance of IgM and particle size in their clearance remains unclear. Here we show that IgM has a size-dependent effect on clearance. Methodology/Principal Findings We used antibody-opsonized sheep red blood cells, different size beads and apoptotic cells to determine the effect of human and mouse IgM on phagocytosis by mouse alveolar macrophages. Our microscopy (light, epifluorescence, confocal) and flow cytometry data show that IgM greatly enhances the clearance of small particles (about 1–2 micron) by these macrophages. There is an inverse relationship between IgM-mediated clearance by macrophages and the particle size; however, macrophages bind and internalize many different size particles coated with IgG. We also show that IgM avidly binds to small size late apoptotic cells or bodies (2–5 micron) and apoptotic microparticles (<2 µm) released from dying cells. IgM also promotes the binding and uptake of microparticle-coated beads. Conclusions/Significance Therefore, while the shape of the particles is important for non-opsonized particle uptake, the particle size matters for antibody-mediated clearance by macrophages. IgM particularly promotes the clearance of small size particles. This finding may have wider implications in IgM-mediated clearing of antigens, microbial pathogens and dying cells by the host. PMID:21448268

  4. 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.

  5. 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

  6. Blood irradiation: Rationale and technique

    SciTech Connect

    Lewis, M.C. )

    1990-01-01

    Upon request by the local American Red Cross, the Savannah Regional Center for Cancer Care irradiates whole blood or blood components to prevent post-transfusion graft-versus-host reaction in patients who have severely depressed immune systems. The rationale for blood irradiation, the total absorbed dose, the type of patients who require irradiated blood, and the regulations that apply to irradiated blood are presented. A method of irradiating blood using a linear accelerator is described.

  7. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  8. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  9. Increased efflux of amyloid-β peptides through the blood-brain barrier by muscarinic acetylcholine receptor inhibition reduces pathological phenotypes in mouse models of brain amyloidosis.

    PubMed

    Paganetti, Paolo; Antoniello, Katia; Devraj, Kavi; Toni, Nicolas; Kieran, Dairin; Madani, Rime; Pihlgren, Maria; Adolfsson, Oskar; Froestl, Wolfgang; Schrattenholz, André; Liebner, Stefan; Havas, Daniel; Windisch, Manfred; Cirrito, John R; Pfeifer, Andrea; Muhs, Andreas

    2014-01-01

    The formation and accumulation of toxic amyloid-β peptides (Aβ) in the brain may drive the pathogenesis of Alzheimer's disease. Accordingly, disease-modifying therapies for Alzheimer's disease and related disorders could result from treatments regulating Aβ homeostasis. Examples are the inhibition of production, misfolding, and accumulation of Aβ or the enhancement of its clearance. Here we show that oral treatment with ACI-91 (Pirenzepine) dose-dependently reduced brain Aβ burden in AβPPPS1, hAβPPSL, and AβPP/PS1 transgenic mice. A possible mechanism of action of ACI-91 may occur through selective inhibition of muscarinic acetylcholine receptors (AChR) on endothelial cells of brain microvessels and enhanced Aβ peptide clearance across the blood-brain barrier. One month treatment with ACI-91 increased the clearance of intrathecally-injected Aβ in plaque-bearing mice. ACI-91 also accelerated the clearance of brain-injected Aβ in blood and peripheral tissues by favoring its urinal excretion. A single oral dose of ACI-91 reduced the half-life of interstitial Aβ peptide in pre-plaque mhAβPP/PS1d mice. By extending our studies to an in vitro model, we showed that muscarinic AChR inhibition by ACI-91 and Darifenacin augmented the capacity of differentiated endothelial monolayers for active transport of Aβ peptide. Finally, ACI-91 was found to consistently affect, in vitro and in vivo, the expression of endothelial cell genes involved in Aβ transport across the Blood Brain Brain (BBB). Thus increased Aβ clearance through the BBB may contribute to reduced Aβ burden and associated phenotypes. Inhibition of muscarinic AChR restricted to the periphery may present a therapeutic advantage as it avoids adverse central cholinergic effects. PMID:24072071

  10. 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)

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. The Development and Implementation of the Kennedy Space Center Umbilical Clearance Tool

    NASA Technical Reports Server (NTRS)

    Chesnutt, David

    2016-01-01

    In preparation for NASAs upcoming Space Launch System program, the Kennedy Space Center is currently developing subsystems to provide fuel, purges and communications to the flight vehicle, known as umbilicals. It is vital to the crew and mission that these umbilicals release at T-0 without re-contacting the vehicle as it is accelerating from the launch pad. To help ensure this requirement is met by the program, a methodology of evaluating the moving bodies was developed and implemented into a tool using MATLAB. The tool, known as the KSC Umbilical Clearance Tool, takes a given elevation of interest and an umbilical retract profile within the plane to evaluate the clearance between the umbilical arm and thousands of independent flight vehicle drift profiles from a Monte Carlo analysis. The presentation will delve into the challenges associated with developing and implementing the tool framed in the context of evaluating the clearance for one of the SLS umbilicals.

  16. The airborne survival of Pasteurella haemolytica and its deposition in and clearance from the mouse lung.

    PubMed

    Gilmour, M I; Wathes, C M; Taylor, F G

    1990-02-01

    Pasteurella haemolytica A1 was aerosolised by a Collison nebuliser in a Henderson apparatus and its survival in air was measured. The organism was fragile in aerosol and survived best at high humidity and warm temperature. Mice were exposed to the aerosol and clearance from the lung measured. Deposition in the mouse lung showed a good linear correlation with bacterial concentration in the spray suspension fluid. Clearance from the lung was rapid over 24 h although some bacteria could be detected 2 and 4 days after exposure. Mice which received a second exposure 2 weeks later exhibited accelerated clearance from the lung whereby no bacteria could be detected after 12 h. This was associated with serum IgG antibody production, and local and splenic lymphocyte responses to bacterial antigen in vitro. PMID:2138372

  17. The importance of splenic blood flow in clearing pneumococcal organisms.

    PubMed Central

    Horton, J; Ogden, M E; Williams, S; Coln, D

    1982-01-01

    Overwhelming infection from encapsulated bacteria occurs after splenectomy. Decreases in IgM, tufsin, and serum opsonin are known to occur in animals and humans after splenectomy. A substantial immunologic advantage exists if some splenic tissue remains, but this may not offer sufficient protection from encapsulated bacteria if splenic arterial blood flow is reduced. This experiment was designed to examine the rate of pneumococcal clearance by the spleen and to determine the relationship between splenic blood flow and splenic tissue mass in bacterial clearance from the blood. Pneumococcal clearance, splenic blood flow, and residual splenic weight were measured in 171 rabbits with normal spleens, ligated splenic arteries, splenic autotransplants, hemisplenectomies, and splenectomies. Interruption of the splenic artery results in delayed pneumococcal clearance that is due to reduced blood flow and not to a decrease in splenic tissue mass. Splenic artery ligation to preserve an injured spleen cannot be assumed to give protection from sepsis. PMID:7055394

  18. 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

  19. 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.

  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. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. Effects of dipyridamole-induced vasodilation on myocardial uptake and clearance kinetics of thallium-201

    SciTech Connect

    Beller, G.A.; Holzgrefe, H.H.; Watson, D.D.

    1983-12-01

    Myocardial thallium-201 (201Tl) uptake and clearance after intravenous administration of dipyridamole (150 micrograms/kg) were determined in 12 open-chest anesthetized dogs with a partial coronary artery stenosis. 201Tl (1.5 mCi) was injected intravenously and myocardial biopsy specimens were obtained 10 min, 60 min, and 2 hr after injection. Serial changes in 201Tl activity in the normal zone and in the zone of partial stenosis were correlated with microsphere-determined regional blood flow and distal coronary pressure. Another nine dogs with equivalent stenosis not given dipyridamole before 201Tl served as controls. Data indicate that dipyridamole-induced vasodilation in the presence of a partial stenosis results in diminished uptake and delayed clearance compared with increased uptake and more rapid clearance in normally perfused myocardium producing an initial 201Tl defect with delayed redistribution.

  9. Comparison of two lung clearance models based on the dissolution rates of oxidized depleted uranium

    SciTech Connect

    Crist, K.C.

    1984-10-01

    An in-vitro dissolution study was conducted on two respirable oxidized depleted uranium samples. The dissolution rates generated from this study were then utilized in the International Commission on Radiological Protection Task Group lung clearance model and a lung clearance model proposed by Cuddihy. Predictions from both models based on the dissolution rates of the amount of oxidized depleted uranium that would be cleared to blood from the pulmonary region following an inhalation exposure were compared. It was found that the predictions made by both models differed considerably. The difference between the predictions was attributed to the differences in the way each model perceives the clearance from the pulmonary region. 33 references, 11 figures, 9 tables.

  10. Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans

    PubMed Central

    Uda, Shinsuke; Kubota, Hiroyuki; Iwaki, Toshinao; Fukuzawa, Hiroki; Komori, Yasunori; Fujii, Masashi; Toyoshima, Yu; Sakaguchi, Kazuhiko; Ogawa, Wataru; Kuroda, Shinya

    2015-01-01

    Homeostatic control of blood glucose is regulated by a complex feedback loop between glucose and insulin, of which failure leads to diabetes mellitus. However, physiological and pathological nature of the feedback loop is not fully understood. We made a mathematical model of the feedback loop between glucose and insulin using time course of blood glucose and insulin during consecutive hyperglycemic and hyperinsulinemic-euglycemic clamps in 113 subjects with variety of glucose tolerance including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). We analyzed the correlation of the parameters in the model with the progression of glucose intolerance and the conserved relationship between parameters. The model parameters of insulin sensitivity and insulin secretion significantly declined from NGT to IGT, and from IGT to T2DM, respectively, consistent with previous clinical observations. Importantly, insulin clearance, an insulin degradation rate, significantly declined from NGT, IGT to T2DM along the progression of glucose intolerance in the mathematical model. Insulin clearance was positively correlated with a product of insulin sensitivity and secretion assessed by the clamp analysis or determined with the mathematical model. Insulin clearance was correlated negatively with postprandial glucose at 2h after oral glucose tolerance test. We also inferred a square-law between the rate constant of insulin clearance and a product of rate constants of insulin sensitivity and secretion in the model, which is also conserved among NGT, IGT and T2DM subjects. Insulin clearance shows a conserved relationship with the capacity of glucose disposal among the NGT, IGT and T2DM subjects. The decrease of insulin clearance predicts the progression of glucose intolerance. PMID:26623647

  11. The measurement of skin lymph flow by isotope clearance--reliability, reproducibility, injection dynamics, and the effect of massage

    SciTech Connect

    Mortimer, P.S.; Simmonds, R.; Rezvani, M.; Robbins, M.; Hopewell, J.W.; Ryan, T.J. )

    1990-12-01

    The measurement of skin lymph flow was investigated using an isotope clearance technique (ICT). Multiple lymph flow determinations were undertaken in the skin of anaesthetized large white pigs to test for reproducibility, ascertain the most suitable tracer, study the influence of injection dynamics, and observe the effect of massage as a stimulus to lymph flow. Blood clearance of tracer was also investigated. Results demonstrated that lymphatic clearance is a monoexponential function with good reproducibility under controlled laboratory conditions. 99mTc-colloid (TCK17 Cis) compared favorably with 131I-human serum albumin as a tracer and both performed better than colloid gold (198Au). Lymph flow was significantly faster in one pig than in the other. No difference existed between left and right sides or between caudal and rostral sites on each flank, but clearance was significantly slower in thigh than flank skin. Sub-epidermal injections cleared faster and more consistently than either deep or subcutaneous injections. Neither injection volume nor needle tract backflow of tracer influenced results, but local massage significantly enhanced clearance. Escape of 99mTc-colloid by the blood was negligible. These results indicate that skin lymph flow can be reliably measured when conditions are controlled. Extrinsic factors such as massage strongly influence lymph flow. Greater sensitivity in detecting degrees of lymphatic insufficiency may be achieved if a standardized stimulus to lymph flow is administered during isotope clearance measurement.

  12. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo.

    PubMed

    Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos; Schoofs, Till; Sarkar, Debolina; Halper-Stromberg, Ariel; Horwitz, Joshua A; Nogueira, Lilian; Golijanin, Jovana; Gazumyan, Anna; Ravetch, Jeffrey V; Caskey, Marina; Chakraborty, Arup K; Nussenzweig, Michel C

    2016-05-20

    Antiretroviral drugs and antibodies limit HIV-1 infection by interfering with the viral life cycle. In addition, antibodies also have the potential to guide host immune effector cells to kill HIV-1-infected cells. Examination of the kinetics of HIV-1 suppression in infected individuals by passively administered 3BNC117, a broadly neutralizing antibody, suggested that the effects of the antibody are not limited to free viral clearance and blocking new infection but also include acceleration of infected cell clearance. Consistent with these observations, we find that broadly neutralizing antibodies can target CD4(+) T cells infected with patient viruses and can decrease their in vivo half-lives by a mechanism that requires Fcγ receptor engagement in a humanized mouse model. The results indicate that passive immunotherapy can accelerate elimination of HIV-1-infected cells. PMID:27199430

  13. Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

    PubMed Central

    Sacks, Harold; Terry, L. Cass

    1981-01-01

    Other investigators have demonstrated that concentrations of immunoreactive somatostatin (IRS) are higher in blood from the hepatic portal vein or its tributaries than in blood from the hepatic or peripheral systemic veins of man and animals. This suggests that there is hepatic extraction of IRS from the portal system in vivo. In the rat, portal vein plasma IRS is reported to be heterogeneous and to contain, in part, a 1,600 mol wt form of IRS which is immunochemically similar to synthetic somatostatin and not significantly bound to high molecular weight plasma protein. Our study was undertaken to determine directly whether unbound synthetic cyclic somatostatin was cleared by the rat liver perfused through the hepatic portal vein in vitro with a recirculating, plasma-free, erythrocyte-containing perfusate. At 37°C and pH 7.40, perfusate IRS, at initial concentrations (1,728 pg/ml) within the range previously reported in rat portal venous blood, was removed by the liver at a rate commensurate with first-order kinetics. Hepatic clearance was 0.84±0.04 ml/min per g postperfusion wet weight (SE). Hepatic extraction was 36±2%, and t½ was 20.0±1.3 min. Recovery of IRS from the perfusate without the liver was >85%, excluding significant degradation by the medium. Clearance, extraction, and t½ of IRS were not changed by an unphysiologic IRS concentration (621,500 pg/ml), or by pharmacologic concentrations of insulin (8.2 μM) or glucagon (2.9 μM). The t½ was prolonged significantly to 28.2±1.9 and 45.6±4.7 min during perfusions at liver temperatures of 25° and 16°C, respectively. At 37°C, the t½ was also significantly increased to 28.7±3.2 and 24.2±1.1 min at perfusate pH 7.06 and 6.78, respectively. These studies indicate that the rat liver clears unbound IRS from the perfusate by a first-order kinetic process that is (a) unsaturable at pharmacologic concentrations, (b) temperature-sensitive and, to a lesser extent, influenced by lowered pH, and (c) not

  14. Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

    PubMed Central

    Jones, Stephen W.; Roberts, Reid A.; Robbins, Gregory R.; Perry, Jillian L.; Kai, Marc P.; Chen, Kai; Bo, Tao; Napier, Mary E.; Ting, Jenny P.Y.; DeSimone, Joseph M.; Bear, James E.

    2013-01-01

    Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopy–based assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte–derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans. PMID:23778144

  15. Role of the lung in total body clearance of circulating drugs.

    PubMed

    Roth, R A; Wiersma, D A

    1979-01-01

    Attention in recent years has focused upon the ability of lung to accumulate and/or to metabolise circulating hormones, drugs and other xenobiotic agents. Although often studied in broken cell preparations, such functions must be examined in intact lung before extrapolation to the situation in vivo is possible. The role of lung in total body clearance of xenobiotic agents is often considered to be small, as compared with the liver it usually has much lower concentrations of degradative enzymes and a smaller mass. However, consideration of such factors as organ blood flow or stimulation of drug metabolising enzymes suggests that the contribution of the lung to total body clearance of some drugs is greater than previously recognised. This may explain some of the alterations in drug clearance seen clinically. For example, cigarette smoking may increase the clearance of certain xenobiotic compounds by stimulating pulmonary drug metabolising enzymes. Pulmonary drug disposition may also be altered by conditions affecting cardiac output, such as exercise, hypoxia, and circulatory shock, or those affecting acid-base balance, such as hyperventilation. In addition, pneumotoxicants may affect pulmonary clearance of circulating drugs and xenobiotics. PMID:41661

  16. Mechanisms of Aβ Clearance and Degradation by Glial Cells.

    PubMed

    Ries, Miriam; Sastre, Magdalena

    2016-01-01

    Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including Alzheimer's disease (AD). One of the most important functions of glial cells in AD is the regulation of Amyloid-β (Aβ) levels in the brain. Microglia and astrocytes have been reported to play a central role as moderators of Aβ clearance and degradation. The mechanisms of Aβ degradation by glial cells include the production of proteases, including neprilysin, the insulin degrading enzyme, and the endothelin-converting enzymes, able to hydrolyse Aβ at different cleavage sites. Besides these enzymes, other proteases have been described to have some role in Aβ elimination, such as plasminogen activators, angiotensin-converting enzyme, and matrix metalloproteinases. Other relevant mediators that are released by glial cells are extracellular chaperones, involved in the clearance of Aβ alone or in association with receptors/transporters that facilitate their exit to the blood circulation. These include apolipoproteins, α2macroglobulin, and α1-antichymotrypsin. Finally, astrocytes and microglia have an essential role in phagocytosing Aβ, in many cases via a number of receptors that are expressed on their surface. In this review, we examine all of these mechanisms, providing an update on the latest research in this field. PMID:27458370

  17. Mechanisms of Aβ Clearance and Degradation by Glial Cells

    PubMed Central

    Ries, Miriam; Sastre, Magdalena

    2016-01-01

    Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including Alzheimer’s disease (AD). One of the most important functions of glial cells in AD is the regulation of Amyloid-β (Aβ) levels in the brain. Microglia and astrocytes have been reported to play a central role as moderators of Aβ clearance and degradation. The mechanisms of Aβ degradation by glial cells include the production of proteases, including neprilysin, the insulin degrading enzyme, and the endothelin-converting enzymes, able to hydrolyse Aβ at different cleavage sites. Besides these enzymes, other proteases have been described to have some role in Aβ elimination, such as plasminogen activators, angiotensin-converting enzyme, and matrix metalloproteinases. Other relevant mediators that are released by glial cells are extracellular chaperones, involved in the clearance of Aβ alone or in association with receptors/transporters that facilitate their exit to the blood circulation. These include apolipoproteins, α2macroglobulin, and α1-antichymotrypsin. Finally, astrocytes and microglia have an essential role in phagocytosing Aβ, in many cases via a number of receptors that are expressed on their surface. In this review, we examine all of these mechanisms, providing an update on the latest research in this field. PMID:27458370

  18. 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

  19. 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.

  20. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  1. 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

  2. Blood Disorders

    MedlinePlus

    ... and protein. Over half of your blood is plasma. The solid part of your blood contains red blood cells, white blood cells and platelets. Blood disorders affect one or more parts of the blood and prevent ...

  3. Effect of hematocrit and systolic blood pressure on cerebral blood flow in newborn infants

    SciTech Connect

    Younkin, D.P.; Reivich, M.; Jaggi, J.L.; Obrist, W.D.; Delivoria-Papadopoulos, M.

    1987-06-01

    The effects of hematocrit and systolic blood pressure on cerebral blood flow were measured in 15 stable, low birth weight babies. CBF was measured with a modification of the xenon-133 (/sup 133/Xe) clearance technique, which uses an intravenous bolus of /sup 133/Xe, an external chest detector to estimate arterial /sup 133/Xe concentration, eight external cranial detectors to measure cephalic /sup 133/Xe clearance curves, and a two-compartmental analysis of the cephalic /sup 133/Xe clearance curves to estimate CBF. There was a significant inverse correlation between hematocrit and CBF, presumably due to alterations in arterial oxygen content and blood viscosity. Newborn CBF varied independently of systolic blood pressure between 60 and 84 mm Hg, suggesting an intact cerebrovascular autoregulatory mechanism. These results indicate that at least two of the factors that affect newborn animal CBF are operational in human newborns and may have important clinical implications.

  4. The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer in mice.

    PubMed

    Pizzo, S V; Pasqua, J J

    1982-10-01

    The clearance of human fibrinogen fragments D1, D2, D3 and fibrin fragment D1 dimer were studied in the mouse model. Clearance of these fragments is a complex process involving clearance from blood into three other compartments. The overall clearance of fragment D1 and its dimer were essentially identical. Fragments D2 and D3 cleared at a progressively slower rate. Competition studies were performed between 125I-labeled fragment D1 and large molar excesses of unlabeled human fragments D1, D2, D3, D1 dimer, fragment E, fibrinogen, macroalbumin, mannan and asialoorosomucoid. Of these ligands only the fragment D variants competed for the clearance of 125I-labeled fragment D1. Cross-competition was observed when 125I-labeled fragment D1 dimer was cleared in the presence of a large molar excesses of fragment D1. Autopsies demonstrated that injected fragments D1, D2, D3 and D1 dimer cleared primarily in liver and kidneys. In some clearance studies, livers were perfused with tissue culture fluid, subjected to light microscopic autoradiography, and silver grain counts performed to localize cleared fragment D1. These experiments indicated that 80% of the liver uptake was in hepatocytes. However, when silver grain counts were normalized for the number of parenchymal and nonparenchymal cells, the distribution of silver grains was essentially identical (1.8 and 1.6 grains per cells, respectively). It is concluded that fragments D1, D2, D3 and D1 dimer are recognized by a similar clearance pathway. Since neither fibrinogen nor fragment E competed for the clearance of fragment D1, it is suggested that determinants present in the fragment D domain become exposed after plasmin attack on fibrinogen and are responsible for clearance. PMID:7138910

  5. Effect of increased surface tension and assisted ventilation on /sup 99m/Tc-DTPA clearance

    SciTech Connect

    Jefferies, A.L.; Kawano, T.; Mori, S.; Burger, R.

    1988-02-01

    Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. /sup 99m/Tc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP (k = 7.57 +/- 0.71%/min (SE)) and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of /sup 99m/Tc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.

  6. Blood sugar test - blood

    MedlinePlus

    ... drink a certain amount of glucose ( oral glucose tolerance test ) How the Test will Feel When the ... a fasting blood glucose, HbA1c test , or glucose tolerance test , depending on your random blood glucose test ...

  7. 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...

  8. 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...

  9. 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

  10. 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...

  11. 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 §...

  12. 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...

  13. 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...

  14. 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...

  15. Menopause accelerates biological aging.

    PubMed

    Levine, Morgan E; Lu, Ake T; Chen, Brian H; Hernandez, Dena G; Singleton, Andrew B; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E; Quach, Austin; Kusters, Cynthia D J; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E; Widschwendter, Martin; Ritz, Beate R; Absher, Devin; Assimes, Themistocles L; Horvath, Steve

    2016-08-16

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  16. 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

  17. 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,...

  18. 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....

  19. 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,...

  20. 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,...

  1. 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,...

  2. 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,...

  3. 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...

  4. 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...

  5. 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...

  6. 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.

  7. 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....

  8. 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....

  9. 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....

  10. 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....

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  20. 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...

  1. 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....

  2. 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....

  3. 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....

  4. 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....

  5. 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....

  6. 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....

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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....

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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).

  13. 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).

  14. Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) may accelerate hematopoietic recovery after HLA-identical sibling allogeneic peripheral blood stem cell transplantation.

    PubMed

    Ozcan, M; Ustün, C; Akçağlayan, E; Akan, H; Arslan, O; Ilhan, O; Beksaç, M; Gürman, G; Demirer, T; Arat, M; Celebi, H; Konuk, N; Uysal, A; Koç, H

    2001-03-01

    We studied the effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation. Fifty-six patients with hematological malignancies who underwent allogeneic PBSC transplantation between 1995 and 1998 were entered into this study. Twenty-eight patients who received daily G-CSF from day +1 after allogeneic PBSC transplantation until the absolute neutrophil count (ANC) reached >0.5 x 10(9)/l for 3 consecutive days were compared with 28 patients (control group) who did not receive G-CSF in a non-randomized manner. The study group and the control group were comparable with respect to baseline patient and transplantation characteristics. Median times to ANC of >0.5 x 10(9)/l and 1 x 10(9)/l with or without G-CSF were 12 days (range 8-21), 13 days (10-32) (P = 0.04) and 13 days (9-21), 15 days (11-44) (P = 0.02), respectively. Median times to reach a platelet count of >20 x 10(9)/l with and without G-CSF were 11 days (0-20) and 13 days (9-26), respectively (P = 0.03). The incidence of febrile episodes was significantly lower with G-CSF, 75% vs 100% (P = 0.008). Patients receiving G-CSF had less grade III-IV mucositis than those who did not receive G-CSF (P = 0.01). There was also no increase in the incidence and severity of acute GVHD in patients using G-CSF (P = 0.22). Although the number of relapsing patients was greater in the G-CSF group (seven vs three patients), this was not statistically significant (P = 0.24). Disease-free and overall survival rates did not differ between the two groups (P = 0.58 and 0.53, respectively). The administration of G-CSF after allogeneic PBSC transplantation provided faster neutrophil and platelet engraftment associated with less severe mucositis and less febrile episodes. PMID:11313683

  15. Vomiting blood

    MedlinePlus

    ... first part of the small intestine, or esophagus Blood clotting disorders Defects in the blood vessels of the ... as a complete blood count (CBC), blood chemistries, blood clotting tests, and liver function tests Esophagogastroduodenoscopy (EGD) (placing ...

  16. Blood pressure

    MedlinePlus Videos and Cool Tools

    Normal blood pressure is important for proper blood flow to the body’s organs and tissues. The force of the blood on the walls of the arteries is called blood pressure. Blood pressure is measured both as the heart ...

  17. Blood transfusions

    MedlinePlus

    ... homologous blood donation. Many communities have a blood bank at which any healthy person can donate blood. ... to arrange with your hospital or local blood bank before your surgery to have directed donor blood. ...

  18. Blood pressure

    MedlinePlus Videos and Cool Tools

    Normal blood pressure is important for proper blood flow to the body’s organs and tissues. The force of the blood on the walls of the arteries is called blood pressure. Blood pressure is measured both ...

  19. Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections

    PubMed Central

    You, Hong; Liu, Sandu; Xie, Yong; Cong, Rui; Sun, Yameng; Ren, Jingjing; Wei, Kangfei; Jin, Xin; Shi, Yujian; Zhang, Haiying; Li, Jie; Wei, Lai; Zhuang, Hui; Cheng, Mingliang; Jia, Jidong

    2014-01-01

    Background and aims A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression. Methods Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance. Results Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9–12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10−5). Conclusions Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance. PMID:26462265

  20. Site of deposition and factors affecting clearance of aerosolized solute from canine lungs

    SciTech Connect

    Rizk, N.W.; Luce, J.M.; Hoeffel, J.M.; Price, D.C.; Murray, J.F.

    1984-01-01

    The influence of several factors on lung solute clearance using aerosolized /sup 99m/Tc-diethylenetriaminepentaacetate was determined. The authors used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 ..mu..m, administered the aerosol in a standard fashion, and determined clearance half times (t/sub 1/2/) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: (1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (V/sub T/) = 15 ml/kg during solute clearance; (2) repeat control, for reproducibility; (3) increased frequency, with f = 25 breaths/min and V/sub T/ = 10 ml/kg; (4) positive end-expiratory pressure (PEEP) of 10 cmH/sub 2/O; (5) unilateral pulmonary arterial occlusion (PAO); and (6) bronchial arterial occlusion (BAO). Control t/sub 1/2/ was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t/sub 1/2/ to 13 +/- 3 min (P < 0.01), and PAO increased it to 37 +/- 6 min (P < 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.

  1. [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

  2. SMTP (Stachybotrys microspora triprenyl phenol) enhances clot clearance in a pulmonary embolism model in rats

    PubMed Central

    2012-01-01

    Background Stachybotrys microspora triprenyl phenols (SMTPs) are a novel family of small molecules that enhance both activation and fibrin-binding of plasminogen. While their effects on fibrinolysis have been characterized in vitro, little is known about their activity in vivo with respect to plasminogen activation and blood clot clearance. Results To select a potent SMTP congener for the evaluation of its action in vitro and in vivo, we tested several SMTP congeners with distinct structural properties for their effects on plasminogen activation. As a result, SMTP-7 (orniplabin) was found to have distinguished activity. Several lines of biochemical evidence supported the idea that SMTP-7 acted as a plasminogen modulator. SMTP-7 elevated plasma level of plasmin-α2-antiplasmin complex, an index of plasmin formation in vivo, 1.5-fold in mice after the intravenous injections at doses of 5 and 10 mg kg-1. In a rat pulmonary embolism model, SMTP-7 (5 mg kg-1) enhanced the rate of clot clearance ~3-fold in the absence of exogenous plasminogen activator. Clot clearance was enhanced further by 5 mg kg-1 of SMTP-7 in combination with single-chain urokinase-type plasminogen activator. Conclusions Our results show that SMTP-7 is a superior plasminogen modulator among the SMTP family compounds and suggest that the agent enhances plasmin generation in vivo, leading to clearance of thrombi in a model of pulmonary embolism. PMID:22230042

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.

    PubMed

    Zhang, Zhuo-Qian; Wang, Jing; Hoy, Zachary; Keegan, Achsah; Bhagwat, Samir; Gigliotti, Francis; Wright, Terry W

    2015-12-01

    Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS

  13. Accelerated Reader.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Accelerated Reader, a system of computerized testing and record-keeping that supplements the regular classroom reading program. Accelerated Reader's primary goal is to increase literature-based reading practice. The program offers a computer-aided reading comprehension and management program intended to motivate…

  14. Rotary blood pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J. (Inventor); Akkerman, James W. (Inventor); Aber, Greg S. (Inventor); Vandamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1993-01-01

    A rotary blood pump is presented. The pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial, and radial clearances of the blades associated with the flow straightener, inducer portion, impeller portion, and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with crosslinked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  15. Rotary Blood Pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1996-01-01

    A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  16. Donating Blood

    MedlinePlus

    ... can give blood every 56 days. Before Donating Blood donation starts before you walk in the door of ... regenerate the red blood cells lost during a blood donation. An iron-fortified diet plus daily iron tablets ...

  17. Blood culture

    MedlinePlus

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  18. Blood Thinners

    MedlinePlus

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  19. 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.

  20. Ileal microvascular permeability: a comparison of PS and sigma d using lymphatic and isotopic protein clearances.

    PubMed

    Townsley, M I; Smith, S M; Reed, R K; Pitts, V H; Taylor, A E

    1992-03-01

    Lymphatic clearances of total protein, albumin, immunoglobulin (Ig) G, and IgM obtained in autoperfused cat ileum as venous pressure (Pv) was elevated were analyzed using traditional methods as well as the newer maximal diffusion (max,diff) method of Reed et al. [Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H728-H740, 1991; Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989] to determine capillary osmotic reflection coefficients (sigma d) and unique permeability surface area products (PS). In a control group (n = 6), sigma d max,diff and PSmax,diff for albumin, IgG, and IgM could not be determined due to their transiently high clearance patterns. These patterns were not altered by treatment with vasodilators (n = 6) to prevent redistribution of blood flow from the mucosal-submucosal to muscularis layer of the ileum, which accompanies elevation of ileal Pv. Furthermore, sigma d values for IgG in both groups were lower than those for both albumin and IgM, a finding inconsistent with predictions based on pore theory, together suggesting that lymphatic protein clearances were influenced by washout of interstitial proteins, a conclusion supported by the decrease in tissue content of albumin and IgG after elevation of Pv. Clearances of radiolabeled albumin (n = 10) and IgG (n = 6), measured after an initial 2-h steady-state period at a constant Pv, were markedly reduced at low lymph flow compared with those obtained in the shorter term experiments. In an additional group (n = 5), albumin clearance peaked at 10 times baseline within 15 min after a step increase in Pv to 30 mmHg but fell to only 3 times baseline within 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1550244

  1. Glucagon clearance is regulated by nutritional state: evidence from experimental studies in mice

    PubMed Central

    Zhou, Alyssa; Pacini, Giovanni; Ahrén, Bo; D’Argenio, David Z.

    2014-01-01

    Aims/hypothesis Given the importance of glucagon in the development of type 2 diabetes and as a potential therapeutic agent, the aim of this study was to characterise glucagon kinetics in mice and its regulation by the nutritional state. Methods Anaesthetised C57BL/6 mice fed normal or high-fat diets, or fasted, were injected intravenously with glucagon (0.1, 0.3, 1.0, 10.0 or 20 μg/kg); blood samples were withdrawn before injection and 1, 3, 5, 10, 20 min thereafter for glucagon assay by RIA. Glucagon kinetics were described by two-compartment models using a population analysis. Results The population mean and between-animal SD of glucagon clearance in the fed mice was 6.03 ± 2.58 ml/min, with a rapid elimination half-life of 2.92 ± 1.21 min. Fasted mice showed a slower glucagon clearance. The kinetics of glucagon in the fed and fasted group was linear across this large dose range. The mice fed a high-fat diet, however, showed non-linear kinetics with a faster terminal clearance of 20.4 ± 5.45 ml/min (p < 0.001) and a shorter elimination half-life of 1.59 ± 0.606 (p < 0.001) min relative to normal mice. Conclusions/interpretation This first systematic dose-ranging study of glucagon kinetics produced several findings: (1) a linear two-compartment model describes glucagon in normal C57BL/6 mice; (2) fasting reduces the clearance of glucagon and (3) high-fat diet enhances the clearance of glucagon. These results may direct future studies on glucagon physiology and indicate that there are other mechanisms, not included in the current model, needed to fully explain glucagon’s kinetics. PMID:24370975

  2. 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

  3. Effect of fixation devices on radiostrontium clearance in the intact canine femur

    SciTech Connect

    Daum, W.J.; Simmons, D.J.; Chang, S.L.; Lehman, R.C.; Webster, D.

    1985-04-01

    Femoral metaphyseal/diaphyseal blood flow was studied by /sup 85/Sr clearance in unfractured segments of dog femurs following compression plating and various control procedures (drilling with and without application of screws). The animals were tested as early as seven days and as late as two months after surgery. The only statistically significant change in strontium clearance (SrC) was an increase produced by the application of stainless-steel bone screws, with or without plates. The presence or absence of compression had no consistent effect on changes in the rate of SrC. During the period of study, no changes in bone mineralization, haversian porosity, or cortical bone thickness accompanied the SrC alterations.

  4. Blood sugar test - blood

    MedlinePlus

    ... in the way you normally talk or behave Fainting spells Seizures (for the first time) SCREENING FOR ... drawn are slight, but may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the ...

  5. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  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. [Plasma clearance of ethanol and its excretion in the milk of rural women who consume pulque].

    PubMed

    Argote-Espinosa, R M; Flores-Huerta, S; Hernández-Montes, H; Villalpando-Hernández, S

    1992-01-01

    Women from rural areas of the central plateau of Mexico drink during pregnancy and lactation a mild alcoholic beverage called pulque as a galactogogue. Ethanol present in milk could have a harmful effect on growth and development of breast-fed children. The purpose of this study was to quantify the ethanol consumed as pulque by eleven lactating rural women as well as its clearance rate in blood and milk. Mothers were separated in two groups depending upon the ethanol ingested in a single dose of pulque 0.21 +/- 0.08 g/kg of body weight (group A) and 0.44 +/- 0.11 g/kg (group B). Maximal concentration of ethanol was reached in milk at 60 minutes and almost equaled that in plasma. Both groups showed a similar clearance pattern regardless of the volume of pulque ingested. Clearance rates between groups were different: ethanol concentration in milk at 60 min were 8.4 +/- 3.0 mg/dL for group A and 26.2 +/- 7.0 mg/dL for group B. Two hours later ethanol levels were 3.6 +/- 3.4 mg/dL and 23.3 +/- 9.4 mg/dL respectively. Clearance rates were slower in mothers showing the highest concentration of ethanol in milk. The present data demonstrate that there is no differential elimination of ethanol in maternal blood and milk following ingestion of a moderate amount of pulque during lactation. The amount of ethanol received by infants through milk is relatively low and therefore it is unlikely to have harmful effects on them. Pulque consumption adds about 350 kcal/day to the customary dietary intake of these lactating women. PMID:1523347

  8. Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam

    PubMed Central

    Hong, Nguyen Van; Rosanas-Urgell, Anna; Phuc, Bui Quang; Ha, Do Manh; Pockele, Evi; Guetens, Pieter; Van, Nguyen Van; Duong, Tran Thanh; Amambua-Ngwa, Alfred; D'Alessandro, Umberto; Erhart, Annette

    2014-01-01

    Reduced susceptibility of Plasmodium falciparum toward artemisinin derivatives has been reported from the Thai-Cambodian and Thai-Myanmar borders. Following increasing reports from central Vietnam of delayed parasite clearance after treatment with dihydroartemisinin-piperaquine (DHA-PPQ), the current first-line treatment, we carried out a study on the efficacy of this treatment. Between September 2012 and February 2013, we conducted a 42-day in vivo and in vitro efficacy study in Quang Nam Province. Treatment was directly observed, and blood samples were collected twice daily until parasite clearance. In addition, genotyping, quantitative PCR (qPCR), and in vitro sensitivity testing of isolates was performed. The primary endpoints were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates, qPCR clearance profiles, in vitro sensitivity results (for chloroquine, dihydroartemisinin, and piperaquine), and genotyping for mutations in the Kelch 13 propeller domain. Out of 672 screened patients, 95 were recruited and 89 available for primary endpoint analyses. The median parasite clearance time (PCT) was 61.7 h (interquartile range [IQR], 47.6 to 83.2 h), and the median parasite clearance rate had a slope half-life of 6.2 h (IQR, 4.4 to 7.5 h). The PCR-corrected efficacy rates were estimated at 100% at day 28 and 97.7% (95% confidence interval, 91.2% to 99.4%) at day 42. At day 3, the P. falciparum prevalence by qPCR was 2.5 times higher than that by microscopy. The 50% inhibitory concentrations (IC50s) of isolates with delayed clearance times (≥72 h) were significantly higher than those with normal clearance times for all three drugs. Delayed parasite clearance (PCT, ≥72 h) was significantly higher among day 0 samples carrying the 543 mutant allele (47.8%) than those carrying the wild-type allele (1.8%; P = 0.048). In central Vietnam, the efficacy of DHA-PPQ is still satisfactory, but the parasite clearance time

  9. Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and Children ≤2 Years of Age: A Comparison of the Predictive Performance of 4 Allometric Models.

    PubMed

    Mahmood, Iftekhar

    2016-06-01

    The objective of this study was to evaluate the predictive performance of 4 allometric models to predict clearance in pediatric ages ranging from premature neonates to children ≤2 years of age. Four allometric models were used to predict clearances of 28 drugs in children from preterm neonates to 2 years of age (n = 564). The 4 models are (1) basal metabolic rate-dependent model; (2) age-dependent exponent model; (3) an allometric model based on kidney and liver weights as well as kidney and liver blood flow; and (4) an allometric model based on a fixed exponent of 0.75. The predictive performance of these models was evaluated by comparing the predicted clearance of the studied drugs with the observed clearance in an individual child. The results of the study indicated that the 3 new proposed models predicted the mean clearance of the drugs with reasonable accuracy (≤50% prediction error). On the other hand, the exponent of 0.75 produced substantial prediction error. Predicted individual clearance values were ≥50% in approximately 30% of the children by the proposed 3 methods and 73% by exponent 0.75. The 3 new proposed allometric models can predict mean clearances of drugs in children from premature neonates to ≤2 years of age with reasonable accuracy and are of practical value during pediatric drug development. PMID:26437918

  10. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  11. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  12. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  13. 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.

  14. 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.

  15. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  16. Quantitation of deposition, clearance and routes of elimination of 3 um insoluble particles in the sheep lung

    SciTech Connect

    Langenback, E.G.

    1984-01-01

    This study is the first to completely determine the number of particles deposited in the lung, the number of particles cleared over a period of a hundred days and the pathways by which the particles exit the lungs. The study uses long lived radioactively (/sup 57/Co) tagged 3 um insoluble polystyrene particles to follow clearance in a sheep animal model. Particle clearance was characterized by 4 phases. Periodic sacrifice and autopsy showed no particle accumulation in regional lymph nodes draining the lung and no particle accumulation in the liver, spleen or kidneys. Urine and blood samples throughout clearance were devoid of particles, but fecal excretion of particles matched lung elimination of particles and mirrored clearance closely. Thus the avenues of long-term clearance of a 3 um polystrene particle has been established from the alveolar portion of the lung: virtually all particles cleared in 101 days were removed by transport from the alveoli to the mucociliary escalator, either as free particles and/or associated with macrophages and subsequently swallowed and excreted. Particles remaining in the lungs after 101 days continued to be cleared from the lungs via the mucociliary escalator with a t/sub 1/2/ = 38 days. This suggests that particles leave a sequestered state, re-enter the airways and are cleared.

  17. 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

  18. 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

  19. 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.

  20. In vitro-in vivo extrapolation of hepatic clearance: biological tools, scaling factors, model assumptions and correct concentrations.

    PubMed

    Pelkonen, O; Turpeinen, M

    2007-01-01

    Although the measurement of metabolite formation or substrate depletion in in vitro systems, from recombinant enzymes to tissue slices, is a relatively routine task, there are a number of more or less unresolved issues in the extrapolation of the enzymatic intrinsic clearance into hepatic metabolic clearance. Nominal concentrations of the drug added to the incubation system are not necessarily the concentration the transporter or the metabolizing enzyme sees. In addition, peculiarities of incubation set-ups should be assessed. Unbound drug fractions (concentrations) in the in vitro system itself should be measured or estimated for the appropriate assessment of enzymatic intrinsic clearance. In addition, blood and/or plasma concentrations to be encountered in the in vivo situation should be measured or estimated for the extrapolation. Extrapolation always means making a number of assumptions and the most important of these, such as scaling factors from recombinant enzymes, microsomes or hepatocytes to the mass unit of the liver, liver weight, blood flow, and distribution volume amongst others, and so on, should be explicitly stated and included in the extrapolation process. Despite all the above-mentioned reservations the in vitro-in vivo extrapolation of metabolic clearance seems to be a useful and mostly fairly precise tool for predicting the important pharmacokinetic processes of a drug. PMID:17968737

  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. Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor

    SciTech Connect

    Johns, Douglas G. . E-mail: Douglas.G.Johns@gsk.com; Ao, Zhaohui; Heidrich, Bradley J.; Hunsberger, Gerald E.; Graham, Taylor; Payne, Lisa; Elshourbagy, Nabil; Lu, Quinn; Aiyar, Nambi; Douglas, Stephen A.

    2007-06-22

    Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [{sup 125}I]-ANP from NPR-C with pM-to-nM K {sub i} values. DNP displaced [{sup 125}I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K {sub i} > 1000 nM). DNP was nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure.

  3. Model-based lamotrigine clearance changes during pregnancy: clinical implication

    PubMed Central

    Polepally, Akshanth R; Pennell, Page B; Brundage, Richard C; Stowe, Zachary N; Newport, Donald J; Viguera, Adele C; Ritchie, James C; Birnbaum, Angela K

    2014-01-01

    Objective The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery. PMID:24883336

  4. Blood typing

    MedlinePlus

    ... typing. The liquid part of your blood without cells (serum) is mixed with blood that is known to be type ... ABO typing: If your blood cells stick together when mixed with: Anti-A serum, you have type A blood Anti-B serum, you have type B blood Both anti-A and ...

  5. Alterations in hepatic production and peripheral clearance of IGF-I after endotoxin.

    PubMed

    Fan, J; Char, D; Kolasa, A J; Pan, W; Maitra, S R; Patlak, C S; Spolarics, Z; Gelato, M C; Lang, C H

    1995-07-01

    Lipopolysaccharide (LPS) produces a rapid and sustained reduction in the circulating concentration of insulin-like growth factor I (IGF-I), which may be responsible, in part, for the alterations in protein metabolism observed in these animals. The purpose of the present study was to determine whether this drop was due to a decreased hepatic production of IGF-I and/or an increased clearance of the peptide from the blood. Four hours after intravenous injection of LPS the plasma IGF-I concentration was decreased 50%. IGF-I release by in situ perfused livers from control rats was constant throughout the 60-min perfusion period and averaged 111 +/- 3 ng/min. In contrast, hepatic IGF-I output was decreased 46% by in vivo LPS. In contrast, livers from LPS-injected rats released more IGF binding proteins-1, -2 and -4 than did control livers. Hepatic cell isolation indicated that LPS decreased the IGF-I content in Kupffer and parenchymal cells, but not endothelial cells, by approximately 45%. Pharmacokinetic analysis of blood 125I-IGF-I decay curves indicated that the half-life for whole body clearance of 125I-IGF-I from the circulation was not altered by LPS. However, LPS increased 125I-IGF-I uptake by spleen, liver, lung, and kidney while decreasing uptake by the pancreas and gastrointestinal tract. These results indicate that the LPS-induced decrease in blood IGF-I concentration is primarily due to a reduction in hepatic production, not a change in whole body peptide clearance, and that a decreased production by both parenchymal and Kupffer cells contributes to this alteration. PMID:7543247

  6. 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

  7. Advance techniques for monitoring human tolerance to +Gz accelerations.

    NASA Technical Reports Server (NTRS)

    Pelligra, R.; Sandler, H.; Rositano, S.; Skrettingland, K.; Mancini, R.

    1972-01-01

    Standard techniques for monitoring the acceleration-stressed human subject have been augmented by measuring (1) temporal, brachial and/or radial arterial blood flow, and (2) indirect systolic and diastolic blood pressure at 60-sec intervals. Results show that the response of blood pressure to positive accelerations is complex and dependent on an interplay of hydrostatic forces, diminishing venous return, redistribution of blood, and other poorly defined compensatory reflexes.

  8. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  9. Effect of inspiratory resistance and PEEP on /sup 99m/Tc-DTPA clearance

    SciTech Connect

    O'Brodovich, H.; Coates, G.; Marrin, M.

    1986-05-01

    Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (/sup 99m/Tc-DTPA). A submicronic aerosol containing /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval (k = 0.21 +/- 12%/min) when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP (0.76 +/- 0.28%/min, P less than 0.01). When PEEP was increased to 15 cmH2O a marked increase in clearance occurred (k = 1.95 +/- 1.08%/min, P less than 0.001). The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of /sup 99m/Tc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP.

  10. Blood Sugar

    MedlinePlus

    Blood sugar, or glucose, is the main sugar found in your blood. It comes from the food you eat, and is your body's main source of energy. Your blood carries glucose to all of your body's cells to use ...

  11. Blood transfusions

    MedlinePlus

    ... are many reasons you may need a blood transfusion: After knee or hip replacement surgery, or other ... your body cannot make enough blood A blood transfusion is a safe and common procedure during which ...

  12. Blood typing

    MedlinePlus

    ... whether or not there are certain proteins, called antigens, on your red blood cells. Blood is often ... There are many antigens besides the major ones (A, B, and Rh). Many minor ones are not routinely detected during blood typing. If ...

  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. Activation of Pattern Recognition Receptors Upregulates Metallothioneins, Thereby Increasing Intracellular Accumulation of Zinc, Autophagy, and Bacterial Clearance by Macrophages

    PubMed Central

    Lahiri, Amit; Abraham, Clara

    2014-01-01

    Background & Aims Continuous stimulation of pattern recognition receptors (PRRs), including nucleotide-binding oligomerization domain-2 (NOD2) (variants in NOD2 have been associated with Crohn's disease), alters the phenotype of myeloid-derived cells, reducing production of inflammatory cytokines and increasing clearance of microbes. We investigated the mechanisms by which microbial clearance increases in macrophages under these conditions. METHODS Monocytes were purified from human peripheral blood mononuclear cells and differentiated to monocyte-derived macrophages (MDMs). We also isolated human intestinal macrophages. Bacterial clearance by MDMs was assessed in gentamicin protection assays. Effects of intracellular zinc and autophagy were measured by flow cytometry, immunoblot, reverse transcription PCR, and microscopy experiments. Small interfering RNAs were used to knock down specific proteins in MDMs. NOD2–/– and C57BL/6J mice, maintained in a specific pathogen-free facility, were given antibiotics, muramyl dipeptide (to stimulate NOD2), or dextran sodium sulfate; intestinal lamina propria cells were collected and analyzed. RESULTS Chronic stimulation of human MDMs through NOD2 upregulated the expression of multiple genes encoding metallothioneins, which bind and regulate levels of intracellular zinc. Intestinal myeloid-derived cells are continually stimulated through PRRs; metallothionein expression was upregulated in human and mouse intestinal myeloid-derived cells. Continuous stimulation of NOD2 increased levels of intracellular zinc, thereby increasing autophagy and bacterial clearance. The metal-regulatory transcription factor-1 (MTF-1) was required for regulation of metallothionein genes in human MDMs. Knockdown of MTF-1 did not affect baseline clearance of bacteria by MDMs. However, the increase in intracellular zinc, autophagy, and bacterial clearance observed with continuous NOD2 stimulation was impaired in MDMs upon MTF-1 knockdown. Addition of

  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. 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....

  8. 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....

  9. 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....

  10. 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....

  11. 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....

  12. 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...

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 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...

  1. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 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...

  2. 14 CFR 27.411 - 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. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  3. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  4. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor...

  5. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 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...

  6. Clearance systems in the brain—implications for Alzheimer disease

    PubMed Central

    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.

    2015-01-01

    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

  7. 50 CFR 14.52 - Clearance of imported wildlife.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 1 2011-10-01 2011-10-01 false Clearance of imported wildlife. 14.52....52 Clearance of imported wildlife. (a) Except as otherwise provided by this subpart, a Service officer must clear all wildlife imported into the United States prior to release from detention by...

  8. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  9. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  10. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 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...

  11. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 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...

  12. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 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...

  13. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 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...

  14. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 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...

  15. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 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...

  16. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 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...

  17. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 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...

  18. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 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...

  19. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 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...

  20. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 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...

  1. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 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...

  2. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 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...

  3. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 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...

  4. 32 CFR 644.527 - Recording Statements of Clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 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...

  5. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 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...

  6. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 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...

  7. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 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. Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2.

    PubMed

    Lang, Elisabeth; Bissinger, Rosi; Fajol, Abul; Salker, Madhuri S; Singh, Yogesh; Zelenak, Christine; Ghashghaeinia, Mehrdad; Gu, Shuchen; Jilani, Kashif; Lupescu, Adrian; Reyskens, Kathleen M S E; Ackermann, Teresa F; Föller, Michael; Schleicher, Erwin; Sheffield, William P; Arthur, J Simon C; Lang, Florian; Qadri, Syed M

    2015-01-01

    The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk(-/-)) and corresponding wild-type mice (msk(+/+)). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk(-/-) and msk(+/+) mice, but reticulocyte count was significantly increased in msk(-/-) mice. Cell membrane PS exposure was similar in untreated msk(-/-) and msk(+/+) erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk(-/-) erythrocytes than in msk(+/+) erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk(-/-) erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk(-/-) mice. The spleens from msk(-/-) mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk(+/+) mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice. PMID:26611568

  9. Serum IgE clearance is facilitated by human FcεRI internalization

    PubMed Central

    Greer, Alexandra M.; Wu, Nan; Putnam, Amy L.; Woodruff, Prescott G.; Wolters, Paul; Kinet, Jean-Pierre; Shin, Jeoung-Sook

    2014-01-01

    The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1–positive (BDCA1+) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1+ DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance. PMID:24569373

  10. 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

  11. Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

    SciTech Connect

    Miller, T.A.; Henagan, J.M.; Loy, T.M.

    1983-09-01

    Using an in vivo canine chambered stomach preparation, the clearance of (/sup 14/C)aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of (/sup 14/C)aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast, when (/sup 14/C)aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.

  12. Clearance Rate and BP-ANN Model in Paraquat Poisoned Patients Treated with Hemoperfusion

    PubMed Central

    Hu, Lufeng; Hong, Guangliang; Ma, Jianshe; Wang, Xianqin; Lin, Guanyang; Zhang, Xiuhua; Lu, Zhongqiu

    2015-01-01

    In order to investigate the effect of hemoperfusion (HP) on the clearance rate of paraquat (PQ) and develop a clearance model, 41 PQ-poisoned patients who acquired acute PQ intoxication received HP treatment. PQ concentrations were determined by high performance liquid chromatography (HPLC). According to initial PQ concentration, study subjects were divided into two groups: Low-PQ group (0.05–1.0 μg/mL) and High-PQ group (1.0–10 μg/mL). After initial HP treatment, PQ concentrations decreased in both groups. However, in the High-PQ group, PQ levels remained in excess of 0.05 μg/mL and increased when the second HP treatment was initiated. Based on the PQ concentrations before and after HP treatment, the mean clearance rate of PQ calculated was 73 ± 15%. We also established a backpropagation artificial neural network (BP-ANN) model, which set PQ concentrations before HP treatment as input data and after HP treatment as output data. When it is used to predict PQ concentration after HP treatment, high prediction accuracy (R = 0.9977) can be obtained in this model. In conclusion, HP is an effective way to clear PQ from the blood, and the PQ concentration after HP treatment can be predicted by BP-ANN model. PMID:25695058

  13. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  14. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  15. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  16. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  17. TGF-β3 and TNFα perturb blood-testis barrier (BTB) dynamics by accelerating the clathrin-mediated endocytosis of integral membrane proteins: A new concept of BTB regulation during spermatogenesis*

    PubMed Central

    Xia, Weiliang; Wong, Elissa W. P.; Mruk, Dolores D.; Cheng, C. Yan

    2008-01-01

    In adult mammals such as rats, the blood-testis barrier (BTB) conferred by adjacent Sertoli cells in the seminiferous epithelium segregates post-meiotic germ cell development from the systemic circulation and is one of the tightest blood-tissue barriers. Yet it must “open” transiently at stage VIII of the epithelial cycle to accommodate the migration of preleptotene/leptotene spermatocytes. While this is a vital event of spermatogenesis, the mechanism(s) that regulates BTB dynamics is virtually unknown. Recent studies have suggested that transforming growth factor-β3 (TGF-β3) and tumor necrosis factor α (TNFα) secreted by Sertoli and germ cells into the microenvironment of the BTB are capable of inducing reversible BTB disruption in vivo, apparently by reducing the steady-state levels of occludin and zonula occludens-1 (ZO-1) at the BTB via the p38 mitogen activated protein (MAP) kinase signaling pathway. In this study, local administration of TGF-β3 (200 ng/testis) to the testis reversibly perturbed the BTB integrity in vivo. We next sought to delineate the mechanism by which these cytokines maintain the steady-state level of integral membrane proteins: occludin, junctional adhesion molecule-A (JAM-A) and N-cadherin at the BTB. Primary Sertoli cells cultured in vitro were shown to establish intact tight junctions and functional BTB within two days when assessed by transepithelial electrical resistance (TER) measurement across the cell epithelium. Sertoli cell integral membrane protein internalization at the BTB was assessed by biotinylation of cell surface proteins, to be followed by tracking the endocytosed/biotinylated proteins by using specific antibodies. Both TGF-β3 (3 ng/ml) and TNFα (10 ng/ml) were shown to significantly accelerate the kinetics of internalization of JAM-A, N-cadherin, and occludin versus controls. Treatment of cells with phenylarsine oxide (PAO) at 10 μM that blocks clathrin-mediated endocytosis was shown to inhibit the TGF-β3

  18. Influences of parameter uncertainties within the ICRP-66 respiratory tract model: particle clearance.

    PubMed

    Bolch, Wesley E; Huston, Thomas E; Farfán, Eduardo B; Vernetson, William G; Bolch, W Emmett

    2003-04-01

    Quantifying radiological risk following the inhalation of radioactive aerosols entails not only an assessment of particle deposition within respiratory tract regions but a full accounting of clearance mechanisms whereby particles may be translocated to adjacent respiratory tissue regions, absorbed to blood, or released to the gastrointestinal tract. The model outlined in ICRP Publication 66 represents to date one of the most complete overall descriptions of particle deposition and clearance, as well as localized radiation dosimetry, within the respiratory tract. In this study, a previous review of the ICRP-66 deposition model is extended to the study of the subsequent clearance model. A systematic review of the clearance component within the ICRP 66 respiratory tract model was conducted in which probability density functions were assigned to all input parameters for both 239PuO2 and 238UO2/238U3O8. These distributions were subsequently incorporated within a computer code LUDUC (Lung Dose Uncertainty Code) in which Latin hypercube sampling techniques are used to generate multiple (e.g., 1,000) sets of input vectors (i.e., trials) for all model parameters needed to assess mechanical clearance and particle dissolution/absorption. Integral numbers of nuclear disintegrations, U(s), in various lung regions were shown to be well-described by lognormal probability distributions. Of the four extrathoracic clearance compartments of the respiratory tract, uncertainties in U(s), expressed as the ratio of its 95% to 5% confidence levels, were highest within the LN(ET) tissues for 239PuO2 (ratio of 50 to 130) and within the ET(seq) tissues for 238UO2/238U3O8 (ratio of 12 to 50). Peak uncertainties in U(s) in these respiratory regions occurred at particle sizes of approximately 0.5-0.6 microm where uncertainties in ET2 particle deposition fractions accounted for only approximately 10% of the total U(s) uncertainty for 239PuO2, and only approximately 30% of the total U

  19. Lung cinescintigraphy in the dynamic assessment of ventilation and mucociliary clearance of asbestos cement workers.

    PubMed Central

    Di Lorenzo, L; Mele, M; Pegorari, M M; Fratello, A; Zocchetti, C; Capozzi, D

    1996-01-01

    OBJECTIVES: To verify in vivo whether lung cinescintigraphy confirms the effect of asbestos on the patency of the smallest airways and on the efficiency of mucociliary clearance in asbestos cement workers. METHODS: 39 male subjects were examined: 30 asbestos cement workers and nine workers never exposed to occupational respiratory irritants. All subjects had a chest radiograph (International Labour Organisation (ILO) 1980); standard questionnaire on chronic bronchitis; spirometry; arterial blood gas analysis; carbon monoxide transfer factor (TLcosb); pulmonary O2 and CO2 ductances (DuO2, DuCO2); electrocardiogram; and lung cinescintigraphy after radioaerosol inhalation for the measurement of mucociliary clearance time in vivo in the smallest ciliated airways and for the assessment of radioaerosol deposition in alveoli (alveolar deposition index). RESULTS: Apart from nine non-exposed subjects, the 30 asbestos cement workers were so classified on the basis of chest radiography: nine of them as healthy exposed, 10 with pleural plaques, and 11 with asbestosis. The four groups had similar ages, work seniority, and smoking habits. Exercise dyspnoea was significantly more frequent in asbestos cement workers. Lung function variables of workers with effects related to asbestos were significantly lower than the other two groups. The PaO2, TLcOsb and DuO2 mean values were significantly lower in exposed workers than non-exposed. The mean PacO2 value was significantly higher in the asbestosis group than in the other three groups. Workers with effects related to asbestos showed a significantly lower alveolar deposition index and a significantly higher mucociliary clearance time than the other two groups. Subjects with asbestosis showed similar differences from those with pleural plaques. CONCLUSIONS: Lung cinescintigraphy confirms in vivo the effects of asbestos on bronchiolar and alveolar patency and on efficiency of mucociliary clearance in the smallest ciliated airways

  20. Natural History of Helicobacter pylori Infection in Mexican Schoolchildren: Incidence and Spontaneous Clearance

    PubMed Central

    Duque, Ximena; Vilchis, Jenny; Mera, Robertino; Trejo-Valdivia, Belem; Goodman, Karen J.; Mendoza, Maria-Eugenia; Navarro, Fabiola; Roque, Victoria; Moran, Segundo; Torres, Javier; Correa, Pelayo

    2013-01-01

    Objectives The aim of the present study was to estimate the incidence and spontaneous clearance rate of Helicobacter pylori infection and the effect of some variables on these outcomes in schoolchildren. Methods From May 2005 to December 2010, 718 schoolchildren enrolled in 3 public boarding schools in Mexico City participated in the follow-up. At the beginning of the study and every 6 months thereafter, breath samples were taken to detect H pylori infection; blood samples and anthropometric measurements were taken to evaluate nutritional status. Data on sociodemographic characteristics were collected. Results The prevalence of H pylori infection was 38%. The incidence rate was 6.36%/year. Schoolchildren with anemia or iron deficiency at the beginning of the study (who received iron supplements) showed a higher infection acquisition rate than those with normal iron nutritional status, hazard ratio (HR) 12.52 (95% confidence interval [CI] 4.01%–39.12%), P <0.001 and HR 2.05 (95% CI 1.09%–3.87%), P = 0.027, respectively. The spontaneous clearance rate of the infection was 4.74%/year. The spontaneous clearance rate was higher in children who had iron deficiency (who received iron supplements), HR 5.02 (95% CI 1.33%–18.99%), P = 0.017, compared with those with normal nutritional iron status. It was lower in schoolchildren with ≥2 siblings compared with schoolchildren with 1 or no siblings, HR 0.23 (95% CI 0.08%–0.63%), P = 0.004. Conclusions H pylori infection status is dynamic in schoolchildren. Variables related to health status and infection transmission, such as iron status and number of siblings, are important for the incidence and spontaneous clearance of H pylori infection. PMID:22227999

  1. Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration.

    PubMed

    Patel, Aateka; Woods, A; Riffo-Vasquez, Yanira; Babin-Morgan, Anna; Jones, Marie-Christine; Jones, Stuart; Sunassee, Kavitha; Clark, Stephen; T M de Rosales, Rafael; Page, Clive; Spina, Domenico; Forbes, Ben; Dailey, Lea Ann

    2016-08-10

    Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of (111)In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p<0.001). When normalised to the delivered lung dose, the clearance kinetics of (111)In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5±0.9h (R(2)=0.995) and 10.6±0.3h (R(2)=1.000) for healthy and inflamed lungs respectively (n=3). In contrast, (111)In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation. PMID:27180635

  2. Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

    PubMed Central

    Qosa, Hisham; Kaddoumi, Amal

    2016-01-01

    Novel animal models of Alzheimer’s disease (AD) are relentlessly being developed and existing ones are being fine-tuned; however, these models face multiple challenges associated with the complexity of the disease where most of these models do not reproduce the full phenotypical disease spectrum. Moreover, different AD models express different phenotypes that could affect their validity to recapitulate disease pathogenesis and/or response to a drug. One of the most important and understudied differences between AD models is differences in the phenotypic characteristics of the background species. Here, we used the brain clearance index (BCI) method to investigate the effect of strain differences on the clearance of amyloid β (Aβ) from the brains of four mouse strains. These mouse strains, namely C57BL/6, FVB/N, BALB/c and SJL/J, are widely used as a background for the development of AD mouse models. Findings showed that while Aβ clearance across the blood-brain barrier (BBB) was comparable between the 4 strains, levels of LRP1, an Aβ clearance protein, was significantly lower in SJL/J mice compared to other mouse strains. Furthermore, these mouse strains showed a significantly different response to rifampicin treatment with regard to Aβ clearance and effect on brain level of its clearance-related proteins. Our results provide for the first time an evidence for strain differences that could affect ability of AD mouse models to recapitulate response to a drug, and opens a new research avenue that requires further investigation to successfully develop mouse models that could simulate clinically important phenotypic characteristics of AD.

  3. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    PubMed

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  4. Early lactate clearance for predicting active bleeding in critically ill patients with acute upper gastrointestinal bleeding: a retrospective study.

    PubMed

    Wada, Tomoki; Hagiwara, Akiyoshi; Uemura, Tatsuki; Yahagi, Naoki; Kimura, Akio

    2016-08-01

    Not all patients with upper gastrointestinal bleeding (UGIB) require emergency endoscopy. Lactate clearance has been suggested as a parameter for predicting patient outcomes in various critical care settings. This study investigates whether lactate clearance can predict active bleeding in critically ill patients with UGIB. This single-center, retrospective, observational study included critically ill patients with UGIB who met all of the following criteria: admission to the emergency department (ED) from April 2011 to August 2014; had blood samples for lactate evaluation at least twice during the ED stay; and had emergency endoscopy within 6 h of ED presentation. The main outcome was active bleeding detected with emergency endoscopy. Classification and regression tree (CART) analyses were performed using variables associated with active bleeding to derive a prediction rule for active bleeding in critically ill UGIB patients. A total of 154 patients with UGIB were analyzed, and 31.2 % (48/154) had active bleeding. In the univariate analysis, lactate clearance was significantly lower in patients with active bleeding than in those without active bleeding (13 vs. 29 %, P < 0.001). Using the CART analysis, a prediction rule for active bleeding is derived, and includes three variables: lactate clearance; platelet count; and systolic blood pressure at ED presentation. The rule has 97.9 % (95 % CI 90.2-99.6 %) sensitivity with 32.1 % (28.6-32.9 %) specificity. Lactate clearance may be associated with active bleeding in critically ill patients with UGIB, and may be clinically useful as a component of a prediction rule for active bleeding. PMID:26837207

  5. Exercise Training During +Gz Acceleration

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Chou, J. L.; Simonson, S. R.; Jackson, C. G. R.; Barnes, P. R.

    1999-01-01

    The overall purpose is to study the effect of passive (without exercise) and active (with exercise) +Gz (head-to-foot) acceleration training, using a short-arm (1.9m radius) centrifuge, on post- training maximal oxygen uptake (VO2 max, work capacity) and 70 deg head-up tilt (orthostatic) tolerance in ambulatory subjects to test the hypothesis that (a) both passive and active acceleration training will improve post-training tilt-tolerance, and (b) there will be no difference in tilt-tolerance between passive and active exercise acceleration training because increased hydrostatic and blood pressures, rather than increased muscular metabolism, will provide the major adaptive stimulus. The purpose of the pilot study was to test the hypothesis that there would be no significant difference in the metabolic responses (oxygen uptake, heart rate, pulmonary ventilation, or respiratory exchange ratio) during supine exercise with moderate +Gz acceleration.

  6. Blood Clots

    MedlinePlus

    ... En Español More Info Images/Videos News Physician Resources Professions Site Index A-Z Blood Clots Blood clots are semi-solid masses of blood that can be stationary (thrombosis) and block blood flow or break loose ( ...

  7. D0 Solenoid Chimney Routing Clearances

    SciTech Connect

    Rucinski, R.; /Fermilab

    1994-02-23

    This engineering note contains information about the measured clearances along the chimney route from the solenoid to the control dewar. This type of information is best conveyed by sketches and a few photos. Twelve photos taken on 2/17/94 are included which gIVe perspective views along the path. The detector was parked in the collision hall on this date. The CF iron was split open to the east and the South EF iron was rolled back. Also the South EndCap Calorimeter was rolled to the south on this day. This allowed personnel access and the photographic opportunity. A full set of raw dimensional sketches are included. These sketches were generated by me using a 25 foot tape measure and a note pad. The sketches are in chronological order with the most recent on top. The first sketch, 5/18/94, describes the 'tightest' location for the upward incline portion of the chimney. The sketches on 2/14/94 thru 2/16/94 are refinements of the early 1992 and 1993 sketches. They pick out quite a bit more detail of specific detector components along the path. The dimensional sketches of 1992 and 1993 gave information in not as much detail and therefore gave a more constrained clearance description. Most of the information of the early sketches was jotted down on the plan view dated 10-29-92. This sketch also had some information lifted from prints which later was superseded by the 1994 sketches. I tried to label components and give views either titled 'Elevation' or 'Plan' which refers to a top view looking down. Also where I could I jotted down direction, ie. South, East etc. Hopefully with a little effort one can decifer it. The curvature of the CC was determined from a three dimensional topographical survey. This survey information is stored in an electronic drawing file 3823.111-ME-317165, 'Solenoid-CC south face 3D shape survey'. The 'z' dimensions for the radial chimney path were picked off this drawing. A curvature was then generated knowing many points by radial and z

  8. Genetic Variation in the IL-6 and HLA-DQB1 Genes Is Associated with Spontaneous Clearance of Hepatitis C Virus Infection

    PubMed Central

    Waldron, Paul Ravi; Belitskaya-Lévy, Ilana; Chary, Aarthi; Won, Johann; Winters, Mark; Monto, Alexander; Ryan, James; Lazzeroni, Laura C.; Holodniy, Mark

    2016-01-01

    Background. Millions of people are infected with hepatitis C virus (HCV) worldwide and 30% spontaneously clear the infection. Reasons for HCV clearance without antiviral treatment are not well understood. Methods. Blood was collected for DNA analysis from patients with chronic HCV infection or evidence of spontaneous clearance. To overcome anticipated limitations of small sample size, primary analyses consisted of a candidate gene analysis of 12 preselected genes based on known association with host immunologic response to HCV infection. To further reduce the impact of multiple testing on power, a single likelihood ratio test was conducted for each gene using all associated SNPs assayed on the Illumina Quad 610/660W chip. Step-down permutation methods were used to adjust for multiple testing in all analyses. Results. Ninety-five and 62 patients with HCV chronic infection or spontaneous clearance, respectively, were included for analysis. HLA-DQB1 (p = 1.76⁎10−5) and IL-6 (p = 0.0007) genes were significantly associated with spontaneous HCV clearance. IL-28B was not significantly associated with spontaneous clearance (p = 0.17). Conclusion. Our whole-gene analytic strategy identified a previously unreported association of IL-6 with spontaneous clearance of HCV infection. We also confirmed the finding that HLA-DQB1 is associated with spontaneous resolution of HCV infection. PMID:27340680

  9. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  10. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  11. Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

    SciTech Connect

    Jacobs, M.P.; Baughman, R.P.; Hughes, J.; Fernandez-Ulloa, M.

    1985-05-01

    Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).

  12. Distribution and clearance of radioactive aerosol on the nasal mucosa.

    PubMed

    McLean, J A; Bacon, J R; Mathews, K P; Thrall, J H; Banas, J M; Hedden, J; Bayne, N K

    1984-03-01

    The distribution and clearance of aerosolized radioactive technetium 99m pertechnate in physiologic buffered saline was analyzed in four human adult asymptomatic volunteers following delivery into one nostril in the same manner as for nasal challenge testing (i.e., 0.1 ml via a 251 DeVilbiss atomizer powered by a compressor delivering 0.10 +/- 0.01 gm/spray). For comparison, squeeze bottles and spray bottles from commercial sources, a 114 and a 127 DeVilbiss atomizer, and a pipette were employed. Lateral imagery via minicomputer processing was used to determine both distribution and clearance of the radiotracer. The counts after 1 minute were lower following pipette delivery than with the other devices. None yielded discernable , wide-spread distribution of aerosol throughout the nasal cavity. Following delivery from the 251 atomizer, mean clearance at 17 minutes was 60.0%. Similar clearance rates were obtained with the other spraying methods except for lower values with the squeeze bottle. Analysis of six hour clearance studies by linear regression showed a relatively rapid initial phase, which is probably due largely to mucociliary clearance, and a prolonged late phase related to the very slow disappearance of residual material located far anteriorly in the nose. Achieving good initial retention and rapid clearance of material deposited anteriorly in the nose are desirable attributes of devices employed for administering materials intranasally. PMID:6328631

  13. Lung Edema Clearance: Relevance to Patients with Lung Injury

    PubMed Central

    Azzam, Zaher S.; Sznajder, Jacob I.

    2015-01-01

    Pulmonary edema clearance is necessary for patients with lung injury to recover and survive. The mechanisms regulating edema clearance from the lungs are distinct from the factors contributing edema formation during injury. Edema clearance is effected via vectorial transport of Na+ out of the airspaces which generates an osmotic gradient causing water to follow the gradient out of the cells. This Na+ transport across the alveolar epithelium is mostly effected via apical Na+ and chloride channels and basolateral Na,K-ATPase. The Na,K-ATPase pumps Na+ out of the cell and K+ into the cell against their respective gradients in an ATP-consuming reaction. Two mechanisms contribute to the regulation of the Na,K-ATPase activity:recruitment of its subunits from intracellular compartments into the basolateral membrane, and transcriptional/translational regulation. Na,K-ATPase activity and edema clearance are increased by catecholamines, aldosterone, vasopressin, overexpression of the pump genes, and others. During lung injury, mechanisms regulating edema clearance are inhibited by yet unclear pathways. Better understanding of the mechanisms that regulate pulmonary edema clearance may lead to therapeutic interventions that counterbalance the inhibition of edema clearance during lung injury and improve the lungs’ ability to clear fluid, which is crucial for patient survival. PMID:26241220

  14. Dynamic modelling and experimental study of cantilever beam with clearance

    NASA Astrophysics Data System (ADS)

    Li, B.; Jin, W.; Han, L.; He, Z.

    2012-05-01

    Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

  15. Inter-individual variation in midazolam clearance in children

    PubMed Central

    Altamimi, Mohammed I; Sammons, Helen; Choonara, Imti

    2015-01-01

    Objectives To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation. Methods A systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined. Results 25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%–170%) than non-critically ill patients (13%–54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%–106% in preterm neonates, 18%–73% in term neonates, 31%–130% in infants, 21%–170% in children and 47%–150% in adolescents. The mean clearance was higher in children (1.1–16.7 mL/min/kg) than in neonates (0.78–2.5 mL/min/kg). Conclusions Large inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents. PMID:25281734

  16. Low-density lipoprotein receptor-related protein-1 : a serial clearance homeostatic mechanism controlling Alzheimer's amyloid β-peptide elimination from the brain

    PubMed Central

    Zlokovic, Berislav V.; Deane, Rashid; Sagare, Abhay P.; Bell, Robert D.; Winkler, Ethan A.

    2010-01-01

    Low-density lipoprotein receptor-related protein-1 (LRP1), a member of the LDL receptor family, has major roles in the cellular transport of cholesterol, endocytosis of forty structurally diverse ligands, transcytosis of ligands across the blood-brain barrier, and transmembrane and nuclear signaling. Recent evidence indicates that LRP1 regulates brain and systemic clearance of Alzheimer's disease (AD) amyloid β-peptide (Aβ). According to the two hit vascular hypothesis for AD, vascular damage precedes cerebrovascular and brain Aβ accumulation (hit 1) which then further amplifies neurovascular dysfunction (hit 2) preceding neurodegeneration. In this study, we discuss the roles of LRP1 during the hit 1 and hit 2 stage of AD pathogenesis and describe a three-level serial LRP1-dependent homeostatic control of Aβ clearance including (i) cell-surface LRP1 at the BBB and cerebrovascular cells mediating brain-to-bloodclearance (ii) circulating LRP1 providing a key endogenous peripheral ‘sink’ activity for plasma Aβ which prevents free Aβ access to the brain, and (iii) LRP1 in the liver mediating systemic Aβ clearance. Pitfalls in experimental Aβ brain clearance measurements with the concurrent use of peptides/proteins such as receptor-associated protein and aprotinin are also discussed. We suggest that LRP1 has a critical role in AD pathogenesis and is an important therapeutic target in AD. PMID:20854368

  17. Blood-brain barrier damage in vascular dementia.

    PubMed

    Ueno, Masaki; Chiba, Yoichi; Matsumoto, Koichi; Murakami, Ryuta; Fujihara, Ryuji; Kawauchi, Machi; Miyanaka, Hiroshi; Nakagawa, Toshitaka

    2016-04-01

    New findings on flow or drainage pathways of brain interstitial fluid and cerebrospinal fluid have been made. The interstitial fluid flow has an effect on the passage of blood-borne substances in the brain parenchyma, especially in areas near blood-brain barrier (BBB)-free regions. Actually, blood-borne substances can be transferred in areas with intact BBB function, such as the hippocampus, the corpus callosum, periventricular areas, and medial portions of the amygdala, presumably through leaky vessels in the subfornical organs or the choroid plexus. Increasing evidence indicates that dysfunction of the BBB function may play a significant role in the pathogenesis of vascular dementia. Accordingly, we have examined which insults seen in patients suffering from vascular dementia have an effect on the BBB using experimental animal models exhibiting some phenotypes of vascular dementia. The BBB in the hippocampus was clearly deteriorated in Mongolian gerbils exposed to acute ischemia followed by reperfusion and also in stroke-prone spontaneously hypertensive rats (SHRSP) showing hypertension. The BBB in the corpus callosum was clearly deteriorated in Wistar rats with permanent ligation of the bilateral common carotid arteries showing chronic hypoperfusion. The BBB in the hippocampus and the olfactory bulb was mildly deteriorated in aged senescence accelerated prone mice (SAMP8) showing cognitive dysfunction. The BBB in the hippocampus was mildly deteriorated in aged animals with hydrocephalus. Mild endothelial damage was seen in hyperglycemic db/db mice. In addition, mRNA expression of osteopontin, matrix metalloproteinase-13 (MMP-13), and CD36 was increased in vessels showing BBB damage in hypertensive SHRSP. As osteopontin, MMP-13 and CD36 are known to be related to brain injury and amyloid β accumulation or clearance, BBB damage followed by increased gene expression of these molecules not only contributes to the pathogenesis of vascular dementia, but also bridges

  18. Aerosol Medications for Treatment of Mucus Clearance Disorders.

    PubMed

    Rubin, Bruce K

    2015-06-01

    Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance. PMID:26070577

  19. Time-of-Flight Tip-Clearance Measurements

    NASA Technical Reports Server (NTRS)

    Dhadwal, H. S.; Kurkov, A. P.; Janetzke, D. C.

    1999-01-01

    In this paper a time-of-flight probe system incorporating the two integrated fiber optic probes which are tilted equally relative to the probe holder centerline, is applied for the first time to measure the tip clearance of an advanced fan prototype. Tip clearance is largely independent of the signal amplitude and it relies on timing measurement. This work exposes optical effects associated with the fan blade stagger angle that were absent during the original spin-rig experiment on the zero stagger rotor. Individual blade tip clearances were measured with accuracy of +/- 127-mm (+/- 0.005-in). Probe features are discussed and improvements to the design are suggested.

  20. Toward a Fast-Response Active Turbine Tip Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.; Kypuros, Javier A.

    2003-01-01

    This paper 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, technologies developed for clearance control can benefit a broad spectrum of current and future turbomachinery. The first portion of the paper addresses the research from a programmatic viewpoint. Recent studies that provide motivation for the work, identification of key technologies, and NASA's plan for addressing deficiencies in the technologies are discussed. The later portion of the paper drills down into one of the key technologies by presenting equations and results for a preliminary dynamic model of the tip clearance phenomena.