Sample records for capillary barrier effect

  1. Characterization for capillary barriers effects in a sand box test using time-lapsed GPR measurements

    NASA Astrophysics Data System (ADS)

    Kuroda, S.; Ishii, N.; Morii, T.

    2017-12-01

    Capillary barriers have been known as the method to protect subsurface regions against infiltration from soil surface. It is caused by essentially heterogeneous structure in permeability or soil physical property and produce non-uniform infiltration process then, in order to estimate the actual situation of the capillary barrier effect, the site-characterization with imaging technique like geophysical prospecting is effective. In this study, we examine the applicability of GPR to characterization for capillary barriers. We built a sand box with 90x340x90cm in which a thin high-permeable gravel layer was embedded as a capillary barrier. We conducted an infiltration test in the sand box using porous tube array for irrigation. It is expected to lead to non-uniform flow of soil water induced by capillary barrier effects. We monitored this process by various types of GPR measurements, including time-lapsed common offset profiling (COP) with multi- frequency antenna and transmission measurements like cross-borehole radar. At first, we conducted GPR common-offset survey. It could show the depth of capillary barrier in sand box. After that we conducted the infiltration test and GPR monitoring for infiltration process. GPR profiles can detect the wetting front and estimate water content change in the soil layer above the capillary barrier. From spatial change in these results we can estimate the effect of capillary barrier and the zone where the break through occur or not. Based on these results, we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil. At first, we conducted GPR common-offset survey. It could show the depth of capillary barrier in sand box. After that we conducted the infiltration test and GPR monitoring for infiltration process. GPR profiles can detect the wetting front and estimate water content change in the soil layer above the capillary barrier. From spatial change in these results we can estimate the effect of capillary barrier and the zone where the break through occur. Based on these results, we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil.

  2. Anisotropic capillary barrier for waste site surface covers

    DOEpatents

    Stormont, J.C.

    1996-08-27

    Waste sites are capped or covered upon closure. The cover structure incorporates a number of different layers each having a contributory function. One such layer is the barrier layer. Traditionally the barriers have been compacted soil and geosynthetics. These types of barriers have not been successfully implemented in unsaturated ground conditions like those found in dry climates. Capillary barriers have been proposed as barrier layers in dry environments, but the divergence length of these barriers has been found to be inadequate. An alternative to the capillary barrier is a anisotropic capillary barrier. An anisotropic capillary barrier has an increased divergence length which results in more water being diverted laterally preventing the majority of water from percolating in a downward direction through the barrier. 10 figs.

  3. Anisotropic capillary barrier for waste site surface covers

    DOEpatents

    Stormont, John C.

    1996-01-01

    Waste sites are capped or covered upon closure. The cover structure incorporates a number of different layers each having a contributory function. One such layer is the barrier layer. Traditionally the barriers have been compacted soil and geosynthetics. These types of barriers have not been successfully implemented in unsaturated ground conditions like those found in dry climates. Capillary barriers have been proposed as barrier layers in dry environments, but the divergence length of these barriers has been found to be inadequate. An alternative to the capillary barrier is a anisotropic capillary barrier. An anisotropic capillary barrier has an increased divergence length which results in more water being diverted laterally preventing the majority of water from percolating in a downward direction through the barrier.

  4. GPR monitoring for non-uniform infiltration through a high permeable gravel layer in the test sand box

    NASA Astrophysics Data System (ADS)

    Kuroda, Seiichiro; Ishii, Nobuyuki; Morii, Toshihiro

    2017-04-01

    Recently capillary barriers have been known as a method to protect subsurface regions against infiltration from soil surface. It has essentially non-uniform structure of permeability or soil physical property. To identify the function of the capillary barrier, the site-characterization technique for non-uniform soil moisture distribution and infiltration process is needed. We built a sand box in which a thin high-permeable gravel layer was embedded and conducted a infiltration test, including non-uniform flow of soil water induced by capillary barrier effects. We monitored this process by various types of GPR measurements, including time-lapsed soundings with multi-frequency antenna and transmission measurements like one using cross-borehole radar. Finally we will discuss the applicability of GPR for monitoring the phenomena around the capillary barrier of soil. This work has partially supported by JSPS Grant-in-aid Scientific Research program, No.16H02580.

  5. Interstitial distribution of charged macromolecules in the dog lung: a kinetic model.

    PubMed

    Parker, J C; Miniati, M; Pitt, R; Taylor, A E

    1987-01-01

    A mathematic model was constructed to investigate conflicting physiologic data concerning the charge effect of continuous capillaries to macromolecules in the lung. We simulated the equilibration kinetics of lactate dehydrogenase (MR 4.2 nM) isozymes LDH 1 (pI = 5.0) and LDH 5 (pI = 7.9) between plasma and lymph using previously measured permeability coefficients, lung tissue distribution volumes (VA) and plasma concentrations (CP) in lung tissue. Our hypothesis is that the fixed anionic charges in interstitium, basement membrane, and cell surfaces determine equilibration rather than charged membrane effects at the capillary barrier, so the same capillary permeability coefficients were used for both isozymes. Capillary filtration rates and protein fluxes were calculated using conventional flux equations. Initial conditions at baseline and increased left atrial pressures (PLA) were those measured in animal studies. Simulated equilibration of isozymes over 30 h in the model at baseline capillary pressures accurately predicted the observed differences in lymph/plasma concentration ratios (CL/CP) between isotopes at 4 h and equilibration of these ratios at 24 h. Quantitative prediction of isozyme CL/CP ratios was also obtained at increased PLA. However, an additional cation selective compartment representing the surface glycocalyx was required to accurately simulate the initial higher transcapillary clearances of cationic LDH 5. Thus experimental data supporting the negative barrier, positive barrier, and no charge barrier hypotheses were accurately reproduced by the model using only the observed differences in interstitial partitioning of isozymes without differences in capillary selectivity.

  6. Liposome-based glioma targeted drug delivery enabled by stable peptide ligands.

    PubMed

    Wei, Xiaoli; Gao, Jie; Zhan, Changyou; Xie, Cao; Chai, Zhilan; Ran, Danni; Ying, Man; Zheng, Ping; Lu, Weiyue

    2015-11-28

    The treatment of glioma is one of the most challenging tasks in clinic. As an intracranial tumor, glioma exhibits many distinctive characteristics from other tumors. In particular, various barriers including enzymatic barriers in the blood and brain capillary endothelial cells, blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) rigorously prevent drug and drug delivery systems from reaching the tumor site. To tackle this dilemma, we developed a liposomal formulation to circumvent multiple-barriers by modifying the liposome surface with proteolytically stable peptides, (D)CDX and c(RGDyK). (D)CDX is a D-peptide ligand of nicotine acetylcholine receptors (nAChRs) on the BBB, and c(RGDyK) is a ligand of integrin highly expressed on the BBTB and glioma cells. Lysosomal compartments of brain capillary endothelial cells are implicated in the transcytosis of those liposomes. However, both peptide ligands displayed exceptional stability in lysosomal homogenate, ensuring that intact ligands could exert subsequent exocytosis from brain capillary endothelial cells and glioma targeting. In the cellular uptake studies, dually labeled liposomes could target both brain capillary endothelial cells and tumor cells, effectively traversing the BBB and BBTB monolayers, overcoming enzymatic barrier and targeting three-dimensional tumor spheroids. Its targeting ability to intracranial glioma was further verified in vivo by ex vivo imaging and histological studies. As a result, doxorubicin liposomes modified with both (D)CDX and c(RGDyK) presented better anti-glioma effect with prolonged median survival of nude mice bearing glioma than did unmodified liposomes and liposomes modified with individual peptide ligand. In conclusion, the liposome suggested in the present study could effectively overcome multi-barriers and accomplish glioma targeted drug delivery, validating its potential value in improving the therapeutic efficacy of doxorubicin for glioma. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Developmental changes in metabolism and transport properties of capillaries isolated from rat brain.

    PubMed

    Betz, A L; Goldstein, G W

    1981-03-01

    1. Capillaries were isolated from the brains of 1- to 45-day-old rats in order to study the development of metabolic and transport aspects of the blood-brain barrier. 2. The hydroxyproline content of capillary hydrolysates increased nearly threefold between 5 and 45 days of age. This finding is consistent with histological studies showing thickening of capillary basement membrane during development. 3. The activities of L-DOPA decarboxylase and monoamine oxidase were greatest in capillaries from 10-day-old rat brain. Thus, the metabolic blood-brain barrier for amine precursors is present during early development. 4. Capillaries from all ages were able to metabolize glucose, beta-hydroxybutyrate and palmitate. The rate of glucose oxidation more than doubled between 21 and 30 days of age but subsequently decreased. In contrast, beta-hydroxybutyrate and palmitate oxidation increased throughout development. These data suggest a sparing effect by alternate fuels on glucose metabolism. 5. Capillary glucose uptake was similar at 10 and 30 days of age and activity of the ouabain-sensitive K+ pump (measured using 86Rb+) was relatively constant at all ages. In contrast, Na+-dependent neutral amino acid transport was not present until after 21 days of age. Since this transport system may be responsible for the active efflux of neutral amino acids from brain to blood, it is likely that this process does not occur at the immature blood-brain barrier. 6. We conclude that various aspects of brain capillary functions show distinct developmental patterns which may be related to changes in blood-brain barrier permeability during development.

  8. Hydrologic behavior of two engineered barriers following extreme wetting.

    PubMed

    Porro, I

    2001-01-01

    Many engineered barriers are expected to function for hundreds of years or longer. Over the course of time, it is likely that some barriers will experience infiltration to the point of breakthrough. This study compares the recovery from breakthrough of two storage-evapotranspiration type engineered barriers. Replicates of test plots comprising thick soil and capillary-biobarrier covers were wetted to breakthrough in 1997. Test plots were kept cleared of vegetation to maximize hydrologic stress during recovery. Following cessation of drainage resulting from the wetting irrigations, water storage levels in all plots were at elevated levels compared with pre-irrigation levels. As a result, infiltration of melting snow during the subsequent spring overloaded the storage capacity and produced drainage in all plots. Relatively rapid melting of accumulated snowfall produced the most significant infiltration events each year during the study. Capillary barriers yielded less total drainage than thick soil barriers. By limiting drainage, capillary barriers increased water storage in the upper portions of the test plots, which led to increased evaporation from the capillary barrier plots compared with thick soil plots. Increased evaporation in the capillary barrier plots allowed more water to infiltrate in the second season following the wetting tests without triggering drainage. All thick soil plots again yielded drainage in the second season. Within two years of intentionally induced breakthrough, evaporation alone (without transpiration) restored the capability of the capillary barrier covers to function as intended, although water storage in these covers remained at elevated levels.

  9. Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.

    PubMed

    Rempe, Ralf G; Hartz, Anika M S; Soldner, Emma L B; Sokola, Brent S; Alluri, Satya R; Abner, Erin L; Kryscio, Richard J; Pekcec, Anton; Schlichtiger, Juli; Bauer, Björn

    2018-05-02

    The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo / ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A 2 Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage. SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A 2 , which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden. Copyright © 2018 the authors 0270-6474/18/384301-15$15.00/0.

  10. Combined effect of capillary barrier and layered slope on water, solute and nanoparticle transfer in an unsaturated soil at lysimeter scale.

    PubMed

    Prédélus, Dieuseul; Coutinho, Artur Paiva; Lassabatere, Laurent; Bien, Le Binh; Winiarski, Thierry; Angulo-Jaramillo, Rafael

    2015-10-01

    It is well recognized that colloidal nanoparticles are highly mobile in soils and can facilitate the transport of contaminants through the vadose zone. This work presents the combined effect of the capillary barrier and soil layer slope on the transport of water, bromide and nanoparticles through an unsaturated soil. Experiments were performed in a lysimeter (1×1×1.6m(3)) called LUGH (Lysimeter for Urban Groundwater Hydrology). The LUGH has 15 outputs that identify the temporal and spatial evolution of water flow, solute flux and nanoparticles in relation to the soil surface conditions and the 3D system configuration. Two different soil structures were set up in the lysimeter. The first structure comprises a layer of sand (0-0.2cm, in diameter) 35cm thick placed horizontally above a layer of bimodal mixture also 35cm thick to create a capillary barrier at the interface between the sand and bimodal material. The bimodal material is composed of a mixture 50% by weight of sand and gravel (0.4-1.1cm, in diameter). The second structure, using the same amount of sand and bimodal mixture as the first structure represents an interface with a 25% slope. A 3D numerical model based on Richards equation for flow and the convection dispersion equations coupled with a mechanical module for nanoparticle trapping was developed. The results showed that under the effect of the capillary barrier, water accumulated at the interface of the two materials. The sloped structure deflects flow in contrast to the structure with zero slope. Approximately 80% of nanoparticles are retained in the lysimeter, with a greater retention at the interface of two materials. Finally, the model makes a good reproduction of physical mechanisms observed and appears to be a useful tool for identifying key processes leading to a better understanding of the effect of capillary barrier on nanoparticle transfer in an unsaturated heterogeneous soil. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model

    PubMed Central

    Wagner, Sylvia; Zensi, Anja; Wien, Sascha L.; Tschickardt, Sabrina E.; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U.; Kreuter, Jörg; von Briesen, Hagen

    2012-01-01

    Background The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. Conclusions/Significance This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier. PMID:22396775

  12. Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

    PubMed

    Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen

    2012-01-01

    The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

  13. On the performance of capillary barriers as landfill cover

    NASA Astrophysics Data System (ADS)

    Kämpf, M.; Montenegro, H.

    Landfills and waste heaps require an engineered surface cover upon closure. The capping system can vary from a simple soil cover to multiple layers of earth and geosynthetic materials. Conventional design features a compacted soil layer, which suffers from drying out and cracking, as well as root and animal intrusion. Capillary barriers consisting of inclined fine-over-coarse soil layers are investigated as an alternative cover system. Under unsaturated conditions, the textural contrast delays vertical drainage by capillary forces. The moisture that builds up above the contact will flow downdip along the interface of the layers. Theoretical studies of capillary barriers have identified the hydraulic properties of the layers, the inclination angle, the length of the field and the infiltration rate as the fundamental characteristics of the system. However, it is unclear how these findings can lead to design criteria for capillary barriers. To assess the uncertainty involved in such approaches, experiments have been carried out in a 8 m long flume and on large scale test sites (40 m x 15 m). In addition, the ability of a numerical model to represent the relevant flow processes in capillary barriers has been examined.

  14. Engineering and Design: Indoor Radon Prevention and Mitigation

    DTIC Science & Technology

    1993-09-15

    slabs on grade, capillary water barrier below floor slabs on grade, dampproofing or waterproofing and protection board on below grade walls, sealants in...will be lapped 12 inches and sealed with adhesives or pressure sensitive tape and sealed at foundation walls with mastic. Capillary water barrier will...Systems, Letter Codes B, C, and D. Sub- slab suction systems consist of 4 inch diameter perforated PVC pipe laid in the capillary water barrier below floor

  15. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, N.J.; Zhang, J.Z.

    1996-10-22

    A multiple capillary biochemical analyzer is disclosed for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal-to-noise ratio. 12 figs.

  16. Multiple capillary biochemical analyzer with barrier member

    DOEpatents

    Dovichi, Norman J.; Zhang, Jian Z.

    1996-01-01

    A multiple capillary biochemical analyzer for sequencing DNA and performing other analyses, in which a set of capillaries extends from wells in a microtiter plate into a cuvette. In the cuvette the capillaries are held on fixed closely spaced centers by passing through a sandwich construction having a pair of metal shims which squeeze between them a rubber gasket, forming a leak proof seal for an interior chamber in which the capillary ends are positioned. Sheath fluid enters the chamber and entrains filament sample streams from the capillaries. The filament sample streams, and sheath fluid, flow through aligned holes in a barrier member spaced close to the capillary ends, into a collection chamber having a lower glass window. The filament streams are illuminated above the barrier member by a laser, causing them to fluoresce. The fluorescence is viewed end-on by a CCD camera chip located below the glass window. The arrangement ensures an equal optical path length from all fluorescing spots to the CCD chip and also blocks scattered fluorescence illumination, providing more uniform results and an improved signal to noise ratio.

  17. Phosphodiesterase-4 inhibition as a therapeutic approach to treat capillary leakage in systemic inflammation.

    PubMed

    Schick, Martin Alexander; Wunder, Christian; Wollborn, Jakob; Roewer, Norbert; Waschke, Jens; Germer, Christoph-Thomas; Schlegel, Nicolas

    2012-06-01

    In sepsis and systemic inflammation, increased microvascular permeability and consecutive breakdown of microcirculatory flow significantly contribute to organ failure and death. Evidence points to a critical role of cAMP levels in endothelial cells to maintain capillary endothelial barrier properties in acute inflammation. However, approaches to verify this observation in systemic models are rare. Therefore we tested here whether systemic application of the phosphodiesterase-4-inhibitors (PD-4-Is) rolipram or roflumilast to increase endothelial cAMP was effective to attenuate capillary leakage and breakdown of microcirculatory flow in severe lipopolysaccharide (LPS)-induced systemic inflammation in rats. Measurements of cAMP in mesenteric microvessels demonstrated significant LPS-induced loss of cAMP levels which was blocked by application of rolipram. Increased endothelial cAMP by application of either PD-4-I rolipram or roflumilast led to stabilization of endothelial barrier properties as revealed by measurements of extravasated FITC-albumin in postcapillary mesenteric venules. Accordingly, microcirculatory flow in mesenteric venules was significantly increased following PD-4-I treatment and blood gas analyses indicated improved metabolism. Furthermore application of PD-4-I after manifestation of LPS-induced systemic inflammation and capillary leakage therapeutically stabilized endothelial barrier properties as revealed by significantly reduced volume resuscitation for haemodynamic stabilization. Accordingly microcirculation was significantly improved following treatment with PD-4-Is. Our results demonstrate that inflammation-derived loss of endothelial cAMP contributes to capillary leakage which was blocked by systemic PD-4-I treatment. Therefore these data suggest a highly clinically relevant and applicable approach to stabilize capillary leakage in sepsis and systemic inflammation.

  18. Lysosomal Trapping Is Present in Retinal Capillary Endothelial Cells: Insight into Its Influence on Cationic Drug Transport at the Inner Blood-Retinal Barrier.

    PubMed

    Kubo, Yoshiyuki; Seko, Narumi; Usui, Takuya; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

    2016-01-01

    Lysosomal trapping was investigated in the retinal capillary endothelial cells that are responsible for the inner blood-retinal barrier (BRB) using LysoTracker(®) Red (LTR). Using confocal microscopy on TR-iBRB2 cells, an in vitro model of the inner BRB, the presence of lysosomal trapping in retinal capillary endothelial cells was suggested since TR-iBRB2 cells exhibited punctuate intracellular localization of LTR that was attenuated by NH4Cl treatment. The study confirmed that LTR uptake by retinal capillary endothelial cells took place in a time- and temperature-dependent manner, and exhibited the 1.58-fold greater uptake at pH 8.4 than that at pH 7.4 while there was no change in uptake between pH 6.4 and pH 7.4, suggesting that passive diffusion is not enough to explain LTR uptake. The inhibition study showed the possible influence of lysosomal trapping on cationic drug transport by retinal capillary endothelial cells since LTR uptake was significantly inhibited by cationic amphiphilic drugs. Inhibition profiling and the estimation of IC50 suggested the influence of lysosomal trapping on propranolol and low-affinity pyrilamine transport while lysosomal trapping had only a partial effect on verapamil, clonidine, nicotine and high-affinity pyrilamine transport in retinal capillary endothelial cells.

  19. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat.

    PubMed

    Arakaki, Xianghong; McCleary, Paige; Techy, Matthew; Chiang, Jiarong; Kuo, Linus; Fonteh, Alfred N; Armstrong, Brian; Levy, Dan; Harrington, Michael G

    2013-03-14

    Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and -3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer.

  20. Na,K-ATPase alpha isoforms at the blood-cerebrospinal fluid-trigeminal nerve and blood-retina interfaces in the rat

    PubMed Central

    2013-01-01

    Background Cerebrospinal fluid (CSF) sodium concentration increases during migraine attacks, and both CSF and vitreous humor sodium increase in the rat migraine model. The Na,K-ATPase is a probable source of these sodium fluxes. Since Na,K-ATPase isoforms have different locations and physiological roles, our objective was to establish which alpha isoforms are present at sites where sodium homeostasis is disrupted. Methods Specific Na,K-ATPase alpha isoforms were identified in rat tissues by immunohistochemistry at the blood-CSF barrier at the choroid plexus, at the blood-CSF-trigeminal barrier at the meninges, at the blood-retina barrier, and at the blood-aqueous barrier at the ciliary body. Calcitonin gene-related peptide (CGRP), occludin, or von Willibrand factor (vWF) were co-localized with Na,K-ATPase to identify trigeminal nociceptor fibers, tight junctions, and capillary endothelial cells respectively. Results The Na,K-ATPase alpha-2 isoform is located on capillaries and intensely at nociceptive trigeminal nerve fibers at the meningeal blood-CSF-trigeminal barrier. Alpha-1 and −3 are lightly expressed on the trigeminal nerve fibers but not at capillaries. Alpha-2 is expressed at the blood-retina barriers and, with alpha-1, at the ciliary body blood aqueous barrier. Intense apical membrane alpha-1 was associated with moderate cytoplasmic alpha-2 expression at the choroid plexus blood-CSF barrier. Conclusion Na,K-ATPase alpha isoforms are present at the meningeal, choroid plexus, and retinal barriers. Alpha-2 predominates at the capillary endothelial cells in the meninges and retinal ganglion cell layer. PMID:23497725

  1. Alkamides from Echinacea angustifolia Interact with P-glycoprotein of primary brain capillary endothelial cells isolated from porcine brain blood vessels.

    PubMed

    Mahringer, Anne; Ardjomand-Woelkart, Karin; Bauer, Rudolf; Fricker, Gert; Efferth, Thomas

    2013-03-01

    The blood-brain barrier prevents the passage of toxic compounds from blood circulation into brain tissue. Unfortunately, drugs for the treatment of neurodegenerative diseases, brain tumors, and other diseases also do not cross the blood-brain barrier. In the present investigation, we used isolated porcine brain capillary endothelial cells and a flow cytometric calcein-AM assay to analyze inhibition of P-glycoprotein, a major constituent of the blood-brain barrier. We tested 8 alkamides isolated from Echinacea angustifolia and found that four of them inhibited P-glycoprotein-mediated calcein transport in porcine brain capillary endothelial cells. Georg Thieme Verlag KG Stuttgart · New York.

  2. Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

    PubMed

    Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

    2017-02-01

    To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study. © 2016, American College of Rheumatology.

  3. Single-step CE for miniaturized and easy-to-use system.

    PubMed

    Ono, Koichi; Kaneda, Shohei; Fujii, Teruo

    2013-03-01

    We developed a novel single-step capillary electrophoresis (SSCE) scheme for miniaturized and easy to use system by using a microchannel chip, which was made from the hydrophilic material polymethyl methacrylate (PMMA), equipped with a capillary stop valve. Taking the surface tension property of liquids into consideration, the capillary effect was used to introduce liquids and control capillary stop valves in a partial barrier structure in the wall of the microchannel. Through the combined action of stop valves and air vents, both sample plug formation for electrophoresis and sample injection into a separation channel were successfully performed in a single step. To optimize SSCE, different stop valve structures were evaluated using actual microchannel chips and the finite element method with the level set method. A partial barrier structure at the bottom of the channel functioned efficiently as a stop valve. The stability of stop valve was confirmed by a shock test, which was performed by dropping the microchannel chip to a floor. Sample plug deformation could be reduced by minimizing the size of the side partial barrier. By dissolving hydroxyl ethyl cellulose and using it as the sample solution, the EOF and adsorption of the sample into the PMMA microchannel were successfully reduced. Using this method, a 100-bp DNA ladder was concentrated; good separation was observed within 1 min. At a separation length of 5 mm, the signal was approximately 20-fold higher than a signal of original sample solution by field-amplified sample stacking effect. All operations, including liquid introduction and sample separation, can be completed within 2 min by using the SSCE scheme. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. In vitro studies of the blood-brain barrier using isolated brain capillaries and cultured endothelial cells.

    PubMed

    Goldstein, G W; Betz, A L; Bowman, P D; Dorovini-Zis, K

    1986-01-01

    The endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier. To learn more about the biology of these specialized cells, we developed methods to prepare suspensions of purified brain microvessels as well as primary cultures of endothelial cells in monolayer. These two preparations allow for direct investigation of the metabolism, transport properties, and receptor content of the brain capillary. We used isolated brain microvessels to study distribution of membrane carriers between the luminal and the abluminal plasma membrane of endothelial cells. We found that Na+K+-ATPase and the A-system amino-acid transport system are located predominantly on the abluminal surface of brain capillary endothelial cells. This distribution of transport carriers is consistent with the low permeability of potassium and small neutral amino acids in the blood-to-brain direction. It suggests, however, that both solutes can be actively transported across brain capillaries from the brain interstitial fluid to the blood. In tissue culture, the endothelial cells form continuous tight junctions with their neighbors. This results in a cellular layer impermeable to protein tracers. When exposed to hyperosmolar solutions, in an attempt to mimic the conditions that open the blood-brain barrier in vivo, we found a reversible separation of the tight junctions between contiguous endothelial cells. No indication of activation of pinocytosis was observed. In vitro systems provide a novel approach for studying the function of the blood-brain barrier and allow for observations not possible with intact animals.

  5. [Effects of electromagnetic pulse on blood-brain barrier permeability and tight junction proteins in rats].

    PubMed

    Qiu, Lian-bo; Ding, Gui-rong; Zhang, Ya-mei; Zhou, Yan; Wang, Xiao-wu; Li, Kang-chu; Xu, Sheng-long; Tan, Juan; Zhou, Jia-xing; Guo, Guo-zhen

    2009-09-01

    To study the effect of electromagnetic pulse (EMP) on the permeability of blood-brain barrier, tight junction (TJ)-associated protein expression and localization in rats. 66 male SD rats, weighing (200 approximately 250) g, were sham or whole-body exposed to EMP at 200 kV/m for 200 pulses. The repetition rate was 1 Hz. The permeability of the blood-brain barrier in rats was assessed by albumin immunohistochemistry. The expression of typical tight junction protein ZO-1 and occludin in both cerebral cortex homogenate and cerebral cortex microvessel homogenate was analyzed by the Western blotting and the distribution of ZO-1 and occludin was examined by immunofluorescence microscopy. In the sham exposure rats, no brain capillaries showed albumin leakage, at 0.5 h after 200 kV/m EMP exposure for 200 pulses; a few brain capillaries with extravasated serum albumin was found, with the time extended, the number of brain capillaries with extravasated serum albumin increased, and reached the peak at 3 h, then began to recover at 6 h. In addition, no change in the distribution of the occludin was found after EMP exposure. Total occludin expression had no significant change compared with the control. However, the expression level of ZO-1 significantly decreased at 1 h and 3 h after EMP exposure in both cerebral cortex homogenate and cerebral cortex microvessel homogenate. Furthermore, immunofluorescence studies also showed alterations in ZO-1 protein localization in cerebral cortex microvessel. The EMP exposure (200 kV/m, 200 pulses) could increase blood-brain barrier permeability in rat, and this change is associated with specific alterations in tight junction protein ZO-1.

  6. PPAR-α, a lipid-sensing transcription factor, regulates blood–brain barrier efflux transporter expression

    PubMed Central

    More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary NY; Miller, David S

    2016-01-01

    Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR-α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood–brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR-α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR-α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood–brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain. PMID:27193034

  7. An oncological view on the blood-testis barrier.

    PubMed

    Bart, Joost; Groen, Harry J M; van der Graaf, Winette T A; Hollema, Harry; Hendrikse, N Harry; Vaalburg, Willem; Sleijfer, Dirk T; de Vries, Elisabeth G E

    2002-06-01

    The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular wall, connected together with narrow tight junctions, and a myoid-cell layer around the seminiferous tubule. Second, an efflux-pump barrier that contains P-glycoprotein in the luminal capillary endothelium and on the myoid-cell layer; and multidrug-resistance associated protein 1 located basolaterally on Sertoli cells. Third, an immunological barrier, consisting of Fas ligand on Sertoli cells. Inhibition of P-glycoprotein function offers the opportunity to increase the delivery of cytotoxic drugs to the testis. In the future, visualisation of function in the blood-testis barrier may also be helpful to identify groups of patients in whom testis conservation is safe or to select drugs that are less harmful to fertility.

  8. The ultrastructure of cerebral blood capillaries in the ratfish, Chimaera monstrosa.

    PubMed

    Bundgaard, M

    1982-01-01

    Sharks and skates (Chondrichthyes: Elasmobranchii) have a glial blood-brain barrier, while all other vertebrates examined so far have an endothelial barrier. For comparative reasons it is desirable to examine the blood-brain barrier in species from the other subclass of cartilaginous fish, the holocephalans. The ultrastructure of cerebral capillaries in the chimaera (Chondrichthyes: Holocephali) is described in the present study. The endothelial cells are remarkably thick. Fenestrae and transendothelial channels were not observed. The endothelial cells are joined by elaborate tight junctions. The perivascular glial processes are separated by wide spaces (15-60 nm) without obliterating junctional complexes. These findings indicate that the chimaera has an endothelial blood-brain barrier.

  9. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

    PubMed

    Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

    2017-04-03

    A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

  10. Influence of local capillary trapping on containment system effectiveness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bryant, Steven

    2014-03-31

    Immobilization of CO 2 injected into deep subsurface storage reservoirs is a critical component of risk assessment for geologic CO 2 storage (GCS). Local capillary trapping (LCT) is a recently established mode of immobilization that arises when CO 2 migrates due to buoyancy through heterogeneous storage reservoirs. This project sought to assess the amount and extent of LCT expected in storage formations under a range of injection conditions, and to confirm the persistence of LCT if the seal overlying the reservoir were to lose its integrity. Numerical simulation using commercial reservoir simulation software was conducted to assess the influence ofmore » injection. Laboratory experiments, modeling and numerical simulation were conducted to assess the effect of compromised seal integrity. Bench-scale (0.6 m by 0.6 m by 0.03 m) experiments with surrogate fluids provided the first empirical confirmation of the key concepts underlying LCT: accumulation of buoyant nonwetting phase at above residual saturations beneath capillary barriers in a variety of structures, which remains immobile under normal capillary pressure gradients. Immobilization of above-residual saturations is a critical distinction between LCT and the more familiar “residual saturation trapping.” To estimate the possible extent of LCT in a storage reservoir an algorithm was developed to identify all potential local traps, given the spatial distribution of capillary entry pressure in the reservoir. The algorithm assumes that the driving force for CO 2 migration can be represented as a single value of “critical capillary entry pressure” P c,entry crit, such that cells with capillary entry pressure greater/less than P c,entry crit act as barriers/potential traps during CO 2 migration. At intermediate values of P c,entry crit, the barrier regions become more laterally extensive in the reservoir, approaching a percolation threshold while non-barrier regions remain numerous. The maximum possible extent of LCT thus occurs at P c,entry crit near this threshold. Testing predictions of this simple algorithm against full-physics simulations of buoyancy-driven CO 2 migration support the concept of critical capillary entry pressure. However, further research is needed to determine whether a single value of critical capillary entry pressure always applies and how that value can be determined a priori. Simulations of injection into high-resolution (cells 0.3 m on a side) 2D and 3D heterogeneous domains show two characteristic behaviors. At small gravity numbers (vertical flow velocity much less than horizontal flow velocity) the CO 2 fills local traps as well as regions that would act as local barriers if CO 2 were moving only due to buoyancy. When injection ceases, the CO 2 migrates vertically to establish large saturations within local traps and residual saturation elsewhere. At large gravity numbers, the CO 2 invades a smaller portion of the perforated interval. Within this smaller swept zone the local barriers are not invaded, but local traps are filled to large saturation during injection and remain during post-injection gravity-driven migration. The small gravity number behavior is expected in the region within 100 m of a vertical injection well at anticipated rates of injection for commercial GCS. Simulations of leakage scenarios (through-going region of large permeability imposed in overlying seal) indicate that LCT persists (i.e. CO 2 remains held in a large fraction of the local iv traps) and the persistence is independent of injection rate during storage. Simulations of leakage for the limiting case of CO 2 migrating vertically from an areally extensive emplacement in the lower portion of a reservoir showed similar strong persistence of LCT. This research has two broad implications for GCS. The first is that LCT can retain a significant fraction of the CO 2 stored in a reservoir – above and beyond the residual saturation -- if the overlying seal were to fail. Thus frameworks for risk assessment should be extended to account for LCT. The second implication is that compared to pressure driven flow in reservoirs, CO 2 migration and trapping behave in a qualitatively different manner in heterogeneous reservoirs when buoyancy is the dominant driving force for flow. Thus simulations of GCS that neglect capillary heterogeneity will fail to capture important features of the CO 2 plume. While commercial reservoir simulation software can account for fine scale capillary heterogeneity, it has not been designed to work efficiently with such domains, and no simulators can handle fine-scale resolution throughout the reservoir. A possible way to upscale the migration and trapping is to apply an “effective residual saturation” to coarse-scale grids. While the extent of overall immobilization can be correlated in this way, all coarser grids failed to capture the distance traveled by the migrating CO 2 for large gravity number. Thus it remains unclear how best to account for LCT in the routine simulation work-flow that will be needed for large-scale GCS. Alternatives meriting investigation include streamline methods, reduced-physics proxies (e.g. particle tracking), and biased invasion percolation algorithms, which are based on precisely the capillary heterogeneity essential for LCT.« less

  11. Continuous-Flow Electrophoresis of DNA and Proteins in a Two-Dimensional Capillary-Well Sieve.

    PubMed

    Duan, Lian; Cao, Zhen; Yobas, Levent

    2017-09-19

    Continuous-flow electrophoresis of macromolecules is demonstrated using an integrated capillary-well sieve arranged into a two-dimensional anisotropic array on silicon. The periodic array features thousands of entropic barriers, each resulting from an abrupt interface between a 2 μm deep well (channel) and a 70 nm capillary. These entropic barriers owing to two-dimensional confinement within the capillaries are vastly steep in relation to those arising from slits featuring one-dimensional confinement. Thus, the sieving mechanisms can sustain relatively large electric field strengths over a relatively small array area. The sieve rapidly sorts anionic macromolecules, including DNA chains and proteins in native or denatured states, into distinct trajectories according to size or charge under electric field vectors orthogonally applied. The baseline separation is achieved in less than 1 min within a horizontal migration length of ∼1.5 mm. The capillaries are self-enclosed conduits in cylindrical profile featuring a uniform diameter and realized through an approach that avoids advanced patterning techniques. The approach exploits a thermal reflow of a layer of doped glass for shape transformation into cylindrical capillaries and for controllably shrinking the capillary diameter. Lastly, atomic layer deposition of alumina is introduced for the first time to fine-tune the capillary diameter as well as to neutralize the surface charge, thereby suppressing undesired electroosmotic flows.

  12. Impact of eliminating fracture intersection nodes in multiphase compositional flow simulation

    NASA Astrophysics Data System (ADS)

    Walton, Kenneth M.; Unger, Andre J. A.; Ioannidis, Marios A.; Parker, Beth L.

    2017-04-01

    Algebraic elimination of nodes at discrete fracture intersections via the star-delta technique has proven to be a valuable tool for making multiphase numerical simulations more tractable and efficient. This study examines the assumptions of the star-delta technique and exposes its effects in a 3-D, multiphase context for advective and dispersive/diffusive fluxes. Key issues of relative permeability-saturation-capillary pressure (kr-S-Pc) and capillary barriers at fracture-fracture intersections are discussed. This study uses a multiphase compositional, finite difference numerical model in discrete fracture network (DFN) and discrete fracture-matrix (DFM) modes. It verifies that the numerical model replicates analytical solutions and performs adequately in convergence exercises (conservative and decaying tracer, one and two-phase flow, DFM and DFN domains). The study culminates in simulations of a two-phase laboratory experiment in which a fluid invades a simple fracture intersection. The experiment and simulations evoke different invading fluid flow paths by varying fracture apertures as oil invades water-filled fractures and as water invades air-filled fractures. Results indicate that the node elimination technique as implemented in numerical model correctly reproduces the long-term flow path of the invading fluid, but that short-term temporal effects of the capillary traps and barriers arising from the intersection node are lost.

  13. Fast DNA sieving through submicrometer cylindrical glass capillary matrix.

    PubMed

    Cao, Zhen; Yobas, Levent

    2014-01-07

    Here, we report on DNA electrophoresis through a novel artificial sieving matrix based on the highly regular submicrometer cylindrical glass capillary segments alternatingly arranged with wells. Such round capillaries pose a higher-order confinement resulting in a lower partition coefficient and greater entropic energy barrier while limiting the driving field strength to a small fraction of the applied electric field. In return, the separation can be performed at high average field strengths (up to 1.6 kV/cm) without encountering the field-dependent loss of resolving power. This leads to fast DNA sieving as demonstrated here on the capillaries of 750 nm in diameter. The 600 bp to 21 kbp long chains are shown to resolve within 4 min after having undergone a fairly limited number of entropic barriers (128 in total). The capillary matrix also exhibits a critical field threshold below which DNA bands fail to launch, and this occurs at a considerably greater magnitude than in other matrixes. The submicrometer capillaries are batch-fabricated on silicon through a fabrication process that does not require high-resolution advanced lithography or well-controlled wafer bonding techniques to define their critical dimension.

  14. Laboratory-based observations of capillary barriers and preferential flow in layered snow

    NASA Astrophysics Data System (ADS)

    Avanzi, F.; Hirashima, H.; Yamaguchi, S.; Katsushima, T.; De Michele, C.

    2015-12-01

    Several evidences are nowadays available that show how the effects of capillary gradients and preferential flow on water transmission in snow may play a more important role than expected. To observe these processes and to contribute in their characterization, we performed observations on the development of capillary barriers and preferential flow patterns in layered snow during cold laboratory experiments. We considered three different layering (all characterized by a finer-over-coarser texture in grain size) and three different water input rates. Nine samples of layered snow were sieved in a cold laboratory, and subjected to a constant supply of dyed tracer. By means of visual inspection, horizontal sectioning and liquid water content measurements, the processes of ponding and preferential flow were characterized as a function of texture and water input rate. The dynamics of each sample were replicated using the multi-layer physically-based SNOWPACK model. Results show that capillary barriers and preferential flow are relevant processes ruling the speed of liquid water in stratified snow. Ponding is associated with peaks in LWC at the boundary between the two layers equal to ~ 33-36 vol. % when the upper layer is composed by fine snow (grain size smaller than 0.5 mm). The thickness of the ponding layer at the textural boundary is between 0 and 3 cm, depending on sample stratigraphy. Heterogeneity in water transmission increases with grain size, while we do not observe any clear dependency on water input rate. The extensive comparison between observed and simulated LWC profiles by SNOWPACK (using an approximation of Richards Equation) shows high performances by the model in estimating the LWC peak over the boundary, while water speed in snow is underestimated by the chosen water transport scheme.

  15. Effects of Different Waveforms on the Performance of Active Capillary Dielectric Barrier Discharge Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Dumlao, Morphy C.; Xiao, Dan; Zhang, Daming; Fletcher, John; Donald, William A.

    2017-04-01

    Active capillary dielectric barrier discharge ionization (DBDI) is emerging as a compact, low-cost, and robust method to form intact ions of small molecules for detection in near real time by portable mass spectrometers. Here, we demonstrate that by using a 10 kHz, 2.5 kVp-p high-voltage square-wave alternating current plasma, active capillary DBDI can consume less than 1 μW of power. In contrast, the power consumed using a sine and triangle alternating current waveform is more than two orders of magnitude higher than that for the square waveform to obtain a similar voltage for plasma generation. Moreover, the plasma obtained using a square waveform can be significantly more homogenous than that obtained using sine and triangle waveforms. Protonated dimethyl methylphosphonate (DMMP) and deprotonated perfluorooctanoic acid (PFOA) can be detected at about the same or higher abundances using square-wave DBDI mass spectrometry compared with the use of sine and triangle waveforms. By use of benzylammonium thermometer ions, the extent of internal energy deposition using square, sine, or triangle waveform excited plasmas are essentially the same at the optimum voltages for ion detection. Using an H-bridge circuit driving a transformer optimized to reduce losses, square-wave active capillary DBDI can be continuously powered for 50 h by common 9 V-battery (PP3).

  16. Capillary Liquid Acquisition Device Heat Entrapment

    NASA Technical Reports Server (NTRS)

    Bolshinskiy, L. G.; Hastings, L. J.; Statham, G.; Turpin, J. B.

    2007-01-01

    Cryogenic liquid acquisition devices (LADs) for space-based propulsion interface directly with the feed system, which can be a significant heat leak source. Further, the accumulation of thermal energy within LAD channels can lead to the loss of subcooled propellant conditions and result in feed system cavitation during propellant outflow. Therefore, the fundamental question addressed by this program was: To what degree is natural convection in a cryogenic liquid constrained by the capillary screen meshes envisioned for LADs? Testing was first conducted with water as the test fluid, followed by LN2 tests. In either case, the basic experimental approach was to heat the bottom of a cylindrical column of test fluid to establish stratification patterns measured by temperature sensors located above and below a horizontal screen barrier position. Experimentation was performed without barriers, with screens, and with a solid barrier. The two screen meshes tested were those typically used by LAD designers, 200x1400 and 325x2300, both with Twill Dutch Weave. Upon consideration of both the water and LN2 data, it was concluded that heat transfer across the screen meshes was dependent upon barrier thermal conductivity and that the capillary screen meshes were impervious to natural convection currents.

  17. Cryogenic Capillary Screen Heat Entrapment

    NASA Technical Reports Server (NTRS)

    Bolshinskiy, L.G.; Hastings, L.J.; Stathman, G.

    2007-01-01

    Cryogenic liquid acquisition devices (LADs) for space-based propulsion interface directly with the feed system, which can be a significant heat leak source. Further, the accumulation of thermal energy within LAD channels can lead to the loss of sub-cooled propellant conditions and result in feed system cavitation during propellant outflow. Therefore, the fundamental question addressed by this program was: "To what degree is natural convection in a cryogenic liquid constrained by the capillary screen meshes envisioned for LADs.?"Testing was first conducted with water as the test fluid, followed by LN2 tests. In either case, the basic experimental approach was to heat the bottom of a cylindrical column of test fluid to establish stratification patterns measured by temperature sensors located above and below a horizontal screen barrier position. Experimentation was performed without barriers, with screens, and with a solid barrier. The two screen meshes tested were those typically used by LAD designers, "200x1400" and "325x2300", both with Twill Dutch Weave. Upon consideration of both the water and LN2 data it was concluded that heat transfer across the screen meshes was dependent upon barrier thermal conductivity and that the capillary screen meshes were impervious to natural convection currents.

  18. Convective diffusion of nanoparticles from the epithelial barrier toward regional lymph nodes.

    PubMed

    Dukhin, Stanislav S; Labib, Mohamed E

    2013-11-01

    Drug delivery using nanoparticles as drug carriers has recently attracted the attention of many investigators. Targeted delivery of nanoparticles to the lymph nodes is especially important to prevent cancer metastasis or infection, and to diagnose disease stage. However, systemic injection of nanoparticles often results in organ toxicity because they reach and accumulate in all the lymph nodes in the body. An attractive strategy would be to deliver the drug-loaded nanoparticles to a subset of draining lymph nodes corresponding to a specific site or organ to minimize systemic toxicity. In this respect, mucosal delivery of nanoparticles to regional draining lymph nodes of a selected site creates a new opportunity to accomplish this task with minimal toxicity. One example is the delivery of nanoparticles from the vaginal lumen to draining lymph nodes to prevent the transmission of HIV in women. Other known examples include mucosal delivery of vaccines to induce immunity. In all cases, molecular and particle transport by means of diffusion and convective diffusion play a major role. The corresponding transport processes have common inherent regularities and are addressed in this review. Here we use nanoparticle delivery from the vaginal lumen to the lymph nodes as an example to address the many aspects of associated transport processes. In this case, nanoparticles penetrate the epithelial barrier and move through the interstitium (tissue) to the initial lymphatics until they finally reach the lymph nodes. Since the movement of interstitial liquid near the epithelial barrier is retarded, nanoparticle transport was found to take place through special foci present in the epithelium. Immediately after nanoparticles emerge from the foci, they move through the interstitium due to diffusion affected by convection (convective diffusion). Specifically, the convective transport of nanoparticles occurs due to their convection together with interstitial fluid through the interstitium toward the initial lymph capillaries. Afterwards, nanoparticles move together with the lymph flow along the initial lymph capillaries and then enter the afferent lymphatics and ultimately reach the lymph node. As the liquid moves through the interstitium toward the initial lymph capillaries due to the axial movement of lymph along the lymphatics, the theory for coupling between lymph flow and concomitant flow through the interstitium is developed to describe this general case. The developed theory is applied to interpret the large uptake of Qdots by lymph nodes during inflammation, which is induced by pre-treating mouse vagina with the surfactant Nonoxynol-9 prior to instilling the Qdots. Inflammation is viewed here to cause broadening of the pores within the interstitium with the concomitant formation of transport channels which function as conduits to transport the nanoparticles to the initial lymph capillaries. We introduced the term "effective channels" to denote those channels which interconnect with foci present in the epithelial barrier and which function to transport nanoparticles to initial lymph capillaries. The time of transport toward the lymph node, predicated by the theory, increases rapidly with increasing the distance y0 between the epithelial barrier and the initial lymph capillaries. Transport time is only a few hours, when y0 is small, about some R (where R is the initial lymph capillary radius), due to the predomination of a rather rapid convection in this case. This transport time to the lymph nodes may be tens of hours (or longer) when y0 is essentially larger and the slow diffusion controls the transport rate in a zone not far from the epithelial barrier, where convection is weak at large y0. Accounting for transport by diffusion only, which is mainly considered in many relevant publications, is not sufficient to explain our nanoparticle uptake kinetics because the possibility of fast transport due to convection is overlooked. Our systematic investigations have revealed that the information about the main transport conditions, namely, y0 and the pore broadening up to the dimension of the interstitial transport channels, is necessary to create the quantitative model of enhanced transport during inflammation with the use of the proposed model as a prerequisite. The modeling for convective diffusion of nanoparticles from the epithelial barrier to the lymph node has been mainly accomplished here, while the diffusion only scenario is accounted for in other studies. This first modeling is a semi-quantitative one. A more rigorous mathematical approach is almost impossible at this stage because the transport properties of the model are introduced here for the first time. These properties include: discovery of foci in the epithelium, formation of transport channels, definition of channels interconnecting with foci (effective foci and channels), generation of flow in the interstitium toward the initial lymph capillaries due to axial flow within afferent lymphatics, deformation of this flow due to hydrodynamic impermeability of the squamous layer with the formation of the hydrodynamic stagnation zone near the epithelial barrier, predomination of slow diffusion transport within the above zone, and predomination of fast convection of nanoparticles near the initial lymph capillaries. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Convective diffusion of nanoparticles from the epithelial barrier towards regional lymph nodes

    PubMed Central

    Dukhin, Stanislav S; Labib, Mohamed E.

    2013-01-01

    Drug delivery using nanoparticles as drug carriers has recently attracted the attention of many investigators. Targeted delivery of nanoparticles to lymph nodes is especially important to prevent cancer metastasis or infection, and to diagnose disease stage. However, systemic injection of nanoparticles often results in organ toxicity because they reach and accumulate in all the lymph nodes in the body. An attractive strategy would be to deliver the drug-loaded nanoparticles to a subset of draining lymph nodes corresponding to a specific site or organ to minimize systemic toxicity. In this respect, mucosal delivery of nanoparticles to regional draining lymph nodes of a selected site creates a new opportunity to accomplish this task with minimal toxicity. One example is the delivery of nanoparticles from the vaginal lumen to draining lymph nodes to prevent the transmission of HIV in women. Other known examples include mucosal delivery of vaccines to induce immunity. In all cases, molecular and particle transport by means of diffusion and convective diffusion play a major role. The corresponding transport processes have common inherent regularities and are addressed in this review. Here we use nanoparticles delivery from the vaginal lumen to lymph nodes as an example to address the many aspects of associated transport processes. In this case, nanoparticles penetrate the epithelial barrier and move through the interstitium (tissue) to the initial lymphatics until they finally reach the lymph nodes. Since the movement of interstitial liquid near the epithelial barrier is retarded, nanoparticles transport was found to take place through special foci present in the epithelium. Immediately after nanoparticles emerge from the foci, they move through the interstitium due to diffusion affected by convection (convective diffusion). Specifically, the convective transport of nanoparticles occurs due to their convection together with interstitial fluid through the interstitium towards the initial lymph capillaries. Afterwards, nanoparticles move together with the lymph flow along the initial lymph capillaries and then enter the afferent lymphatics and ultimately reach the lymph node. As the liquid moves through the interstitium towards the initial lymph capillaries due to the axial movement of lymph along the lymphatics, the theory for coupling between lymph flow and concomitant flow through the interstitium is developed to describe this general case. The developed theory is applied to interpret the large uptake of Qdots by lymph nodes during inflammation, which is induced by pre-treating mouse vagina with the surfactant Nonoxynol-9 prior to instilling the Qdots. Inflammation is viewed here to cause broadening of the pores within the interstitium with the concomitant formation of transport channels which function as conduits to transport the nanoparticles to the initial lymph capillaries. We introduced the term “effective channels” to denote those channels which interconnect with foci present in the epithelial barrier and which function to transport nanoparticles to initial lymph capillaries. The time of transport towards the lymph node, predicated by the theory, increases rapidly with increasing the distance y0 between the epithelial barrier and the initial lymph capillaries. Transport time is only a few hours, when y0 is small, about some R (where R is the initial lymph capillary radius), due to the predomination of a rather rapid convection in this case. This transport time to lymph nodes may be tens of hours (or longer) when y0 is essentially larger and the slow diffusion controls the transport rate in a zone not far from the epithelial barrier, where convection is weak at large y0. Accounting for transport by diffusion only, which is mainly considered in many relevant publications, is not sufficient to explain our nanoparticles uptake kinetics because the possibility of fast transport due to convection is overlooked. Our systematic investigations have revealed that the information about the main transport conditions, namely, y0 and the pore broadening up to the dimension of the interstitial transport channels, is necessary to create the quantitative model of enhanced transport during inflammation with the use of the proposed model as a prerequisite. The modeling for convective diffusion of nanoparticles from the epithelial barrier to the lymph node has been mainly accomplished here, while the diffusion only scenario is accounted for in other studies. This first modeling is a semi-quantitative one. A more rigorous mathematical approach is almost impossible at this stage because the transport properties of the model are introduced here for the first time. These properties include: discovery of foci in the epithelium, formation of transport channels, definition of channels interconnecting with foci (effective foci and channels), generation of flow in the interstitium towards the initial lymph capillaries due to axial flow within afferent lymphatics, deformation of this flow due to hydrodynamic impermeability of the squamous layer with the formation of the hydrodynamic stagnation zone near the epithelial barrier, predomination of slow diffusion transport within the above zone, and predomination of fast convection of nanoparticles near the initial lymph capillaries. PMID:23859221

  20. Evaluating the long-term hydrology of an evapotranspiration-capillary barrier with a 1000 year design life: HYDROLOGY OF A 1000 YEAR ETC BARRIER

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Z. Fred

    A surface barrier (or cover) is a commonly used technology for subsurface remediation. A key function of the barrier is to reduce or eliminate the movement of meteoric precipitation into the underlying waste zone, where it could mobilize and transport contaminants. Surface barriers are expected to perform for centuries to millennia, yet there are very few examples of performance for periods longer than a decade. The Prototype Hanford Barrier was constructed in 1994 over an existing waste site to demonstrate its long-term performance for a design period of 1000 years. This barrier is a field-scale evapotranspiration-capillary (ETC) barrier. In thismore » design, the storage layer consists of 2-m-thick silt loam. The 19-year monitoring results show that the store-and-release mechanism for the ETC barrier worked efficiently as the storage layer was recharged in the winter season (November to March) and the stored water was released to the atmosphere in the summer season (April to October) via soil evaporation and plant transpiration. The capillary break functioned normally in improving the storage capacity and minimizing drainage. The maximum drainage observed through the ET barrier at any of the monitoring stations was only 0.178 mm yr-1 (under an enhanced precipitation condition), which is less than the design criterion. A very small amount (2.0 mm yr-1 on average) of runoff was observed during the 19-year monitoring period. The observed storage capacity of the storage layer was considerably (39%) larger than the estimated value based on the method of equilibrium of water pressure. After a controlled fire in 2008, the newly grown vegetation (primarily shallow-rooted grasses) could still release the stored water and summer precipitation to the atmosphere via transpiration. The findings are useful for predicting water storage and ET under different precipitation conditions and for the design of future barriers.« less

  1. Adenovirus-delivered GFP-HO-1C[INCREMENT]23 attenuates blood-spinal cord barrier permeability after rat spinal cord contusion.

    PubMed

    Chang, Sheng; Bi, Yunlong; Meng, Xiangwei; Qu, Lin; Cao, Yang

    2018-03-21

    The blood-spinal cord barrier (BSCB) plays a key role in maintaining the microenvironment and is primarily composed of tight junction proteins and nonfenestrated capillary endothelial cells. After injury, BSCB damage results in increasing capillary permeability and release of inflammatory factors. Recent studies have reported that haem oxygenase-1 (HO-1) fragments lacking 23 amino acids at the C-terminus (HO-1C[INCREMENT]23) exert novel anti-inflammatory and antioxidative effects in vitro. However, no study has identified the role of HO-1C[INCREMENT]23 in vivo. We aimed to investigate the protective effects of HO-1C[INCREMENT]23 on the BSCB after spinal cord injury (SCI) in a rat model. Here, adenoviral HO-1C[INCREMENT]23 (Ad-GFP-HO-1C[INCREMENT]23) was intrathecally injected into the 10th thoracic spinal cord segment (T10) 7 days before SCI. In addition, nuclear and cytoplasmic extraction and immunofluorescence staining of HO-1 were used to examine the effect of Ad-GFP-HO-1C[INCREMENT]23 on HO-1 nuclear translocation. Evan's blue staining served as an index of capillary permeability and was detected by fluorescence microscopy at 633 nm. Western blotting was also performed to detect tight junction protein expression. The Basso, Beattie and Bresnahan score was used to evaluate kinematic functional recovery through the 28th day after SCI. In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hiratsuka, Tatsumasa; Tanaka, Hideki, E-mail: tanaka@cheme.kyoto-u.ac.jp; Miyahara, Minoru T., E-mail: miyahara@cheme.kyoto-u.ac.jp

    Capillary condensation in the regime of developing hysteresis occurs at a vapor pressure, P{sub cond}, that is less than that of the vapor-like spinodal. This is because the energy barrier for the vapor-liquid transition from a metastable state at P{sub cond} becomes equal to the energy fluctuation of the system; however, a detailed mechanism of the spontaneous transition has not been acquired even through extensive experimental and simulation studies. We therefore construct accurate atomistic silica mesopore models for MCM-41 and perform molecular simulations (gauge cell Monte Carlo and grand canonical Monte Carlo) for argon adsorption on the models at subcriticalmore » temperatures. A careful comparison between the simulation and experiment reveals that the energy barrier for the capillary condensation has a critical dimensionless value, W{sub c}{sup *} = 0.175, which corresponds to the thermal fluctuation of the system and depends neither on the mesopore size nor on the temperature. We show that the critical energy barrier W{sub c}{sup *} controls the capillary condensation pressure P{sub cond} and also determines a boundary between the reversible condensation/evaporation regime and the developing hysteresis regime.« less

  3. Activation of PKC isoform beta(I) at the blood-brain barrier rapidly decreases P-glycoprotein activity and enhances drug delivery to the brain.

    PubMed

    Rigor, Robert R; Hawkins, Brian T; Miller, David S

    2010-07-01

    P-glycoprotein is an ATP (adenosine triphosphate)-driven drug efflux transporter that is highly expressed at the blood-brain barrier (BBB) and is a major obstacle to the pharmacotherapy of central nervous system diseases, including brain tumors, neuro-AIDS, and epilepsy. Previous studies have shown that P-glycoprotein transport activity in rat brain capillaries is rapidly reduced by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha) acting through protein kinase C (PKC)-dependent signaling. In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA). Western blotting of brain capillary extracts with phospho-specific antibodies showed that dPPA activated PKCbeta(I), but not PKCbeta(II). Moreover, in intact rats, intracarotid infusion of dPPA potently increased brain accumulation of the P-glycoprotein substrate, [(3)H]-verapamil without compromising tight junction integrity. Thus, PKCbeta(I) activation selectively reduced P-glycoprotein activity both in vitro and in vivo. Targeting PKCbeta(I) at the BBB may prove to be an effective strategy for enhancing the delivery of small molecule therapeutics to the brain.

  4. Influence of capillary barrier effect on biogas distribution at the base of passive methane oxidation biosystems: Parametric study.

    PubMed

    Ahoughalandari, Bahar; Cabral, Alexandre R

    2017-05-01

    The efficiency of methane oxidation in passive methane oxidation biosystems (PMOBs) is influenced by, among other things, the intensity and distribution of the CH 4 loading at the base of the methane oxidation layer (MOL). Both the intensity and distribution are affected by the capillary barrier that results from the superposition of the two materials constituting the PMOB, namely the MOL and the gas distribution layer (GDL). The effect of capillary barriers on the unsaturated flow of water has been well documented in the literature. However, its effect on gas flow through PMOBs is still poorly documented. In this study, sets of numerical simulations were performed to evaluate the effect of unsaturated hydraulic characteristics of the MOL material on the value and distribution of moisture and hence, the ease and uniformity in the distribution of the upward flow of biogas along the GDL-MOL interface. The unsaturated hydraulic parameters of the materials used to construct the experimental field plot at the St-Nicephore landfill (Quebec, Canada) were adopted to build the reference simulation of the parametric study. The behavior of the upward flow of biogas for this particular material was analyzed based on its gas intrinsic permeability function, which was obtained in the laboratory. The parameters that most influenced the distribution and the ease of biogas flow at the base of the MOL were the saturated hydraulic conductivity and pore size distribution of the MOL material, whose effects were intensified as the slope of the interface increased. The effect of initial dry density was also assessed herein. Selection of the MOL material must be made bearing in mind that these three parameters are key in the effort to prevent unwanted restriction in the upward flow of biogas, which may result in the redirection of biogas towards the top of the slope, leading to high CH 4 fluxes (hotspots). In a well-designed PMOB, upward flow of biogas across the GDL-MOL interface is unrestricted and moisture distribution is uniform. This paper tries to show how to obtain this. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Wnt/β-catenin signaling controls development of the blood–brain barrier

    PubMed Central

    Liebner, Stefan; Corada, Monica; Bangsow, Thorsten; Babbage, Jane; Taddei, Andrea; Czupalla, Cathrin J.; Reis, Marco; Felici, Angelina; Wolburg, Hartwig; Fruttiger, Marcus; Taketo, Makoto M.; von Melchner, Harald; Plate, Karl Heinz; Gerhardt, Holger; Dejana, Elisabetta

    2008-01-01

    The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown. PMID:18955553

  6. In vitro models of the blood–brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use

    PubMed Central

    Helms, Hans C; Abbott, N Joan; Burek, Malgorzata; Cecchelli, Romeo; Couraud, Pierre-Olivier; Deli, Maria A; Förster, Carola; Galla, Hans J; Romero, Ignacio A; Shusta, Eric V; Stebbins, Matthew J; Vandenhaute, Elodie; Weksler, Babette

    2016-01-01

    The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described. PMID:26868179

  7. Single photon emission computed tomography and positron emission tomography imaging of multi-drug resistant P-glycoprotein--monitoring a transport activity important in cancer, blood-brain barrier function and Alzheimer's disease.

    PubMed

    Piwnica-Worms, David; Kesarwala, Aparna H; Pichler, Andrea; Prior, Julie L; Sharma, Vijay

    2006-11-01

    Overexpression of multi-drug resistant P-glycoprotein (Pgp) remains an important barrier to successful chemotherapy in cancer patients and impacts the pharmacokinetics of many important drugs. Pgp is also expressed on the luminal surface of brain capillary endothelial cells wherein Pgp functionally comprises a major component of the blood-brain barrier by limiting central nervous system penetration of various therapeutic agents. In addition, Pgp in brain capillary endothelial cells removes amyloid-beta from the brain. Several single photon emission computed tomography and positron emission tomography radiopharmaceutical have been shown to be transported by Pgp, thereby enabling the noninvasive interrogation of Pgp-mediated transport activity in vivo. Therefore, molecular imaging of Pgp activity may enable noninvasive dynamic monitoring of multi-drug resistance in cancer, guide therapeutic choices in cancer chemotherapy, and identify transporter deficiencies of the blood-brain barrier in Alzheimer's disease.

  8. Blood-brain barrier transport of drugs for the treatment of brain diseases.

    PubMed

    Gabathuler, Reinhard

    2009-06-01

    The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

  9. Dynamics and Stability of Capillary Surfaces: Liquid Switches at Small Scales

    NASA Technical Reports Server (NTRS)

    Steen, Paul H.; Bhandar, Anand; Vogel, Michael J.; Hirsa, Amir H.

    2004-01-01

    The dynamics and stability of systems of interfaces is central to a range of technologies related to the Human Exploration and Development of Space (HEDS). Our premise is that dramatic shape changes can be manipulated to advantage with minimal input, if the system is near instability. The primary objective is to develop the science base to allow novel approaches to liquid management in low-gravity based on this premise. HEDS requires efficient, reliable and lightweight technologies. Our poster will highlight our progress toward this goal using the capillary switch as an example. A capillary surface is a liquid/liquid or liquid/gas interface whose shape is determined by surface tension. For typical liquids (e.g., water) against gas on earth, capillary surfaces occur on the millimeterscale and smaller where shape deformation due to gravity is unimportant. In low gravity, they can occur on the centimeter scale. Capillary surfaces can be combined to make a switch a system with multiple stable states. A capillary switch can generate motion or effect force. To be practical, the energy barriers of such a switch must be tunable, its switching time (kinetics) short and its triggering mechanism reliable. We illustrate these features with a capillary switch that consists of two droplets, coupled by common pressure. As long as contact lines remained pinned, motions are inviscid, even at sub-millimeter scales, with consequent promise of low-power consumption at the device level. Predictions of theory are compared to experiment on i) a soap-film prototype at centimeter scale and ii) a liquid droplet switch at millimeter-scale.

  10. Changes in permeability of the alveolar-capillary barrier in firefighters.

    PubMed Central

    Minty, B D; Royston, D; Jones, J G; Smith, D J; Searing, C S; Beeley, M

    1985-01-01

    The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range. PMID:3899161

  11. Changes in permeability of the alveolar-capillary barrier in firefighters.

    PubMed

    Minty, B D; Royston, D; Jones, J G; Smith, D J; Searing, C S; Beeley, M

    1985-09-01

    The effect on alveolar-capillary barrier permeability of chronic exposure to a smoke produced by the partial combusion of diesel oil, paraffin, and wood was examined. An index of permeability was determined from the rate of transfer from the lung into the blood of the hydrophilic, labelled chelate 99mTc diethylene triamine penta-acetate (MW 492 dalton). The results of this test were expressed as the half time clearance of the tracer from the lung into the blood (T1/2 LB). The study was carried out at the Royal Naval Firefighting School, HMS Excellent. Permeability index was measured on seven non-smoking naval firefighting instructors who had worked at the school for periods of longer than two and a half months. Tests of airway function and carbon monoxide transfer factor were performed on four of these seven instructors. The results of the permeability index showed a T1/2 LB of 26 min +/- 5 (SEM) which differed significantly from that of normal non-smokers. By contrast all other lung function tests had values within the predicted normal range.

  12. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress.

    PubMed

    Arredondo Zamarripa, David; Díaz-Lezama, Nundehui; Meléndez García, Rodrigo; Chávez Balderas, Jesús; Adán, Norma; Ledesma-Colunga, Maria G; Arnold, Edith; Clapp, Carmen; Thebault, Stéphanie

    2014-01-01

    Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK) production contributes to the increased transport through the blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE) components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO) synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC), blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC) monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19) cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS) in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  13. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress

    PubMed Central

    Arredondo Zamarripa, David; Díaz-Lezama, Nundehui; Meléndez García, Rodrigo; Chávez Balderas, Jesús; Adán, Norma; Ledesma-Colunga, Maria G.; Arnold, Edith; Clapp, Carmen; Thebault, Stéphanie

    2014-01-01

    Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK) production contributes to the increased transport through the blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE) components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO) synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC), blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC) monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19) cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS) in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies. PMID:25368550

  14. The impact of a shallow biobarrier on water recharge patterns in a semi-arid environment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Laundre, J.W.

    1997-12-31

    This study attempted to measure the effect of a shallow biobarrier of gravel and cobble on water flow patterns during spring snow melt and recharge. The design consisted of 30 metal culverts 3 m in diameter and 1.6 m long, positioned on end. Test culverts contained 50-cm biobarrier of gravel or cobble and then an additional 50 cm of soil placed above the barrier layer. A neutron probe was used to measure soil moisture above and below the barrier. Measurements were made in the fall and again immediately after snow melt in the spring. During recharge, the biobarriers provided amore » capillary break which resulted in a pooling of water above the barrier layer. With sufficient snowmelt, the water can penetrate the break and possibly penetrate deeper than in the absence of the barrier layer.« less

  15. Long-Term Drainage from the Riprap Side Slope of a Surface Barrier

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Zhuanfang

    Surface barriers designed to isolate underground nuclear waste in place are expected to function for at least 1000 years. To achieve this long design life, such barriers need to be protected with side slopes against wind- and water-induced erosion and damage by natural or human activities. However, the side slopes are usually constructed with materials coarser than the barrier. Their hydrological characteristics must be understood so that any drainage from them is considered in the barrier design and will not compromise the barrier function. The Prototype Hanford Barrier, an evapotranspiration-capillary (ETC) barrier, was constructed in 1994 at the Hanford Sitemore » in southeastern Washington state, with a gravel side slope and a riprap side slope. The soil water content in the gravel side slope and drainage from both side slopes have been monitored since the completion of construction. The monitoring results show that under natural precipitation the annual drainage rates from the two types of side slopes were very similar and about 5 times the typical recharge from local soil with natural vegetation and 40 times the barrier design criterion. The higher recharge from the side slopes results in some of the drainage migrating laterally to the region beneath the ETC barrier. This edge effect of the enhanced drainage was evaluated for a period of 1000 years by numerical simulation. The edge effect was quantified by the amount of water across the barrier edges and the affecting distance of the barrier edges. These results indicate that design features can be adjusted to reduce the edge effect when necessary.« less

  16. A simulation model of the oxygen alveolo-capillary exchange in normal and pathological conditions.

    PubMed

    Brighenti, Chiara; Gnudi, Gianni; Avanzolini, Guido

    2003-05-01

    This paper presents a mathematical model of the oxygen alveolo-capillary exchange to provide the capillary oxygen partial pressure profile in normal and pathological conditions. In fact, a thickening of the blood-gas barrier, heavy exercise or a low oxygen partial pressure (PO2) in the alveolar space can reduce the O2 alveolo-capillary exchange. Since the reversible binding between haemoglobin and oxygen makes it impossible to determine the closed form for the mathematical description of the PO2 profile along the pulmonary capillaries, an approximate analytical solution of the capillary PO2 profile is proposed. Simulation results are compared with the capillary PO2 profile obtained by numerical integration and by a piecewise linear interpolation of the oxyhaemoglobin dissociation curve. Finally, the proposed model is evaluated in a large range of physiopathological diffusive conditions. The good fit to numerical solutions in all experimental conditions seems to represent a substantial improvement with respect to the approach based on a linear approximation of the oxyhaemoglobin dissociation curve, and makes this model a candidate to be incorporated into the integrated descriptions of the entire respiratory system, where the datum of primary interest is the value of end capillary PO2.

  17. [Structure of newly formed capillaries of the rabbit cornea (electron microscopic study)].

    PubMed

    Gurina, O Iu; Karaganov, Ia L

    1984-08-01

    Owing to a complex application of topical analysis and tracer technique, it is possible to carry out a light optic and electron microscopic investigation of newly formed capillaries growing in the rabbit cornea after its chemical burn. The ultrastructural analysis demonstrates certain polymorphism of morphological organization of endotheliocyte in the newly formed capillaries. There is a rather elevated amount of free ribosomes, mitochondria, microtubules and microfilaments in cytoplasm. The granular endoplasmic reticulum and Golgi complex are hypertrophied. Weibel--Palade bodies appear. Taking into account certain morpho-functional peculiarities of endothelial cells along the course of the growing capillaries, on the 8th day of growth three zone are distinguished: 1--area of nondifferentiated endothelium (apex of the capillary), 2--transitional zone, 3--zone of relatively differentiated endothelium situating in the place where the capillary gets off the parental vessel. According to the zones distinguished, the ways of trans-endothelial transport of molecules are investigated. In formation of the capillary barrier-transport function an important role belongs to polymorphism of the endothelial cells along the course of the growing capillary which is determined by differentiation degree of these cells depending on their participation in permeability.

  18. X-ray imaging of water motion during capillary imbibition: A study on how compaction bands impact fluid flow in Bentheim sandstone

    NASA Astrophysics Data System (ADS)

    Pons, A.; David, C.; Fortin, J.; Stanchits, S.; MenéNdez, B.; Mengus, J. M.

    2011-03-01

    To investigate the effect of compaction bands (CB) on fluid flow, capillary imbibition experiments were performed on Bentheim sandstone specimens (initial porosity ˜22.7%) using an industrial X-ray scanner. We used a three-step procedure combining (1) X-ray imaging of capillary rise in intact Bentheim sandstone, (2) formation of compaction band under triaxial tests, at 185 MPa effective pressure, with acoustic emissions (AE) recording for localization of the induced damage, and (3) again X-ray imaging of capillary rise in the damaged specimens after the unloading. The experiments were performed on intact cylindrical specimens, 5 cm in diameter and 10.5 cm in length, cored in different orientations (parallel or perpendicular to the bedding). Analysis of the images obtained at different stages of the capillary imbibition shows that the presence of CB slows down the imbibition and disturbs the geometry of water flow. In addition, we show that the CB geometry derived from X-ray density maps analysis is well correlated with the AE location obtained during triaxial test. The analysis of the water front kinetics was conducted using a simple theoretical model, which allowed us to confirm that compaction bands act as a barrier for fluid flow, not fully impermeable though. We estimate a contrast of permeability of a factor of ˜3 between the host rock and the compaction bands. This estimation of the permeability inside the compaction band is consistent with estimations done in similar sandstones from field studies but differs by 1 order of magnitude from estimations from previous laboratory measurements.

  19. Evaluating the long-term hydrology of an evapotranspiration-capillary barrier with a 1000 year design life

    NASA Astrophysics Data System (ADS)

    Zhang, Z. Fred

    2016-06-01

    A surface barrier is a commonly used technology for isolation of subsurface contaminants. Surface barriers for isolating radioactive waste are expected to perform for centuries to millennia, yet there are very few data for field-scale surface barriers for periods approaching a decade or longer. The Prototype Hanford Barrier (PHB) with a design life of 1000 years was constructed over an existing radioactive waste site in 1994 to demonstrate its long-term performance. The primary element of the PHB is an evapotranspiration-capillary (ETC) barrier in which precipitation water is stored in a fine-textured soil layer and later released to the atmosphere via evapotranspiration. To address the barrier performance under extreme conditions, this study included an enhanced precipitation stress test from 1995 to 1997 to determine barrier response to extreme precipitation events. During this period a 1000 year 24 h return rainstorm was simulated in March every year. The loss of vegetation on barrier hydrology was tested with a controlled fire test in 2008. The 19 year monitoring record shows that the store-and-release mechanism worked as well as or better than the design criterion. Average drainage from the ETC barrier amounted to an average of 0.005 mm yr-1, which is well below the design criterion of 0.5 mm yr-1. After a simulated wildfire, the naturally reestablished vegetation and increased evaporation combined to release the stored water and summer precipitation to the atmosphere such that drainage did not occur in the 5 years subsequent to the fire.

  20. Quantitative fine structure of capillaries in subregions of the rat subfornical organ.

    PubMed

    Shaver, S W; Sposito, N M; Gross, P M

    1990-04-01

    The differentiated cytology across subregions of the rat subfornical organ (SFO) prompted our hypothesis that ultrastructural features of capillary endothelial cells would vary topographically and quantitatively within this small nucleus. We used electron microscopic and computer-based morphometric methods to assess fine structural dimensions of the capillary endothelium in four distinct subregions of the SFO from Long-Evans and homozygous Brattleboro rats. Three types of capillary were present. Type III capillaries (resembling those of endocrine glands) had an average wall thickness of 0.17 microns, 54% thinner than those of Type I and II capillaries. Pericapillary spaces around Type III capillaries measured 56 microns2, 100% larger than for Type I vessels (resembling those of skeletal muscle). Only Type III capillaries contained fenestrations (9 per microns2 of endothelial cell) and were the predominant type of capillary in central and caudal subregions of the SFO. Type I capillaries, prevalent in the transitional subregion between the central and rostral parts of the SFO, had 10 cytoplasmic vesicles per micron2 of endothelial cell area, a number not different from that of Type III capillaries but 3x the frequency found in Type II vessels. Type II capillaries (those typical of "blood-brain barrier" endothelium) had low vesicular density (3 per microns2), no fenestrations, and no pericapillary spaces. Luminal diameters and the densities of mitochondria and intercellular junctions were not different among capillary types or subregions in the SFO. Furthermore, there were no morphometric differences for any capillary dimensions between Long-Evans and Brattleboro rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Effect of intravascular-to-extravascular water exchange on the determination of blood-to-tissue transfer constant by magnetic resonance imaging.

    PubMed

    Cao, Y; Brown, S L; Knight, R A; Fenstermacher, J D; Ewing, J R

    2005-02-01

    Water exchange across capillary walls couples intra- and extravascular (IV-EV) protons and their magnetization. A bolus i.v. injection of an extracellular MRI contrast agent (MRCA) causes a large increase in the spin-lattice relaxation rate, R1, of water protons in the plasma and blood cells within the capillaries and changes the effective relaxation rate R1eff in tissue via IV-EV water exchange. An analysis of the effect of plasma-red cell and IV-EV water exchange on the MRI-measured influx and permeability of capillaries to the MRCA is presented and focused on the brain and the blood-brain barrier. The effect of arrival of a bolus of an MRCA in the capillary on the relaxation rate R1eff in tissue via IV-EV water exchange occurs more rapidly than the MRCA uptake in tissue and can dominate the initial time curve of the R1eff change before the MRCA uptake in tissue becomes significant. This raises the possibility that (tissue dependent) IV-EV rate of exchange of water molecules can affect estimates of MRCA transfer constant. We demonstrate that an approach that considers IV-EV water exchange and uses the theoretical model of blood-brain tracer distribution developed by Patlak et al. (J Cereb Blood Flow Metab 1983;3:1-7) can lead to an accurate estimate of the MRI-determined influx rate constant of the MRCA and to an underestimation of the tissue blood volume.

  2. Water relations in cutover peatlands

    NASA Astrophysics Data System (ADS)

    Price, Jonathan S.; Ketcheson, Scott J.

    Sphagnum mosses, the dominant peat-forming plant in many northern peatlands, generally do not regenerate spontaneously in mined peatlands because water transfer between the cutover peat and incipient moss diaspores cannot overcome the capillary barrier effect between the two hydraulically distinct layers. Artificial drainage networks established throughout peatlands, coupled with the removal of the acrotelm during the peat extraction process, drastically alter the natural system function through the exposure of more decomposed catotelm peat and increased compression, oxidation, and shrinkage, subsequently decreasing average pore diameter and enhancing this capillary barrier effect. Water table (WT) fluctuations, constrained within the reduced specific yield of the altered catotelm, exhibit increased variability and rapid decline. The increased effective stress caused by a declining WT can result in seasonal surface subsidence of 8 to 10 cm, thereby reducing saturated hydraulic conductivity by three orders of magnitude. Restoration efforts aim to alter the disturbed hydrological regime, creating conditions more favorable for the recolonization of Sphagnum mosses and the ultimate reestablishment of an upper acrotelm layer. Due to the large areal coverage and high organic carbon content, the response of peatlands to disturbances caused by resource extraction, and their return to functioning ecosystems, must be thoroughly addressed. This paper integrates both published and unpublished work to facilitate an overview of our understanding of the hydrological impact of peat cutting and its implications for restoration.

  3. Diesel Exhaust Particle Exposure Causes Redistribution of Endothelial Tube VE-Cadherin

    PubMed Central

    Chao, Ming-Wei; Kozlosky, John; Po, Iris P.; Strickland, Pamela Ohman; Svoboda, Kathy K. H.; Cooper, Keith; Laumbach, Robert; Gordon, Marion K.

    2010-01-01

    Whether diesel exhaust particles (DEPs) potentially have a direct effect on capillary endothelia was examined by following the adherens junction component, vascular endothelial cell cadherin (VE-cadherin). This molecule is incorporated into endothelial adherens junctions at the cell surface, where it forms homodimeric associations with adjacent cells and contributes to the barrier function of the vasculature (Dejana et al., 2008; Venkiteswaran et al., 2002; Villasante et al., 2007). Human umbilical vein endothelial cells (HUVECs) that were pre-formed into capillary-like tube networks in vitro were exposed to DEPs for 24 hr. After exposure, the integrity of VE-cadherin in adherens junctions was assessed by immunofluorescence analysis, and demonstrated that increasing concentrations of DEPs caused increasing redistribution of VE-cadherin away from the cell-cell junctions toward intracellular locations. Since HUVEC tube networks are three-dimensional structures, whether particles entered the endothelial cells or tubular lumens was also examined. The data indicate that translocation of the particles does occur. The results, obtained in a setting that removes the confounding effects of inflammatory cells or blood components, suggest that if DEPs encounter alveolar capillaries in vivo, they may be able to directly affect the endothelial cell-cell junctions. PMID:20887764

  4. Effects of simvastatin on CAT-1-mediated arginine transport and NO level under high glucose conditions in conditionally immortalized rat inner blood-retinal barrier cell lines (TR-iBRB).

    PubMed

    Tun, Temdara; Kang, Young-Sook

    2017-05-01

    Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB. The NO level released from TR-iBRB cells was examined using Griess reagents. Under high glucose conditions, [ 3 H]l-arginine uptake was decreased in TR-iBRB cells. Simvastatin pretreatment elevated [ 3 H]l-arginine uptake, the expression levels of CAT-1 and eNOS mRNA, and NO production under high-glucose conditions. Moreover, the co-treatment with simvastatin and NOS inhibitors reduced [ 3 H]l-arginine uptake compared to pretreatment with simvastatin alone. Our results suggest that, in the presence of high-glucose levels, increased l-arginine uptake due to simvastatin treatment was associated with increased CAT-1 and eNOS mRNA levels, leading to higher NO production in TR-iBRB cells. Thus, simvastatin might be a good modulator for diabetic retinopathy therapy by increasing of the l-arginine uptake and improving endothelial function in retinal capillary endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Lung heparan sulfates modulate Kfc during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction

    PubMed Central

    Cluff, Mark; Kingston, Joseph; Hill, Denzil; Chen, Haiyan; Hoehne, Soeren; Malleske, Daniel T.; Kaur, Rajwinederjit

    2012-01-01

    Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient (Kfc) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in Kfc. Isolated perfused rat lung preparation was used to measure Kfc in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered Kfc in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on Kfc, demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in Kfc. Ventilation strategies altered lung NO concentration and the Kfc response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies. PMID:22160307

  6. PILOT-SCALE EVALUATION OF ENGINEERED BARIER SYSTEMS FOR THE YUCCA MOUNTAIN PROJECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    S.W. Webb; J.T. George; R.E. Finley

    This paper describes two quarter-scale experiments (1.4 m diameter) and associated numerical analyses on granular backfill engineered barrier systems in support of the Yucca Mountain Project for the potential repository. The two configurations include a sloped capillary barrier and a plain backfill. The tests involve application of dyed water as a constant line infiltration source along the top of the test set-up, monitoring water movement through the test, and measuring water exiting the experiments. A complete water balance estimate is made for each test, and observed water movement is compared with (1) detailed numerical analyses conducted using the TOUGH2 codemore » for unsaturated flow in porous media and (2) posttest observations. The results of the testing and analyses show that for the injection rates and configuration applied, the capillary barrier design diverts a significant amount of all injected water and the TOUGH2 pretest predictions show qualitative and quantitative agreement with the experimental data.« less

  7. Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

    PubMed

    Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

    2015-01-01

    The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

  8. Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery

    NASA Astrophysics Data System (ADS)

    Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.

    1993-04-01

    Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

  9. Improved single-cell culture achieved using micromolding in capillaries technology coupled with poly (HEMA).

    PubMed

    Ye, Fang; Jiang, Jin; Chang, Honglong; Xie, Li; Deng, Jinjun; Ma, Zhibo; Yuan, Weizheng

    2015-07-01

    Cell studies at the single-cell level are becoming more and more critical for understanding the complex biological processes. Here, we present an optimization study investigating the positioning of single cells using micromolding in capillaries technology coupled with the cytophobic biomaterial poly (2-hydroxyethyl methacrylate) (poly (HEMA)). As a cytophobic biomaterial, poly (HEMA) was used to inhibit cells, whereas the glass was used as the substrate to provide a cell adhesive background. The poly (HEMA) chemical barrier was obtained using micromolding in capillaries, and the microchannel networks used for capillarity were easily achieved by reversibly bonding the polydimethylsiloxane mold and the glass. Finally, discrete cell adhesion regions were presented on the glass surface. This method is facile and low cost, and the reagents are commercially available. We validated the cytophobic abilities of the poly (HEMA), optimized the channel parameters for higher quality and more stable poly (HEMA) patterns by investigating the effects of changing the aspect ratio and the width of the microchannel on the poly (HEMA) grid pattern, and improved the single-cell occupancy by optimizing the dimensions of the cell adhesion regions.

  10. Capillary device refilling. [liquid rocket propellant tank tests

    NASA Technical Reports Server (NTRS)

    Blatt, M. H.; Merino, F.; Symons, E. P.

    1980-01-01

    An analytical and experimental study was conducted dealing with refilling start baskets (capillary devices) with settled fluid. A computer program was written to include dynamic pressure, screen wicking, multiple-screen barriers, standpipe screens, variable vehicle mass for computing vehicle acceleration, and calculation of tank outflow rate and vapor pullthrough height. An experimental apparatus was fabricated and tested to provide data for correlation with the analytical model; the test program was conducted in normal gravity using a scale-model capillary device and ethanol as the test fluid. The test data correlated with the analytical model; the model is a versatile and apparently accurate tool for predicting start basket refilling under actual mission conditions.

  11. Nucleation time of nanoscale water bridges.

    PubMed

    Szoszkiewicz, Robert; Riedo, Elisa

    2005-09-23

    Water capillaries bind together grains of sand. They also can bind an atomic force microscope tip to a substrate. The kinetics of capillary condensation at the nanoscale is studied here using friction force microscopy. At 40% relative humidity we find that the meniscus nucleation times increase from 0.7 to 4.2 ms when the temperature decreases from 332 to 299 K. The nucleation times grow exponentially with the inverse temperature 1/T obeying an Arrhenius law. We obtain a nucleation energy barrier of 7.8 x 10(-20) J and an attempt frequency ranging between 4 and 250 GHz, in excellent agreement with theoretical predictions. These results provide direct experimental evidence that capillary condensation is a thermally activated phenomenon.

  12. Claudin-19 and the Barrier Properties of the Human Retinal Pigment Epithelium

    PubMed Central

    Peng, Shaomin; Rao, Veena S.; Adelman, Ron A.

    2011-01-01

    Purpose. The retinal pigment epithelium (RPE) separates photoreceptors from choroidal capillaries, but in age-related macular degeneration (AMD) capillaries breach the RPE barrier. Little is known about human RPE tight junctions or the effects of serum on the retinal side of the RPE. Methods. Cultured human fetal RPE (hfRPE) was assessed by the transepithelial electrical resistance (TER) and the transepithelial diffusion of methylated polyethylene glycol (mPEG). Claudins and occludin were monitored by quantitative RT-PCR, immunoblotting, and immunofluorescence. Results. Similar to freshly isolated hfRPE, claudin-19 mRNA was 25 times more abundant than claudin-3. Other detectable claudin mRNAs were found in even lesser amounts, as little as 3000 times less abundant than claudin-19. Claudin-1 and claudin-10b were detected only in subpopulations of cells, whereas others were undetectable. Knockdown of claudin-19 by small interfering RNA (siRNA) eliminated the TER. siRNAs for other claudins had minimal effects. Serum affected tight junctions only when presented to the retinal side of the RPE. The TER increased 2 times, and the conductance of K+ relative to Na+ decreased without affecting the permeability of mPEG. These effects correlated with increased steady-state levels of occludin. Conclusions. Fetal human RPE is a claudin-19–dominant epithelium that has regional variations in claudin-expression. Apical serum decreases RPE permeability, which might be a defense mechanism that would retard the spread of edema due to AMD. PMID:21071746

  13. Pericytes of the neurovascular unit: Key functions and signaling pathways

    PubMed Central

    Sweeney, Melanie D.; Ayyadurai, Shiva; Zlokovic, Berislav V.

    2017-01-01

    Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies. PMID:27227366

  14. Alterations of the Blood-Brain Barrier and Regional Perfusion in Tumor Development: MRI Insights from a Rat C6 Glioma Model.

    PubMed

    Huhndorf, Monika; Moussavi, Amir; Kramann, Nadine; Will, Olga; Hattermann, Kirsten; Stadelmann, Christine; Jansen, Olav; Boretius, Susann

    2016-01-01

    Angiogenesis and anti-angiogenetic medications play an important role in progression and therapy of glioblastoma. In this context, in vivo characterization of the blood-brain-barrier and tumor vascularization may be important for individual prognosis and therapy optimization. We analyzed perfusion and capillary permeability of C6-gliomas in rats at different stages of tumor-growth by contrast enhanced MRI and dynamic susceptibility contrast (DSC) MRI at 7 Tesla. The analyses included maps of relative cerebral blood volume (CBV) and signal recovery derived from DSC data over a time period of up to 35 days after tumor cell injections. In all rats tumor progression was accompanied by temporal and spatial changes in CBV and capillary permeability. A leakage of the blood-brain barrier (slow contrast enhancement) was observed as soon as the tumor became detectable on T2-weighted images. Interestingly, areas of strong capillary permeability (fast signal enhancement) were predominantly localized in the center of the tumor. In contrast, the tumor rim was dominated by an increased CBV and showed the highest vessel density compared to the tumor center and the contralateral hemisphere as confirmed by histology. Substantial regional differences in the tumor highlight the importance of parameter maps in contrast or in addition to region-of-interest analyses. The data vividly illustrate how MRI including contrast-enhanced and DSC-MRI may contribute to a better understanding of tumor development.

  15. Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow

    PubMed Central

    Kwee, Ingrid L.

    2017-01-01

    The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics. PMID:28820467

  16. Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

    PubMed

    Nakada, Tsutomu; Kwee, Ingrid L; Igarashi, Hironaka; Suzuki, Yuji

    2017-08-18

    The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

  17. Asymmetric and speed-dependent contact angle hysteresis and relaxation of a suddenly stopped moving contact line

    NASA Astrophysics Data System (ADS)

    Guan, Dongshi; Wang, Yong Jian; Charlaix, Elisabeth; Tong, Penger

    We report direct atomic-force-microscope measurements of capillary force hysteresis and relaxation of a circular moving contact line (CL) formed on a long micron-sized hydrophobic fiber intersecting a water-air interface. The measured capillary force hysteresis and CL relaxation show a strong asymmetric speed dependence in the advancing and receding directions. A unified model based on force-assisted barrier-crossing is utilized to find the underlying energy barrier Eb and size λ associated with the defects on the fiber surface. The experiment demonstrates that the pinning (relaxation) and depinning dynamics of the CL can be described by a common microscopic frame-work, and the advancing and receding CLs are influenced by two different sets of relatively wetting and non-wetting defects on the fiber surface. Work supported in part by the Research Grants Council of Hong Kong SAR.

  18. Miniaturized technology for DNA typing: cassette PCR.

    PubMed

    Manage, Dammika P; Pilarski, Linda M

    2015-01-01

    With the smaller size, low cost, and rapid testing capabilities, miniaturized lab-on-a-chip devices can change the way medical diagnostics are currently performed in the health-care system. We have demonstrated such a device that is self-contained, simple, disposable, and inexpensive. It is capable of performing DNA amplification on an inexpensive instrument suitable for near point of care settings. This technology will enable on the spot evaluation of patients in the clinic for faster medical decision-making and more informed therapeutic choices. Our device, a gel capillary cassette, termed cassette PCR, contains capillary reaction units each holding a defined primer set, with arrays of capillary reaction units for simultaneously detecting multiple targets. With the exception of the sample to be tested, each capillary reaction unit holds all the reagents needed for PCR in a desiccated form that can be stored at room temperature for up to 3 months and even longer in colder conditions. It relies on capillary forces for sample delivery of microliter volumes through capillaries, hence avoiding the need for pumps or valves. In the assembled cassette, the wax architecture supporting the capillaries melts during the PCR and acts as a vapor barrier as well as segregating capillaries with different primer sets. No other chip sealing techniques are required. Cassette PCR accepts raw samples such as urine, genital swabs, and blood. The cassette is made with off-the-shelf components and contains integrated positive and negative controls.

  19. In situ formation of phosphate barriers in soil

    DOEpatents

    Moore, Robert C.

    2002-01-01

    Reactive barriers and methods for making reactive barriers in situ in soil for sequestering soil ontaminants including actinides and heavy metals. The barrier includes phosphate, and techniques are disclosed for forming specifically apatite barriers. The method includes injecting dilute reagents into soil in proximity to a contamination plume or source such as a waste drum to achieve complete or partial encapsulation of the waste. Controlled temperature and pH facilitates rapid formation of apatite, for example, where dilute aqueous calcium chloride and dilute aqueous sodium phosphate are the selected reagents. Mixing of reagents to form precipitate is mediated and enhanced through movement of reagents in soil as a result of phenomena including capillary action, movement of groundwater, soil washing and reagent injection pressure.

  20. Dietary supplementation with soybean lecithin increases pulmonary PAF bioactivity in asthmatic rats.

    PubMed

    Muehlmann, Luis A; Zanatta, Ana L; Farias, Carolina L A; Bieberbach, Eloyse W; Mazzonetto, Ana C; Michellotto, Pedro V; Fernandes, Luiz C; Nishiyama, Anita

    2010-06-01

    The prevalence of asthma has risen over the last few decades, and some studies correlate this with the greater consumption of polyunsaturated fatty acids (PUFAs). Dietary PUFAs are known to increase the susceptibility of biological structures to lipid peroxidation, a process by which platelet-activating factor (PAF)-like lipids can be generated. These lipids functionally mimic the bioactivity of PAF, a potent proinflammatory mediator that exerts several deleterious effects on asthma. Thus, this work aimed to investigate if dietary supplementation with soybean lecithin (SL), a source of PUFAs, increases lipid peroxidation and PAF bioactivity in lungs of asthmatic Wistar rats. Animals were separated into groups: control, supplemented, asthmatic, asthmatic supplemented with SL (2 g/kg body weight), asthmatic supplemented with SL (2 g/kg body weight) and DL-alpha-tocopheryl acetate (100 mg/kg body weight). Asthmatic inflammation increased pulmonary lipid peroxidation, PAF bioactivity, alveolar-capillary barrier permeability and production of nitric oxide. In asthmatics, dietary supplementation with SL promoted an increase in pulmonary lipid peroxidation and PAF bioactivity, and an increase in the permeability of the alveolar-capillary barrier. Moreover, the treatment of asthmatic rats with DL-alpha-tocopheryl acetate inhibited the lipid peroxidation and decreased the PAF bioactivity. Therefore, the increase in pulmonary PAF bioactivity in asthmatic individuals elicited by the dietary supplementation with SL probably involves the generation of PAF-like lipids. This finding suggests that PAF-like lipids may account for the deleterious effects of dietary PUFAs on asthma. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Learning from our failures in blood-brain permeability: what can be done for new drug discovery?

    PubMed

    Martel, Sylvain

    2015-03-01

    Many existing pharmaceuticals are rendered ineffective in the treatment of cerebral diseases due to a permeability barrier well known as the blood-brain barrier (BBB). Such barrier between the blood within brain capillaries and the extracellular fluid in brain tissue has motivated several approaches aimed at delivering therapeutics to the brain. These approaches rely on strategies that can be classified as molecular modifications, the use of BBB bypassing pathways, and BBB disruptions. Although several of these approaches that have been investigated so far show promising results, none has addressed the optimization of the ratio of the dose of the drug molecules that contributes to the therapeutic effects. As such, the extensive research efforts, such as prioritizing the enhancement of the BBB permeability alone is likely to fail to provide the best therapeutic effects for a given dose if prior systemic circulation is not avoided while enhancing the spatial targeting only to regions of the brain that need treatment. Hence, new therapeutics for the brain could be synthesized to take advantage of recent technologies for non-systemic delivery and spatially targeted brain uptake.

  2. [The blood-brain barrier in ageing persons].

    PubMed

    Haaning, Nina; Damsgaard, Else Marie; Moos, Torben

    2018-03-26

    Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier (BBB). The permeability of the BBB increases with increasing age and neurovascular and neurodegenerative diseases. Major defects of the BBB can be initiated by increased permeability to plasma proteins in small arteriosclerotic arteries and release of proteins from degenerating neurons into the brain extracellular space. These proteins deposit in perivascular spaces, and subsequently negatively influence the BECs leading to decreased expression of barrier proteins. Detection of BBB defects by the use of non-invasive techniques is relevant for clinical use in settings with advanced age and severe brain disorders.

  3. Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

    PubMed

    Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

    2010-12-01

    Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

  4. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    PubMed

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

  5. [Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

    PubMed

    Kubo, Yoshiyuki

    2015-01-01

    Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

  6. Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases.

    PubMed

    Gabathuler, Reinhard

    2010-01-01

    The central nervous system is protected by barriers which control the entry of compounds into the brain, thereby regulating brain homeostasis. The blood-brain barrier, formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and facilitates nutrients essential for normal metabolism to reach brain cells. This very tight regulation of the brain homeostasis results in the inability of some small and large therapeutic compounds to cross the blood-brain barrier (BBB). Therefore, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. In this review, we will address the different approaches used to increase the transport of therapeutics from blood into the brain parenchyma. We will mainly concentrate on the physiologic approach which takes advantage of specific receptors already expressed on the capillary endothelial cells forming the BBB and necessary for the survival of brain cells. Among all the approaches used for increasing brain delivery of therapeutics, the most accepted method is the use of the physiological approach which takes advantage of the transcytosis capacity of specific receptors expressed at the BBB. The low density lipoprotein receptor related protein (LRP) is the most adapted for such use with the engineered peptide compound (EPiC) platform incorporating the Angiopep peptide in new therapeutics the most advanced with promising data in the clinic.

  7. Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart.

    PubMed

    Wang, Zhong; Zhu, Tong; Qiao, Chunping; Zhou, Liqiao; Wang, Bing; Zhang, Jian; Chen, Chunlian; Li, Juan; Xiao, Xiao

    2005-03-01

    Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.

  8. Quantitative aspects of vibratory mobilization and break-up of non-wetting fluids in porous media

    NASA Astrophysics Data System (ADS)

    Deng, Wen

    Seismic stimulation is a promising technology aimed to mobilize the entrapped non-wetting fluids in the subsurface. The applications include enhanced oil recovery or, alternatively, facilitation of movement of immiscible/partly-miscible gases far into porous media, for example, for CO2 sequestration. This work is devoted to detailed quantitative studies of the two basic pore-scale mechanisms standing behind seismic stimulation: the mobilization of bubbles or drops entrapped in pore constrictions by capillary forces and the break-up of continuous long bubbles or drops. In typical oil-production operations, oil is produced by the natural reservoir-pressure drive during the primary stage and by artificial water flooding at the secondary stage. Capillary forces act to retain a substantial residual fraction of reservoir oil even after water flooding. The seismic stimulation is an unconventional technology that serves to overcome capillary barriers in individual pores and liberate the entrapped oil by adding an oscillatory inertial forcing to the external pressure gradient. According to our study, the effect of seismic stimulation on oil mobilization is highly dependent on the frequencies and amplitudes of the seismic waves. Generally, the lower the frequency and the larger the amplitude, more effective is the mobilization. To describe the mobilization process, we developed two theoretical hydrodynamics-based models and justified both using computational fluid dynamics (CFD). Our theoretical models have a significant advantage over CFD in that they reduce the computational time significantly, while providing correct practical guidance regarding the required field parameters of vibroseismic stimulation, such as the amplitude and frequency of the seismic field. The models also provide important insights into the basic mechanisms governing the vibration-driven two-phase flow in constricted capillaries. In a waterflooded reservoir, oil can be recovered most efficiently by forming continuous streams from isolated droplets. The longer the continuous oil phase under a certain pressure gradient, the more easily it overcomes its capillary barrier. However, surface tension between water and oil causes the typically non-wetting oil, constituting the core phase in the channels, to break up at the pore constriction into isolated beads, which inhibits further motion. The break-up thus counteracts the mobilization. We developed a theoretical model that provides an exact quantitative description of the dynamics of the oil-snap-off process. It also formulates a purely geometric criterion that controls, based on pore geometry only, whether the oil core phase stays continuous or disintegrates into droplets. Both the theoretical model and the break-criterion have been validated against CFD simulations. The work completed elucidates the basic physical mechanisms behind the enhanced oil recovery by seismic waves and vibrations. This creates a theoretical foundation for the further development of corresponding field technologies.

  9. The angiopoietin1-Akt pathway regulates barrier function of the cultured spinal cord microvascular endothelial cells through Eps8.

    PubMed

    Liu, Xinchun; Zhou, Xiaoshu; Yuan, Wei

    2014-10-15

    In mammalian central nervous system (CNS), the integrity of the blood-spinal cord barrier (BSCB), formed by tight junctions (TJs) between adjacent microvascular endothelial cells near the basement membrane of capillaries and the accessory structures, is important for relatively independent activities of the cellular constituents inside the spinal cord. The barrier function of the BSCB are tightly regulated and coordinated by a variety of physiological or pathological factors, similar with but not quite the same as its counterpart, the blood-brain barrier (BBB). Herein, angiopoietin 1 (Ang1), an identified ligand of the endothelium-specific tyrosine kinase receptor Tie-2, was verified to regulate barrier functions, including permeability, junction protein interactions and F-actin organization, in cultured spinal cord microvascular endothelial cells (SCMEC) of rat through the activity of Akt. Besides, these roles of Ang1 in the BSCB in vitro were found to be accompanied with an increasing expression of epidermal growth factor receptor pathway substrate 8 (Eps8), an F-actin bundling protein. Furthermore, the silencing of Eps8 by lentiviral shRNA resulted in an antagonistic effect vs. Ang1 on the endothelial barrier function of SCMEC. In summary, the Ang1-Akt pathway serves as a regulator in the barrier function modulation of SCMEC via the actin-binding protein Eps8. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Protein kinase C restricts transport of carnitine by amino acid transporter ATB(0,+) apically localized in the blood-brain barrier.

    PubMed

    Michalec, Katarzyna; Mysiorek, Caroline; Kuntz, Mélanie; Bérézowski, Vincent; Szczepankiewicz, Andrzej A; Wilczyński, Grzegorz M; Cecchelli, Roméo; Nałęcz, Katarzyna A

    2014-07-15

    Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood-brain barrier (BBB). Expression and presence of two carnitine transporters - organic cation/carnitine transporter (OCTN2) and amino acid transporter B(0,+) (ATB(0,+)) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB(0,+) sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB(0,+) can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB(0,+) luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB(0,+) was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB(0,+) present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB(0,+) inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM

    PubMed Central

    Hicks, R. M.

    1966-01-01

    Permeability barriers must exist in transitional epithelium to prevent the free flow of water from underlying blood capillaries through the epithelium into the hypertonic urine, and such a barrier has now been demonstrated in isolated bladders. This barrier is passive in function and can be destroyed by damaging the luminal surface of the transitional epithelium with sodium hydroxide and 8 M urea solutions, by digesting it with trypsin, lecithinase C, and lecithinase D, or by treating it with lipid solvents such as Triton x 100 and saponin. From this it is concluded that the barrier depends on the integrity of lipoprotein cell membranes. The barrier function is also destroyed by sodium thioglycollate solutions, and electron microscope investigations show that sodium thioglycollate damages the thick asymmetric membrane which limits the luminal face of the superficial squamous cell. Cytochemical staining shows the epithelium to contain disulfide and thiol groups and to have a concentration of these groups at the luminal margin of the superficial cells. It thus appears that the permeability barrier also depends on the presence of disulfide bridges in the epithelium, and it is presumed that these links are located in keratin. Because of the effect of thioglycollates, both on the barrier function and on the morphology of the membrane, it is suggested that keratin may be incorporated in the thick barrier membrane. It is proposed that the cells lining the urinary bladder and ureters should be regarded as a keratinizing epitheluim. PMID:5901498

  12. Multilayer coatings for flexible high-barrier materials

    NASA Astrophysics Data System (ADS)

    Vaško, Karol; Noller, Klaus; Mikula, Milan; Amberg-Schwab, Sabine; Weber, Ulrike

    2009-06-01

    A multilayer, flexible, and transparent high-barrier system based on flexible plastic foils, polyethyleneterephthalate (PET) and ethylene-tetrafluoroethylene-copolymer (ETFE), combined with vacuum-deposited, inorganic SiOx layers and hybrid ORMOCER® varnish layers were prepared in different orders on a semiproduction level. Barrier properties of prepared systems, as water vapour transmission (WVTR) and oxygen transmission (OTR), were measured and studied in connection with surface energy, surface topography, and water vapour adsorption properties. Correlations among layers sequence, barrier properties, and other parameters are presented, including some basic principles of permeation of substances through multilayer barrier systems. A combination of several inorganic and hybrid varnish layers is necessary to achieve the technological demands from a barrier standpoint. It is easier to suppress the oxygen transport than the water transport, due to the additional active penetration of water through hydrogen bonds and silanol creations at oxide interfaces, capillary condensation, and swelling with high internal pressure, leading to new defects.

  13. Fluid balance within the canine anterolateral compartment and its relationship to compartment syndromes.

    PubMed

    Hargens, A R; Akeson, W H; Mubarak, S J; Owen, C A; Evans, K L; Garetto, L P; Gonsalves, M R; Schmidt, D A

    1978-06-01

    Fluid homeostasis within muscle compartments is maintained by four pressures: capillary blood pressure, capillary blood oncotic pressure, tissue-fluid pressure, and tissue fluid oncotic pressure. As determined in the canine anterolateral compartment, capillary blood pressure is 25 +/- 3 millimeters of mercury; capillary blood oncotic pressure, 26 +/- 3 millimeters of mercury, tissue-pbessure, -2 +/- 2 millimeters of mercury; and tissue-fluid oncotic pressure, 11 +/- 1 millimeters of mercury. The wick technique allows direct measurement of tissue-fluid pressure in skeletal muscle and, with minor modifications, is adapted to collect microsamples of interstitial fluid for determinations of tissue-fluid oncotic pressure. The wick technique detects very slight fluctuations in intracompartmental pressure such as light finger compression, injection of small volumes of fluid, and even pulsation due to adjacent arterial pressure. Adjacent muscle compartments may contain different tissue-fluid pressure due to impermeable osseofascial barriers. Our results obtained in canine muscle compartments pressurized by infusion of autologous plasma suggest that risks of muscle damage are significant at intracompartmental pressures greater than thirty millimeters of mercury.

  14. Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood–brain barrier

    PubMed Central

    Mairey, Emilie; Genovesio, Auguste; Donnadieu, Emmanuel; Bernard, Christine; Jaubert, Francis; Pinard, Elisabeth; Seylaz, Jacques; Olivo-Marin, Jean-Christophe; Nassif, Xavier; Duménil, Guillaume

    2006-01-01

    Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood–brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development. PMID:16864659

  15. Effects of microstructure on water imbibition in sandstones using X-ray computed tomography and neutron radiography

    NASA Astrophysics Data System (ADS)

    Zhao, Yixin; Xue, Shanbin; Han, Songbai; Chen, Zhongwei; Liu, Shimin; Elsworth, Derek; He, Linfeng; Cai, Jianchao; Liu, Yuntao; Chen, Dongfeng

    2017-07-01

    Capillary imbibition in variably saturated porous media is important in defining displacement processes and transport in the vadose zone and in low-permeability barriers and reservoirs. Nonintrusive imaging in real time offers the potential to examine critical impacts of heterogeneity and surface properties on imbibition dynamics. Neutron radiography is applied as a powerful imaging tool to observe temporal changes in the spatial distribution of water in porous materials. We analyze water imbibition in both homogeneous and heterogeneous low-permeability sandstones. Dynamic observations of the advance of the imbibition front with time are compared with characterizations of microstructure (via high-resolution X-ray computed tomography (CT)), pore size distribution (Mercury Intrusion Porosimetry), and permeability of the contrasting samples. We use an automated method to detect the progress of wetting front with time and link this to square-root-of-time progress. These data are used to estimate the effect of microstructure on water sorptivity from a modified Lucas-Washburn equation. Moreover, a model is established to calculate the maximum capillary diameter by modifying the Hagen-Poiseuille and Young-Laplace equations based on fractal theory. Comparing the calculated maximum capillary diameter with the maximum pore diameter (from high-resolution CT) shows congruence between the two independent methods for the homogeneous silty sandstone but less effectively for the heterogeneous sandstone. Finally, we use these data to link observed response with the physical characteristics of the contrasting media—homogeneous versus heterogeneous—and to demonstrate the sensitivity of sorptivity expressly to tortuosity rather than porosity in low-permeability sandstones.

  16. Mechanisms That Modulate Peripheral Oxygen Delivery during Exercise in Heart Failure.

    PubMed

    Kisaka, Tomohiko; Stringer, William W; Koike, Akira; Agostoni, Piergiuseppe; Wasserman, Karlman

    2017-07-01

    Oxygen uptake ([Formula: see text]o 2 ) measured at the mouth, which is equal to the cardiac output (CO) times the arterial-venous oxygen content difference [C(a-v)O 2 ], increases more than 10- to 20-fold in normal subjects during exercise. To achieve this substantial increase in oxygen uptake [[Formula: see text]o 2  = CO × C(a-v)O 2 ] both CO and the arterial-venous difference must simultaneously increase. Although this occurs in normal subjects, patients with heart failure cannot achieve significant increases in cardiac output and must rely primarily on changes in the arterial-venous difference to increase [Formula: see text]o 2 during exercise. Inadequate oxygen delivery to the tissue during exercise in heart failure results in tissue anaerobiosis, lactic acid accumulation, and reduction in exercise tolerance. H + is an important regulatory and feedback mechanism to facilitate additional oxygen delivery to the tissue (Bohr effect) and further aerobic production of ATP when tissue anaerobic metabolism increases the production of lactate (anaerobic threshold). This H + production in the muscle capillary promotes the continued unloading of oxygen (oxyhemoglobin desaturation) while maintaining the muscle capillary Po 2 (Fick principle) at a sufficient level to facilitate aerobic metabolism and overcome the diffusion barriers from capillary to mitochondria ("critical capillary Po 2 ," 15-20 mm Hg). This mechanism is especially important during exercise in heart failure where cardiac output increase is severely constrained. Several compensatory mechanisms facilitate peripheral oxygen delivery during exercise in both normal persons and patients with heart failure.

  17. Hyperfiltration-mediated injury in the remaining kidney of a transplant donor.

    PubMed

    Srivastava, Tarak; Hariharan, Sundaram; Alon, Uri S; McCarthy, Ellen T; Sharma, Ram; El-Meanawy, Ashraf; Savin, Virginia J; Sharma, Mukut

    2018-05-29

    Kidney donors face a small but definite risk of end-stage renal disease 15-30 years postdonation. The development of proteinuria, hypertension with gradual decrease in kidney function in the donor after surgical resection of 1 kidney has been attributed to hyperfiltration. Genetic variations, physiological adaptations, and co-morbidities exacerbate the hyperfiltration-induced loss of kidney function in the years following donation. A focus on glomerular hemodynamics and capillary pressure has led to the development of drugs that target the renin-angiotensin-aldosterone system (RAAS), but these agents yield mixed results in transplant recipients and donors. Recent work on glomerular biomechanical forces highlights the differential effects of tensile stress and fluid flow shear stress (FFSS) from hyperfiltration. Capillary wall stretch due to glomerular capillary pressure increases tensile stress on podocyte foot processes that cover the capillary. In parallel, increased flow of the ultrafiltrate due to single nephron glomerular filtration rate elevates FFSS on the podocyte cell body. While tensile stress invokes the RAAS, FFSS predominantly activates the COX2-PGE2-EP2 axis. Distinguishing these 2 mechanisms is critical, as current therapeutic approaches focus on the RAAS system. A better understanding of the biomechanical forces can lead to novel therapeutic agents to target FFSS through the COX2-PGE2-EP2 axis in hyperfiltration-mediated injury. We present an overview of several aspects of the risk to transplant donors and discuss the relevance of FFSS in podocyte injury, loss of glomerular barrier function leading to albuminuria and gradual loss of renal function, and potential therapeutic strategies to mitigate hyperfiltration-mediated injury to the remaining kidney.

  18. Targeted drug delivery to the brain using magnetic nanoparticles.

    PubMed

    Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Moos, Torben

    2015-01-01

    Brain capillary endothelial cells denote the blood-brain barrier (BBB), and conjugation of nanoparticles with antibodies that target molecules expressed by these endothelial cells may facilitate their uptake and transport into the brain. Magnetic nanoparticles can be encapsulated in liposomes and carry large molecules with therapeutic potential, for example, siRNA, cDNA and polypeptides. An additional approach to enhance the transport of magnetic nanoparticles across the BBB is the application of extracranially applied magnetic force. Stepwise targeting of magnetic nanoparticles to brain capillary endothelial cells followed by transport through the BBB using magnetic force may prove a novel mechanism for targeted therapy of macromolecules to the brain.

  19. Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1.

    PubMed

    Banks, W A; Wustrow, D J; Cody, W L; Davis, M D; Kastin, A J

    1995-10-09

    Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic potential. We used multiple-time regression analysis to measure the unidirectional influx constant (Ki) of a tritiated analog of NT8-13, NT1, with improved metabolic stability. The Ki of [3H]NT1 across the blood-brain barrier (BBB) was 5.12(10(-4)) ml/g-min and was decreased 66% by unlabeled NT1 system. The amount of NT1 crossing the BBB, 0.087% of the injected dose per gram of brain, is consistent with its exerting central effects after peripheral administration. The stable [3H]NT1 crossed the BBB in intact form as assessed by HPLC and completely crossed the endothelial cells that comprise the BBB as assessed by the capillary depletion method. The presence of a transport system could be important for the development of NT analogs.

  20. Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

    PubMed

    Bragin, Denis E; Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

    2017-03-01

    Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

  1. Pericytes as Inducers of Rapid, Matrix Metalloproteinase-9-Dependent Capillary Damage during Ischemia

    PubMed Central

    Underly, Robert G.; Levy, Manuel; Hartmann, David A.; Grant, Roger I.; Watson, Ashley N.

    2017-01-01

    Blood–brain barrier disruption (BBB) and release of toxic blood molecules into the brain contributes to neuronal injury during stroke and other cerebrovascular diseases. While pericytes are builders and custodians of the BBB in the normal brain, their impact on BBB integrity during ischemia remains unclear. We imaged pericyte-labeled transgenic mice with in vivo two-photon microscopy to examine the relationship between pericytes and blood plasma leakage during photothrombotic occlusion of cortical capillaries. Upon cessation of capillary flow, we observed that plasma leakage occurred with three times greater frequency in regions where pericyte somata adjoined the endothelium. Pericyte somata covered only 7% of the total capillary length in cortex, indicating that a disproportionate amount of leakage occurred from a small fraction of the capillary bed. Plasma leakage was preceded by rapid activation of matrix metalloproteinase (MMP) at pericyte somata, which was visualized at high resolution in vivo using a fluorescent probe for matrix metalloproteinase-2/9 activity, fluorescein isothiocyanate (FITC)-gelatin. Coinjection of an MMP-9 inhibitor, but not an MMP-2 inhibitor, reduced pericyte-associated FITC-gelatin fluorescence and plasma leakage. These results suggest that pericytes contribute to rapid and localized proteolytic degradation of the BBB during cerebral ischemia. SIGNIFICANCE STATEMENT Pericytes are a key component of the neurovascular unit and are essential for normal BBB function. However, during acute ischemia, we find that pericytes are involved in creating rapid and heterogeneous BBB disruption in the capillary bed. The mechanism by which pericytes contribute to BBB damage warrants further investigation, as it may yield new therapeutic targets for acute stroke injury and other neurological diseases involving capillary flow impairment. PMID:28053036

  2. Fetal villosity and microvasculature of the bovine placentome in the second half of gestation

    PubMed Central

    LEISER, R.; KREBS, C.; KLISCH, K.; EBERT, B.; DANTZER, V.; SCHULER, G.; HOFFMANN, B.

    1997-01-01

    The architecture of the fetal villous tree and its vasculature in the bovine placentome were studied in the second half of gestation using both conventional histology and histology of ink-filled blood vessels. These were compared with corrosion casts of plastic fillings of the vasculature, prepared for scanning electron microscopy. This combination of morphological methods allows perception of the villous tree throughout gestation from broad-conical to tall-conical form where branch ramification occurs mainly at right angles to the stem. The stem villus typically contains a single central artery and several peripheral veins arranged in parallel. The proximal branches to the stem, the intermediate villi, contain a central arteriole and accompanying venules. The distal branches, the terminal villi, enclose capillary convolutions which consist of an afferent arterial capillary limb, capillary loops and efferent venous capillary limbs. Vascular interconnections exist within the terminal villi, as capillaries or venules between the capillary convolutions, serially bridging them in up to 5 places, and as capillary anastomoses between the capillary loops. Coiling and sinusoidal dilatations of these loops develop near the end of gestation. The intraplacentomal rearrangement of villous trees with progressive gestation and their morphological vascular adaptations are discussed in relation to placental function, including the ever increasing need for transplacental substance exchange. This adaptation allows the blood to traverse the shortest possible arterioarteriolar route to the periphery of the trees where exchange takes place. The need for an increasing blood flow stimulates capillary growth and at the same time optimises the blood flow reaching the placental barrier represented by the vessel cast surface. The capillaries also carry the blood back into the very voluminous system of venules and veins where back diffusion may occur. The total volume of terminal villi of bovine placentome, the ‘working part’ of villous trees, hence distinctly increases with respect to the stem and intermediate villi, the ‘supplying part’ of the villous tree. In morphological terms the efficiency of the bovine transplacental diffusional exchange is higher than in the closely related ‘co-ruminants’ sheep and goats and distinctly higher when compared with the human placenta. PMID:9449071

  3. Cationic amino acid transporter 1-mediated L-arginine transport at the inner blood-retinal barrier.

    PubMed

    Tomi, Masatoshi; Kitade, Naohisa; Hirose, Shirou; Yokota, Noriko; Akanuma, Shin-Ichi; Tachikawa, Masanori; Hosoya, Ken-ichi

    2009-11-01

    The purpose of this study was to identify the transporter mediating l-arginine transport at the inner blood-retinal barrier (BRB). The apparent uptake clearance of [(3)H]L-arginine into the rat retina was found to be 118 microL/(min.g retina), supporting a carrier-mediated influx transport of L-arginine at the BRB. [(3)H]L-arginine uptake by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), used as an in vitro model of the inner BRB, was primarily an Na(+)-independent and saturable process with Michaelis-Menten constants of 11.2 microM and 530 microM. This process was inhibited by rat cationic amino acid transporter (CAT) 1-specific small interfering RNA as well as substrates of CATs, L-arginine, L-lysine, and L-ornithine. The expression of cationic amino acid transporter (CAT) 1 mRNA was 25.9- and 796-fold greater than that of CAT3 in TR-iBRB2 and magnetically isolated rat retinal vascular endothelial cells, respectively. The expression of CAT1 protein was detected in TR-iBRB2 cells and immunostaining of CAT1 was observed along the rat retinal capillaries. In conclusion, CAT1 is localized in retinal capillary endothelial cells and at least in part mediates L-arginine transport at the inner BRB. This process seems to be closely involved in visual functions by supplying precursors of biologically important molecules like nitric oxide in the neural retina.

  4. Inner Blood-Retinal Barrier Dominantly Expresses Breast Cancer Resistance Protein: Comparative Quantitative Targeted Absolute Proteomics Study of CNS Barriers in Pig.

    PubMed

    Zhang, Zhengyu; Uchida, Yasuo; Hirano, Satoshi; Ando, Daisuke; Kubo, Yoshiyuki; Auriola, Seppo; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi; Urtti, Arto; Terasaki, Tetsuya; Tachikawa, Masanori

    2017-11-06

    The purpose of this study was to determine absolute protein expression levels of transporters at the porcine inner blood-retinal barrier (BRB) and to compare the transporter protein expression quantitatively among the inner BRB, outer BRB, blood-brain barrier (BBB), and blood-cerebrospinal fluid barrier (BCSFB). Crude membrane fractions of isolated retinal capillaries (inner BRB) and isolated retinal pigment epithelium (RPE, outer BRB) were prepared from porcine eyeballs, while plasma membrane fractions were prepared from isolated porcine brain capillaries (BBB) and isolated choroid plexus (BCSFB). Protein expression levels of 32 molecules, including 16 ATP-binding-cassette (ABC) transporters and 13 solute-carrier (SLC) transporters, were measured using a quantitative targeted absolute proteomic technique. At the inner BRB, five molecules were detected: breast cancer resistance protein (BCRP, ABCG2; 22.8 fmol/μg protein), multidrug resistance protein 1 (MDR1, ABCB1; 8.70 fmol/μg protein), monocarboxylate transporter 1 (MCT1, SLC16A1; 4.83 fmol/μg protein), glucose transporter 1 (GLUT1, SLC2A1; 168 fmol/μg protein), and sodium-potassium adenosine triphosphatase (Na + /K + -ATPase; 53.7 fmol/μg protein). Other proteins were under the limits of quantification. Expression of MCT1 was at least 17.6-, 11.0-, and 19.2-fold greater than those of MCT2, 3, and 4, respectively. The transporter protein expression at the inner BRB was most highly correlated with that at the BBB (R 2 = 0.8906), followed by outer BRB (R 2 = 0.7988) and BCSFB (R 2 = 0.4730). Sodium-dependent multivitamin transporter (SMVT, SLC5A6) and multidrug resistance-associated protein 1 (MRP1, ABCC1) were expressed at the outer BRB (0.378 and 1.03 fmol/μg protein, respectively) but were under the limit of quantification at the inner BRB. These findings may be helpful for understanding differential barrier function.

  5. Effect of Capillary Tube’s Shape on Capillary Rising Regime for Viscos Fluids

    NASA Astrophysics Data System (ADS)

    Soroush, F.; Moosavi, A.

    2018-05-01

    When properties of the displacing fluid are considered, the rising profile of the penetrating fluid in a capillary tube deviates from its classical Lucas-Washburn profile. Also, shape of capillary tube can affect the rising profile in different aspects. In this article, effect of capillary tube’s shape on the vertical capillary motion in presence of gravity is investigated by considering the properties of the displacing fluid. According to the fact that the differential equation of the capillary rising for a non-simple wall type is very difficult to solve analytically, a finite element simulation model is used for this study. After validation of the simulation model with an experiment that has been done with a simple capillary tube, shape of the capillary tube’s wall is changed in order to understand its effects on the capillary rising and different motion regimes that may appear according to different geometries. The main focus of this article is on the sinusoidal wall shapes and comparing them with a simple wall.

  6. Pulse wave myelopathy: An update of an hypothesis highlighting the similarities between syringomyelia and normal pressure hydrocephalus.

    PubMed

    Bateman, Grant A

    2015-12-01

    Most hypotheses trying to explain the pathophysiology of idiopathic syringomyelia involve mechanisms whereby CSF is pumped against a pressure gradient, from the subarachnoid space into the cord parenchyma. On review, these theories have universally failed to explain the disease process. A few papers have suggested that the syrinx fluid may originate from the cord capillary bed itself. However, in these papers, the fluid is said to accumulate due to impaired fluid drainage out of the cord. Again, there is little evidence to substantiate this. This proffered hypothesis looks at the problem from the perspective that syringomyelia and normal pressure hydrocephalus are almost identical in their manifestations but only differ in their site of effect within the neuraxis. It is suggested that the primary trigger for syringomyelia is a reduction in the compliance of the veins draining the spinal cord. This reduces the efficiency of the pulse wave dampening, occurring within the cord parenchyma, increasing arteriolar and capillary pulse pressure. The increased capillary pulse pressure opens the blood-spinal cord barrier due to a direct effect upon the wall integrity and interstitial fluid accumulates due to an increased secretion rate. An increase in arteriolar pulse pressure increases the kinetic energy within the cord parenchyma and this disrupts the cytoarchitecture allowing the fluid to accumulate into small cystic regions in the cord. With time the cystic regions coalesce to form one large cavity which continues to increase in size due to the ongoing interstitial fluid secretion and the hyperdynamic cord vasculature. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  7. Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1α to Reduce Acute Lung Inflammation and Injury in Mice

    PubMed Central

    Quintero, Pablo A.; Knolle, Martin D.; Cala, Luisa F.; Zhuang, Yuehong; Owen, Caroline A.

    2010-01-01

    To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8−/− mice versus WT mice or subjected the mice to hyperoxia (95% O2) and measured lung inflammation and injury at intervals. MMP-8−/− mice with ALI had greater increases in lung PMN and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8−/− mice had more macrophage inflammatory protein-1α (MIP-1α) than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1α−/− mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1α promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1α in MMP-8−/− mice abrogated the increased lung inflammation and injury and mortality in MMP-8−/− mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1α in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1α-degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1α. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI. PMID:20042585

  8. Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells.

    PubMed

    Nielsen, Simone S E; Siupka, Piotr; Georgian, Ana; Preston, Jane E; Tóth, Andrea E; Yusof, Siti R; Abbott, N Joan; Nielsen, Morten S

    2017-09-24

    The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 ± 80 Ω cm 2 , and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10 -6 ± 0.13 10 -6 cm sec -1 (mean ± SEM, n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking.

  9. Experimental Investigation of the Influence of Small Scale Geological Heterogeneity on Capillary Trapping of CO2 Using Engineered Beadpacks

    NASA Astrophysics Data System (ADS)

    Ganesan Krishnamurthy, P.; Trevisan, L.; Meckel, T. A.

    2017-12-01

    During geologic CO2 sequestration, most of the storage domain far from the injection sites is likely to be dominated by buoyancy and capillary forces. Under such flow regimes, small scale geological heterogeneities have been shown to dampen plume migration rates and cause trapping beneath capillary barriers. To understand the impact of such heterogeneities on CO2 trapping processes experimentally, many core-scale and lab scale flow studies have been conducted. Reservoir cores are limited by the scale of investigation possible and most lab experiments are conducted in macroheterogeneous media constructed by arranging homogeneous units to represent heterogeneity. However, most natural sedimentary facies display heterogeneity at a hierarchy of scales, and heterogeneity at the mesoscale (mm to decimeters) goes unrepresented in laboratory experiments due to the difficulty in reproducibility. This work presents results from buoyancy driven migration experiments conducted at the meter scale using glass beads packed in a quasi 2D glass cell and complementary reduced physics simulations. We demonstrate a novel automated technique to build beadpacks with 2D heterogeneous sedimentary features in a reproducible manner. A fluid pair that mimics the phase density and viscosity contrasts, and interfacial tension of CO2-Brine at reservoir pressures and temperatures is employed for the flow experiments. Light transmission technique is used for visualization, and to calibrate and quantify saturation of the trapped non-wetting fluid during the experiments. Invasion Percolation is used to simulate the buoyancy driven flow. With the ability to generate different types of heterogeneous structures in a reproducible manner, and by comparing experiments and simulations, a systematic investigation of the effect of heterogeneity on capillary trapping becomes possible.

  10. A 3D Real-Scale, Biomimetic, and Biohybrid Model of the Blood-Brain Barrier Fabricated through Two-Photon Lithography.

    PubMed

    Marino, Attilio; Tricinci, Omar; Battaglini, Matteo; Filippeschi, Carlo; Mattoli, Virgilio; Sinibaldi, Edoardo; Ciofani, Gianni

    2018-02-01

    The investigation of the crossing of exogenous substances through the blood-brain barrier (BBB) is object of intensive research in biomedicine, and one of the main obstacles for reliable in vitro evaluations is represented by the difficulties at the base of developing realistic models of the barrier, which could resemble as most accurately as possible the in vivo environment. Here, for the first time, a 1:1 scale, biomimetic, and biohybrid BBB model is proposed. Microtubes inspired to the brain capillaries were fabricated through two-photon lithography and used as scaffolds for the co-culturing of endothelial-like bEnd.3 and U87 glioblastoma cells. The constructs show the maturation of tight junctions, good performances in terms of hindering dextran diffusion through the barrier, and a satisfactory trans-endothelial electrical resistance. Moreover, a mathematical model is developed, which assists in both the design of the 3D microfluidic chip and its characterization. Overall, these results show the effective formation of a bioinspired cellular barrier based on microtubes reproducing brain microcapillaries to scale. This system will be exploited as a realistic in vitro model for the investigation of BBB crossing of nanomaterials and drugs, envisaging therapeutic and diagnostic applications for several brain pathologies, including brain cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Distribution of endogenous albumin in the glomerular wall of proteinuric patients.

    PubMed Central

    Russo, P. A.; Bendayan, M.

    1990-01-01

    Glomerular proteinuria seems to be related, in part, to loss or impairment of the normal barrier function of the glomerular capillary wall. To investigate the functional properties of this barrier, endogenous albumin was revealed in the glomerular wall of proteinuric patients and compared with a nonproteinuric control by immunoelectron microscopy using the protein A-gold method. In the control biopsy, peaks of albumin accumulation were noted in the subendothelial area and in the inner portion of the lamina densa, with gradual tapering of the distribution toward the epithelial side of the basement membrane. The urinary space and epithelial cells were weakly labeled. In tissues from proteinuric patients, albumin was distributed throughout the entire width of the glomerular basement membrane, although the pattern of accumulation varied between patients. The urinary space showed significant labeling associated with some flocculent material. Mesangial areas were heavily labeled in tissues from both control and proteinuric patients. In the latter, lysozomes in glomerular and tubular epithelial cells also accumulated albumin, which is evidence of reabsorption. These results reveal the existence, in normal conditions, of a barrier located in the subendothelial area of the glomerular basement membrane, the loss of which, as in the idiopathic nephrotic syndrome, leads to diffuse distribution of albumin in the glomerular capillary wall. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2260634

  12. Enhanced expression by the brain matrix of P-glycoprotein in brain capillary endothelial cells.

    PubMed

    Tatsuta, T; Naito, M; Mikami, K; Tsuruo, T

    1994-10-01

    P-glycoprotein (PGP), an active efflux pump of antitumor agents in multidrug-resistant tumor cells, exists in brain capillary endothelium and could be functionally involved in the blood-brain barrier. To study the regulatory mechanism of PGP expression in brain capillary endothelium, various mouse tissue matrices were tested for their abilities to enhance the expression of PGP in mouse brain capillary endothelial cells (MBEC), which express relatively small amounts of PGP. Of the four tissue matrices we examined, PGP expression in MBEC cultured on the brain matrix increased 2.0-fold. The PGP-inducing activity was similarly detected in bovine brain matrix, and the activity was enriched in the fraction of pl 9.0 by isoelectric focusing. The fraction, named PIC-fraction (PGP-inducing component), increased the PGP expression in MBEC 3.5-fold. By Northern blot analysis, a 3.3-fold enhancement of mdr gene expression was observed in MBEC cultured on the PIC-fraction. The PGP-inducing activity of the PIC-fraction was reduced by the treatment with trypsin but not with collagenase, suggesting that a proteinaceous factor distinct from type I collagen might be responsible for the PGP-inducing activity of PIC-fraction. Although the PIC-fraction increased the PGP expression in other mouse brain capillary endothelial cells, the PIC-fraction did not increase PGP expression in mouse aortic endothelial cells and KB carcinoma cell lines expressing various amounts of PGP. These observations suggest that PGP expression in brain capillary endothelium is specifically regulated by a tissue-specific factor in the brain matrix.

  13. Capillary evaporation of the ionic liquid [EMIM][BF4] in nanoscale solvophobic confinement

    NASA Astrophysics Data System (ADS)

    Shrivastav, Gourav; Remsing, Richard C.; Kashyap, Hemant K.

    2018-05-01

    Solvent density fluctuations play a crucial role in liquid-vapor transitions in solvophobic confinement and can also be important for understanding solvation of polar and apolar solutes. In the case of ionic liquids (ILs), density fluctuations can be used to understand important processes in the context of nanoscale aggregation and colloidal self-assemblies. In this article, we explore the nature of density fluctuations associated with capillary evaporation of the IL 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]) in the confined region of model solvophobic nanoscale sheets by using molecular dynamics simulations combined with non-Boltzmann sampling techniques. We demonstrate that density fluctuations of the confined IL play an important role in capillary evaporation, suggesting analogies to dewetting transitions involving water. Significant changes in the interfacial structure of the IL are also detailed and suggested to underlie a non-classical (non-parabolic) dependence of the free energy barrier to evaporation on the degree of confinement.

  14. Expression of thyroid hormone transporters and deiodinases at the brain barriers in the embryonic chicken: Insights into the regulation of thyroid hormone availability during neurodevelopment.

    PubMed

    Van Herck, Stijn L J; Delbaere, Joke; Bourgeois, Nele M A; McAllan, Bronwyn M; Richardson, Samantha J; Darras, Veerle M

    2015-04-01

    Thyroid hormones (THs) are key regulators in the development of the vertebrate brain. Therefore, TH access to the developing brain needs to be strictly regulated. The brain barriers separate the central nervous system from the rest of the body and impose specific transport mechanisms on the exchange of molecules between the general circulation and the nervous system. As such they form ideal structures for regulating TH exchange between the blood and the brain. To investigate the mechanism by which the developing brain regulates TH availability, we investigated the ontogenetic expression profiles of TH transporters, deiodinases and the TH distributor protein transthyretin (TTR) at the brain barriers during embryonic and early postnatal development using the chicken as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), organic anion transporting polypeptide 1C1 (OATP1C1) and L-type amino acid transporter 1 (LAT1) and the inactivating type 3 deiodinase (D3) in the choroid plexus which forms the blood-cerebrospinal fluid barrier. This was confirmed by quantitative PCR which additionally indicated strongly increasing expression of TTR as well as detectable expression of the activating type 2 deiodinase (D2) and the (in)activating type 1 deiodinase (D1). In the brain capillaries forming the blood-brain barrier in situ hybridisation showed exclusive expression of LAT1 and D2. The combined presence of LAT1 and D2 in brain capillaries suggests that the blood-brain barrier forms the main route for receptor-active T3 uptake into the embryonic chicken brain. Expression of multiple transporters, deiodinases and TTR in the choroid plexus indicates that the blood-cerebrospinal fluid barrier is also important in regulating early TH availability. The impact of these barrier systems can be deduced from the clear difference in T3 and T4 levels as well as the T3/T4 ratio between the developing brain and the general circulation. We conclude that the tight regulation of TH exchange at the brain barriers from early embryonic stages is one of the factors needed to allow the brain to develop within a relative microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Posterior reversible encephalopathy syndrome (PRES) after granulocyte-colony stimulating factor (G-CSF) therapy: a report of 2 cases.

    PubMed

    Stübgen, Joerg-Patrick

    2012-10-15

    Two patients with recurrent lymphoma developed an acute, transient encephalopathy following administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF), filgrastim, in anticipation of leukapheresis for hematopoietic stem cell transplantation. Head magnetic resonance imaging showed evidence of blood-brain barrier (BBB) breakdown, compatible with posterior reversible encephalopathy syndrome (PRES). The proposed pathogenesis of PRES was rhG-CSF-induced neutrophil mobilization and activation with the release of inflammatory mediators, resulting in transient alteration of barrier permeability and capillary leakage. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

    PubMed Central

    Baer, Kerstin; Mikolajczak, Sebastian A.; Kappe, Stefan H. I.; Frevert, Ute

    2012-01-01

    Plasmodium falciparum malaria is responsible for nearly one million annual deaths worldwide. Because of the difficulty in monitoring the pathogenesis of cerebral malaria in humans, we conducted a study in various mouse models to better understand disease progression in experimental cerebral malaria (ECM). We compared the effect on the integrity of the blood brain barrier (BBB) and the histopathology of the brain of P. berghei ANKA, a known ECM model, P. berghei NK65, generally thought not to induce ECM, P. yoelii 17XL, originally reported to induce human cerebral malaria-like histopathology, and P. yoelii YM. As expected, P. berghei ANKA infection caused neurological signs, cerebral hemorrhages, and BBB dysfunction in CBA/CaJ and Swiss Webster mice, while Balb/c and A/J mice were resistant. Surprisingly, PbNK induced ECM in CBA/CaJ mice, while all other mice were resistant. P. yoelii 17XL and P. yoelii YM caused lethal hyperparasitemia in all mouse strains; histopathological alterations, BBB dysfunction, or neurological signs were not observed. Intravital imaging revealed that infected erythrocytes containing mature parasites passed slowly through capillaries making intimate contact with the endothelium, but did not arrest. Except for relatively rare microhemorrhages, mice with ECM presented no obvious histopathological alterations that would explain the widespread disruption of the BBB. Intravital imaging did reveal, however, that postcapillary venules, but not capillaries or arterioles, from mice with ECM, but not hyperparasitemia, exhibit platelet marginalization, extravascular fibrin deposition, CD14 expression, and extensive vascular leakage. Blockage of LFA-1 mediated cellular interactions prevented leukocyte adhesion, vascular leakage, neurological signs, and death from ECM. The endothelial barrier-stabilizing mediators imatinib and FTY720 inhibited vascular leakage and neurological signs and prolonged survival to ECM. Thus, it appears that neurological signs and coma in ECM are due to regulated opening of paracellular-junctional and transcellular-vesicular fluid transport pathways at the neuroimmunological BBB. PMID:23133375

  17. Adaptations to the air breathing in the posterior intestine of the catfish (Corydoras aeneus, Callichthyidae). A histological and ultrastructural study.

    PubMed

    Podkowa, Dagmara; Goniakowska-Witalińska, Lucyna

    2002-01-01

    A light and transmission electron microscopic study of the intestine of catfish C. aeneus shows that the anterior part of the intestine is a site of digestion and absorption and its structure is typical of that of other teleostean fishes. However, in this species the thin-walled posterior intestine is adapted to air breathing. In this region mucosa is smooth and lined with respiratory epithelium with capillary network. Several types of cells are observed in the epithelium: flattened respiratory epithelial cells with short microvili, goblet cells, scarce epithelial cells with numerous longer microvilli, and two types of endocrine cells (EC). The solitary brush cells with several long and thick microvilli described here are the first observation of such cells in the gastrointestinal tract of fishes. Bodies of respiratory epithelial cells lie between capillaries. Their cytoplasm, apart from typical organelles contains dense and lamellar bodies, which are a site of accumulation of surfactant. In regions where capillaries are covered by thin cytoplasmic sheets of respiratory epithelial cells, a thin (0.24-3.00 microm) air-blood barrier is formed, thus enabling gas exchange. Epithelial cells with longer microvilli do not participate in the formation of the air-blood barrier and are probably responsible for absorbtion. EC of the closed type are dispersed within the epithelium. Their cytoplasm contains characteristic round or oval dense core vesicles 69 to 230 nm in diameter. The role of EC and brush cells in the regulation of processes related to absorbtion, and to respiration, is disscused.

  18. Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

    PubMed

    Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

    2018-02-13

    Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

  19. Internalization of targeted quantum dots by brain capillary endothelial cells in vivo.

    PubMed

    Paris-Robidas, Sarah; Brouard, Danny; Emond, Vincent; Parent, Martin; Calon, Frédéric

    2016-04-01

    Receptors located on brain capillary endothelial cells forming the blood-brain barrier are the target of most brain drug delivery approaches. Yet, direct subcellular evidence of vectorized transport of nanoformulations into the brain is lacking. To resolve this question, quantum dots were conjugated to monoclonal antibodies (Ri7) targeting the murine transferrin receptor. Specific transferrin receptor-mediated endocytosis of Ri7-quantum dots was first confirmed in N2A and bEnd5 cells. After intravenous injection in mice, Ri7-quantum dots exhibited a fourfold higher volume of distribution in brain tissues, compared to controls. Immunofluorescence analysis showed that Ri7-quantum dots were sequestered throughout the cerebral vasculature 30 min, 1 h, and 4 h post injection, with a decline of signal intensity after 24 h. Transmission electron microscopic studies confirmed that Ri7-quantum dots were massively internalized by brain capillary endothelial cells, averaging 37 ± 4 Ri7-quantum dots/cell 1 h after injection. Most quantum dots within brain capillary endothelial cells were observed in small vesicles (58%), with a smaller proportion detected in tubular structures or in multivesicular bodies. Parenchymal penetration of Ri7-quantum dots was extremely low and comparable to control IgG. Our results show that systemically administered Ri7-quantum dots complexes undergo extensive endocytosis by brain capillary endothelial cells and open the door for novel therapeutic approaches based on brain endothelial cell drug delivery. © The Author(s) 2015.

  20. Ion guiding in macro-size insulating capillaries: straight, tapered, and curved shapes

    NASA Astrophysics Data System (ADS)

    Kojima, Takao M.

    2018-02-01

    When keV energy ions are injected into a tilted insulating capillary, a certain fraction of the injected ions are transported through the tilt angle of the capillary. This ion guiding phenomenon is considered to be caused by a self-organizing charge distribution, where the inner wall of the capillary becomes charged by initial incoming ions. The charge distribution, which is formed, can guide following ions toward the exit of the capillary. Since the initial discovery of this effect, studies of ion guiding by insulating capillaries have been extended to various materials, and different sizes and shapes of capillaries. In recent years, some investigations of the guiding effect of macro-size curved capillaries have also been reported. In this review, relevant studies in a history of ion guiding in curved capillaries are discussed and future directions in this field are considered.

  1. Terrestrial Testing of the CapiBRIC, a Microgravity Optimized Brine Processor

    NASA Technical Reports Server (NTRS)

    Sargusingh, Miriam J.; Callahan, Michael R.; Weislogel, Mark M.

    2016-01-01

    Utilizing geometry based static phase separation exhibited in the radial vaned capillary drying tray, a system was conceived to recover water from brine. This technology has been named the Capillary BRIC; abbreviated CapiBRIC. The CapiBRIC utilizes a capillary drying tray within a drying chamber. Water is recovered from clean water vapor evaporating from the free surface leaving waste brine solids behind. A novel approach of optimizing the containment geometry to support passive capillary flow and static phase separation provides the opportunity for a low power system that is not as susceptible to fouling as membranes or other technologies employing physical barriers across the free brine surface to achieve phase separation in microgravity. Having been optimized for operation in microgravity, full-scale testing of the CapiBRIC as designed cannot be performed on the ground as the force of gravity would dominate over the capillary forces. However, subscale units relevant to full-scale design were used to characterize fill rates, containment stability, and interaction with a variable volume reservoir in the PSU Dryden Drop Tower (DDT) facility. PSU also using tested units scaled such that capillary forces dominated in a 1-g environment to characterize evaporation from a free-surface in 1-g upward, sideways and downward orientations. In order to augment the subscale testing performed by PSU, a full scale 1-g analogue of the CapiBRIC drying unit was initiated to help validate performance predictions regarding expected water recovery ratio, estimated processing time, and interface definitions for inlets, outlets, and internal processes, including vent gas composition. This paper describes the design, development and test of the terrestrial CapiBRIC prototypes.

  2. Improving the analytical performance and versatility of paper spray mass spectrometry via paper microfluidics.

    PubMed

    Murray, Ian; Walker, Glenn; Bereman, Michael S

    2016-06-20

    Two paper-based microfluidic techniques, photolithography and wax patterning, were investigated for their potential to improve upon the sensitivity, reproducibility, and versatility of paper spray mass spectrometry. The main limitation of photolithography was the significant signal (approximately three orders of magnitude) above background which was attributed to the chemicals used in the photoresist process. Hydrophobic barriers created via wax patterning were discovered to have approximately 2 orders of magnitude less background signal compared to analogous barriers created using photolithography. A minimum printed wax barrier thickness of approximately 0.3 mm was necessary to consistently retain commonly used paper spray solvents (1 : 1 water : acetonitrile/methanol) and avoid leakage. Constricting capillary flow via wax-printed channels yielded both a significant increase in signal and detection time for detection of model analytes. This signal increase, which was attributed to restricting the radial flow of analyte/solvent on paper (i.e., a concentrating effect), afforded a significant increase in sensitivity (p ≪ 0.05) for the detection of pesticides spiked into residential tap water using a five-point calibration curve. Finally, unique mixing designs using wax patterning can be envisioned to perform on-paper analyte derivatization.

  3. Laser direct writing and inkjet printing for a sub-2 μm channel length MoS2 transistor with high-resolution electrodes

    NASA Astrophysics Data System (ADS)

    Kwon, Hyuk-Jun; Chung, Seungjun; Jang, Jaewon; Grigoropoulos, Costas P.

    2016-10-01

    Patterns formed by the laser direct writing (LDW) lithography process are used either as channels or barriers for MoS2 transistors fabricated via inkjet printing. Silver (Ag) nanoparticle ink is printed over patterns formed on top of the MoS2 flakes in order to construct high-resolution source/drain (S/D) electrodes. When positive photoresist is used, the produced grooves are filled with inkjetted Ag ink by capillary forces. On the other hand, in the case of negative photoresist, convex barrier-like patterns are written on the MoS2 flakes and patterns, dividing the printed Ag ink into the S/D electrodes by self-alignment. LDW lithography combined with inkjet printing is applied to MoS2 thin-film transistors that exhibit moderate electrical performance such as mobility and subthreshold swing. However, especially in the linear operation regime, their features are limited by the contact effect. The Y-function method can exclude the contact effect and allow proper evaluation of the maximum available mobility and contact resistance. The presented fabrication methods may facilitate the development of cost-effective fabrication processes.

  4. Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats

    PubMed Central

    Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

    2016-01-01

    Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood–brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved. PMID:28155574

  5. Evaluation of lung clearance of inhaled pertechnegas.

    PubMed

    Fanti, S; Compagnone, G; Pancaldi, D; Franchi, R; Corbelli, C; Marengo, M; Onofri, C; Galassi, R; Levorato, M; Monetti, N

    1996-02-01

    Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

  6. Type XVIII collagen degradation products in acute lung injury

    PubMed Central

    Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

    2009-01-01

    Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

  7. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction.

    PubMed

    Czikora, Istvan; Sridhar, Supriya; Gorshkov, Boris; Alieva, Irina B; Kasa, Anita; Gonzales, Joyce; Potapenko, Olena; Umapathy, Nagavedi S; Pillich, Helena; Rick, Ferenc G; Block, Norman L; Verin, Alexander D; Chakraborty, Trinad; Matthay, Michael A; Schally, Andrew V; Lucas, Rudolf

    2014-01-01

    Antibiotic treatment of patients infected with G(-) or G(+) bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion. Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting. GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the former of which dominates the latter.

  8. Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening

    NASA Astrophysics Data System (ADS)

    Wu, Sheng-Kai; Chu, Po-Chun; Chai, Wen-Yen; Kang, Shih-Tsung; Tsai, Chih-Hung; Fan, Ching-Hsiang; Yeh, Chih-Kuang; Liu, Hao-Li

    2017-04-01

    Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as surrogates to allow molecule-penetrated quantification, BBB-opened observation, and MBs circulation/persistence. Cavitation activity was measured via the passive cavitation detection (PCD) setup to correlate with the exposure level and the histological effect. Under given and identical MB concentrations, the three MBs induced similar and equivalent BBB-opening effects and persistence. In addition, a treatment paradigm by adapting exposure time is proposed to compensate MB decay to retain the persistence of BBB-opening efficiency in multiple FUS exposures. The results potentially improve understanding of the equivalence among MBs in focused ultrasound CNS drug delivery, and provide an effective strategy for securing persistence in this treatment modality.

  9. Influence of capillary end effects on steady-state relative permeability estimates from direct pore-scale simulations

    NASA Astrophysics Data System (ADS)

    Guédon, Gaël Raymond; Hyman, Jeffrey De'Haven; Inzoli, Fabio; Riva, Monica; Guadagnini, Alberto

    2017-12-01

    We investigate and characterize the influence of capillary end effects on steady-state relative permeabilities obtained in pore-scale numerical simulations of two-phase flows. Our study is motivated by the observation that capillary end effects documented in two-phase laboratory-scale experiments can significantly influence permeability estimates. While numerical simulations of two-phase flows in reconstructed pore-spaces are increasingly employed to characterize relative permeabilities, a phenomenon which is akin to capillary end effects can also arise in such analyses due to the constraints applied at the boundaries of the computational domain. We profile the relative strength of these capillary end effects on the calculation of steady-state relative permeabilities obtained within randomly generated porous micro-structures using a finite volume-based two-phase flow solver. We suggest a procedure to estimate the extent of the regions influenced by these capillary end effects, which in turn allows for the alleviation of bias in the estimation of relative permeabilities.

  10. Interfacial free energy of the NaCl crystal-melt interface from capillary wave fluctuations.

    PubMed

    Benet, Jorge; MacDowell, Luis G; Sanz, Eduardo

    2015-04-07

    In this work we study, by means of molecular dynamics simulations, the solid-liquid interface of NaCl under coexistence conditions. By analysing capillary waves, we obtain the stiffness for different orientations of the solid and calculate the interfacial free energy by expanding the dependency of the interfacial free energy with the solid orientation in terms of cubic harmonics. We obtain an average value for the solid-fluid interfacial free energy of 89 ± 6 mN m(-1) that is consistent with previous results based on the measure of nucleation free energy barriers [Valeriani et al., J. Chem. Phys. 122, 194501 (2005)]. We analyse the influence of the simulation setup on interfacial properties and find that facets prepared as an elongated rectangular stripe give the same results as those prepared as squares for all cases but the 111 face. For some crystal orientations, we observe at small wave-vectors a behaviour not consistent with capillary wave theory and show that this behavior does not depend on the simulation setup.

  11. High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity.

    PubMed

    Qosa, Hisham; Mohamed, Loqman A; Al Rihani, Sweilem B; Batarseh, Yazan S; Duong, Quoc-Viet; Keller, Jeffrey N; Kaddoumi, Amal

    2016-07-06

    The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 μM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

  12. High-throughput screening for identification of blood-brain barrier integrity enhancers: a drug repurposing opportunity to rectify vascular amyloid toxicity

    PubMed Central

    Qosa, Hisham; Mohamed, Loqman A.; Al Rihani, Sweilem B.; Batarseh, Yazan S.; Duong, Quoc-Viet; Keller, Jeffrey N.; Kaddoumi, Amal

    2016-01-01

    The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer’s disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76–4.56 μM. Of these 7 drugs, five were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD. PMID:27392852

  13. Capillary electrophoresis electrospray ionization mass spectrometry interface

    DOEpatents

    Smith, Richard D.; Severs, Joanne C.

    1999-01-01

    The present invention is an interface between a capillary electrophoresis separation capillary end and an electrospray ionization mass spectrometry emitter capillary end, for transporting an anolyte sample from a capillary electrophoresis separation capillary to a electrospray ionization mass spectrometry emitter capillary. The interface of the present invention has: (a) a charge transfer fitting enclosing both of the capillary electrophoresis capillary end and the electrospray ionization mass spectrometry emitter capillary end; (b) a reservoir containing an electrolyte surrounding the charge transfer fitting; and (c) an electrode immersed into the electrolyte, the electrode closing a capillary electrophoresis circuit and providing charge transfer across the charge transfer fitting while avoiding substantial bulk fluid transfer across the charge transfer fitting. Advantages of the present invention have been demonstrated as effective in providing high sensitivity and efficient analyses.

  14. Vortex focusing of ions produced in corona discharge.

    PubMed

    Kolomiets, Yuri N; Pervukhin, Viktor V

    2013-06-15

    Completeness of the ion transportation into an analytical path defines the efficiency of ionization analysis techniques. This is of particular importance for atmospheric pressure ionization sources like corona discharge, electrospray, ionization with radioactive ((3)H, (63)Ni) isotopes that produce nonuniform spatial distribution of sample ions. The available methods of sample ion focusing are either efficient at reduced pressure (~1Torr) or feature high sample losses. This paper deals with experimental research into atmospheric pressure focusing of unipolar (positive) ions using a highly swirled air stream with a well-defined vortex core. Effects of electrical fields from corona needle and inlet capillary of mass spectrometer on collection efficiency is considered. We used a corona discharge to produce an ionized unipolar sample. It is shown experimentally that with an electrical field barrier efficient transportation and focusing of an ionized sample are possible only when a metal plate restricting the stream and provided with an opening covered with a grid is used. This gives a five-fold increase of the transportation efficiency. It is shown that the electric field barrier in the vortex sampling region reduces the efficiency of remote ionized sample transportation two times. The difference in the efficiency of light ion focusing observed may be explained by a high mobility and a significant effect of the electric field barrier upon them. It is possible to conclude based on the experimental data that the presence of the field barrier narrows considerably (more than by one and half) the region of the vortex sample ion focusing. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Ozone generation in a kHz-pulsed He-O2 capillary dielectric barrier discharge operated in ambient air

    NASA Astrophysics Data System (ADS)

    Sands, Brian L.; Ganguly, Biswa N.

    2013-12-01

    The generation of reactive oxygen species using nonequilibrium atmospheric pressure plasma jet devices has been a subject of recent interest due to their ability to generate localized concentrations from a compact source. To date, such studies with plasma jet devices have primarily utilized radio-frequency excitation. In this work, we characterize ozone generation in a kHz-pulsed capillary dielectric barrier discharge configuration comprised of an active discharge plasma jet operating in ambient air that is externally grounded. The plasma jet flow gas was composed of helium with an admixture of up to 5% oxygen. A unipolar voltage pulse train with a 20 ns pulse risetime was used to drive the discharge at repetition rates between 2-25 kHz. Using UVLED absorption spectroscopy centered at 255 nm near the Hartley-band absorption peak, ozone was detected over 1 cm from the capillary axis. We observed roughly linear scaling of ozone production with increasing pulse repetition rate up to a "turnover frequency," beyond which ozone production steadily dropped and discharge current and 777 nm O(5P→5S°) emission sharply increased. The turnover in ozone production occurred at higher pulse frequencies with increasing flow rate and decreasing applied voltage with a common energy density of 55 mJ/cm3 supplied to the discharge. The limiting energy density and peak ozone production both increased with increasing O2 admixture. The power dissipated in the discharge was obtained from circuit current and voltage measurements using a modified parallel plate dielectric barrier discharge circuit model and the volume-averaged ozone concentration was derived from a 2D ozone absorption measurement. From these measurements, the volume-averaged efficiency of ozone production was calculated to be 23 g/kWh at conditions for peak ozone production of 41 mg/h at 11 kV applied voltage, 3% O2, 2 l/min flow rate, and 13 kHz pulse repetition rate, with 1.79 W dissipated in the discharge.

  16. Tunable separations based on a molecular size effect for biomolecules by poly(ethylene glycol) gel-based capillary electrophoresis.

    PubMed

    Kubo, Takuya; Nishimura, Naoki; Furuta, Hayato; Kubota, Kei; Naito, Toyohiro; Otsuka, Koji

    2017-11-10

    We report novel capillary gel electrophoresis (CGE) with poly(ethylene glycol) (PEG)-based hydrogels for the effective separations of biomolecules containing sugars and DNAs based on a molecular size effect. The gel capillaries were prepared in a fused silica capillary modified with 3-(trimethoxysilyl)propylmethacrylate using a variety of the PEG-based hydrogels. After the fundamental evaluations in CGE regarding the separation based on the molecular size effect depending on the crosslinking density, the optimized capillary provided the efficient separation of glucose ladder (G1 to G20). In addition, another capillary showed the successful separation of DNA ladder in the range of 10-1100 base pair, which is superior to an authentic acrylamide-based gel capillary. For both glucose and DNA ladders, the separation ranges against the molecular size were simply controllable by alteration of the concentration and/or units of ethylene oxide in the PEG-based crosslinker. Finally, we demonstrated the separations of real samples, which included sugars carved out from monoclonal antibodies, mAbs, and then the efficient separations based on the molecular size effect were achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Factors affecting the separation performance of proteins in capillary electrophoresis.

    PubMed

    Zhu, Yueping; Li, Zhenqing; Wang, Ping; Shen, Lisong; Zhang, Dawei; Yamaguchi, Yoshinori

    2018-04-15

    Capillary electrophoresis (CE) is an effective tool for protein separation and analysis. Compared with capillary gel electrophoresis (CGE), non-gel sieving capillary electrophoresis (NGSCE) processes the superiority on operation, repeatability and automaticity. Herein, we investigated the effect of polymer molecular weight and concentration, electric field strength, and the effective length of the capillary on the separation performance of proteins, and find that (1) polymer with high molecular weight and concentration favors the separation of proteins, although concentrated polymer hinders its injection into the channel of the capillary due to its high viscosity. (2) The resolution between the adjacent proteins decreases with the increase of electric field strength. (3) When the effective length of the capillary is long, the separation performance improves at the cost of separation time. (4) 1.4% (w/v) hydroxyethyl cellulose (HEC), 100 V/cm voltage and 12 cm effective length offers the best separation for the proteins with molecular weight from 14,400 Da to 97,400 Da. Finally, we employed the optimal electrophoretic conditions to resolve Lysozyme, Ovalbumin, BSA and their mixtures, and found that they were baseline resolved within 15 min. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Minimized Capillary End Effect During CO2 Displacement in 2-D Micromodel by Manipulating Capillary Pressure at the Outlet Boundary in Lattice Boltzmann Method

    NASA Astrophysics Data System (ADS)

    Kang, Dong Hun; Yun, Tae Sup

    2018-02-01

    We propose a new outflow boundary condition to minimize the capillary end effect for a pore-scale CO2 displacement simulation. The Rothman-Keller lattice Boltzmann method with multi-relaxation time is implemented to manipulate a nonflat wall and inflow-outflow boundaries with physically acceptable fluid properties in 2-D microfluidic chip domain. Introducing a mean capillary pressure acting at CO2-water interface to the nonwetting fluid at the outlet effectively prevents CO2 injection pressure from suddenly dropping upon CO2 breakthrough such that the continuous CO2 invasion and the increase of CO2 saturation are allowed. This phenomenon becomes most pronounced at capillary number of logCa = -5.5, while capillary fingering and massive displacement of CO2 prevail at low and high capillary numbers, respectively. Simulations with different domain length in homogeneous and heterogeneous domains reveal that capillary pressure and CO2 saturation near the inlet are reproducible compared with those with a proposed boundary condition. The residual CO2 saturation uniquely follows the increasing tendency with increasing capillary number, corroborated by experimental evidences. The determination of the mean capillary pressure and its sensitivity are also discussed. The proposed boundary condition is commonly applicable to other pore-scale simulations to accurately capture the spatial distribution of nonwetting fluid and corresponding displacement ratio.

  19. Paper Capillary Enables Effective Sampling for Microfluidic Paper Analytical Devices.

    PubMed

    Shangguan, Jin-Wen; Liu, Yu; Wang, Sha; Hou, Yun-Xuan; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

    2018-06-06

    Paper capillary is introduced to enable effective sampling on microfluidic paper analytical devices. By coupling mac-roscale capillary force of paper capillary and microscale capillary forces of native paper, fluid transport can be flexibly tailored with proper design. Subsequently, a hybrid-fluid-mode paper capillary device was proposed, which enables fast and reliable sampling in an arrayed form, with less surface adsorption and bias for different components. The resulting device thus well supports high throughput, quantitative, and repeatable assays all by hands operation. With all these merits, multiplex analysis of ions, proteins, and microbe have all been realized on this platform, which has paved the way to level-up analysis on μPADs.

  20. Effects of anesthesia on the cerebral capillary blood flow in young and old mice

    NASA Astrophysics Data System (ADS)

    Moeini, Mohammad; Tabatabaei, Maryam S.; Bélanger, Samuel; Avti, Pramod; Castonguay, Alexandre; Pouliot, Philippe; Lesage, Frédéric

    2015-03-01

    Despite recent findings on the possible role of age-related cerebral microvasculature changes in cognition decline, previous studies of capillary blood flow in aging (using animal models) are scarce and limited to anesthetized conditions. Since anesthesia can have different effects in young and old animals, it may introduce a confounding effect in aging studies. The present study aimed to eliminate the potential confound introduced by anesthesia by measuring capillary blood flow parameters in both awake conditions and under isoflurane anesthesia. We used 2-photon laser scanning fluorescence microscopy to measure capillary diameter, red blood cell velocity and flux, hematocrit and capillary volumetric flow in individual capillaries in the barrel cortex of 6- and 24-month old C57Bl/6 mice. It was observed that microvascular properties are significantly affected by anesthesia leading to different trends in capillary blood flow parameters with aging when measured under awake or anesthetized conditions. The findings in this study suggest taking extra care in interpreting aging studies from anesthetized animals.

  1. Developmental changes of l-arginine transport at the blood-brain barrier in rats.

    PubMed

    Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

    2018-05-01

    l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Human blood-brain barrier insulin-like growth factor receptor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

    1988-02-01

    Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefoldmore » greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of /sup 125/I-IGF-1, /sup 125/I-IGF-2, and /sup 125/I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin.« less

  3. Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.

    PubMed

    Hsia, Connie C W; Carbayo, Juan J Polo; Yan, Xiao; Bellotto, Dennis J

    2005-05-12

    To examine the effects of chronic high altitude (HA) exposure on lung structure during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for 1, 3, or 6 months, while their respective male littermates were simultaneously raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was measured at different lung volumes. The right lung was fixed at a constant airway pressure for morphometric analysis under light and electron microscopy. In animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar-capillary blood volume (V(c)) were elevated above LA control values. Following 3-6 months of HA exposure, increases in lung volume and alveolar surface area persisted while the initial increase in V(c) normalized. Additional adaptation occurred, including a higher epithelial cell volume, septal tissue volume and capillary surface area, a lower alveolar duct volume and lower harmonic mean diffusion barrier resulting in higher membrane and lung diffusing capacities. These data demonstrate enhanced alveolar septal growth and progressive acinar remodeling during chronic HA exposure with long-term augmentation of alveolar dimensions as well as functional compensation in lung compliance and diffusive gas transport.

  4. Assessment of the capillary zone electrophoretic behavior of proteins in the presence of electroosmotic modifiers: protein-polyamine interaction studied using a polyacrylamide-coated capillary.

    PubMed

    Kubo, K; Hattori, A

    2001-10-01

    The use of polyamines as electroosmotic modifiers has been shown to be effective in enhancing resolution of protein glycoforms in capillary zone electrophoresis (CZE) using a bare capillary tube. In this study, effectiveness was evaluated by using a polyacrylamide-coated capillary tube instead of a bare capillary tube. Electropherograms obtained in the presence of polyamines were inferior to those obtained in their absence with respect to resolution. Electrophoretic mobility of the proteins decreased and their peaks were broadened by polyamines bound to them. This unfavorable effect was dependent on both the species of polyamines and the pH values of the electrolyte buffer. The reduction of resolution caused by polyamines was in the following order: spermidine (SPD) approximately spermidine-tri-hydrochloride (SPD-HCI) > putrescine (PUT) > hexamethonium chloride (HMC). The observed effect can be ascribed to the formation of complexes between the proteins and the polyamines. In addition, for the bare capillary tube the complexes showed interaction with the inner surface, resulting in local suppression of electroosmosis and poor resolution. The high resolution obtained in the coated capillary tube was reduced in the presence of the polyamines. Thus, the use of the polyamines has a negative effect on the analysis of protein microheterogeneity as a result of protein-polyamine interaction.

  5. *NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier.

    PubMed

    Blasig, I E; Giese, H; Schroeter, M L; Sporbert, A; Utepbergenov, D I; Buchwalow, I B; Neubert, K; Schönfelder, G; Freyer, D; Schimke, I; Siems, W E; Paul, M; Haseloff, R F; Blasig, R

    2001-09-01

    To investigate the relevance of *NO and oxyradicals in the blood-brain barrier (BBB), differentiated and well-proliferating brain capillary endothelial cells (BCEC) are required. Therefore, rat BCEC (rBCEC) were transfected with immortalizing genes. The resulting lines exhibited endothelial characteristics (factor VIII, angiotensin-converting enzyme, high prostacyclin/thromboxane release rates) and BBB markers (gamma-glutamyl transpeptidase, alkaline phosphatase). The control line rBCEC2 (mock transfected) revealed fibroblastoid morphology, less factor VIII, reduced gamma-glutamyl transpeptidase, weak radical defence, low prostanoid metabolism, and limited proliferation. Lines transfected with immortalizing genes (especially rBCEC4, polyoma virus large T antigen) conserved primary properties: epitheloid morphology, subcultivation with high proliferation rate under pure culture conditions, and powerful defence against reactive oxygen species (Mn-, Cu/Zn-superoxide dismutase, catalase, glutathione peroxidase, glutathione) effectively controlling radical metabolism. Only 100 microM H2O2 overcame this defence and stimulated the formation of eicosanoids similarly as in primary cells. Some BBB markers were expressed to a lower degree; however, cocultivation with astrocytes intensified these markers (e.g., alkaline phosphatase) and paraendothelial tightness, indicating induction of BBB properties. Inducible NO synthase was induced by a cytokine plus lipopolysaccharide mixture in all lines and primary cells, resulting in *NO release. Comparing the cell lines obtained, rBCEC4 are stable immortalized and reveal the best conservation of properties from primary cells, including enzymes producing or decomposing reactive species. These cells can be subcultivated in large amounts and, hence, they are suitable to study the role of radical metabolism in the BBB and in the cerebral microvasculature. Copyright 2001 Academic Press.

  6. Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.

    PubMed

    Kaya, Mehmet; Orhan, Nurcan; Karabacak, Emrah; Bahceci, Metin Berkant; Arican, Nadir; Ahishali, Bulent; Kemikler, Gonul; Uslu, Atilla; Cevik, Aydin; Yilmaz, Canan Ugur; Kucuk, Mutlu; Gürses, Candan

    2013-03-12

    This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed. Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus. The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Revisiting nanoparticle technology for blood-brain barrier transport: Unfolding at the endothelial gate improves the fate of transferrin receptor-targeted liposomes.

    PubMed

    Johnsen, Kasper Bendix; Moos, Torben

    2016-01-28

    An unmet need exists for therapeutic compounds to traverse the brain capillary endothelial cells that denote the blood-brain barrier (BBB) to deliver effective treatment to the diseased brain. The use of nanoparticle technology for targeted delivery to the brain implies that targeted liposomes encapsulating a drug of interest will undergo receptor-mediated uptake and transport through the BBB with a subsequent unfolding of the liposomal content inside the brain, hence revealing drug release to adjacent drug-demanding neurons. As transferrin receptors (TfRs) are present on brain capillary endothelial, but not on endothelial cells elsewhere in the body, the use of TfR-targeted liposomes - colloidal particulates with a phospholipid bilayer membrane - remains the most relevant strategy to obtain efficient drug delivery to the brain. However, many studies have failed to provide sufficient quantitative data to proof passage of the BBB and significant appearance of drugs inside the brain parenchyma. Here, we critically evaluate the current evidence on the use of TfR-targeted liposomes for brain drug delivery based on a thorough investigation of all available studies within this research field. We focus on issues with respect to experimental design and data analysis that may provide an explanation to conflicting reports, and we discuss possible explanations for the current lack of sufficient transcytosis across the BBB for implementation in the design of TfR-targeted liposomes. We finally provide a list of suggestions for strategies to obtain substantial uptake and transport of drug carriers at the BBB with a concomitant transport of therapeutics into the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Quantification of Transporter and Receptor Proteins in Dog Brain Capillaries and Choroid Plexus: Relevance for the Distribution in Brain and CSF of Selected BCRP and P-gp Substrates.

    PubMed

    Braun, Clemens; Sakamoto, Atsushi; Fuchs, Holger; Ishiguro, Naoki; Suzuki, Shinobu; Cui, Yunhai; Klinder, Klaus; Watanabe, Michitoshi; Terasaki, Tetsuya; Sauer, Achim

    2017-10-02

    Transporters at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) play a pivotal role as gatekeepers for efflux or uptake of endogenous and exogenous molecules. The protein expression of a number of them has already been determined in the brains of rodents, nonhuman primates, and humans using quantitative targeted absolute proteomics (QTAP). The dog is an important animal model for drug discovery and development, especially for safety evaluations. The purpose of the present study was to clarify the relevance of the transporter protein expression for drug distribution in the dog brain and CSF. We used QTAP to examine the protein expression of 17 selected transporters and receptors at the dog BBB and BCSFB. For the first time, we directly linked the expression of two efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), to regional brain and CSF distribution using specific substrates. Two cocktails, each containing one P-gp substrate (quinidine or apafant) and one BCRP substrate (dantrolene or daidzein) were infused intravenously prior to collection of the brain. Transporter expression varied only slightly between the capillaries of different brain regions and did not result in region-specific distribution of the investigated substrates. There were, however, distinct differences between brain capillaries and choroid plexus. Largest differences were observed for BCRP and P-gp: both were highly expressed in brain capillaries, but no BCRP and only low amounts of P-gp were detected in the choroid plexus. K p,uu,brain and K p,uu,CSF of both P-gp substrates were indicative of drug efflux. Also, K p,uu,brain for the BCRP substrates was low. In contrast, K p,uu,CSF for both BCRP substrates was close to unity, resulting in K p,uu,CSF /K p,uu,brain ratios of 7 and 8, respectively. We conclude that the drug transporter expression profiles differ between the BBB and BCSFB in dogs, that there are species differences in the expression profiles, and that CSF is not a suitable surrogate for unbound brain concentrations of BCRP substrates in dogs.

  9. Managment of superficial infantile capillary hemangiomas with topical timolol maleate solution.

    PubMed

    Rizvi, Syed Ali Raza; Yusuf, Faraz; Sharma, Rajeev; Rizvi, Syed Wajahat Ali

    2015-01-01

    Capillary hemangioma is the most common benign tumor of eyelids and orbit in children. Recently, a topical beta blocker has been reported as an effective treatment for superficial capillary hemangiomas. We present a case report of two children having large capillary hemangiomas who responded well to topical treatment by 0.5% timolol maleate solution. After 12 months of treatment, the lesion has significantly reduced in size, thickness, and color in both cases. Thus, we conclude that long-term use of topical 0.5% timolol maleate solution is safe and effective in treating superficial capillary hemangiomas.

  10. Van der waals forces on thin liquid films in capillary tubes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herdt, G.C.; Swanson, L.W.

    1993-10-01

    A theory of the van der Waals attraction between a thin liquid films and a capillary tube is presented assuming the presence of a vapor-liquid interface. The model is based on the surface mode analysis method of van Kampen et al. Values for the van der Waals interaction energy per unit area were calculated for liquid films of pentane on a gold substrate assuming a thin liquid film. Results indicate that the effect of capillary curvature on the van der Waals interaction increases as the ratio of the liquid film thickness to the capillary radius is increased. This trend ismore » consistent with predictions based on the Hamaker theory. Deviations from results based on the Hamaker theory are easily explained in terms of retardation of the van der Waals interaction. Because the effect of capillary curvature increases in the regime where retardation effects become important, curvature effects constitute a small correction to the van der Waals forces in a capillary tube.« less

  11. The Influence of Seal Properties on Pressure Buildup and Leakage of Carbon Dioxide from Sequestration Reservoirs (Invited)

    NASA Astrophysics Data System (ADS)

    Benson, S. M.; Chabora, E.

    2009-12-01

    The transport properties of seals, namely permeability, relative permeability, and capillary pressure control both migration of carbon dioxide and brine through the seal. Only recently has the the importance of brine migration emerged as key issue in the environmental performance of carbon dioxide sequestration projects. In this study we use numerical simulation to show that brine migration through the seal can be either advantageous or deleterious to the environmental performance of a carbon dioxide sequestration project. Brine migration through the seal can lower the pressure buildup in the storage reservoir, thereby reducing the risk of leakage or geomechanical stresses on the seal. On the other hand, if the seal is penetrated by a permeable fault it can lead to focused flow up a fault, which could lead to brine migration into drinking water aquifers. We also show that as the carbon dioxide plume grows, brine flow undergoes a complex evolution from upward flow to downward flows driven by countercurrent migration of carbon dioxide and brine in the seal and capillary pressure gradients at the base of the seal. Finally, we discuss desirable attributes seals, taking into account both carbon dioxide and brine migration through the seal. In particular, identifying seals that provide an effective capillary barrier to block the flow of carbon dioxide while allowing some brine migration through the seal can help to control pressure buildup and allow more efficient utilization of a sequestration reservoir. This could be particularly important in those settings that may be limited by the maximum allowable pressure buildup.

  12. The effect of using a geotextile in a monolithic (evapotranspiration) alternative landfill cover on the resulting water balance.

    PubMed

    Sun, Jianlei; Yuen, Samuel T S; Fourie, Andy B

    2010-11-01

    This paper examines the potential effects of a geotextile layer used in a lysimeter pan experiment conducted in a monolithic (evapotranspiration) soil cover trial on its resulting water balance performance. The geotextile was added to the base of the lysimeter to serve as a plant root barrier in order to delineate the root zone depth. Both laboratory data and numerical modelling results indicated that the geotextile creates a capillary barrier under certain conditions and retains more water in the soil above the soil/geotextile interface than occurs without a geotextile. The numerical modelling results also suggested that the water balance of the soil cover could be affected by an increase in plant transpiration taking up this extra water retained above the soil/geotextile interface. This finding has a practical implication on the full-scale monolithic cover design, as the absence of the geotextile in the full-scale cover may affect the associated water balance and hence cover performance. Proper consideration is therefore required to assess the final monolithic cover water balance performance if its design is based on the lysimeter results. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. DipTest: A litmus test for E. coli detection in water.

    PubMed

    Gunda, Naga Siva Kumar; Dasgupta, Saumyadeb; Mitra, Sushanta K

    2017-01-01

    We have developed a new litmus paper test (DipTest) for detecting Escherichia coli (E. coli) in water samples by performing enzymatic reactions directly on the porous paper substrate. The paper strip consists of a long narrow piece of cellulose blotting paper coated with chemoattractant (at bottom edge), wax hydrophobic barrier (at the top edge), and custom formulated chemical reagents (at reaction zone immediately below the wax hydrophobic barrier). When the paper strip is dipped in water, E. coli in the water sample is attracted toward the paper strip due to a chemotaxic mechanism followed by the ascent along the paper strip toward the reaction zone due to a capillary wicking mechanism, and finally the capillary motion is arrested at the top edge of the paper strip by the hydrophobic barrier. The E. coli concentrated at the reaction zone of the paper strip will react with custom formulated chemical reagents to produce a pinkish-red color. Such a color change on the paper strip when dipped into water samples indicates the presence of E. coli contamination in potable water. The performance of the DipTest device has been checked with different known concentrations of E. coli contaminated water samples using different dip and wait times. The DipTest device has also been tested with different interfering bacteria and chemical contaminants. It has been observed that the different interfering contaminants do not have any impact on the DipTest, and it can become a potential solution for screening water samples for E. coli contamination at the point of source.

  14. DipTest: A litmus test for E. coli detection in water

    PubMed Central

    Gunda, Naga Siva Kumar; Dasgupta, Saumyadeb

    2017-01-01

    We have developed a new litmus paper test (DipTest) for detecting Escherichia coli (E. coli) in water samples by performing enzymatic reactions directly on the porous paper substrate. The paper strip consists of a long narrow piece of cellulose blotting paper coated with chemoattractant (at bottom edge), wax hydrophobic barrier (at the top edge), and custom formulated chemical reagents (at reaction zone immediately below the wax hydrophobic barrier). When the paper strip is dipped in water, E. coli in the water sample is attracted toward the paper strip due to a chemotaxic mechanism followed by the ascent along the paper strip toward the reaction zone due to a capillary wicking mechanism, and finally the capillary motion is arrested at the top edge of the paper strip by the hydrophobic barrier. The E. coli concentrated at the reaction zone of the paper strip will react with custom formulated chemical reagents to produce a pinkish-red color. Such a color change on the paper strip when dipped into water samples indicates the presence of E. coli contamination in potable water. The performance of the DipTest device has been checked with different known concentrations of E. coli contaminated water samples using different dip and wait times. The DipTest device has also been tested with different interfering bacteria and chemical contaminants. It has been observed that the different interfering contaminants do not have any impact on the DipTest, and it can become a potential solution for screening water samples for E. coli contamination at the point of source. PMID:28877199

  15. Receptor-mediated transcytosis of cyclophilin B through the blood-brain barrier.

    PubMed

    Carpentier, M; Descamps, L; Allain, F; Denys, A; Durieux, S; Fenart, L; Kieda, C; Cecchelli, R; Spik, G

    1999-07-01

    Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein mainly located in intracellular vesicles and secreted in biological fluids. In previous works, we demonstrated that CyPB interacts with T lymphocytes and enhances in vitro cellular incorporation and activity of CsA. In addition to its immunosuppressive activity, CsA is able to promote regeneration of damaged peripheral nerves. However, the crossing of the drug from plasma to neural tissue is restricted by the relative impermeability of the blood-brain barrier. To know whether CyPB might also participate in the delivery of CsA into the brain, we have analyzed the interactions of CyPB with brain capillary endothelial cells. First, we demonstrated that CyPB binds to two types of binding sites present at the surface of capillary endothelial cells from various species of tissues. The first type of binding sites (K(D) = 300 nM; number of sites = 3 x 10(6)) is related to interactions with negatively charged compounds such as proteoglycans. The second type of binding sites, approximately 50,000 per cell, exhibits a higher affinity for CyPB (K(D) = 15 nM) and is involved in an endocytosis process, indicating it might correspond to a functional receptor. Finally, the use of an in vitro model of blood-brain barrier allowed us to demonstrate that CyPB is transcytosed by a receptor-mediated pathway (flux = 16.5 fmol/cm2/h). In these conditions, CyPB did not significantly modify the passage of CsA, indicating that it is unlikely to provide a pathway for CsA brain delivery.

  16. [Features of the structure and parameters of the intra-alveolar septa in residents of Western Siberia].

    PubMed

    Shishkin, G S; Ustiuzhaninova, N V

    1998-01-01

    In inhabitants of Novosibirsk and Moscow district intraalveolar septum, the basic functional element of the lung consists of interstitial connective tissue and capillar network, limited with basement membranes, on which cells of epithelial lining are placed. There are no principal differences in septal structure between individuals from both regions. The majority of morphometric parameters are statistically similar, although certain peculiarities were noted in human subjects from Siberia, the most important of which is that air-blood barrier in them is 33% thinner than those in inhabitants of Moscow district. Majority of capillaries possess the air-blood barrier from both sides. This increases diffous capacity of the lungs and blood oxygenation level.

  17. Models of Cerebral-Body Perfusion and Cerebral Chemical Transport.

    DTIC Science & Technology

    1988-03-01

    Pressure Waves 22 Conchusion 23 References 36 A Compartmental Brain Model for Chemical Transport and CO2 Controlled Blood Flow Abstract 37 Introduction 38...surrounding the body, e.g., atmospheric pressure , pressure al high and low altitudes, high underwater pressure , vacuum and excessive gravity acceleration...Resistance of the AreriolarNenous capillary, accounting for the pressure drop observed between them. RCB Resistance of the Blood -Brain barrier (between

  18. On ultrasound-induced microbubble oscillation in a capillary blood vessel and its implications for the blood-brain barrier

    NASA Astrophysics Data System (ADS)

    Wiedemair, W.; Tuković, Ž.; Jasak, H.; Poulikakos, D.; Kurtcuoglu, V.

    2012-02-01

    The complex interaction between an ultrasound-driven microbubble and an enclosing capillary microvessel is investigated by means of a coupled, multi-domain numerical model using the finite volume formulation. This system is of interest in the study of transient blood-brain barrier disruption (BBBD) for drug delivery applications. The compliant vessel structure is incorporated explicitly as a distinct domain described by a dedicated physical model. Red blood cells (RBCs) are taken into account as elastic solids in the blood plasma. We report the temporal and spatial development of transmural pressure (Ptm) and wall shear stress (WSS) at the luminal endothelial interface, both of which are candidates for the yet unknown mediator of BBBD. The explicit introduction of RBCs shapes the Ptm and WSS distributions and their derivatives markedly. While the peak values of these mechanical wall parameters are not affected considerably by the presence of RBCs, a pronounced increase in their spatial gradients is observed compared to a configuration with blood plasma alone. The novelty of our work lies in the explicit treatment of the vessel wall, and in the modelling of blood as a composite fluid, which we show to be relevant for the mechanical processes at the endothelium.

  19. Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy.

    PubMed

    Masago, Kayo; Kihara, Yasuyuki; Yanagida, Keisuke; Hamano, Fumie; Nakagawa, Shinsuke; Niwa, Masami; Shimizu, Takao

    2018-07-02

    Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to the accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood-brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls. Using in vitro BBB model, LPA disrupted the structural integrity of tight junction proteins including claudin-5, occludin, and ZO-1. Furthermore, LPA decreased transendothelial electrical resistances in in vitro BBB model, and induced cell contraction in brain endothelial monolayer cultures, both being inhibited by a Rho-associated protein kinase inhibitor, Y-27632. The brain capillary endothelial cells predominantly expressed LPA 6 mRNA, whose knockdown blocked the LPA-induced endothelial cell contraction. Taken together, the up-regulation of serum ATX in hepatic encephalopathy may activate the LPA-LPA 6 -G 12/13 -Rho pathway in brain capillary endothelial cells, leading to enhancement of BBB permeability and brain edema. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Solid-Phase Microextraction Coupled to Capillary Atmospheric Pressure Photoionization-Mass Spectrometry for Direct Analysis of Polar and Nonpolar Compounds.

    PubMed

    Mirabelli, Mario F; Zenobi, Renato

    2018-04-17

    A novel capillary ionization source based on atmospheric pressure photoionization (cAPPI) was developed and used for the direct interfacing between solid-phase microextraction (SPME) and mass spectrometry (MS). The efficiency of the source was evaluated for direct and dopant-assisted photoionization, analyzing both polar (e.g., triazines and organophosphorus pesticides) and nonpolar (polycyclic aromatic hydrocarbons, PAHs) compounds. The results show that the range of compound polarity, which can be addressed by direct SPME-MS can be substantially extended by using cAPPI, compared to other sensitive techniques like direct analysis in real time (DART) and dielectric barrier discharge ionization (DBDI). The new source delivers a very high sensitivity, down to sub parts-per-trillion (ppt), making it a viable alternative when compared to previously reported and less comprehensive direct approaches.

  1. Formation of nanoscale water bridges

    NASA Astrophysics Data System (ADS)

    Riedo, Elisa; Szoszkiewicz, Robert; Li, Tai-De; Gao, Jianping; Landman, Uzi

    2006-03-01

    The water bridges provide stability to sand castles, act as transport channels for dip-pen nanolitography and increase adhesion and friction in micro- and nano- devices such as MEMS. The kinetics of capillary condensation and growth at the nanoscale is studied here using friction force microscopy and molecular dynamics calculations. At 40% relative humidity we find that the meniscus nucleation times increase from 0.7 ms up to 4.2 ms when the temperature decreases from 332 K to 299 K. The nucleation times grow exponentially with the inverse temperature 1/T obeying an Arrhenius law. We obtain a nucleation energy barrier of 7.8*10̂-20˜J and an attempt frequency ranging between 4-250˜GHz, in excellent agreement with theoretical predictions. These results provide direct experimental evidence that capillary condensation is a thermally activated phenomenon.

  2. Cyclodextrins, blood-brain barrier, and treatment of neurological diseases.

    PubMed

    Vecsernyés, Miklós; Fenyvesi, Ferenc; Bácskay, Ildikó; Deli, Mária A; Szente, Lajos; Fenyvesi, Éva

    2014-11-01

    Biological barriers are the main defense systems of the homeostasis of the organism and protected organs. The blood-brain barrier (BBB), formed by the endothelial cells of brain capillaries, not only provides nutrients and protection to the central nervous system but also restricts the entry of drugs, emphasizing its importance in the treatment of neurological diseases. Cyclodextrins are increasingly used in human pharmacotherapy. Due to their favorable profile to form hydrophilic inclusion complexes with poorly soluble active pharmaceutical ingredients, they are present as excipients in many marketed drugs. Application of cyclodextrins is widespread in formulations for oral, parenteral, nasal, pulmonary, and skin delivery of drugs. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for centrally acting marketed drugs like antiepileptics, but also as active pharmaceutical ingredients to treat neurological diseases. Hydroxypropyl-β-cyclodextrin received orphan drug designation for the treatment of Niemann-Pick type C disease. In addition to this rare lysosomal storage disease with neurological symptoms, experimental research revealed the potential therapeutic use of cyclodextrins and cyclodextrin nanoparticles in neurodegenerative diseases, stroke, neuroinfections and brain tumors. In this context, the biological effects of cyclodextrins, their interaction with plasma membranes and extraction of different lipids are highly relevant at the level of the BBB. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  3. Unusual effect of water vapor pressure on dehydration of dibasic calcium phosphate dihydrate.

    PubMed

    Kaushal, Aditya M; Vangala, Venu R; Suryanarayanan, Raj

    2011-04-01

    Dibasic calcium phosphate occurs as an anhydrate (DCPA; CaHPO₄) and as a dihydrate (DCPD; CaHPO₄•2H₂O). Our objective was to investigate the unusual behavior of these phases. Dibasic calcium phosphate dihydrate was dehydrated in a (i) differential scanning calorimeter (DSC) in different pan configurations; (ii) variable-temperature X-ray diffractometer (XRD) at atmospheric and under reduced pressure, and in sealed capillaries; and (iii) water vapor sorption analyzer at varying temperature and humidity conditions. Dehydration was complete by 210°C in an open DSC pan and under atmospheric pressure in the XRD. Unlike "conventional" hydrates, the dehydration of DCPD was facilitated in the presence of water vapor. Variable-temperature XRD in a sealed capillary and DSC in a hermetic pan with pinhole caused complete dehydration by 100°C and 140°C, respectively. Under reduced pressure, conversion to the anhydrate was incomplete even at 300°C. The increase in dehydration rate with increase in water vapor pressure has been explained by the Smith-Topley effect. Under "dry" conditions, a coating of poorly crystalline product is believed to form on the surface of particles and act as a barrier to further dehydration. However, in the presence of water vapor, recrystallization occurs, creating cracks and channels and facilitating continued dehydration. Copyright © 2010 Wiley-Liss, Inc.

  4. Profile of capillary bridges between two vertically stacked cylindrical fibers under gravitational effect

    NASA Astrophysics Data System (ADS)

    Sun, Xiaohang; Lee, Hoon Joo; Michielsen, Stephen; Wilusz, Eugene

    2018-05-01

    Although profiles of axisymmetric capillary bridges between two cylindrical fibers have been extensively studied, little research has been reported on capillary bridges under external forces such as the gravitational force. This is because external forces add significant complications to the Laplace-Young equation, making it difficult to predict drop profiles based on analytical approaches. In this paper, simulations of capillary bridges between two vertically stacked cylindrical fibers with gravitational effect taken into consideration are studied. The asymmetrical structure of capillary bridges that are hard to predict based on analytical approaches was studied via a numerical approach based on Surface Evolver (SE). The axial and the circumferential spreading of liquids on two identical fibers in the presence of gravitational effects are predicted to determine when the gravitational effects are significant or can be neglected. The effect of liquid volume, equilibrium contact angle, the distance between two fibers and fiber radii. The simulation results were verified by comparing them with experimental measurements. Based on SE simulations, curves representing the spreading of capillary bridges along the two cylindrical fibers were obtained. The gravitational effect was scaled based on the difference of the spreading on upper and lower fibers.

  5. Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

    PubMed

    Yeh, D Y-W; Yang, Y-C; Wang, J-J

    2015-05-01

    Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Multiscale smeared finite element model for mass transport in biological tissue: From blood vessels to cells and cellular organelles.

    PubMed

    Kojic, M; Milosevic, M; Simic, V; Koay, E J; Kojic, N; Ziemys, A; Ferrari, M

    2018-05-21

    One of the basic and vital processes in living organisms is mass exchange, which occurs on several levels: it goes from blood vessels to cells and organelles within cells. On that path, molecules, as oxygen, metabolic products, drugs, etc. Traverse different macro and micro environments - blood, extracellular/intracellular space, and interior of organelles; and also biological barriers such as walls of blood vessels and membranes of cells and organelles. Many aspects of this mass transport remain unknown, particularly the biophysical mechanisms governing drug delivery. The main research approach relies on laboratory and clinical investigations. In parallel, considerable efforts have been directed to develop computational tools for additional insight into the intricate process of mass exchange and transport. Along these lines, we have recently formulated a composite smeared finite element (CSFE) which is composed of the smeared continuum pressure and concentration fields of the capillary and lymphatic system, and of these fields within tissue. The element offers an elegant and simple procedure which opens up new lines of inquiry and can be applied to large systems such as organs and tumors models. Here, we extend this concept to a multiscale scheme which concurrently couples domains that span from large blood vessels, capillaries and lymph, to cell cytosol and further to organelles of nanometer size. These spatial physical domains are coupled by the appropriate connectivity elements representing biological barriers. The composite finite element has "degrees of freedom" which include pressures and concentrations of all compartments of the vessels-tissue assemblage. The overall model uses the standard, measurable material properties of the continuum biological environments and biological barriers. It can be considered as a framework into which we can incorporate various additional effects (such as electrical or biochemical) for transport through membranes or within cells. This concept and the developed FE software within our package PAK offers a computational tool that can be applied to whole-organ systems, while also including specific domains such as tumors. The solved examples demonstrate the accuracy of this model and its applicability to large biological systems. Copyright © 2018. Published by Elsevier Ltd.

  7. Solute Carriers in the Blood-Brain Barier: Safety in Abundance.

    PubMed

    Nałęcz, Katarzyna A

    2017-03-01

    Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5, SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the blood-brain barriers has been demonstrated are characterized with a special emphasis put on polarity of transporters localization in a luminal (blood side) versus an abluminal (brain side) membrane.

  8. Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

    PubMed Central

    Natarajan, Reka; Northrop, Nicole

    2017-01-01

    The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

  9. Loss of endothelial barrier antigen immunoreactivity as a marker of Clostridium perfringens type D epsilon toxin-induced microvascular damage in rat brain.

    PubMed

    Finnie, J W; Manavis, J; Chidlow, G

    2014-01-01

    The epsilon toxin elaborated by Clostridium perfringens type D in the intestine of domestic livestock is principally responsible for the neurological disease produced after its absorption in excessive quantities into the systemic circulation. The fundamental basis of the cerebral damage induced by epsilon toxin appears to be microvascular injury with ensuing severe, diffuse vasogenic oedema. Endothelial barrier antigen (EBA), which is normally expressed by virtually all capillaries and venules in the rat brain, was used in this study as a marker of blood-brain barrier (BBB) integrity. After exposure to high levels of circulating epsilon toxin, there was substantial loss of EBA in many brain microvessels, attended by widespread plasma albumin extravasation. These results support microvascular injury and subsequent BBB breakdown as a key factor in the pathogenesis of epsilon toxin-induced neurological disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. An experimental study of the flow of LPG as refrigerant inside an adiabatic helical coiled capillary tube in vapour compression refrigeration system

    NASA Astrophysics Data System (ADS)

    Punia, Sanjeev Singh; Singh, Jagdev

    2015-11-01

    This paper presents an experimental investigation for the flow of liquefied petroleum gas (LPG) as a refrigerant inside an adiabatic helically coiled capillary tube in vapour compression refrigeration system. The effect of various geometric parameters and operating conditions like capillary tube inner diameter, length of capillary tube, coil diameter and different inlet subcoolings on the mass flow rate of LPG through the helical coiled capillary tube geometry has been investigated. It has been established that the coil diameter significantly influences the mass flow rate of LPG through the adiabatic helical capillary tube. It has been concluded that the effect of coiling of capillary tube reduces the mass flow rate by 5-12 % as compared to those of the straight capillary tube operating under similar conditions. The data obtained from the experiments are analyzed and a dimensionless correlation has been developed. The proposed correlation predicts that more than 90 % of experimental data which is in agreement with measured data in an error band of ±10 %.

  11. Characterization of pulsed atmospheric-pressure plasma streams (PAPS) generated by a plasma gun

    NASA Astrophysics Data System (ADS)

    Robert, E.; Sarron, V.; Riès, D.; Dozias, S.; Vandamme, M.; Pouvesle, J.-M.

    2012-06-01

    An experimental study of atmospheric-pressure rare gas plasma propagation in a high-aspect-ratio capillary is reported. The plasma is generated with a plasma gun device based on a dielectric barrier discharge (DBD) reactor powered by either nanosecond or microsecond rise-time high-voltage pulses at single-shot to multi-kHz frequencies. The influence of the voltage waveform, pulse polarity, pulse repetition rate and capillary material have been studied using nanosecond intensified charge-coupled device imaging and plasma-front velocity measurements. The evolution of the plasma appearance during its propagation and the study of the role of the different experimental parameters lead us to suggest a new denomination of pulsed atmospheric-pressure plasma streams to describe all the plasma features, including the previously so-called plasma bullet. The unique properties of such non-thermal plasma launching in capillaries, far from the primary DBD plasma, are associated with a fast ionization wave travelling with velocity in the 107-108 cm s-1 range. Voltage pulse tailoring is shown to allow for a significant improvement of such plasma delivery. Thus, the plasma gun device affords unique opportunities in biomedical endoscopic applications.

  12. Disruption of the blood-brain barrier as the primary effect of CNS irradiation.

    PubMed

    Rubin, P; Gash, D M; Hansen, J T; Nelson, D F; Williams, J P

    1994-04-01

    The blood-brain barrier (BBB) is believed to be unique in organ microcirculation due to the 'tight junctions' which exist between endothelial cells and, some argue, the additional functional components represented by the perivascular boundary of neuroglial cells; these selectively exclude proteins and drugs from the brain parenchyma. This study was designed to examine the effects of irradiation on the BBB and determine the impact of the altered pathophysiology on the production of central nervous system (CNS) late effects such as demyelination, gliosis and necrosis. Rats, irradiated at 60 Gy, were serially sacrificed at 2, 6, 12 and 24 weeks. Magnetic resonance image analysis (MRI) was obtained prior to sacrifice with selected animals from each group. The remaining animals underwent horse-radish peroxidase (HRP) perfusion at the time of sacrifice. The serial studies showed a detectable disruption of the BBB at 2 weeks post-irradiation and this was manifested as discrete leakage; late injury seen at 24 weeks indicated diffuse vasculature leakage, severe loss of the capillary network, cortical atrophy and white matter necrosis. Reversal or repair of radiation injury was seen between 6 and 12 weeks, indicating a bimodal peak in events. Blood-brain barrier disruption is an early, readily recognizable pathophysiological event occurring after radiation injury, is detectable in vivo/in vitro by MRI and HRP studies, and appears to precede white matter necrosis. Dose response studies over a wide range of doses, utilizing both external and interstitial irradiation, are in progress along with correlative histopathologic and ultrastructural studies.

  13. Irradiation as a hazard for mucociliary clearance.

    PubMed

    Foltin, Viktor; Schrott-Fischer, Annelies; Zilinek, Viliam; Freysinger, Wolfgang

    2016-07-01

    In this paper we study effects of irradiation to pulmonary tissue on a micro and ultrastructural level to get insights into the dynamics of morphological changes and associated post-radiative physiological conditions. Animal and human pulmonary tissue with and without radiation damage was subject to light, transmission, scanning and polarization microscopy and morphometric evaluation. The present investigations on the influence of irradiation on experimental and human lung tissue demonstrate that complex changes are induced in the cells which are essential for mucociliary clearance. These changes are a shortage of alveolar macrophages, cell apoptosis, proliferation of collagen ligament in the barrier of gaseous exchange, retraction of endothelial lining of capillaries and significant broadening of the gaseous exchange barrier, resulting in serious damage for the O2 and CO2 exchange. These changes at microscopic, cellular, and ciliary level trigger conditions for various diseases of the respiratory system, which is further assessed by a simultaneous computer aided estimation of ciliary function. With the concurrent world-wide increase of respiratory diseases, these findings are important knowledge for the clinical practice.

  14. Laser beam coupling with capillary discharge plasma for laser wakefield acceleration applications

    NASA Astrophysics Data System (ADS)

    Bagdasarov, G. A.; Sasorov, P. V.; Gasilov, V. A.; Boldarev, A. S.; Olkhovskaya, O. G.; Benedetti, C.; Bulanov, S. S.; Gonsalves, A.; Mao, H.-S.; Schroeder, C. B.; van Tilborg, J.; Esarey, E.; Leemans, W. P.; Levato, T.; Margarone, D.; Korn, G.

    2017-08-01

    One of the most robust methods, demonstrated to date, of accelerating electron beams by laser-plasma sources is the utilization of plasma channels generated by the capillary discharges. Although the spatial structure of the installation is simple in principle, there may be some important effects caused by the open ends of the capillary, by the supplying channels etc., which require a detailed 3D modeling of the processes. In the present work, such simulations are performed using the code MARPLE. First, the process of capillary filling with cold hydrogen before the discharge is fired, through the side supply channels is simulated. Second, the simulation of the capillary discharge is performed with the goal to obtain a time-dependent spatial distribution of the electron density near the open ends of the capillary as well as inside the capillary. Finally, to evaluate the effectiveness of the beam coupling with the channeling plasma wave guide and of the electron acceleration, modeling of the laser-plasma interaction was performed with the code INF&RNO.

  15. Hysteresis of the Contact Angle of a Meniscus Inside a Capillary with Smooth, Homogeneous Solid Walls.

    PubMed

    Kuchin, Igor V; Starov, Victor M

    2016-05-31

    A theory of contact angle hysteresis of a meniscus inside thin capillaries with smooth, homogeneous solid walls is developed in terms of surface forces (disjoining/conjoining pressure isotherm) using a quasi-equilibrium approach. The disjoining/conjoining pressure isotherm includes electrostatic, intermolecular, and structural components. The values of the static receding θr, advancing θa, and equilibrium θe contact angles in thin capillaries were calculated on the basis of the shape of the disjoining/conjoining pressure isotherm. It was shown that both advancing and receding contact angles depend on the capillary radius. The suggested mechanism of the contact angle hysteresis has a direct experimental confirmation: the process of receding is accompanied by the formation of thick β-films on the capillary walls. The effect of the transition from partial to complete wetting in thin capillaries is predicted and analyzed. This effect takes place in very thin capillaries, when the receding contact angle decreases to zero.

  16. Development of KMnO(4)-releasing composites for in situ chemical oxidation of TCE-contaminated groundwater.

    PubMed

    Liang, S H; Chen, K F; Wu, C S; Lin, Y H; Kao, C M

    2014-05-01

    The objective of this study was to develop a controlled-oxidant-release technology combining in situ chemical oxidation (ISCO) and permeable reactive barrier (PRB) concepts to remediate trichloroethene (TCE)-contaminated groundwater. In this study, a potassium permanganate (KMnO4)-releasing composite (PRC) was designed for KMnO4 release. The components of this PRC included polycaprolactone (PCL), KMnO4, and starch with a weight ratio of 1.14:2:0.96. Approximately 64% (w/w) of the KMnO4 was released from the PRC after 76 days of operation in a batch system. The results indicate that the released KMnO4 could oxidize TCE effectively. The results from a column study show that the KMnO4 released from 200 g of PRC could effectively remediate 101 pore volumes (PV) of TCE-contaminated groundwater (initial TCE concentration = 0.5 mg/L) and achieve up to 95% TCE removal. The effectiveness of the PRC system was verified by the following characteristics of the effluents collected after the PRC columns (barrier): (1) decreased TCE concentrations, (2) increased ORP and pH values, and (3) increased MnO2 and KMnO4 concentrations. The results of environmental scanning electron microscope (ESEM) analysis show that the PCL and starch completely filled up the pore spaces of the PRC, creating a composite with low porosity. Secondary micro-scale capillary permeability causes the KMnO4 release, mainly through a reaction-diffusion mechanism. The PRC developed could be used as an ISCO-based passive barrier system for plume control, and it has the potential to become a cost-effective alternative for the remediation of chlorinated solvent-contaminated groundwater. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Zhuanfang Fred; Strickland, Christopher E.; Link, Steven O.

    Surface barrier technology is used to isolate radioactive waste and to reduce or eliminate recharge water to the waste zone for 1000 years or longer. However, the design and evaluation of such a barrier is challenging because of the extremely long design life. The Prototype Hanford Barrier (PHB) was designed as a 1000-year barrier with pre-determined design and performance objectives and demonstrated in field from 1994 to present. The barrier was tested to evaluate surface-barrier design and performance at the field scale under conditions of enhanced and natural precipitation and of no vegetation. The monitoring data demonstrate that the barriermore » satisfied nearly all key objectives. The PHB far exceeded the Resource Conservation and Recovery Act criteria, functioned in Hanford’s semiarid climate, limited drainage to well below the 0.5 mm yr-1 performance criterion, limited runoff, and minimized erosion. Given the two-decade record of successful performance and consideration of all the processes and mechanisms that could degrade the stability and hydrology in the future, the results suggest the PHB is very likely to perform for its 1000-year design life. This conclusion is based on two assumptions: (1) the exposed subgrade receives protection against erosion and (2) institutional controls prevent inadvertent human activity at the barrier. The PHB design can serve as the base for site-specific barriers over waste sites containing underground nuclear waste, uranium mine tailings, and hazardous mine waste.« less

  18. Laser probe for measuring 2-D wave slope spectra of ocean capillary waves

    NASA Technical Reports Server (NTRS)

    Palm, C. S.; Anderson, R. C.; Reece, A. M.

    1977-01-01

    A laser-optical instrument for use in determining the two-dimensional wave-slope spectrum of ocean capillary waves is described. The instrument measures up to a 35-deg tip angle of the surface normal by measuring the position of a refracted laser beam directed vertically upward through a water surface. A telescope, a continuous two-dimensional Schottky barrier photodiode, and a pair of analog dividers render the signals independent of water height and insensitive to laser-beam intensity fluctuations. Calibration is performed entirely in the laboratory before field use. Sample records and wave-slope spectra are shown for one-dimensional wave-tank tests and for two-dimensional ocean tests. These are presented along with comparison spectra for calm and choppy water conditions. A mechanical wave follower was used to adjust the instrument position in the presence of large ocean swell and tides.

  19. Self organized spatio-temporal structure within the fractured Vadose Zone: The influence of dynamic overloading at fracture intersections

    NASA Astrophysics Data System (ADS)

    LaViolette, Randall A.; Glass, Robert J.

    2004-09-01

    Under low flow conditions (where gravity and capillary forces dominate) within an unsaturated fracture network, fracture intersections act as capillary barriers to integrate flow from above and then release it as a pulse below. Water exiting a fracture intersection is often thought to enter the single connected fracture with the lowest invasion pressure. When the accumulated volume varies between intersections, the smaller volume intersections can be overloaded to cause all of the available fractures exiting an intersection to flow. We included the dynamic overloading process at fracture intersections within our previously discussed model where intersections were modeled as tipping buckets connected within a two-dimensional diamond lattice. With dynamic overloading, the flow behavior transitioned smoothly from diverging to converging flow with increasing overload parameter, as a consequence of a heterogeneous field, and they impose a dynamic structure where additional pathways activate or deactivate in time.

  20. Exact Solution for Capillary Bridges Properties by Shooting Method

    NASA Astrophysics Data System (ADS)

    Qiang-Nian, Li; Jia-Qi, Zhang; Feng-Xi, Zhou

    2017-04-01

    The investigation of liquid bridge force acting between wet particles has great significance in many fields. In this article, the exact solution of capillary force between two unequal-sized spherical particles is investigated. Firstly, The Young-Laplace equation with moving boundary is converted into a set of ordinary differential equations with two fix point boundary using variable substitution technique, in which the gravity effects have been neglected. The geometry of the liquid bridge between two particles is solved by shooting method. After that, the gorge method is applied to calculate the capillary-bridge force that is consists of contributions from the capillary suction and surface tension. Finally, the effect of various parameters including distance between two spheres, radii of spheres, and contact angles on the capillary force are investigated. It is shown that the presented approach is an efficient and accurate algorithm for capillary force between two particles in complex situations.

  1. Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

    PubMed Central

    Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T

    1996-01-01

    The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926

  2. A model for capillary rise in micro-tube restrained by a sticky layer

    NASA Astrophysics Data System (ADS)

    Shen, Anqi; Xu, Yun; Liu, Yikun; Cai, Bo; Liang, Shuang; Wang, Fengjiao

    2018-06-01

    Fluid transport in a microscopic capillary under the effects of a sticky layer was theoretically investigated. A model based on the classical Lucas-Washburn (LW) model is proposed for the meniscus rise with the sticky layer present. The sticky layer consists of two parts: a fixed (located at the wall) and a movable part (located on the inside of the capillary), affecting the micro-capillary flow in different ways. Within our model, the movable layer is defined by the capillary radius and pressure gradient. From the model it follows that the fixed sticky layer leads to a decrease of capillary radius, while the movable sticky layer increases flow resistance. The movable layer thickness varies with the pressure gradient, which in turn varies with the rising of the meniscus. The results of our theoretical calculation also prove that the capillary radius has a greater effect on the meniscus height, rather than the additional resistance caused by the movable layer. Moreover, the fixed sticky layer, which affects the capillary radius, has a greater influence than the movable sticky layer. We conclude that the sticky layer causes a lower imbibition height than the LW model predicts.

  3. Multiphase flow and transport caused by spontaneous gas phase growth in the presence of dense non-aqueous phase liquid

    NASA Astrophysics Data System (ADS)

    Roy, James W.; Smith, James E.

    2007-01-01

    Disconnected bubbles or ganglia of trapped gas may occur below the top of the capillary fringe through a number of mechanisms. In the presence of dense non-aqueous phase liquid (DNAPL), the disconnected gas phase experiences mass transfer of dissolved gases, including volatile components from the DNAPL. The properties of the gas phase interface can also change. This work shows for the first time that when seed gas bubbles exist spontaneous gas phase growth can be expected to occur and can significantly affect water-gas-DNAPL distributions, fluid flow, and mass transfer. Source zone behaviour was observed in three different experiments performed in a 2-dimensional flow cell. In each case, a DNAPL pool was created in a zone of larger glass beads over smaller glass beads, which served as a capillary barrier. In one experiment effluent water samples were analyzed to determine the vertical concentration profile of the plume above the pool. The experiments effectively demonstrated a) a cycle of spontaneous gas phase expansion and vertical advective mobilization of gas bubbles and ganglia above the DNAPL source zone, b) DNAPL redistribution caused by gas phase growth and mobilization, and c) that these processes can significantly affect mass transport from a NAPL source zone.

  4. Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs.

    PubMed

    Parker, J C; Ivey, C L

    1997-12-01

    To separate the contributions of cellular and basement membrane components of the alveolar capillary barrier to the increased microvascular permeability induced by high pulmonary venous pressures (Ppv), we subjected isolated rat lungs to increases in Ppv, which increased capillary filtration coefficient (Kfc) without significant hemorrhage (31 cmH2O) and with obvious extravasation of red blood cells (43 cmH2O). Isoproterenol (20 microM) was infused in one group (Iso) to identify a reversible cellular component of injury, and residual blood volumes were measured to assess extravasation of red blood cells through ruptured basement membranes. In untreated lungs (High Ppv group), Kfc increased 6.2 +/- 1.3 and 38.3 +/- 15.2 times baseline during the 31 and 43 cmH2O Ppv states. In Iso lungs, Kfc was 36.2% (P < 0.05) and 64.3% of that in the High Ppv group at these Ppv states. Residual blood volumes calculated from tissue hemoglobin contents were significantly increased by 53-66% in the high Ppv groups, compared with low vascular pressure controls, but there was no significant difference between High Ppv and Iso groups. Thus isoproterenol significantly attenuated vascular pressure-induced Kfc increases at moderate Ppv, possibly because of an endothelial effect, but it did not affect red cell extravasation at higher vascular pressures.

  5. Multiphase flow and transport caused by spontaneous gas phase growth in the presence of dense non-aqueous phase liquid.

    PubMed

    Roy, James W; Smith, James E

    2007-01-30

    Disconnected bubbles or ganglia of trapped gas may occur below the top of the capillary fringe through a number of mechanisms. In the presence of dense non-aqueous phase liquid (DNAPL), the disconnected gas phase experiences mass transfer of dissolved gases, including volatile components from the DNAPL. The properties of the gas phase interface can also change. This work shows for the first time that when seed gas bubbles exist spontaneous gas phase growth can be expected to occur and can significantly affect water-gas-DNAPL distributions, fluid flow, and mass transfer. Source zone behaviour was observed in three different experiments performed in a 2-dimensional flow cell. In each case, a DNAPL pool was created in a zone of larger glass beads over smaller glass beads, which served as a capillary barrier. In one experiment effluent water samples were analyzed to determine the vertical concentration profile of the plume above the pool. The experiments effectively demonstrated a) a cycle of spontaneous gas phase expansion and vertical advective mobilization of gas bubbles and ganglia above the DNAPL source zone, b) DNAPL redistribution caused by gas phase growth and mobilization, and c) that these processes can significantly affect mass transport from a NAPL source zone.

  6. Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype.

    PubMed

    Katt, Moriah E; Xu, Zinnia S; Gerecht, Sharon; Searson, Peter C

    2016-01-01

    The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial cells (hBMECs) from human induced pluripotent stem cells (iPSCs) may provide a solution to this problem. Here we demonstrate the derivation of hBMECs extended to two new human iPSC lines: BC1 and GFP-labeled BC1. These hBMECs highly express adherens and tight junction proteins VE-cadherin, ZO-1, occludin, and claudin-5. The addition of retinoic acid upregulates VE-cadherin expression, and results in a significant increase in transendothelial electrical resistance to physiological values. The permeabilities of tacrine, rhodamine 123, and Lucifer yellow are similar to values obtained for MDCK cells. The efflux ratio for rhodamine 123 across hBMECs is in the range 2-4 indicating polarization of efflux transporters. Using the rod assay to assess cell organization in small vessels and capillaries, we show that hBMECs resist elongation with decreasing diameter but show progressive axial alignment. The derivation of hBMECs with a blood-brain barrier phenotype from the BC1 cell line highlights that the protocol is robust. The expression of GFP in hBMECs derived from the BC1-GFP cell line provides an important new resource for BBB research.

  7. Microgravity Investigation of Capillary Driven Imbibition

    NASA Astrophysics Data System (ADS)

    Dushin, V. R.; Nikitin, V. F.; Smirnov, N. N.; Skryleva, E. I.; Tyurenkova, V. V.

    2018-05-01

    The goal of the present paper is to investigate the capillary driven filtration in porous media under microgravity conditions. New mathematical model that allows taking into account the blurring of the front due to the instability of the displacement that is developing at the front is proposed. The constants in the mathematical model were selected on the basis of the experimental data on imbibition into unsaturated porous media under microgravity conditions. The flow under the action of a combination of capillary forces and a constant pressure drop or a constant flux is considered. The effect of capillary forces and the type of wettability of the medium on the displacement process is studied. A criterion in which case the capillary effects are insignificant and can be neglected is established.

  8. Nonequilibrium capillarity effects in multiphase flow through small volume fractured porous media

    NASA Astrophysics Data System (ADS)

    Tang, M.; Zhan, H.; Lu, S.

    2017-12-01

    Analyzing and understanding the capillary pressure curves in fractured porous media is a crucial subject in a number of industrial applications, such as crude oil recovery in the fractured reservoir, CO2 sequestration in fractured brine aquifers and shale gas development. Many studies have observed the significant nonequilibrium capillarity effects in multiphase flow through porous media and proposed that conventional equilibrium capillary pressure may not accurately describe transient two-phase flow behavior under dynamical conditions. To date, only several laboratory experiments and numerical models have been conducted into investigating the characteristic of nonequilibrium capillary pressure in unfractured porous media, a clear picture of the effects of fractures on the dynamic capillary pressure in fractured porous media remains elusive. In this study, four digital porous models were built based on CT image data from ZEISS Xradia 520 Versa CT scanning, a series of direct simulations of multiphase flow in fractured porous media were carried out based on lattice Boltzmann method and three-dimensional porous models. The results show that both the aperture and orientation of the fractures have significant effects on the nonequilibrium capillary pressure coefficients and multiphase flow behaviors. The nonequilibrium capillary pressure coefficients in fractured porous media are one to two orders of magnitude lower than unfractured porous media. This study presents a new direct simulation based methodology for the detailed analysis of nonequilibrium capillary pressure in fractured porous media.

  9. A Theoretical Analysis of the Influence of Electroosmosis on the Effective Ionic Mobility in Capillary Zone Electrophoresis

    ERIC Educational Resources Information Center

    Hijnen, Hens

    2009-01-01

    A theoretical description of the influence of electroosmosis on the effective mobility of simple ions in capillary zone electrophoresis is presented. The mathematical equations derived from the space-charge model contain the pK[subscript a] value and the density of the weak acid surface groups as parameters characterizing the capillary. It is…

  10. ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.

    PubMed

    Rothschild, Pierre-Raphaël; Salah, Sawsen; Berdugo, Marianne; Gélizé, Emmanuelle; Delaunay, Kimberley; Naud, Marie-Christine; Klein, Christophe; Moulin, Alexandre; Savoldelli, Michèle; Bergin, Ciara; Jeanny, Jean-Claude; Jonet, Laurent; Arsenijevic, Yvan; Behar-Cohen, Francine; Crisanti, Patricia

    2017-08-18

    In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

  11. Noise suppressing capillary separation system

    DOEpatents

    Yeung, Edward S.; Xue, Yongjun

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans.

  12. Noise suppressing capillary separation system

    DOEpatents

    Yeung, E.S.; Xue, Y.

    1996-07-30

    A noise-suppressing capillary separation system for detecting the real-time presence or concentration of an analyte in a sample is provided. The system contains a capillary separation means through which the analyte is moved, a coherent light source that generates a beam which is split into a reference beam and a sample beam that irradiate the capillary, and a detector for detecting the reference beam and the sample beam light that transmits through the capillary. The laser beam is of a wavelength effective to be absorbed by a chromophore in the capillary. The system includes a noise suppressing system to improve performance and accuracy without signal averaging or multiple scans. 13 figs.

  13. 200-BP-1 Prototype Hanford Barrier -- 15 Years of Performance Monitoring

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ward, Anderson L.; Draper, Kathryn E.; Link, Steven O.

    2011-09-30

    Monitoring is an essential component of engineered barrier system design and operation. A composite capacitive cover, including a capillary break and an evapotranspiration (ET) barrier at the Hanford Site, is generating data that can be used to help resolve these issues. The prototype Hanford barrier was constructed over the 216-B-57 Crib in 1994 to evaluate surface-barrier constructability, construction costs, and physical and hydrologic performance at the field scale. The barrier has been routinely monitored between November 1994 and September 1998 as part of a Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) treatability test of barrier performance formore » the 200 BP 1 Operable Unit. Since FY 1998, monitoring has focused on a more limited set of key water balance, stability, and biotic parameters. In FY 2009, data collection was focused on: (1) water-balance monitoring, consisting of precipitation, runoff, soil moisture storage, and drainage measurements with evapotranspiration calculated by difference; (2) stability monitoring, consisting of asphalt-layer-settlement, basalt-side-slope-stability, and surface-elevation measurements; (3) vegetation dynamics; and (4) animal use. September 2009 marked 15 years since the start of monitoring and the collection of performance data. This report describes the results of monitoring activities during the period October 1, 2008, through September 30, 2009, and summarizes the 15 years of performance data collected from September 1994 through September 2009.« less

  14. Bombarding Cancer: Biolistic Delivery of therapeutics using Porous Si Carriers

    PubMed Central

    Zilony, Neta; Tzur-Balter, Adi; Segal, Ester; Shefi, Orit

    2013-01-01

    A new paradigm for an effective delivery of therapeutics into cancer cells is presented. Degradable porous silicon carriers, which are tailored to carry and release a model anti-cancer drug, are biolistically bombarded into in-vitro cancerous targets. We demonstrate the ability to launch these highly porous microparticles by a pneumatic capillary gene gun, which is conventionally used to deliver cargos by heavy metal carriers. By optimizing the gun parameters e.g., the accelerating gas pressure, we have successfully delivered the porous carriers, to reach deep targets and to cross a skin barrier in a highly spatial resolution. Our study reveals significant cytotoxicity towards the target human breast carcinoma cells following the delivery of drug-loaded carriers, while administrating empty particles results in no effect on cell viability. The unique combination of biolistics with the temporal control of payload release from porous carriers presents a powerful and non-conventional platform for designing new therapeutic strategies. PMID:23975675

  15. Kidneys: Key Modulators of HDL Levels and Function

    PubMed Central

    Yang, Haichun; Fogo, Agnes B.; Kon, Valentina

    2016-01-01

    Purpose of review This review will examine advances in our understanding of the role kidneys play in HDL metabolism and the effect on levels, composition, and function of HDL particles. Recent findings Components of the HDL particles can cross the glomerular filtration barrier. Some of these components, including apolipoproteins and enzymes involved in lipid metabolism, are taken up by the proximal tubule and degraded, modified, salvaged/returned to the circulation, or lost in the urine. Injury of the glomerular capillaries or tubules can affect these intrarenal processes and modify HDL. Changes in the plasma and urine levels of HDL may be novel markers of kidney damage and/or mechanism(s) of kidney disease. Summary The kidneys have a significant role in metabolism of individual HDL components, which in turn modulate HDL levels, composition and functionality of HDL particles. These intrarenal effects may be useful markers of kidney damage and have consequences on kidney-related perturbations in HDL. PMID:27008596

  16. Capillary damage in the area postrema by venom of the northern black-tailed rattlesnake (Crotalus molossus molossus)

    PubMed Central

    Meléndez-Martínez, David; Macias-Rodríguez, Eduardo; Vargas-Caraveo, Alejandra; Martínez-Martínez, Alejandro; Gatica-Colima, Ana; Plenge-Tellechea, Luis Fernando

    2014-01-01

    The Northern black-tailed rattlesnake (Crotalus molossus molossus) venom is mainly hemotoxic, hemorrhagic, and neurotoxic. Its effects in the central nervous system are unknown and only poorly described for all Viperidae species in general. This is why we are interested in describe the damage induced by C. m. molossus venom in rat brain, particularly in the area postrema capillaries. Four C. m. molossus venom doses were tested (0.02, 0.05, 0.10 and 0.20mg/kg) injected intramuscularly at the lower limb, incubated by 24 hours and the brains were harvested. Area postrema coronal sections were stained with Haematoxylin and Eosin, and examined to observe the venom effect in quantity of capillaries and porphology. Starting from the 0.10mg/kg treatment we observed lysed extravasated erythrocytes and also capillary breakdown, as a consequence of hemorrhages appearance. The number of capillaries decreased significantly in response to the venom dose increment. Hemorrhages could be caused by the metalloproteinase activity on the basal membrane and the apoptosis generated by L-amino acid oxidases. Hemolysis could be caused by phospholipase A2 hemotoxic effect. We conclude that C. m. molossus crude venom produces hemolysis, capillary breakdown, hemorrhages, and the reduction in number of capillaries in the area postrema. PMID:25035793

  17. Low-pressure barrier discharge ion source using air as a carrier gas and its application to the analysis of drugs and explosives.

    PubMed

    Usmanov, Dilshadbek T; Yu, Zhan; Chen, Lee Chuin; Hiraoka, Kenzo; Yamabe, Shinichi

    2016-02-01

    In this work, a low-pressure air dielectric-barrier discharge (DBD) ion source using a capillary with the inner diameter of 0.115 and 12 mm long applicable to miniaturized mass spectrometers was developed. The analytes, trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), 1,3,5,7-tetranitroperhydro-1,3,5,7-tetrazocine (HMX), pentaerythritol tetranitrate (PETN), nitroglycerine (NG), hexamethylene triperoxide diamine (HMTD), caffeine, cocaine and morphine, introduced through the capillary, were ionized by a low-pressure air DBD. The ion source pressures were changed by using various sizes of the ion sampling orifice. The signal intensities of those analytes showed marked pressure dependence. TNT was detected with higher sensitivity at lower pressure but vice versa for other analytes. For all analytes, a marked signal enhancement was observed when a grounded cylindrical mesh electrode was installed in the DBD ion source. Among nine analytes, RDX, HMX, NG and PETN could be detected as cluster ions [analyte + NO3 ](-) even at low pressure and high temperature up to 180 °C. The detection indicates that these cluster ions are stable enough to survive under present experimental conditions. The unexpectedly high stabilities of these cluster ions were verified by density functional theory calculation. Copyright © 2016 John Wiley & Sons, Ltd.

  18. String Vessel Formation is Increased in the Brain of Parkinson Disease.

    PubMed

    Yang, Panzao; Pavlovic, Darja; Waldvogel, Henry; Dragunow, Mike; Synek, Beth; Turner, Clinton; Faull, Richard; Guan, Jian

    2015-01-01

    String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

  19. A physics link between venous stenosis and multiple sclerosis.

    PubMed

    Tucker, Trevor W

    2011-12-01

    This paper hypothesizes that a stenosis or obstruction at a lower extremity of an internal jugular vein (IJV) would, in accordance with the physics of fluid dynamics, cause a standing pressure wave within the vein. This pressure wave would possess regions of large pressure fluctuations and other regions of relatively little fluctuation which also have substantially lower peak pressure values. If the wavelength of the hypothesized pressure wave is comparable to the distance from the obstruction to the venule end of the capillary bed, then a region of high pressure fluctuation would exist at the venules. Depending on the degree of obstruction, the pressure fluctuations at the venules of the capillary bed would be substantially greater than those that would exist in a healthy unobstructed vein. This increase in blood pressure fluctuation located at the venule end of the capillary bed, which would be equivalent to local hypertension, is predicted to reduce the pressure drop across the bed which, in turn, would reduce blood flow through the bed in accordance with Darcy's Law. Such a reduction in blood flow through the bed would be accompanied by a reduction in the transfer of oxygen, glucose and other nutrients into the brain tissue in accordance with Fick's Principle. The reduction in oxygen levels in the brain tissue (i.e. hypoxia), would, in turn, be associated with increased fatigue and decreased mental acuity in the subject patient. Also the deprivation of oxygen in the brain tissue may result in the death of oligodendrocyte cells, which, in turn would result in the deterioration of the myelin surrounding the brain's neural axons. In addition, the paper also predicts that, in cases of extreme obstruction, the predicted localized hypertension at the venule end of the capillary bed may be sufficiently high to cause a localized disruption in the blood-brain barrier. Such a disruption of the blood-brain barrier could then allow the migration of leukocytes (auto-immune attack cells), from the blood into the brain tissue, enabling them to attack myelin, which has degenerated or deteriorated from the reduction in repair function normally provided by oligodendrocyte cells. Such leukocyte attack on myelin has long been associated with multiple sclerosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Image-Based Modeling of Blood Flow and Oxygen Transfer in Feto-Placental Capillaries

    PubMed Central

    Brownbill, Paul; Janáček, Jiří; Jirkovská, Marie; Kubínová, Lucie; Chernyavsky, Igor L.; Jensen, Oliver E.

    2016-01-01

    During pregnancy, oxygen diffuses from maternal to fetal blood through villous trees in the placenta. In this paper, we simulate blood flow and oxygen transfer in feto-placental capillaries by converting three-dimensional representations of villous and capillary surfaces, reconstructed from confocal laser scanning microscopy, to finite-element meshes, and calculating values of vascular flow resistance and total oxygen transfer. The relationship between the total oxygen transfer rate and the pressure drop through the capillary is shown to be captured across a wide range of pressure drops by physical scaling laws and an upper bound on the oxygen transfer rate. A regression equation is introduced that can be used to estimate the oxygen transfer in a capillary using the vascular resistance. Two techniques for quantifying the effects of statistical variability, experimental uncertainty and pathological placental structure on the calculated properties are then introduced. First, scaling arguments are used to quantify the sensitivity of the model to uncertainties in the geometry and the parameters. Second, the effects of localized dilations in fetal capillaries are investigated using an idealized axisymmetric model, to quantify the possible effect of pathological placental structure on oxygen transfer. The model predicts how, for a fixed pressure drop through a capillary, oxygen transfer is maximized by an optimal width of the dilation. The results could explain the prevalence of fetal hypoxia in cases of delayed villous maturation, a pathology characterized by a lack of the vasculo-syncytial membranes often seen in conjunction with localized capillary dilations. PMID:27788214

  1. Pore-scale modeling of Capillary Penetration of Wetting Liquid into 3D Fibrous Media: A Critical Examination of Equivalent Capillary Concept

    NASA Astrophysics Data System (ADS)

    Palakurthi, Nikhil Kumar; Ghia, Urmila; Comer, Ken

    2013-11-01

    Capillary penetration of liquid through fibrous porous media is important in many applications such as printing, drug delivery patches, sanitary wipes, and performance fabrics. Historically, capillary transport (with a distinct liquid propagating front) in porous media is modeled using capillary-bundle theory. However, it is not clear if the capillary model (Washburn equation) describes the fluid transport in porous media accurately, as it assumes uniformity of pore sizes in the porous medium. The present work investigates the limitations of the applicability of the capillary model by studying liquid penetration through virtual fibrous media with uniform and non-uniform pore-sizes. For the non-uniform-pore fibrous medium, the effective capillary radius of the fibrous medium was estimated from the pore-size distribution curve. Liquid penetration into the 3D virtual fibrous medium at micro-scale was simulated using OpenFOAM, and the numerical results were compared with the Washburn-equation capillary-model predictions. Preliminary results show that the Washburn equation over-predicts the height rise in the early stages (purely inertial and visco-inertial stages) of capillary transport.

  2. Capillarics: pre-programmed, self-powered microfluidic circuits built from capillary elements.

    PubMed

    Safavieh, Roozbeh; Juncker, David

    2013-11-07

    Microfluidic capillary systems employ surface tension effects to manipulate liquids, and are thus self-powered and self-regulated as liquid handling is structurally and chemically encoded in microscale conduits. However, capillary systems have been limited to perform simple fluidic operations. Here, we introduce complex capillary flow circuits that encode sequential flow of multiple liquids with distinct flow rates and flow reversal. We first introduce two novel microfluidic capillary elements including (i) retention burst valves and (ii) robust low aspect ratio trigger valves. These elements are combined with flow resistors, capillary retention valves, capillary pumps, and open and closed reservoirs to build a capillary circuit that, following sample addition, autonomously delivers a defined sequence of multiple chemicals according to a preprogrammed and predetermined flow rate and time. Such a circuit was used to measure the concentration of C-reactive protein. This work illustrates that as in electronics, complex capillary circuits may be built by combining simple capillary elements. We define such circuits as "capillarics", and introduce symbolic representations. We believe that more complex circuits will become possible by expanding the library of building elements and formulating abstract design rules.

  3. Influence of chronobiology on the nanoparticle-mediated drug uptake into the brain.

    PubMed

    Kreuter, Jörg

    2015-02-03

    Little attention so-far has been paid to the influence of chronobiology on the processes of nanoparticle uptake and transport into the brain, even though this transport appears to be chronobiologically controlled to a significant degree. Nanoparticles with specific surface properties enable the transport across the blood-brain barrier of many drugs that normally cannot cross this barrier. A clear dependence of the central antinociceptive (analgesic) effects of a nanoparticle-bound model drug, i.e., the hexapeptide dalargin, on the time of day was observable after intravenous injection in mice. In addition to the strongly enhanced antinociceptive effect due to the binding to the nanoparticles, the minima and maxima of the pain reaction with the nanoparticle-bound drug were shifted by almost half a day compared to the normal circadian nociception: The maximum in the pain reaction after i.v. injection of the nanoparticle-bound dalargin occurred during the later rest phase of the animals whereas the normal pain reaction and that of a dalargin solution was highest during the active phase of the mice in the night. This important shift could be caused by an enhanced endo- and exocytotic particulates transport activity of the brain capillary endothelial cells or within the brain during the rest phase.

  4. Functional respiratory morphology in the newborn quokka wallaby (Setonix brachyurus)

    PubMed Central

    Makanya, A N; Tschanz, S A; Haenni, B; Burri, P H

    2007-01-01

    A morphological and morphometric study of the lung of the newborn quokka wallaby (Setonix brachyurus) was undertaken to assess its morphofunctional status at birth. Additionally, skin structure and morphometry were investigated to assess the possibility of cutaneous gas exchange. The lung was at canalicular stage and comprised a few conducting airways and a parenchyma of thick-walled tubules lined by stretches of cuboidal pneumocytes alternating with squamous epithelium, with occasional portions of thin blood–gas barrier. The tubules were separated by abundant intertubular mesenchyme, aggregations of developing capillaries and mesenchymal cells. Conversion of the cuboidal pneumocytes to type I cells occurred through cell broadening and lamellar body extrusion. Superfluous cuboidal cells were lost through apoptosis and subsequent clearance by alveolar macrophages. The establishment of the thin blood–gas barrier was established through apposition of the incipient capillaries to the formative thin squamous epithelium. The absolute volume of the lung was 0.02 ± 0.001 cm3 with an air space surface area of 4.85 ± 0.43 cm2. Differentiated type I pneumocytes covered 78% of the tubular surface, the rest 22% going to long stretches of type II cells, their precursors or low cuboidal transitory cells with sparse lamellar bodies. The body weight-related diffusion capacity was 2.52 ± 0.56 mL O2 min−1 kg−1. The epidermis was poorly developed, and measured 29.97 ± 4.88 µm in thickness, 13% of which was taken by a thin layer of stratum corneum, measuring 4.87 ± 0.98 µm thick. Superficial capillaries were closely associated with the epidermis, showing the possibility that the skin also participated in some gaseous exchange. Qualitatively, the neonate quokka lung had the basic constituents for gas exchange but was quantitatively inadequate, implying the significance of percutaneous gas exchange. PMID:17553103

  5. A Composite Medium Approximation for Moisture Tension-Dependent Anisotropy in Unsaturated Layered Sediments

    NASA Astrophysics Data System (ADS)

    Pruess, K.

    2001-12-01

    Sedimentary formations often have a layered structure in which hydrogeologic properties have substantially larger correlation length in the bedding plane than perpendicular to it. Laboratory and field experiments and observations have shown that even small-scale layering, down to millimeter-size laminations, can substantially alter and impede the downward migration of infiltrating liquids, while enhancing lateral flow. The fundamental mechanism is that of a capillary barrier: at increasingly negative moisture tension (capillary suction pressure), coarse-grained layers with large pores desaturate more quickly than finer-grained media. This strongly reduces the hydraulic conductivity of the coarser (higher saturated hydraulic conductivity) layers, which then act as barriers to downward flow, forcing water to accumulate and spread near the bottom of the overlying finer-grained material. We present a "composite medium approximation" (COMA) for anisotropic flow behavior on a typical grid block scale (0.1 - 1 m or larger) in finite-difference models. On this scale the medium is conceptualized as consisting of homogeneous horizontal layers with uniform thickness, and capillary equilibrium is assumed to prevail locally. Directionally-dependent relative permeabilities are obtained by considering horizontal flow to proceed via "conductors in parallel," while vertical flow involves "resistors in series." The model is formulated for the general case of N layers, and implementation of a simplified two-layer (fine-coarse) approximation in the multiphase flow simulator TOUGH2 is described. The accuracy of COMA is evaluated by comparing numerical simulations of plume migration in 1-D and 2-D unsaturated flow with results of fine-grid simulations in which all layers are discretized explicitly. Applications to water seepage and solute transport at the Hanford site are also described. This work was supported by the U.S. Department of Energy under Contract No. DE-AC03-76SF00098 through Memorandum Purchase Order 248861-A-B2 between Pacific Northwest National Laboratory and Lawrence Berkeley National Laboratory.

  6. Capillary density: An important parameter in nailfold capillaroscopy.

    PubMed

    Emrani, Zahra; Karbalaie, Abdolamir; Fatemi, Alimohammad; Etehadtavakol, Mahnaz; Erlandsson, Björn-Erik

    2017-01-01

    Nailfold capillaroscopy is one of the various noninvasive bioengineering methods used to investigate skin microcirculation. It is an effective examination for assessing microvascular changes in the peripheral circulation; hence it has a significant role for the diagnosis of Systemic sclerosis with the classic changes of giant capillaries as well as the decline in capillary density with capillary dropout. The decline in capillary density is one of microangiopathic features existing in connective tissue disease. It is detectable with nailfold capillaroscopy. This parameter is assessed by applying quantitative measurement. In this article, we reviewed a common method for calculating the capillary density and the relation between the number of capillaries as well as the existence of digital ulcers, pulmonary arterial hypertension, autoantibodies, scleroderma patterns and different scoring system. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. On the Asymmetric Focusing of Low-Emittance Electron Bunches via Active Lensing by Using Capillary Discharges

    NASA Astrophysics Data System (ADS)

    Bulanov, Stepan; Bagdasarov, Gennadiy; Bobrova, Nadezhda; Boldarev, Alexey; Olkhovskaya, Olga; Sasorov, Pavel; Gasilov, Vladimir; Barber, Samuel; Gonsalves, Anthony; Schroeder, Carl; van Tilborg, Jeroen; Esarey, Eric; Leemans, Wim; Levato, Tadzio; Margarone, Daniele; Korn, Georg; Kando, Masaki; Bulanov, Sergei

    2017-10-01

    A novel method for asymmetric focusing of electron beams is proposed. The scheme is based on the active lensing technique, which takes advantage of the strong inhomogeneous magnetic field generated inside the capillary discharge plasma to focus the ultrarelativistic electrons. The plasma and magnetic field parameters inside a capillary discharge are described theoretically and modeled with dissipative MHD simulations to enable analysis of capillaries of oblong rectangle cross-sections implying that large aspect ratio rectangular capillaries can be used to form flat electron bunches. The effect of the capillary cross-section on the electron beam focusing properties were studied using the analytical methods and simulation- derived magnetic field map showing the range of the capillary discharge parameters required for producing the high quality flat electron beams.

  8. Enhancing separation in short-capillary electrophoresis via pressure-driven backflow.

    PubMed

    Tian, Miaomiao; Wang, Yujia; Mohamed, Amara Camara; Guo, Liping; Yang, Li

    2015-07-01

    We present a novel easy-to-operate and efficient method to improve the separation efficiency in short-capillary electrophoresis by introducing steady backflow to counterbalance electro-osmotic flow without the use of any external pressure. The backflow was easily generated by tapering the capillary end, which was achieved by heating a straight capillary and stretching it with a constant force. We investigated the net fluidic transport rate under different tip lengths and separation voltages. Good run-to-run repeatability and capillary-to-capillary reproducibility of the present method were obtained with RSD less than 1.5%, indicating the stability of the fluid transport rate in the tapered capillary, which ensures the quantification and repeatability of capillary zone electrophoresis (CZE) analysis. Enhanced separation of the tapered short capillary electrophoresis was demonstrated by CZE analyzing amino acids and positional isomers. Baseline separations were achieved in less than 60 s using a tapered capillary with the effective length of 5 cm, while no separation was achieved using a normal capillary without a tapered tip. The present study provides a promising method to use pressure-driven backflow to enhance separation efficiency in short-capillary electrophoresis, which would be of potential value in a wide application for fast analysis of complex samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Comparison of histamine and hyperosmotic arabinose infusion on brain capillary permeability to hydrophilic solutes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lucchesi, K.J.

    1986-03-01

    The effect of bilateral intracarotid infusion of histamine (HA) on capillary permeability-surface area products (PS) of two metabolically inert tracers was determined and compared to that of L(+)arabinose (ARAB) in rat brain. Ringer's solution alone, or with 1 mg/kg HA diphosphate or 1.6M ARAB added, was infused (0.9 ml over 0.5 min) into each external carotid artery (CA). Five minutes later, a bolus of /sup 14/C-sucrose and /sup 3/H-L-glucose was injected i.v. Estimates of PS for both tracers were computed by the method of Ohno et al after brain concentration was corrected for tracer within cerebral blood vessels. Brain bloodmore » volume, based on the /sup 14/C-dextran space, was the same (.016 ml/g) in discrete cortical and midbrain regions of all rats except those treated with ARAB. The latter yielded .033 ml/g, presumably due to dextran extravasation. Infusion of ARAB, HA and Ringer's increased the PS's of sucrose and L-glucose by 10x, 8x, and 3x in brain regions perfused by the internal CA's. The ratio, PS-sucrose/PS-L-glucose was unchanged by any treatment. Both ARAB and HA caused transient falls in arterial pressure, but only ARAB caused deaths (3 of 9 rats). While as effective as ARAB in opening the blood-brain barrier, HA may be safer than hyperosmotic shock to enhance delivery of chemotherapeutic agents to brain tumors.« less

  10. A lattice Boltzmann investigation of steady-state fluid distribution, capillary pressure and relative permeability of a porous medium: Effects of fluid and geometrical properties

    NASA Astrophysics Data System (ADS)

    Li, Zi; Galindo-Torres, Sergio; Yan, Guanxi; Scheuermann, Alexander; Li, Ling

    2018-06-01

    Simulations of simultaneous steady-state two-phase flow in the capillary force-dominated regime were conducted using the state-of-the-art Shan-Chen multi-component lattice Boltzmann model (SCMC-LBM) based on two-dimensional porous media. We focused on analyzing the fluid distribution (i.e., WP fluid-solid, NP fluid-solid and fluid-fluid interfacial areas) as well as the capillary pressure versus saturation curve which was affected by fluid and geometrical properties (i.e., wettability, adhesive strength, pore size distribution and specific surface area). How these properties influenced the relative permeability versus saturation relation through apparent effective permeability and threshold pressure gradient was also explored. The SCMC-LBM simulations showed that, a thin WP fluid film formed around the solid surface due to the adhesive fluid-solid interaction, resulting in discrete WP fluid distributions and reduction of the WP fluid mobility. Also, the adhesive interaction provided another source of capillary pressure in addition to capillary force, which, however, did not affect the mobility of the NP fluid. The film fluid effect could be enhanced by large adhesive strength and fine pores in heterogeneous porous media. In the steady-state infiltration, not only the NP fluid but also the WP fluid were subjected to the capillary resistance. The capillary pressure effect could be alleviated by decreased wettability, large average pore radius and improved fluid connectivity in heterogeneous porous media. The present work based on the SCMC-LBM investigations elucidated the role of film fluid as well as capillary pressure in the two-phase flow system. The findings have implications for ways to improve the macroscopic flow equation based on balance of force for the steady-state infiltration.

  11. Nerve injury affects the capillary supply in rat slow and fast muscles differently.

    PubMed

    Cebasek, Vita; Radochová, Barbora; Ribaric, Samo; Kubínová, Lucie; Erzen, Ida

    2006-02-01

    The goal of this study was to determine the acute effects of permanent denervation on the length density of the capillary network in rat slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles and the effect of short-lasting reinnervation in slow muscle only. Denervation was performed by cutting the sciatic nerve. Both muscles were excised 2 weeks later. Reinnervation was studied 4 weeks after nerve crush in SOL muscle only. Capillaries and muscle fibres were visualised by triple immunofluorescent staining with antibodies against CD31 and laminin and with fluorescein-labelled Griffonia (Bandeira) simplicifolia lectin. A recently developed stereological approach allowing the estimation of the length of capillaries adjacent to each individual fibre (Lcap/Lfib) was employed. Three-dimensional virtual test grids were applied to stacks of optical images captured with a confocal microscope and their intersections with capillaries and muscle fibres were counted. Interrelationships among capillaries and muscle fibres were demonstrated with maximum intensity projection of the acquired stacks of optical images. The course of capillaries in EDL seemed to be parallel to the fibre axes, whereas in SOL, their preferential direction deviated from the fibre axes and formed more cross-connections among neighbouring capillaries. Lcap/Lfib was clearly reduced in denervated SOL but remained unchanged in EDL, although the muscle fibres significantly atrophied in both muscle types. When soleus muscle was reinnervated, capillary length per unit fibre length was completely restored. The physiological background for the different responses of the capillary network in slow and fast muscle is discussed.

  12. Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

    PubMed

    Govoni, Virginia; Sanders, Thomas A B; Reidlinger, Dianne P; Darzi, Julia; Berry, Sarah E E; Goff, Louise M; Seed, Paul T; Chowienczyk, Philip J; Hall, Wendy L

    2017-04-01

    Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

  13. The effect of contact angles and capillary dimensions on the burst frequency of super hydrophilic and hydrophilic centrifugal microfluidic platforms, a CFD study.

    PubMed

    Kazemzadeh, Amin; Ganesan, Poo; Ibrahim, Fatimah; He, Shuisheng; Madou, Marc J

    2013-01-01

    This paper employs the volume of fluid (VOF) method to numerically investigate the effect of the width, height, and contact angles on burst frequencies of super hydrophilic and hydrophilic capillary valves in centrifugal microfluidic systems. Existing experimental results in the literature have been used to validate the implementation of the numerical method. The performance of capillary valves in the rectangular and the circular microfluidic structures on super hydrophilic centrifugal microfluidic platforms is studied. The numerical results are also compared with the existing theoretical models and the differences are discussed. Our experimental and computed results show a minimum burst frequency occurring at square capillaries and this result is useful for designing and developing more sophisticated networks of capillary valves. It also predicts that in super hydrophilic microfluidics, the fluid leaks consistently from the capillary valve at low pressures which can disrupt the biomedical procedures in centrifugal microfluidic platforms.

  14. The Effect of Contact Angles and Capillary Dimensions on the Burst Frequency of Super Hydrophilic and Hydrophilic Centrifugal Microfluidic Platforms, a CFD Study

    PubMed Central

    Kazemzadeh, Amin; Ganesan, Poo; Ibrahim, Fatimah; He, Shuisheng; Madou, Marc J.

    2013-01-01

    This paper employs the volume of fluid (VOF) method to numerically investigate the effect of the width, height, and contact angles on burst frequencies of super hydrophilic and hydrophilic capillary valves in centrifugal microfluidic systems. Existing experimental results in the literature have been used to validate the implementation of the numerical method. The performance of capillary valves in the rectangular and the circular microfluidic structures on super hydrophilic centrifugal microfluidic platforms is studied. The numerical results are also compared with the existing theoretical models and the differences are discussed. Our experimental and computed results show a minimum burst frequency occurring at square capillaries and this result is useful for designing and developing more sophisticated networks of capillary valves. It also predicts that in super hydrophilic microfluidics, the fluid leaks consistently from the capillary valve at low pressures which can disrupt the biomedical procedures in centrifugal microfluidic platforms. PMID:24069169

  15. Amyloid-β efflux from the CNS into the plasma

    PubMed Central

    Roberts, Kaleigh Filisa; Elbert, Donald L.; Kasten, Tom P.; Patterson, Bruce W.; Sigurdson, Wendy C.; Connors, Rose E.; Ovod, Vitaliy; Munsell, Ling Y.; Mawuenyega, Kwasi G.; Miller-Thomas, Michelle M.; Moran, Christopher J.; Cross, Dewitte T.; Derdeyn, Colin P.; Bateman, Randall J.

    2015-01-01

    Objective The aim of this study was to measure the flux of amyloid-β (Aβ) across the human cerebral capillary bed in order to determine if transport into the blood is a significant mechanism of clearance for Aβ produced in the central nervous system (CNS). Methods Time-matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing Inferior Petrosal Sinus Sampling (IPSS). For each plasma sample, Aβ concentration was assessed by three assays and the venous to arterial Aβ concentration ratios were determined. Results Aβ concentration was increased by ~7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood (p < 0.0001). There was no difference in peripheral venous Aβ concentration compared to arterial blood concentration. Interpretation Our results are consistent with clearance of CNS-derived Aβ into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aβ across the blood-brain barrier accounts for ~25% of Aβ clearance, and reabsorption of cerebrospinal fluid Aβ accounts for ~25% of the total CNS Aβ clearance in humans. PMID:25205593

  16. Application of the string method to the study of critical nuclei in capillary condensation.

    PubMed

    Qiu, Chunyin; Qian, Tiezheng; Ren, Weiqing

    2008-10-21

    We adopt a continuum description for liquid-vapor phase transition in the framework of mean-field theory and use the string method to numerically investigate the critical nuclei for capillary condensation in a slit pore. This numerical approach allows us to determine the critical nuclei corresponding to saddle points of the grand potential function in which the chemical potential is given in the beginning. The string method locates the minimal energy path (MEP), which is the most probable transition pathway connecting two metastable/stable states in configuration space. From the MEP, the saddle point is determined and the corresponding energy barrier also obtained (for grand potential). Moreover, the MEP shows how the new phase (liquid) grows out of the old phase (vapor) along the most probable transition pathway, from the birth of a critical nucleus to its consequent expansion. Our calculations run from partial wetting to complete wetting with a variable strength of attractive wall potential. In the latter case, the string method presents a unified way for computing the critical nuclei, from film formation at solid surface to bulk condensation via liquid bridge. The present application of the string method to the numerical study of capillary condensation shows the great power of this method in evaluating the critical nuclei in various liquid-vapor phase transitions.

  17. African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions.

    PubMed

    Kristensson, Krister; Nygård, Mikael; Bertini, Giuseppe; Bentivoglio, Marina

    2010-06-01

    The extracellular parasite Trypanosoma brucei causes human African trypanosomiasis (HAT), also known as sleeping sickness. Trypanosomes are transmitted by tsetse flies and HAT occurs in foci in sub-Saharan Africa. The disease, which is invariably lethal if untreated, evolves in a first hemo-lymphatic stage, progressing to a second meningo-encephalitic stage when the parasites cross the blood-brain barrier. At first, trypanosomes are restricted to circumventricular organs and choroid plexus in the brain outside the blood-brain barrier, and to dorsal root ganglia. Later, parasites cross the blood-brain barrier at post-capillary venules, through a multi-step process similar to that of lymphocytes. Accumulation of parasites in the brain is regulated by cytokines and chemokines. Trypanosomes can alter neuronal function and the most prominent manifestation is represented by sleep alterations. These are characterized, in HAT and experimental rodent infections, by disruption of the sleep-wake 24h cycle and internal sleep structure. Trypanosome infections alter also some, but not all, other endogenous biological rhythms. A number of neural pathways and molecules may be involved in such effects. Trypanosomes secrete prostaglandins including the somnogenic PGD2, and they interact with the host's immune system to cause release of pro-inflammatory cytokines. From the sites of early localization of parasites in the brain and meninges, such molecules could affect adjacent brain areas implicated in sleep-wakefulness regulation, including the suprachiasmatic nucleus and its downstream targets, to cause the changes characteristic of the disease. This raises challenging issues on the effects of cytokines on synaptic functions potentially involved in sleep-wakefulness alterations. (c) 2009 Elsevier Ltd. All rights reserved.

  18. Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier.

    PubMed

    Zhang, Zhuanfang Fred; Strickland, Christopher E; Link, Steven O

    2017-02-01

    Surface barrier technology is used to isolate radioactive waste and to reduce or eliminate recharge water to the waste zone for 1000 years or longer. However, the design and evaluation of such a barrier is challenging because of the extremely long design life. After establishing a set of design and performance objectives, a package of design solutions was developed for 1000-year surface barriers over nuclear waste sites. The Prototype Hanford Barrier (PHB) was then constructed in 1994 in the field over an existing waste site as a demonstration. The barrier was tested to evaluate surface-barrier design and performance at the field scale under conditions of enhanced and natural precipitation and of no vegetation. The monitoring data demonstrate that the barrier satisfied nearly all objectives in the past two decades. The PHB far exceeded the Resource Conservation and Recovery Act criteria, functioned in Hanford's semiarid climate, limited drainage to well below the 0.5 mm yr -1 performance criterion, limited runoff, and minimized erosion and bio-intrusion. Given the two-decade record of successful performance and consideration of the processes and mechanisms that could affect barrier stability and hydrology in the future, the results suggest the PHB is very likely to perform for its 1000-year design life. This conclusion is based on two assumptions: (1) the exposed subgrade receives protection against erosion and (2) institutional controls prevent inadvertent human activity at the barrier. The PHB design can serve as the basis for site-specific barriers over waste sites containing underground nuclear waste, uranium mine tailings, and hazardous mine waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Susceptibility cancellation of a microcoil wound with a paramagnetic-liquid-filled copper capillary

    NASA Astrophysics Data System (ADS)

    Takeda, Kazuyuki; Takasaki, Tomoya; Takegoshi, K.

    2015-09-01

    Even though microcoils improve the sensitivity of NMR measurement of tiny samples, magnetic-field inhomogeneity due to the bulk susceptibility effect of the coil material can cause serious resonance-line broadening. Here, we propose to fabricate the microcoil using a thin, hollow copper capillary instead of a wire and fill paramagnetic liquid inside the capillary, so as to cancel the diamagnetic contribution of the copper. Susceptibility cancellation is demonstrated using aqueous solution of NiSO4. In addition, the paramagnetic liquid serves as coolant when it is circulated through the copper capillary, effectively transferring the heat generated by radiofrequency pulses.

  20. Evaporation effect on two-dimensional wicking in porous media.

    PubMed

    Benner, Eric M; Petsev, Dimiter N

    2018-03-15

    We analyze the effect of evaporation on expanding capillary flow for losses normal to the plane of a two-dimensional porous medium using the potential flow theory formulation of the Lucas-Washburn method. Evaporation induces a finite steady state liquid flux on capillary flows into fan-shaped domains which is significantly greater than the flux into media of constant cross section. We introduce the evaporation-capillary number, a new dimensionless quantity, which governs the frontal motion when multiplied by the scaled time. This governing product divides the wicking behavior into simple regimes of capillary dominated flow and evaporative steady state, as well as the intermediate regime of evaporation influenced capillary driven motion. We also show flow dimensionality and evaporation reduce the propagation rate of the wet front relative to the Lucas-Washburn law. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Capillary descent.

    PubMed

    Delannoy, Joachim; de Maleprade, Hélène; Clanet, Christophe; Quéré, David

    2018-05-31

    A superhydrophobic capillary tube immersed in water and brought in contact with the bath surface will be invaded by air, owing to its aerophilicity. We discuss this phenomenon where the ingredients of classical capillary rise are inverted, which leads to noticeable dynamical features. (1) The main regime of air invasion is linear in time, due to the viscous resistance of water. (2) Menisci in tubes with millimetre-size radii strongly oscillate before reaching their equilibrium depth, a consequence of inertia. On the whole, capillary descent provides a broad variety of dynamics where capillary effects, viscous friction and liquid inertia all play a role.

  2. Investigation of energy dissipation due to contact angle hysteresis in capillary effect

    NASA Astrophysics Data System (ADS)

    Athukorallage, Bhagya; Iyer, Ram

    2016-06-01

    Capillary action or Capillarity is the ability of a liquid to flow in narrow spaces without the assistance of, and in opposition to, external forces like gravity. Three effects contribute to capillary action, namely, adhesion of the liquid to the walls of the confining solid; meniscus formation; and low Reynolds number fluid flow. We investigate the dissipation of energy during one cycle of capillary action, when the liquid volume inside a capillary tube first increases and subsequently decreases while assuming quasi-static motion. The quasi-static assumption allows us to focus on the wetting phenomenon of the solid wall by the liquid and the formation of the meniscus. It is well known that the motion of a liquid on an non-ideal surface involves the expenditure of energy due to contact angle hysteresis. In this paper, we derive the equations for the menisci and the flow rules for the change of the contact angles for a liquid column in a capillary tube at a constant temperature and volume by minimizing the Helmholtz free energy using calculus of variations. We describe the numerical solution of these equations and present results from computations for the case of a capillary tube with 1 mm diameter.

  3. Wettability control on fluid-fluid displacements in patterned microfluidics and porous media

    NASA Astrophysics Data System (ADS)

    Juanes, Ruben; Trojer, Mathias; Zhao, Benzhong

    2014-11-01

    While it is well known that the wetting properties are critical in two-phase flows in porous media, the effect of wettability on fluid displacement continues to challenge our microscopic and macroscopic descriptions. Here we study this problem experimentally, starting with the classic experiment of two-phase flow in a capillary tube. We image the shape of the meniscus and measure the associated capillary pressure for a wide range of capillary numbers. We synthesize new observations on the dependence of the dynamic capillary pressure on wetting properties (contact angle) and flow conditions (viscosity contrast and capillary number). We then conduct experiments on a planar microfluidic device patterned with vertical posts. We track the evolution of the fluid-fluid interface and elucidate the impact of wetting on the cooperative nature of fluid displacement during pore invasion events. We use the insights gained from the capillary tube and patterned microfluidics experiments to elucidate the effect of wetting properties on viscous fingering and capillary fingering in a Hele-Shaw cell filled with glass beads, where we observe a contact-angle-dependent stabilizing behavior for the emerging flow instabilities, as the system transitions from drainage to imbibition.

  4. Regression of Lingual Lymphatic Vessels in Sodium-restricted Mice.

    PubMed

    He, Lianying; McCluskey, Lynnette Phillips

    2018-05-01

    Lymphatic vessel networks can expand and regress, with consequences for interstitial fluid drainage and nutrient supply to tissues, inflammation, and tumor spread. A diet high in sodium stimulates hyperplasia of cutaneous lymphatic capillaries. We hypothesized that dietary sodium restriction would have the opposite effect, shrinking lymphatic capillaries in the tongue. Lingual lymphatic capillary density and size was significantly reduced in mice fed a low-sodium diet (0.03%) for 3 weeks compared with control-fed mice. Blood vessel density was unchanged. Despite lymphatic capillary shrinkage, lingual edema was not observed. The effect on lymphatic capillaries was reversible, as lymphatic density and size in the tongue were restored by 3 weeks on a control diet. Lymphatic hyperplasia induced by a high-sodium diet is dependent on infiltrating macrophages. However, lingual CD68+ macrophage density was unchanged by sodium deficiency, indicating that distinct mechanisms may mediate lymphatic regression. Further studies are needed to test whether dietary sodium restriction is an effective, non-invasive co-therapy for oral cancer.

  5. Current Scaling in an Atmospheric Pressure Capillary Dielectric Barrier Discharge (POSTPRINT)

    DTIC Science & Technology

    2010-01-01

    have significant advantages in terms of enhanced plasma chemistry at atmospheric pressure,7 and has recently been used to demonstrate the high-speed depo...sition of SiO2 films. 8 This motivates a more detailed look at the properties of the discharge and the factors that can affect the plasma chemistry near...N. van Berkel, E. R. Kieft, and E. Stoffels, Proceedings of the 16th International Symposium on Plasma Chemistry , 2005, Vol. 22, pp. 295–308. FIG. 4

  6. Measurement of the refractive index of microquantity liquid filled in a capillary and a capillary wall without destruction.

    PubMed

    Li, Qiang; Pu, Xiaoyun

    2013-07-20

    A method for measuring the refractive index (RI) of a small volume of liquid and a capillary wall is presented in this paper. A transparent capillary filled with liquid is used as a cylindrical positive lens; subsequently, the focal length of the lens is derived through the base of paraxial approximation, which is recorded as a function of the RIs of the liquid and capillary wall. With the RI of a capillary wall known, the RI of the liquid can be obtained by measuring the focal length of the lens, which is characterized by a microquantity liquid, spatial resolution, and easy operation. The RI of the capillary wall can be calculated without ruining the capillary if the capillary is filled with a standard liquid (RI is known), the deviation of which is less than 0.003 RIU. The factors affecting accuracy of the measurement, for instance, the depth of a field (DOF) in a reading microscope system and the outer and inner diameters of a capillary are analyzed, while illustrating that the effective DOF plays an essential role in accurate measurement.

  7. A Chip-Capillary Hybrid Device for Automated Transfer of Sample Pre-Separated by Capillary Isoelectric Focusing to Parallel Capillary Gel Electrophoresis for Two-Dimensional Protein Separation

    PubMed Central

    Lu, Joann J.; Wang, Shili; Li, Guanbin; Wang, Wei; Pu, Qiaosheng; Liu, Shaorong

    2012-01-01

    In this report, we introduce a chip-capillary hybrid device to integrate capillary isoelectric focusing (CIEF) with parallel capillary sodium dodecyl sulfate – polyacrylamide gel electrophoresis (SDS-PAGE) or capillary gel electrophoresis (CGE) toward automating two-dimensional (2D) protein separations. The hybrid device consists of three chips that are butted together. The middle chip can be moved between two positions to re-route the fluidic paths, which enables the performance of CIEF and injection of proteins partially resolved by CIEF to CGE capillaries for parallel CGE separations in a continuous and automated fashion. Capillaries are attached to the other two chips to facilitate CIEF and CGE separations and to extend the effective lengths of CGE columns. Specifically, we illustrate the working principle of the hybrid device, develop protocols for producing and preparing the hybrid device, and demonstrate the feasibility of using this hybrid device for automated injection of CIEF-separated sample to parallel CGE for 2D protein separations. Potentials and problems associated with the hybrid device are also discussed. PMID:22830584

  8. Etude du comportement hydrogeologique de couvertures avec effet de barriere capillaire faites entierement de materiaux miniers

    NASA Astrophysics Data System (ADS)

    Kalonji, Alex Kabambi

    The acid mining drainage (AMD) generating mine sites must be restored to limit their long-term contamination of the environment. At the end of mining operations, covers with capillary barrier effects (CCBE), generally made of natural materials soils, are used as an oxygen barrier to isolate the tailings that generate acid mining drainage (AMD) from their immediate environment. Due to economic and social acceptability contraints and to the environmental impact of stripping (footprint) of natural soil pits, mining companies are increasingly interested in using non-acid generating waste rock as a substitute for natural soils as base materials to form capillary break layers in covers. The overall objective of this study was to evaluate the hydrogeological behaviour of CCBE made entirely of mining materials (desulphurized tailings from a desulphurization process and non-acid generating waste rock). The specific objectives of this project were : 1) to characterize the hydrogeological properties of waste rock (with truncated size) and desulphurized tailings; 2) to evaluate in laboratory instrumented columns the effectiveness of CCBE made entirely of mining materials; 3) to simulate the column tests using a 1D numerical code to model the fluid (water and gas) flow in the unsaturated media; and 4) to validate with 2D numerical modeling the ability to restore LaRonde tailings impoundment (Agnico Eagle Mines Limited) using a CCBE made of low-sulfide tailings and non-acid generating waste rock. To achieve the objectives, samples of waste rock were collected from Bousquet waste rock pile and tailings from the ore concentration plant before being pumped to the tailings impoundment. Desulphurized tailings with less than 2% S were produced in order to construct a non-reactive CCBE. After the physical, chemical, mineralogical and hydrogeotechnical characterization of cover materials, laboratory physical models of CCBC in instrumented columns were performed. Three configurations were tested. The first two columns had a different waste rock grain size (0-20 mm and 0-50 mm) in their lower coarse layers, and the tailings were introduced at a high solid percent, approximatively 74% (simulating mechanical deposition). The third column also had waste rock with particle size 0-50 mm in its bottom coarse layer, but with tailings placed a lower solid percent, approximatively 55% (simulating hydraulic deposition). The particle size of the coarse waste rock in the top layers was set at 0-50 mm for all three columns. Several cycles of wetting drainage in the three columns were performed. The results of these laboratory investigations in terms of volumetric water content and suction profiles confirm the potential of non-acid generating waste rock to be used in the capillary break layers of CCBE. To assess the long-term performance, several scenarios of numerical modeling were performed using Vadose/W 2007 numerical codes, by Geoslope int. A variation of the depth of the water table and natural and extreme climatic conditions were considered in this parametric study. The results of these predictions confirmed the long-term effectiveness of covers with mine waste rock in capillary break layers. The effectiveness was evaluated in terms of oxygen flux at the interface between the moisture-retaining layer (MRL) and the bottom capillary break layer. Under natural and extreme climatic conditions (two months without infiltration), and a variation of the depth of the water table level from 2 to 6 m, cumulative oxygen flux over a one year period varied between 10.6 and 97.5 g/m 2/year. For extreme climatic conditions, and for the same variation of the depth of the water table, the oxygen flux varied between 14.3 and 117.9 g/m2/year. The highest oxygen flux (117 g/m2/year) was obtained for a water table depth of 6 m under extreme climatic conditions. The influence of the particle size contrast between the water retention layer and the bottom capillary break layer on the oxygen flux was further highlighted using relatively fine and coarse sand in the coarse bottom layer. The numerical modeling results obtained with the coarse sand were almost similar to those obtained with waste rock. In the absence of the strong contrast (when the relatively fine sand was used), the water retention layer was drained and the oxygen flux which reached at the bottom of this layer increased considerably. The water table depth, the grain size, and the hydraulic contrast between the MRL and the bottom capillary break layer (CBL) proved to be the key parameters of the simulated model. In field conditions, CCBE are often inclined, and that this inclination can affect the performance of the cover to control the migration of oxygen. 2D modeling was also performed. The numerical model was built to represent approximatively the case of one of the dams of LaRonde tailings impoundment. Preliminary results show that CCBE made entirely of mining materials are effective even when placed over slopes. The degree of saturation of the two slopes in the numerical model was higher than 85%. The influence of the slope has not significantly affected yet the performance of the cover for the model studied in this thesis. The cumulative oxygen flux over one year at the bottom of the MRL (for horizontal distance of 182 m of the numerical model) are 4031.3g (22.1 g/m2/year) and 4617.7g (25.3 g/m2/year) for natural and extreme climatic conditions respectively. This study confirms that waste rocks have good potential to be used as capillary break materials in the configuration of such CCBE. Thereby, it is suggested that the option of using only mining materials be included in the analysis of the optimal mode of mine reclamation. This project also suggests that good management of the tailings and waste rock produced during mining operations will provide the materials which could then be used to restore the site. More research is recommended to further investigate this reclamation option through field experimental cells. If further research validates the laboratory results at the intermediate scale, the use of mining materials would be considered as an effective option for CCBE used to control post-closure pollution. This scenario could reduce the construction costs while promoting the social acceptability of mining projects by reducing the use of natural soils.

  9. Transient studies of capillary-induced flow

    NASA Technical Reports Server (NTRS)

    Reagan, M. K.; Bowman, W. J.

    1993-01-01

    This paper presents the numerical and experimental results of a study performed on the transient rise of fluid in a capillary tube. The capillary tube problem provides an excellent mechanism from which to launch an investigation into the transient flow of a fluid in a porous wick structure where capillary forces must balance both adverse gravitational effects and frictional losses. For the study, a capillary tube, initially charged with a small volume of water, was lowered into a pool of water. The behavior of the column of fluid during the transient that followed as more water entered the tube from the pool was both numerically and experimentally studied.

  10. Regulation of the pulmonary circulation

    PubMed Central

    Lee, G. de J.

    1971-01-01

    Factors regulating pressure and flow in the lungs are reviewed with particular emphasis on their role in regulating blood flow velocity and distribution within the lung capillaries. The behaviour of the pulmonary arterial, system, alveolar capillaries, and pulmonary venous system are considered individually. The effect of heart disease on lung capillary blood flow is examined. PMID:4929437

  11. Analysis of flow dynamics through small diameter gas sampling systems

    NASA Technical Reports Server (NTRS)

    Brown, K. G.

    1984-01-01

    The removal of gas material through a capillary opening in a surface is analyzed. The gas, from which the sample is removed, is moving past the surface at supersonic velocities. A variety of possible conditions of temperature, pressure and composition are discussed in an effort to emulate conditions that might be found at the surface of a vehicle traversing the altitude range 100-50 km, or might exist at the surface of a model in the stream of a high enthalpy wind tunnel. Aspects discussed include: (1) the throughput of the capillary for conditions of different lengths and different L/a (length/radius) ratios; (2) the total throughput when the surface in question contains many hundreds of these capillaries; (3) the effect of the capillaries upon the composition of the analyzed gas; (4) the effect of the capillary or capillaries upon the gas stream itself; and (5) the implications of the calculations upon the possible implementation of this type of device as an inlet for a mass spectrometer to be developed for analyzing the upper atmosphere.

  12. Effect of hypothermic pulmonary artery flushing on capillary filtration coefficient.

    PubMed

    Andrade, R S; Wangensteen, O D; Jo, J K; Tsai, M Y; Bolman, R M

    2000-07-27

    We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution. Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant. We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfc immediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfc after pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc during hypothermic pulmonary artery flushing. Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing. Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

  13. The effects of capillary forces on the axisymmetric propagation of two-phase, constant-flux gravity currents in porous media

    NASA Astrophysics Data System (ADS)

    Golding, Madeleine J.; Huppert, Herbert E.; Neufeld, Jerome A.

    2013-03-01

    The effects of capillary forces on the propagation of two-phase, constant-flux gravity currents in a porous medium are studied analytically and numerically in an axisymmetric geometry. The fluid within a two-phase current generally only partially saturates the pore space it invades. For long, thin currents, the saturation distribution is set by the vertical balance between gravitational and capillary forces. The capillary pressure and relative permeability of the fluid in the current depend on this saturation. The action of capillary forces reduces the average saturation, thereby decreasing the relative permeability throughout the current. This results in a thicker current, which provides a steeper gradient to drive flow, and a more blunt-nose profile. The relative strength of gravity and capillary forces remains constant within a two-phase gravity current fed by a constant flux and spreading radially, due to mass conservation. For this reason, we use an axisymmetric representation of the framework developed by Golding et al. ["Two-phase gravity currents in porous media," J. Fluid Mech. 678, 248-270 (2011)], 10.1017/jfm.2011.110, to investigate the effect on propagation of varying the magnitude of capillary forces and the pore-size distribution. Scaling analysis indicates that axisymmetric two-phase gravity currents fed by a constant flux propagate like t1/2, similar to their single-phase counterparts [S. Lyle, H. E. Huppert, M. Hallworth, M. Bickle, and A. Chadwick, "Axisymmetric gravity currents in a porous medium," J. Fluid Mech. 543, 293-302 (2005)], 10.1017/S0022112005006713, with the effects of capillary forces encapsulated in the constant of proportionality. As a practical application of our new concepts and quantitative evaluations, we discuss the implications of our results for the process of carbon dioxide (CO2) sequestration, during which gravity currents consisting of supercritical CO2 propagate in rock saturated with aqueous brine. We apply our two-phase model including capillary forces to quantitatively assess seismic images of CO2 spreading at Sleipner underneath the North Sea.

  14. Wicking Tests for Unidirectional Fabrics: Measurements of Capillary Parameters to Evaluate Capillary Pressure in Liquid Composite Molding Processes.

    PubMed

    Pucci, Monica Francesca; Liotier, Pierre-Jacques; Drapier, Sylvain

    2017-01-27

    During impregnation of a fibrous reinforcement in liquid composite molding (LCM) processes, capillary effects have to be understood in order to identify their influence on void formation in composite parts. Wicking in a fibrous medium described by the Washburn equation was considered equivalent to a flow under the effect of capillary pressure according to the Darcy law. Experimental tests for the characterization of wicking were conducted with both carbon and flax fiber reinforcement. Quasi-unidirectional fabrics were then tested by means of a tensiometer to determine the morphological and wetting parameters along the fiber direction. The procedure was shown to be promising when the morphology of the fabric is unchanged during capillary wicking. In the case of carbon fabrics, the capillary pressure can be calculated. Flax fibers are sensitive to moisture sorption and swell in water. This phenomenon has to be taken into account to assess the wetting parameters. In order to make fibers less sensitive to water sorption, a thermal treatment was carried out on flax reinforcements. This treatment enhances fiber morphological stability and prevents swelling in water. It was shown that treated fabrics have a linear wicking trend similar to those found in carbon fabrics, allowing for the determination of capillary pressure.

  15. Modeling of the capillary wicking of flax fibers by considering the effects of fiber swelling and liquid absorption.

    PubMed

    Testoni, Guilherme Apolinario; Kim, Sihwan; Pisupati, Anurag; Park, Chung Hae

    2018-09-01

    We propose a new model for the capillary rise of liquid in flax fibers whose diameter is changed by liquid absorption. Liquid absorption into the flax fibers is taken into account in a new modified Washburn equation by considering the mass of the liquid absorbed inside the fibers as well as that imbibed between the fibers. The change of permeability and hydraulic radius of pores in a fibrous medium due to the fiber swelling is modeled by a statistical approach considering a non-uniform distribution of flax fiber diameter. By comparisons between capillary rise test results and modeling results, we prove the validity of the proposed modified Washburn model to take into account the effects from fiber swelling and liquid absorption on the decrease of capillary rise velocity. The experimental observation of long-term capillary rise tests show that the swelling behavior of the fibers highly packed in a closed volume and its influence on the capillary wicking are different from those of an individual single fiber in a free space. The current approach was useful to characterize the swelling of fibers highly packed in a closed volume and its influence of the long-term behavior of capillary wicking. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The circumventricular organs: an atlas of comparative anatomy and vascularization.

    PubMed

    Duvernoy, Henri M; Risold, Pierre-Yves

    2007-11-01

    The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

  17. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    PubMed Central

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  18. Effect of ultrasonic capillary dynamics on the mechanics of thermosonic ball bonding.

    PubMed

    Huang, Yan; Shah, Aashish; Mayer, Michael; Zhou, Norman Y; Persic, John

    2010-01-01

    Microelectronic wire bonding is an essential step in today's microchip production. It is used to weld (bond) microwires to metallized pads of integrated circuits using ultrasound with hundreds of thousands of vibration cycles. Thermosonic ball bonding is the most popular variant of the wire bonding process and frequently investigated using finite element (FE) models that simplify the ultrasonic dynamics of the process with static or quasistatic boundary conditions. In this study, the ultrasonic dynamics of the bonding tool (capillary), made from Al(2)O(3), is included in a FE model. For more accuracy of the FE model, the main material parameters are measured. The density of the capillary was measured to be rho(cap) = 3552 +/- 100 kg/m(3). The elastic modulus of the capillary, E(cap) = 389 +/- 11 GPa, is found by comparing an auxiliary FE model of the free vibrating capillary with measured values. A capillary "nodding effect" is identified and found to be essential when describing the ultrasonic vibration shape. A main FE model builds on these results and adds bonded ball, pad, chip, and die attach components. There is excellent agreement between the main model and the ultrasonic force measured at the interface on a test chip with stress microsensors. Bonded ball and underpad stress results are reported. When adjusted to the same ultrasonic force, a simplified model without ultrasonic dynamics and with an infinitely stiff capillary tip is substantially off target by -40% for the maximum underpad stress. The compliance of the capillary causes a substantial inclination effect at the bonding interface between wire and pad. This oscillating inclination effect massively influences the stress fields under the pad and is studied in more detail. For more accurate results, it is therefore recommended to include ultrasonic dynamics of the bonding tool in mechanical FE models of wire bonding.

  19. Some Experiments on Evaporation of High-TDS Phreatic Water in an Arid Area

    NASA Astrophysics Data System (ADS)

    Li, X.; Jin, M.; Zhou, J.; Liu, Y.; Zhao, Y.

    2012-12-01

    Most experiments that had been done on evaporation of phreatic water were limited to waters with fresh or low total dissolved solids (TDS, no more than 10g/L). The TDS of phreatic water is always dozens or even hundreds of grams per liter in extremely arid areas. Thus, experiments on phreatic water evaporation of different TDS (3g/L, 30g/L, 100g/L, 250g/L) were carried out in an arid plain of south Xinjiang, China. The results showed that there was significant linear positive correlation between TDS of phreatic water and cumulative salinity in soil profile. The variation of phreatic water evaporation was lag behind the change of surface water measured by E20 equipment, but both of them were more drastic at nighttime than the daytime. The research shows that the daytime evaporation capacity has significant effect on nighttime evaporation, and the soil water vapor condense at profile also is an important driving factor for the nighttime evaporation. Capillary rise is a significant contributor of soil salinity in extremely arid areas. Experiments about effects of different grains of sand soil and TDS of phreatic water (1, 30, 100, 250 g/L) on capillary rise showed that TDS had significant effects on capillary rise in later stage of experiments. For coarse sand, the higher TDS made the lower height of capillary rise. But for fine sand, the height of capillary rise of 1g/L was obviously larger than others. The sequence of height from larger to lower of capillary rise in silt was 30, 100, 250 and 1g/L. At the beginning of experiments on coarse sand, the higher TDS made the lower velocity of capillary rise, but other soil groups were not. Compared to high-TDS, the grain of sand soil was a more primary controlling factor of capillary rise. The research indicates that high-TDS not only changes the gravity of capillary water but also the pore size of soil during the processes of capillary rise in fine sand.

  20. Surfactant effects on contact line alteration of a liquid drop in a capillary tube

    NASA Astrophysics Data System (ADS)

    Yulianti, K.; Marwati, R.

    2018-05-01

    In this paper, the effect of an insoluble surfactant on the moving contact line of an interface between two fluids filling a capillary tube is studied. The governing equations are the incompressible Navier-Stokes equations with the couple of Eulerian fluid variables and Lagrangian interfacial markers. In our model, capillary force plays a role in the fluids motion. Here, we propose that besides lowering the interfacial tension which affects the capillary force, the surfactant also decreases the surface tension between fluids and a solid surface. That condition is applied to the unbalanced Young condition at the contact line. The front-tracking method is used to solve numerically the free boundary motion of the interface. Results show that the surfactant has a significant effect on the motion of the contact line.

  1. The Effect of Faraday Waves on Gas Transport

    NASA Astrophysics Data System (ADS)

    Saylor, J. R.; Handler, R. A.

    1996-11-01

    The increase in the rate of gas transport at the onset of capillary wave formation is a frequently observed phenomenon. However, a causal relationship between the presence of capillary waves and enhanced gas transport has not been experimentally demonstrated. Here we present experimental results of CO2 transport rates across Faraday waves. The piston velocity versus wave slope data explicitly demonstrates an enhancement in gas transport due to these waves. The functional relationship between gas flux and wave slope is also obtained. The Faraday wave system permits investigation of capillary waves in the absence of the obfuscating effects of air turbulence, water turbulence, droplets and bubbles, all of which are present in wind/wave tank studies. Hence, our results are solely due to the effects of capillary wave action. Data for wave frequencies varying from 20Hz to 200Hz are presented.

  2. A Study of Ignition Effects on Thruster Performance of a Multi-Electrode Capillary Discharge Using Visible Emission Spectroscopy Diagnostics

    DTIC Science & Technology

    2009-09-01

    observed today, it is discussed further in Section 1.1. In addition to the work done in propulsion with coaxial electro thermal pulse plasma thrusters (PPTs...initial plasma conditions. The literature supported these findings for more basic laboratory capillaries, but the effect on a thruster device was unknown...An in- depth investigation of different ignition systems were conducted for a capillary discharge based pulsed plasma thruster. In addition to

  3. Thermal Performance of Surface Wick Structures.

    NASA Astrophysics Data System (ADS)

    Chen, Yongkang; Tavan, Noel; Baker, John; Melvin, Lawrence; Weislogel, Mark

    2010-03-01

    Microscale surface wick structures that exploit capillary driven flow in interior corners have been designed. In this study we examine the interplay between capillary flow and evaporative heat transfer that effectively reduces the surface temperature. The tests are performed by raising the surface temperature to various levels before the flow is introduced to the surfaces. Certainly heat transfer weakens the capillary driven flow. It is observed, however, the surface temperature can be reduced significantly. The effects of geometric parameters and interconnectivity are to be characterized to identify optimal configurations.

  4. Effects of Riot Control Training on Systemic Microvascular Reactivity and Capillary Density.

    PubMed

    Pereira, Flavio; de Moraes, Roger; Van Bavel, Diogo; De Lorenzo, Andrea; Tibirica, Eduardo

    2018-03-14

    The main aim of the present study is to evaluate the effects of strenuous exercise, related to special military training for riot control, on systemic microvascular endothelial function and skin capillary density. Endothelium-dependent microvascular reactivity was evaluated in the forearm skin of healthy military trainees (age 23.4 ± 2.3 yr; n = 15) using laser speckle contrast imaging coupled with cutaneous acetylcholine (ACh) iontophoresis and post-occlusive reactive hyperemia (PORH). Functional capillary density was assessed using high-resolution, intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using PORH. Microcirculatory tests were performed before and after a 5-wk special military training for riot control. Microvascular endothelium-dependent vasodilatory responses were markedly and significantly reduced after training, compared with values obtained before training. The peak values of microvascular conductance obtained during iontophoresis of ACh or PORH before training (0.84 ± 0.22 and 0.94 ± 0.72 APU/mmHg, respectively) were markedly reduced after training (0.47 ± 0.11 and 0.71 ± 0.14 APU/mmHg; p < 0.0001 and p = 0.0037, respectively). Endothelium-dependent capillary recruitment was significantly reduced after training (before 101 ± 9 and after 95 ± 8 capillaries/mm2; p = 0.0007). The present study showed that a 5-wk strenuous military training, performed in unfavorable climatic conditions, induces marked systemic microvascular dysfunction, mainly characterized by reduced endothelium-dependent microvascular vasodilation and blunted capillary recruitment.

  5. Modeling capillary bridge dynamics and crack healing between surfaces of nanoscale roughness

    NASA Astrophysics Data System (ADS)

    Soylemez, Emrecan; de Boer, Maarten P.

    2017-12-01

    Capillary bridge formation between adjacent surfaces in humid environments is a ubiquitous phenomenon. It strongly influences tribological performance with respect to adhesion, friction and wear. Only a few studies, however, assess effects due to capillary dynamics. Here we focus on how capillary bridge evolution influences crack healing rates. Experimental results indicated a logarithmic decrease in average crack healing velocity as the energy release rate increases. Our objective is to model that trend. We assume that capillary dynamics involve two mechanisms: capillary bridge growth and subsequently nucleation followed by growth. We show that by incorporating interface roughness details and the presence of an adsorbed water layer, the behavior of capillary force dynamics can be understood quantitatively. We identify three important regimes that control the healing process, namely bridge growth, combined bridge growth and nucleation, and finally bridge nucleation. To fully capture the results, however, the theoretical model for nucleation time required an empirical modification. Our model enables significant insight into capillary bridge dynamics, with a goal of attaining a predictive capability for this important microelectromechanical systems (MEMS) reliability failure mechanism.

  6. A Simple Double-Source Model for Interference of Capillaries

    ERIC Educational Resources Information Center

    Hou, Zhibo; Zhao, Xiaohong; Xiao, Jinghua

    2012-01-01

    A simple but physically intuitive double-source model is proposed to explain the interferogram of a laser-capillary system, where two effective virtual sources are used to describe the rays reflected by and transmitted through the capillary. The locations of the two virtual sources are functions of the observing positions on the target screen. An…

  7. Astrocyte–endothelial interactions and blood–brain barrier permeability*

    PubMed Central

    Abbott, N Joan

    2002-01-01

    The blood–brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFβ, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain endothelial permeability has been shown for a number of small chemical mediators produced by astrocytes and other nearby cell types. It is clear that endothelial cells are involved in both long- and short-term chemical communication with neighbouring cells, with the perivascular end feet of astrocytes being of particular importance. The role of barrier induction and modulation in normal physiology and in pathology is discussed. PMID:12162730

  8. Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function.

    PubMed

    Pan, Yijun; Short, Jennifer L; Choy, Kwok H C; Zeng, Annie X; Marriott, Philip J; Owada, Yuji; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A

    2016-11-16

    Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5 +/+ and FABP5 -/- mice using a battery of memory paradigms. FABP5 -/- mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring 14 C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5 +/+ and FABP5 -/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA, 14 C-DHA uptake into brain endothelial cells and brain capillaries of FABP5 -/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5 +/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5 -/- mice are associated with reduced CNS access of DHA. Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5 -/- mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role for FABP5 in the maintenance of cognitive function via regulating the brain uptake of DHA, and suggests that upregulation of FABP5 in neurodegenerative diseases, where brain DHA levels are possibly diminished (e.g., Alzheimer's disease), may provide a novel therapeutic approach for restoring cognitive function. Copyright © 2016 the authors 0270-6474/16/3611756-13$15.00/0.

  9. Cement hydration from hours to centuries controlled by diffusion through barrier shells of C-S-H

    NASA Astrophysics Data System (ADS)

    Rahimi-Aghdam, Saeed; Bažant, Zdeněk P.; Abdolhosseini Qomi, M. J.

    2017-02-01

    Although a few good models for cement hydration exist, they have some limitations. Some do not take into account the complete range of variation of pore relative humidity and temperature, and apply over durations limited from up a few months to up to about a year. The ones that are applicable for long durations are either computationally too intensive for use in finite element programs or predict the hydration to terminate after few months. However, recent tests of autogenous shrinkage and swelling in water imply that the hydration may continue, at decaying rate, for decades, provided that a not too low relative pore humidity (above 0.7) persists for a long time, as expected for the cores of thick concrete structural members. Therefore, and because design lifetimes of over hundred years are required for large concrete structures, a new hydration model for a hundred year lifespan and beyond is developed. The new model considers that, after the first day of hydration, the remnants of anhydrous cement grains, gradually consumed by hydration, are enveloped by contiguous, gradually thickening, spherical barrier shells of calcium-silicate hydrate (C-S-H). The hydration progress is controlled by transport of water from capillary pores through the barrier shells toward the interface with anhydrous cement. The transport is driven by a difference of humidity, defined by equivalence with the difference in chemical potential of water. Although, during the period of 4-24 h, the C-S-H forms discontinuous nano-globules around the cement grain, an equivalent barrier shell control was formulated for this period, too, for ease and effectiveness of calculation. The entire model is calibrated and validated by published test data on the evolution of hydration degree for various cement types, particle size distributions, water-cement ratios and temperatures. Computationally, this model is sufficiently effective for calculating the evolution of hydration degree (or aging) at every integration point of every finite element in a large structure.

  10. Quantitative targeted proteomics for understanding the blood-brain barrier: towards pharmacoproteomics.

    PubMed

    Ohtsuki, Sumio; Hirayama, Mio; Ito, Shingo; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-06-01

    The blood-brain barrier (BBB) is formed by brain capillary endothelial cells linked together via complex tight junctions, and serves to prevent entry of drugs into the brain. Multiple transporters are expressed at the BBB, where they control exchange of materials between the circulating blood and brain interstitial fluid, thereby supporting and protecting the CNS. An understanding of the BBB is necessary for efficient development of CNS-acting drugs and to identify potential drug targets for treatment of CNS diseases. Quantitative targeted proteomics can provide detailed information on protein expression levels at the BBB. The present review highlights the latest applications of quantitative targeted proteomics in BBB research, specifically to evaluate species and in vivo-in vitro differences, and to reconstruct in vivo transport activity. Such a BBB quantitative proteomics approach can be considered as pharmacoproteomics.

  11. Inhibition of nuclear factor of activated T cells (NFAT) c3 activation attenuates acute lung injury and pulmonary edema in murine models of sepsis

    PubMed Central

    Karpurapu, Manjula; Lee, Yong Gyu; Qian, Ziqing; Wen, Jin; Ballinger, Megan N.; Rusu, Luiza; Chung, Sangwoon; Deng, Jing; Qian, Feng; Reader, Brenda F.; Nirujogi, Teja Srinivas; Park, Gye Young; Pei, Dehua; Christman, John W.

    2018-01-01

    Specific therapies targeting cellular and molecular events of sepsis induced Acute Lung Injury (ALI) pathogenesis are lacking. We have reported a pivotal role for Nuclear Factors of Activated T cells (NFATc3) in regulating macrophage phenotype during sepsis induced ALI and subsequent studies demonstrate that NFATc3 transcriptionally regulates macrophage CCR2 and TNFα gene expression. Mouse pulmonary microvascular endothelial cell monolayer maintained a tighter barrier function when co-cultured with LPS stimulated NFATc3 deficient macrophages whereas wild type macrophages caused leaky monolayer barrier. More importantly, NFATc3 deficient mice showed decreased neutrophilic lung inflammation, improved alveolar capillary barrier function, arterial oxygen saturation and survival benefit in lethal CLP sepsis mouse models. In addition, survival of wild type mice subjected to the lethal CLP sepsis was not improved with broad-spectrum antibiotics, whereas the survival of NFATc3 deficient mice was improved to 40–60% when treated with imipenem. Passive adoptive transfer of NFATc3 deficient macrophages conferred protection against LPS induced ALI in wild type mice. Furthermore, CP9-ZIZIT, a highly potent, cell-permeable peptide inhibitor of Calcineurin inhibited NFATc3 activation. CP9-ZIZIT effectively reduced sepsis induced inflammatory cytokines and pulmonary edema in mice. Thus, this study demonstrates that inhibition of NFATc3 activation by CP9-ZIZIT provides a potential therapeutic option for attenuating sepsis induced ALI/pulmonary edema. PMID:29535830

  12. Transport of drugs across the blood-brain barrier by nanoparticles.

    PubMed

    Wohlfart, Stefanie; Gelperina, Svetlana; Kreuter, Jörg

    2012-07-20

    The central nervous system is well protected by the blood-brain barrier (BBB) which maintains its homeostasis. Due to this barrier many potential drugs for the treatment of diseases of the central nervous system (CNS) cannot reach the brain in sufficient concentrations. One possibility to deliver drugs to the CNS is the employment of polymeric nanoparticles. The ability of these carriers to overcome the BBB and to produce biologic effects on the CNS was shown in a number of studies. Over the past few years, progress in understanding of the mechanism of the nanoparticle uptake into the brain was made. This mechanism appears to be receptor-mediated endocytosis in brain capillary endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants enabling the adsorption of specific plasma proteins are necessary for this receptor-mediated uptake. The delivery of drugs, which usually are not able to cross the BBB, into the brain was confirmed by the biodistribution studies and pharmacological assays in rodents. Furthermore, the presence of nanoparticles in the brain parenchyma was visualized by electron microscopy. The intravenously administered biodegradable polymeric nanoparticles loaded with doxorubicin were successfully used for the treatment of experimental glioblastoma. These data, together with the possibility to employ nanoparticles for delivery of proteins and other macromolecules across the BBB, suggest that this technology holds great promise for non-invasive therapy of the CNS diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula.

    PubMed

    Bernstein, Hans-Gert; Hildebrandt, Jens; Dobrowolny, Henrik; Steiner, Johann; Bogerts, Bernhard; Pahnke, Jens

    2016-11-01

    There is increasing evidence that microvascular abnormalities and malfunction of the blood-brain barrier (BBB) significantly contribute to schizophrenia pathophysiology. The ATP-binding cassette transporter ABCB1 is an important molecular component of the intact BBB, which has been implicated in a number of neurodegenerative and psychiatric disorders, including schizophrenia. However, the regional and cellular expression of ABCB1 in schizophrenia is yet unexplored. Therefore, we studied ABCB1 protein expression immunohistochemically in twelve human post-mortem brain regions known to play a role in schizophrenia, in 13 patients with schizophrenia and nine controls. In ten out of twelve brain regions under study, no significant differences were found with regard to the numerical density of ABCB1-expressing capillaries between all patients with schizophrenia and control cases. The left and right habenular complex, however, showed significantly reduced capillary densities in schizophrenia patients. In addition, we found a significantly reduced density of ABCB1-expressing neurons in the left habenula. Reduced ABCB1 expression in habenular capillaries might contribute to increased brain levels of proinflammatory cytokines in patients with schizophrenia, while decreased expression of this protein in a subpopulation of medial habenular neurons (which are probably purinergic) might be related to abnormalities of purines and their receptors found in this disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Effect of Pore Size and Pore Connectivity on Unidirectional Capillary Penetration Kinetics in 3-D Porous Media using Direct Numerical Simulation

    NASA Astrophysics Data System (ADS)

    Fu, An; Palakurthi, Nikhil; Konangi, Santosh; Comer, Ken; Jog, Milind

    2017-11-01

    The physics of capillary flow is used widely in multiple fields. Lucas-Washburn equation is developed by using a single pore-sized capillary tube with continuous pore connection. Although this equation has been extended to describe the penetration kinetics into porous medium, multiple studies have indicated L-W does not accurately predict flow patterns in real porous media. In this study, the penetration kinetics including the effect of pore size and pore connectivity will be closely examined since they are expected to be the key factors effecting the penetration process. The Liquid wicking process is studied from a converging and diverging capillary tube to the complex virtual 3-D porous structures with Direct Numerical Simulation (DNS) using the Volume-Of-Fluid (VOF) method within the OpenFOAM CFD Solver. Additionally Porous Medium properties such as Permeability (k) , Tortuosity (τ) will be also analyzed.

  15. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation.

    PubMed

    Lemmen, Julia; Tozakidis, Iasson E P; Bele, Prachee; Galla, Hans-Joachim

    2013-03-21

    ATP-driven efflux transporters are considered to be the major hurdle in the treatment of central nervous system (CNS) diseases. Abcb1 (P-glycoprotein) and Abcg2 (breast cancer resistance protein/brain multidrug resistance protein) belong to the best known ABC-transporters. These ABC-transporters limit the permeability of the blood-brain barrier and protect the brain against toxic compounds in the blood but on the other hand they also reduce the efficacy of CNS pharmacotherapy. Even after 40 years of extensive research, the regulatory mechanisms of these efflux transporters are still not completely understood. To unravel the efflux transporter regulation, we analyzed the effect of the nuclear receptor CAR (constitutive androstane receptor) on the expression of Abcb1 and Abcg2 in primary cultures of porcine brain capillary endothelial cells (PBCEC). CAR is a xenobiotic-activated transcription factor, which is, like the other important nuclear receptor pregnane X receptor (PXR), highly expressed in barrier tissue and known to be a positive regulator of ABC-transporters. We demonstrate that activation of porcine CAR by the human CAR (hCAR) ligand CITCO (6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde) leads to an up-regulation of both transporters, whereas the mouse-specific CAR ligand TCPOBOP (1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene) had no effect on transporter expression. The stimulation of PBCEC with CITCO caused a significant up-regulation of both efflux-transporters on RNA-level, protein level and transport level. Furthermore the additional application of a CAR inhibitor significantly decreased the transporter expression to control niveau. In conclusion our data prove CAR activation only by the human ligand CITCO leading to an increased ABC-transporter expression and transport activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier.

    PubMed

    Thomsen, Maj Schneider; Birkelund, Svend; Burkhart, Annette; Stensballe, Allan; Moos, Torben

    2017-03-01

    The brain vascular basement membrane is important for both blood-brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of this study was to analyse four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). mBCECs, pericytes and glial cells (mainly astrocytes and microglia) were prepared from brains of C57BL/6 mice. The mBCECs were grown as monoculture, in co-culture with pericytes or mixed glial cells, or as a triple-culture with both pericytes and mixed glial cells. The integrity of the BBB models was validated by measures of transendothelial electrical resistance (TEER) and passive permeability to mannitol. The expression of basement membrane proteins was analysed using RT-qPCR, mass spectrometry and immunocytochemistry. Co-culturing mBCECs with pericytes, mixed glial cells, or both significantly increased the TEER compared to the monoculture, and a low passive permeability was correlated with high TEER. The mBCECs expressed all major basement membrane proteins such as laminin-411, laminin-511, collagen [α1(IV)] 2 α2(IV), agrin, perlecan, and nidogen 1 and 2 in vitro. Increased expression of the laminin α5 subunit correlated with the addition of BBB-inducing factors (hydrocortisone, Ro 20-1724, and pCPT-cAMP), whereas increased expression of collagen IV α1 primarily correlated with increased levels of cAMP. In conclusion, BCECs cultured in vitro coherently form a BBB and express basement membrane proteins as a feature of maturation. Cover Image for this issue: doi: 10.1111/jnc.13789. © 2016 International Society for Neurochemistry.

  17. Morphological peculiarities of respiratory compartments of arctic animal lungs.

    PubMed

    Shishkin, G S; Ustyuzhaninova, N V

    1997-04-01

    Morphological and ultrastructural peculiarities of interalveolar septa in endemic arctic animals (reindeer, polar fox, lemming) are compared with laboratory animals (rat,dog). For light microscopy, tissue samples were taken from the central and peripheral sections of all lobes of the right lung. They were fixed in 10% neutral formalin and embedded in paraffin. For electron microscopy, samples were taken from subpleural sections of the caudal lobe of the right lung, fixed in 4% paraformaldehyde for 24 hours, subsequently postfixed in 2% OsO4. for 2.0 hours. Samples were dehydrated in acetone and embedded in a mixture of Epon 812 and Araldite. Ultrathin sections were photographed at a magnification of x4,000. For each interalveolar septum, lengths and diameters were recorded and the squares of septa surface, air-blood barrier surface and the number of the structures were determined. The topography of capillaries and the ultrastructure of interstitium were described. Acini in the arctic animals (reindeer, polar fox, lemming) are compact. In all lobes they are fully expanded and uniformly filled with air. There is no physiological atelectasis. Alveoli appear straight and homogeneous in form and size. In the polar fox, the quantity of interalveolar pores of Kohn is twice that in the dog. The number of pores in the lemming are similar to those in the rat but their size is 1.6 times greater in diameter. In arctic animals more capillaries connect with both alveolar surfaces by an air-blood barrier and simultaneously participate in the gas exchange of two adjoining alveoli. In the polar fox and lemming the thickness of the air-blood barrier is 1.3-1.4 times less than that in the dog and rat. The set of morpho-functional peculiarities of the acini of arctic animals allows for an increase in gas exchange in the respiratory compartments of the lungs and provides necessary oxygenation of arterial blood at a low partial pressure of oxygen in the alveolar gas.

  18. Early regimes of water capillary flow in slit silica nanochannels.

    PubMed

    Oyarzua, Elton; Walther, Jens H; Mejía, Andrés; Zambrano, Harvey A

    2015-06-14

    Molecular dynamics simulations are conducted to investigate the initial stages of spontaneous imbibition of water in slit silica nanochannels surrounded by air. An analysis is performed for the effects of nanoscopic confinement, initial conditions of liquid uptake and air pressurization on the dynamics of capillary filling. The results indicate that the nanoscale imbibition process is divided into three main flow regimes: an initial regime where the capillary force is balanced only by the inertial drag and characterized by a constant velocity and a plug flow profile. In this regime, the meniscus formation process plays a central role in the imbibition rate. Thereafter, a transitional regime takes place, in which, the force balance has significant contributions from both inertia and viscous friction. Subsequently, a regime wherein viscous forces dominate the capillary force balance is attained. Flow velocity profiles identify the passage from an inviscid flow to a developing Poiseuille flow. Gas density profiles ahead of the capillary front indicate a transient accumulation of air on the advancing meniscus. Furthermore, slower capillary filling rates computed for higher air pressures reveal a significant retarding effect of the gas displaced by the advancing meniscus.

  19. Changes in materials properties explain the effects of humidity on gecko adhesion.

    PubMed

    Puthoff, Jonathan B; Prowse, Michael S; Wilkinson, Matt; Autumn, Kellar

    2010-11-01

    Geckos owe their remarkable stickiness to millions of dry setae on their toes, and the mechanism of adhesion in gecko setae has been the topic of scientific scrutiny for over two centuries. Previously, we demonstrated that van der Waals forces are sufficient for strong adhesion and friction in gecko setae, and that water-based capillary adhesion is not required. However, recent studies demonstrated that adhesion increases with relative humidity (RH) and proposed that surface hydration and capillary water bridge formation is important or even necessary. In this study, we confirmed a significant effect of RH on gecko adhesion, but rejected the capillary adhesion hypothesis. While contact forces of isolated tokay gecko setal arrays increased with humidity, the increase was similar on hydrophobic and hydrophilic surfaces, inconsistent with a capillary mechanism. Contact forces increased with RH even at high shear rates, where capillary bridge formation is too slow to affect adhesion. How then can a humidity-related increase in adhesion and friction be explained? The effect of RH on the mechanical properties of setal β-keratin has escaped consideration until now. We discovered that an increase in RH softens setae and increases viscoelastic damping, which increases adhesion. Changes in setal materials properties, not capillary forces, fully explain humidity-enhanced adhesion, and van der Waals forces remain the only empirically supported mechanism of adhesion in geckos.

  20. Stereological Study on the Positive Effect of Running Exercise on the Capillaries in the Hippocampus in a Depression Model.

    PubMed

    Chen, Linmu; Zhou, Chunni; Tan, Chuanxue; Wang, Feifei; Gao, Yuan; Huang, Chunxia; Zhang, Yi; Jiang, Lin; Tang, Yong

    2017-01-01

    Running exercise is an effective method to improve depressive symptoms when combined with drugs. However, the underlying mechanisms are not fully clear. Cerebral blood flow perfusion in depressed patients is significantly lower in the hippocampus. Physical activity can achieve cerebrovascular benefits. The purpose of this study was to evaluate the impacts of running exercise on capillaries in the hippocampal CA1 and dentate gyrus (DG) regions. The chronic unpredictable stress (CUS) depression model was used in this study. CUS rats were given 4 weeks of running exercise from the fifth week to the eighth week (20 min every day from Monday to Friday each week). The sucrose consumption test was used to measure anhedonia. Furthermore, stereological methods were used to investigate the capillary changes among the control group, CUS/Standard group and CUS/Running group. Sucrose consumption significantly increased in the CUS/Running group. Running exercise has positive effects on the capillaries parameters in the hippocampal CA1 and DG regions, such as the total volume, total length and total surface area. These results demonstrated that capillaries are protected by running exercise in the hippocampal CA1 and DG might be one of the structural bases for the exercise-induced treatment of depression-like behavior. These results suggest that drugs and behavior influence capillaries and may be considered as a new means for depression treatment in the future.

  1. Acquisition system environmental effects study. [for capillary-screen propellant retention devices

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The effects of vibration, warm gas exposure, and feed system startup/shutdown fluid dynamics on capillary-screen propellant retention capabilities are quantified. The existing technology is extended to the point where quantitative conlusions in terms of design criteria may be drawn.

  2. Finite volume solution for two-phase flow in a straight capillary

    NASA Astrophysics Data System (ADS)

    Yelkhovsky, Alexander; Pinczewski, W. Val

    2018-04-01

    The problem of two-phase flow in straight capillaries of polygonal cross section displays many of the dynamic characteristics of rapid interfacial motions associated with pore-scale displacements in porous media. Fluid inertia is known to be important in these displacements but is usually ignored in network models commonly used to predict macroscopic flow properties. This study presents a numerical model for two-phase flow which describes the spatial and temporal evolution of the interface between the fluids. The model is based on an averaged Navier-Stokes equation and is shown to be successful in predicting the complex dynamics of both capillary rise in round capillaries and imbibition along the corners of polygonal capillaries. The model can form the basis for more realistic network models which capture the effect of capillary, viscous, and inertial forces on pore-scale interfacial dynamics and consequent macroscopic flow properties.

  3. Dispersion and viscous attenuation of capillary waves with finite amplitude

    NASA Astrophysics Data System (ADS)

    Denner, Fabian; Paré, Gounséti; Zaleski, Stéphane

    2017-04-01

    We present a comprehensive study of the dispersion of capillary waves with finite amplitude, based on direct numerical simulations. The presented results show an increase of viscous attenuation and, consequently, a smaller frequency of capillary waves with increasing initial wave amplitude. Interestingly, however, the critical wavenumber as well as the wavenumber at which the maximum frequency is observed remain the same for a given two-phase system, irrespective of the wave amplitude. By devising an empirical correlation that describes the effect of the wave amplitude on the viscous attenuation, the dispersion of capillary waves with finite initial amplitude is shown to be, in very good approximation, self-similar throughout the entire underdamped regime and independent of the fluid properties. The results also shown that analytical solutions for capillary waves with infinitesimal amplitude are applicable with reasonable accuracy for capillary waves with moderate amplitude.

  4. Capillary optics for radiation focusing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peurrung, A.J.; Reeder, P.L.; Bliss, M.

    Capillary lens technology may ultimately bring benefits to neutron and x-ray-based science like conventional lenses with visible light. Although the technology is not yet 10 years old, these lenses have already had a significant impact in engineering, science, and medicine. Capillary lenses are advantageous when it is desirable to increase the radiation flux at a location without regard to its angular divergence. PNNL has worked to improve the technology in several ways. A single, optimally tapered capillary was manufactured, which allows intensity gains of a factor of 270 for an initially parallel, incident x-ray beam. Feasibility of constructing neutron lensesmore » using {sup 58}Ni (particularly effective at reflecting neutrons) has been explored. Three applications for capillary optics have been identified and studied: neutron telescope, Gandolphi x-ray diffractometry, and neutron radiotherapy. A brief guide is given for determining which potential applications are likely to be helped by capillary optics.« less

  5. High lung volume increases stress failure in pulmonary capillaries

    NASA Technical Reports Server (NTRS)

    Fu, Z.; Costello, M. L.; Tsukimoto, K.; Prediletto, R.; Elliott, A. R.; Mathieu-Costello, O.; West, J. B.

    1992-01-01

    We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.

  6. Injectable barriers for waste isolation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Persoff, P.; Finsterle, S.; Moridis, G.J.

    In this paper the authors report laboratory work and numerical simulation done in support of development and demonstration of injectable barriers formed from either of two fluids: colloidal silica or polysiloxane. Two principal problems addressed here are control of gel time and control of plume emplacement in the vadose zone. Gel time must be controlled so that the viscosity of the barrier fluid remains low long enough to inject the barrier, but increases soon enough to gel the barrier in place. During injection, the viscosity must be low enough to avoid high injection pressures which could uplift or fracture themore » formation. To test the grout gel time in the soil, the injection pressure was monitored as grouts were injected into sandpacks. When grout is injected into the vadose zone, it slumps under the influence of gravity, and redistributes due to capillary forces as it gels. The authors have developed a new module for the reservoir simulator TOUGH2 to model grout injection into the vadose zone, taking into account the increase of liquid viscosity as a function of gel concentration and time. They have also developed a model to calculate soil properties after complete solidification of the grout. The numerical model has been used to design and analyze laboratory experiments and field pilot tests. The authors present the results of computer simulations of grout injection, redistribution, and solidification.« less

  7. Control of electroosmosis in coated quartz capillaries

    NASA Technical Reports Server (NTRS)

    Herren, Blair J.; Van Alstine, James; Snyder, Robert S.; Shafer, Steven G.; Harris, J. Milton

    1987-01-01

    The effectiveness of various coatings for controlling the electroosmotic fluid flow that hinders electrophoretic processes is studied using analytical particle microelectrophoresis. The mobilities of 2-micron diameter glass and polystyrene latex spheres (exhibiting both negative and zero effective surface charge) were measured in 2-mm diameter quartz capillaries filled with NaCl solutions within the 3.5-7.8 pH range. It is found that capillary inner surface coatings using 5000 molecular weight (or higher) poly(ethylene glycol): significantly reduced electroosmosis within the selected pH range, were stable for long time periods, and appeared to be more effective than dextran, methylcellulose, or silane coatings.

  8. Role of Vascular and Lymphatic Endothelial Cells in Hantavirus Pulmonary Syndrome Suggests Targeted Therapeutic Approaches

    PubMed Central

    Gorbunova, Elena E.; Dalrymple, Nadine A.; Gavrilovskaya, Irina N.

    2013-01-01

    Abstract Background Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. Results We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Conclusions Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease. PMID:24024573

  9. Role of vascular and lymphatic endothelial cells in hantavirus pulmonary syndrome suggests targeted therapeutic approaches.

    PubMed

    Mackow, Erich R; Gorbunova, Elena E; Dalrymple, Nadine A; Gavrilovskaya, Irina N

    2013-09-01

    Hantaviruses in the Americas cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically infect microvascular and lymphatic endothelial cells and cause dramatic changes in barrier functions without disrupting the endothelium. Hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions. The endothelium of arteries, veins, and lymphatic vessels are unique and central to the function of vast pulmonary capillary beds that regulate pulmonary fluid accumulation. We have found that HPS-causing hantaviruses alter vascular barrier functions of microvascular and lymphatic endothelial cells by altering receptor and signaling pathway responses that serve to permit fluid tissue influx and clear tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to cause acute pulmonary edema, as well as potential therapeutic targets for reducing the severity of HPS disease. Here we discuss interactions of HPS-causing hantaviruses with the endothelium, roles for unique lymphatic endothelial responses in HPS, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

  10. Drug transport across the blood–brain barrier

    PubMed Central

    Pardridge, William M

    2012-01-01

    The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport. PMID:22929442

  11. Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

    PubMed

    Wang, Bin; Caluch, Adam; Fodil, Redouane; Féréol, Sophie; Zadigue, Patricia; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2012-01-01

    Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h. We used RGD-coated ferromagnetic beads and measured permeability before and after stress application. We find that endothelial permeability increases in the stressed endothelium, hence reflecting a loss of integrity. Structural and mechanical results suggest that this endothelial barrier alteration would be due to physically-founded discrepancies in latero-basal reinforcement of adhesion sites in response to the global increase in CSK stiffness or centripetal intracellular forces. Basal reinforcement of adhesion is presently evidenced by the marked redistribution of αvβ3 integrin with cluster formation in the stressed endothelium.

  12. Capillary Versus Aspiration Biopsy: Effect of Needle Size and Length on the Cytopathological Specimen Quality

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hopper, Kenneth D.; Grenko, Ronald T.; Fisher, Alicia I.

    1996-09-15

    Purpose: To test the value of the nonaspiration, or capillary, biopsy technique by experimental comparison with the conventional fine-needle aspiration technique using various needle gauges and lengths. Methods: On fresh hepatic and renal tissue from five autopsies, multiple biopsy specimens were taken with 20, 22, and 23-gauge Chiba needles of 5, 10, 15, and 20-cm length, using the aspiration technique and the capillary technique. The resultant specimens were graded on the basis of a grading scheme by a cytopathologist who was blinded to the biopsy technique. Results: The capillary technique obtained less background blood or clot which could obscure diagnosticmore » tissue, although not significantly different from the aspiration technique (p= 0.2). However, for the amount of cellular material obtained, retention of appropriate architecture, and mean score, the capillary technique performed statistically worse than aspiration biopsy (p < 0.01). In addition, with decreasing needle caliber (increasing needle gauge) and increasing length, the capillary biopsy was inferior to the aspiration biopsy. Conclusion: The capillary biopsy technique is inferior to the aspiration technique according to our study. When the capillary technique is to be applied, preference should be given to larger caliber, shorter needles.« less

  13. Instability of the capillary bridge

    NASA Astrophysics Data System (ADS)

    Pare, Gounseti; Hoepffner, Jerome

    2014-11-01

    Capillary adhesion is a physical mechanism that maintains two bodies in contact by capillarity through a liquid ligament. The capillary bridge is an idealization of this capillary adhesion. In this study we first focus on the classical case of the stability of the capillary bridge. Secondly we study a slightly more complex configuration, imagining a flow in the capillary bridge as in the case of the dynamics of the neck of a liquid ligament, in its withdrawal under the effect of capillarity. Inspired by the experiments on soap films of Plateau, the configuration analyzed consists of an initially axisymmetric, mass of fluid held by surface tension forces between two parallel, coaxial, solid pipes of the same diameter. The results presented are obtained by numerical simulations using the free software, Gerris Flow Solver. We first focus on the capillary Venturi. In the static configuration the stability diagram of the capillary bridge obtained is in perfect agreement with the results of Lev A. Slobozhanin. In the dynamic case we develop a matlab code based on the one dimensional equations of Eggers and Dupont. The comparison of the bifurcation diagram obtained and the numerical simulations shows a good agreement.

  14. Capillary Array Waveguide Amplified Fluorescence Detector for mHealth

    PubMed Central

    Balsam, Joshua; Bruck, Hugh Alan; Rasooly, Avraham

    2013-01-01

    Mobile Health (mHealth) analytical technologies are potentially useful for carrying out modern medical diagnostics in resource-poor settings. Effective mHealth devices for underserved populations need to be simple, low cost, and portable. Although cell phone cameras have been used for biodetection, their sensitivity is a limiting factor because currently it is too low to be effective for many mHealth applications, which depend on detection of weak fluorescent signals. To improve the sensitivity of portable phones, a capillary tube array was developed to amplify fluorescence signals using their waveguide properties. An array configured with 36 capillary tubes was demonstrated to have a ~100X increase in sensitivity, lowering the limit of detection (LOD) of mobile phones from 1000 nM to 10 nM for fluorescein. To confirm that the amplification was due to waveguide behavior, we coated the external surfaces of the capillaries with silver. The silver coating interfered with the waveguide behavior and diminished the fluorescence signal, thereby proving that the waveguide behavior was the main mechanism for enhancing optical sensitivity. The optical configuration described here is novel in several ways. First, the use of capillaries waveguide properties to improve detection of weak florescence signal is new. Second we describe here a three dimensional illumination system, while conventional angular laser waveguide illumination is spot (or line), which is functionally one-dimensional illumination, can illuminate only a single capillary or a single column (when a line generator is used) of capillaries and thus inherently limits the multiplexing capability of detection. The planar illumination demonstrated in this work enables illumination of a two dimensional capillary array (e.g. x columns and y rows of capillaries). In addition, the waveguide light propagation via the capillary wall provides a third dimension for illumination along the axis of the capillaries. Such an array can potentially be used for sensitive analysis of multiple fluorescent detection assays simultaneously. The simple phone based capillary array approach presented in this paper is capable of amplifying weak fluorescent signals thereby improving the sensitivity of optical detectors based on mobile phones. This may allow sensitive biological assays to be measured with low sensitivity detectors and may make mHealth practical for many diagnostics applications, especially in resource-poor and global health settings. PMID:24039345

  15. Modeling of the anode of a liquid-feed DMFC: Inhomogeneous compression effects and two-phase transport phenomena

    NASA Astrophysics Data System (ADS)

    García-Salaberri, Pablo A.; Vera, Marcos; Iglesias, Immaculada

    2014-01-01

    An isothermal two-phase 2D/1D across-the-channel model for the anode of a liquid-feed Direct Methanol Fuel Cell (DMFC) is presented. The model takes into account the effects of the inhomogeneous assembly compression of the Gas Diffusion Layer (GDL), including the spatial variations of porosity, diffusivity, permeability, capillary pressure, and electrical conductivity. The effective anisotropic properties of the GDL are evaluated from empirical data reported in the literature corresponding to Toray carbon paper TGP-H series. Multiphase transport is modeled according to the classical theory of porous media (two-fluid model), considering the effect of non-equilibrium evaporation and condensation of methanol and water. The numerical results evidence that the hydrophobic Leverett J-function approach is physically inconsistent to describe capillary transport in the anode of a DMFC when assembly compression effects are considered. In contrast, more realistic results are obtained when GDL-specific capillary pressure curves reflecting the mixed-wettability characteristics of GDLs are taken into account. The gas coverage factor at the GDL/channel interface also exhibits a strong influence on the gas-void fraction distribution in the GDL, which in turn depends on the relative importance between the capillary resistance induced by the inhomogeneous compression, Rc(∝ ∂pc / ∂ ε) , and the capillary diffusivity, Dbarc(∝ ∂pc / ∂ s) .

  16. Effect of anti-vertigo granule on the opening number and blood flow of mouse ear capillary network

    NASA Astrophysics Data System (ADS)

    Li, Chongxian; Liu, Xiaobin; Li, Jun; Hao, Shaojun; Wang, Xidong; Li, Wenjun; Zhang, Zhengchen

    2018-04-01

    To observe the effects of anti-glare particles on the open number and blood flow in the auricle of mice with microcirculation disturbance model. Sixty mice, half male and half female, were randomly divided into 6 groups. The mice were given Kangxuan granule suspension, serum brain granule suspension and normal saline of the same volume, respectively, once a day. The mice were anesthetized by intraperitoneal injection of chloral hydrate at 1 hour after the last administration. The mouse was fixed on the observation platform and the auricle was placed on the transmission stage. BZ-2000 microcirculation microscope and microcirculation analysis system were used to observe the changes of blood velocity and capillary opening volume in auricle of mice before administration. The changes of blood velocity and capillaries opening volume of mouse auricle were observed 2 min after epinephrine injection into tail vein of mice. Bear fruit: Compared with those before epinephrine, the opening number of capillary reticulum of auricle in large dose Kangxuan granule group was significantly decreased (P<0.05), and in normal saline group and middle group. In the small dose Kangxuan granule group, the opening number of capillary network of auricle decreased significantly (P<0.01). Compared with the model group, the large dose Kangxuan granule group could significantly increase the opening number of the auricle capillary network in mice (P<0.01). Yangxuannao granule group could significantly increase the opening number of auricle capillary reticulum in mice (P<0.05), compared with the model group by Ridit test. Both Kangxuan granule group and Yangxuannao granule group could significantly improve the auricle hair of mice with microcirculation disorder. The blood flow in fine blood vessels (P<0.01). Kangxuan granule has a good effect on the opening number of capillary network of auricle and blood flow in mice with microcirculation disorder.

  17. Enhanced solar evaporation of water from porous media, through capillary mediated forces and surface treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Canbazoglu, F. M.; Fan, B.; Kargar, A.

    2016-08-15

    The relative influence of the capillary, Marangoni, and hydrophobic forces in mediating the evaporation of water from carbon foam based porous media, in response to incident solar radiation, are investigated. It is indicated that inducing hydrophilic interactions on the surface, through nitric acid treatment of the foams, has a similar effect to reduced pore diameter and the ensuing capillary forces. The efficiency of water evaporation may be parameterized through the Capillary number (Ca), with a lower Ca being preferred. The proposed study is of much relevance to efficient solar energy utilization.

  18. An application of polymer-enhanced capillary transient isotachophoresis with an emissive boronic acid functionalized squarylium dye as an on-capillary labeling agent for gram-positive bacteria.

    PubMed

    Saito, Shingo; Maeda, Takeshi; Nakazumi, Hiroyuki; Colyer, Christa L

    2013-01-01

    In this paper, the characterization and application of the "PectI" (polymer-enhanced capillary transient isotachophoresis) technique for the separation and detection of same genus, gram-positive bacteria, Bacillus globigii (Bg) and Bacillus subtilis, is demonstrated by employing a boronic acid-functionalized squarylium dye (SQ-BA) as an on-capillary labeling agent, including the quantitative performance and applicability to crude samples. The effect of borate in the separation buffer was also investigated, which revealed that borate strongly affects the separation behavior of bacteria.

  19. The Effect of Surface Tension on the Gravity-driven Thin Film Flow of Newtonian and Power-law Fluids.

    PubMed

    Hu, Bin; Kieweg, Sarah L

    2012-07-15

    Gravity-driven thin film flow is of importance in many fields, as well as for the design of polymeric drug delivery vehicles, such as anti-HIV topical microbicides. There have been many prior works on gravity-driven thin films. However, the incorporation of surface tension effect has not been well studied for non-Newtonian fluids. After surface tension effect was incorporated into our 2D (i.e. 1D spreading) power-law model, we found that surface tension effect not only impacted the spreading speed of the microbicide gel, but also had an influence on the shape of the 2D spreading profile. We observed a capillary ridge at the front of the fluid bolus. Previous literature shows that the emergence of a capillary ridge is strongly related to the contact line fingering instability. Fingering instabilities during epithelial coating may change the microbicide gel distribution and therefore impact how well it can protect the epithelium. In this study, we focused on the capillary ridge in 2D flow and performed a series of simulations and showed how the capillary ridge height varies with other parameters, such as surface tension coefficient, inclination angle, initial thickness, and power-law parameters. As shown in our results, we found that capillary ridge height increased with higher surface tension, steeper inclination angle, bigger initial thickness, and more Newtonian fluids. This study provides the initial insights of how to optimize the flow and prevent the appearance of a capillary ridge and fingering instability.

  20. Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus

    PubMed Central

    2012-01-01

    Background There is increasing awareness that, aside from producing cerebrospinal fluid, the choroid plexus (CP) might be a key regulator of immune activity in the central nervous system (CNS) during neuroinflammation. Specifically, the CP has recently been posited to control entry of sentinel T cells into the uninflamed CNS during the early stages of neuroinflammatory diseases, like multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). As the CP is compartmentalized into a stromal core containing fenestrated capillaries devoid of typical blood–brain barrier properties, surrounded by a tight junction-expressing choroidal epithelium, each of these compartments might mount unique responses that instigate the neuroinflammatory process. Methods To discern responses of the respective CP stromal capillary and choroidal epithelial tissues during evolving neuroinflammation, we investigated morphology and in situ expression of 93 immune-related genes during early stages of EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Specifically, 3-D immunofluorescent imaging was employed to gauge morphological changes, and laser capture microdissection was coupled to an Immune Panel TaqMan Low Density Array to detail alterations in gene expression patterns at these separate CP sites on days 9 and 15 post-immunization (p.i.). To resolve CP effects due to autoimmunity against MOG peptide, from those due to complete Freund’s adjuvant (CFA) and pertussis toxin (PTX) included in the immunization, analysis was performed on MOG-CFA/PTX-treated, CFA/PTX-treated, and naïve cohorts. Results The CP became swollen and displayed significant molecular changes in response to MOG-CFA/PTX immunization. Both stromal capillary and choroidal epithelial tissues mounted vigorous, yet different, changes in expression of numerous genes over the time course analyzed - including those encoding adhesion molecules, cytokines, chemokines, statins, interleukins, T cell activation markers, costimulatory molecules, cyclooxygenase, pro-inflammatory transcription factors and pro-apoptotic markers. Moreover, CFA/PTX-treatment, alone, resulted in extensive, though less robust, alterations in both CP compartments. Conclusions MOG-CFA/PTX immunization significantly affects CP morphology and stimulates distinct expression patterns of immune-related genes in CP stromal capillary and epithelial tissues during evolving EAE. CFA/PTX treatment, alone, causes widespread gene alterations that could prime the CP to unlock the CNS to T cell infiltration during neuroinflammatory disease. PMID:22870943

  1. Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

    PubMed

    Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

    2015-01-01

    Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing to curtail transcapillary albumin leakage and resulting in increasingly positive net fluid balances. GIPS may represent a third hit after the initial insult and the ischaemia reperfusion injury. Novel markers like the capillary leak index, extravascular lung water and pulmonary permeability index may help the clinician in guiding appropriate fluid management. Capillary leak is an inflammatory condition with diverse triggers that results from a common pathway that includes ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function. Fluid overload should be avoided in this setting.

  2. Unilateral renal ischaemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased capillary permeability

    PubMed Central

    Bivol, Liliana Monica; Iversen, Bjarne Magnus; Hultström, Michael; Wallace, Paal William; Reed, Rolf Kåre

    2015-01-01

    Key points Transient reduction in renal blood flow results in inflammation and is a primary cause of acute kidney injury, thereby representing a major clinical problem.It is not known whether the inflammatory reaction is local only or part of a systemic response.We accessed the renal microenvironment through isolation of lymph and were in this way able to investigate whether the inflammatory reaction is local or systemic.Transient ischaemia followed by reperfusion resulted in a rapid production of inflammatory mediators locally in the renal interstitium.We moreover showed that the injury response affected the glomerular as well as the non‐glomerular barrier and resulted in a reduced size and charge selectivity of the glomerular capillaries. Abstract A better understanding of the inflammatory process associated with renal ischaemia–reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and returned to control levels after 120 min reperfusion. The responses were differentiated; interleukin‐1β, monocyte chemoattractant protein‐1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischaemic kidney. Tumour necrosis factor‐α  was the only mediator showing elevated lymph‐to‐plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR‐induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14‐ to 166‐fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischaemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph. PMID:26584508

  3. Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

    PubMed Central

    Lu, Y.; Michel, C. C.

    2012-01-01

    To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance. PMID:22604885

  4. Comparison between ray-tracing and physical optics for the computation of light absorption in capillaries--the influence of diffraction and interference.

    PubMed

    Qin, Yuan; Michalowski, Andreas; Weber, Rudolf; Yang, Sen; Graf, Thomas; Ni, Xiaowu

    2012-11-19

    Ray-tracing is the commonly used technique to calculate the absorption of light in laser deep-penetration welding or drilling. Since new lasers with high brilliance enable small capillaries with high aspect ratios, diffraction might become important. To examine the applicability of the ray-tracing method, we studied the total absorptance and the absorbed intensity of polarized beams in several capillary geometries. The ray-tracing results are compared with more sophisticated simulations based on physical optics. The comparison shows that the simple ray-tracing is applicable to calculate the total absorptance in triangular grooves and in conical capillaries but not in rectangular grooves. To calculate the distribution of the absorbed intensity ray-tracing fails due to the neglected interference, diffraction, and the effects of beam propagation in the capillaries with sub-wavelength diameter. If diffraction is avoided e.g. with beams smaller than the entrance pupil of the capillary or with very shallow capillaries, the distribution of the absorbed intensity calculated by ray-tracing corresponds to the local average of the interference pattern found by physical optics.

  5. A sensitive gas chromatography detector based on atmospheric pressure chemical ionization by a dielectric barrier discharge.

    PubMed

    Kirk, Ansgar T; Last, Torben; Zimmermann, Stefan

    2017-02-03

    In this work, we present a novel concept for a gas chromatography detector utilizing an atmospheric pressure chemical ionization which is initialized by a dielectric barrier discharge. In general, such a detector can be simple and low-cost, while achieving extremely good limits of detection. However, it is non-selective apart from the use of chemical dopants. Here, a demonstrator manufactured entirely from fused silica capillaries and printed circuit boards is shown. It has a size of 75×60×25mm 3 and utilizes only 2W of power in total. Unlike other known discharge detectors, which require high-purity helium, this detector can theoretically be operated using any gas able to form stable ion species. Here, purified air is used. With this setup, limits of detection in the low parts-per-billion range have been obtained for acetone. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Capillary flow enhancement in rectangular polymer microchannels with a deformable wall.

    PubMed

    Anoop, R; Sen, A K

    2015-07-01

    We report the capillary flow enhancement in rectangular polymer microchannels, when one of the channel walls is a deformable polymer membrane. We provide detailed insight into the physics of elastocapillary interaction between the capillary flow and elastic membrane, which leads to significant improvements in capillary flow performance. As liquid flows by capillary action in such channels, the deformable wall deflects inwards due to the Young-Laplace pressure drop across the liquid meniscus. This, in turn, decreases the radius of curvature of the meniscus and increases the driving capillary pressure. A theoretical model is proposed to predict the resultant increase in filling speed and rise height, respectively, in deformable horizontal and vertical microchannels having large aspect ratios. A non-dimensional parameter J, which represents the ratio of the capillary force to the mechanical restoring force, is identified to quantify the elastocapillary effects in terms of the improvement in filling speed (for J>0.238) and the condition for channel collapse (J>1). The theoretical predictions show good agreement with experimental data obtained using deformable rectangular poly(dimethylsiloxane) microchannels. Both model predictions and experimental data show that over 15% improvement in the Washburn coefficient in horizontal channels, and over 30% improvement in capillary rise height in vertical channels, are possible prior to channel collapse. The proposed technique of using deformable membranes as channel walls is a viable method for capillary flow enhancement in microfluidic devices.

  7. In situ formation of magnetite reactive barriers in soil for waste stabilization

    DOEpatents

    Moore, Robert C.

    2003-01-01

    Reactive barriers containing magnetite and methods for making magnetite reactive barriers in situ in soil for sequestering soil contaminants including actinides and heavy metals, organic materials, iodine and technetium are disclosed. According to one embodiment, a two-step reagent introduction into soil takes place. In the first step, free oxygen is removed from the soil by separately injecting into the soil aqueous solutions of iron (II) salt, for example FeCl.sub.2, and base, for example NaOH or NH.sub.3 in about a 1:1 volume ratio. Then, in the second step, similar reagents are injected a second time (however, according to about a 1:2 volume ratio, iron to salt) to form magnetite. The magnetite formation is facilitated, in part, due to slow intrusion of oxygen into the soil from the surface. The invention techniques are suited to injection of reagents into soil in proximity to a contamination plume or source allowing in situ formation of the reactive barrier at the location of waste or hazardous material. Mixing of reagents to form. precipitate is mediated and enhanced through movement of reagents in soil as a result of phenomena including capillary action, movement of groundwater, soil washing and reagent injection pressure.

  8. Experimental characterization of the effects induced by passive plasma lens on high brightness electron bunches

    NASA Astrophysics Data System (ADS)

    Marocchino, A.; Anania, M. P.; Bellaveglia, M.; Biagioni, A.; Bini, S.; Bisesto, F.; Brentegani, E.; Chiadroni, E.; Cianchi, A.; Croia, M.; Di Giovenale, D.; Ferrario, M.; Filippi, F.; Giribono, A.; Lollo, V.; Marongiu, M.; Mostacci, A.; Di Pirro, G.; Pompili, R.; Romeo, S.; Rossi, A. R.; Scifo, J.; Shpakov, V.; Vaccarezza, C.; Villa, F.; Zigler, A.

    2017-10-01

    We report on the experimental characterization of the effect that a passive plasma lens in the overdense regime has on high-brightness bunch quality by means of 6D phase-space analysis. The passive lens is generated by confining hydrogen gas with a capillary tube pre-ionized with a high-voltage discharge. We observed that the optimum condition is retrieved at the end of the overdense regime with almost no effect on bunch brightness. The presence of gas jets, leaking from the hollow capillary end-points, extends the lens effects also outside of the capillary, resulting in longer focusing channels. Experimental results are supported with numerical simulations of the complete accelerator line together with the plasma channel section.

  9. Protein vs electrolytes and all of the Starling forces.

    PubMed

    Peters, R M; Hargens, A R

    1981-10-01

    Hemodilution-induced reductions of the intravascular protein concentration in patients and experimental animals with intact capillaries do not lead to pulmonary edema, despite significant increases in the amount of extravascular water in the systemic interstitial space. The protective factors are a drop in the extravascular concentration of protein, a rise in interstitial tissue pressure, and an increase in lymph flow. If the capillary endothelium is damaged, protein leaks into the extravascular space, and protein infusion has a diminished effect on fluid exchange across the capillary. Whether capillaries are intact or injured, prevention of increases in capillary hydrostatic pressure is the most important factor in preventing pulmonary edema. Administration of hypertonic fluids may provide a useful method of limiting total fluid infusion and reducing cell swelling after blood loss.

  10. Numerical simulation of flow for viscoelastic neutrophil models in a rectangular capillary network: effects of capillary shape and cell stiffness on transit time.

    PubMed

    Shirai, Atsushi; Fujita, Ryo; Hayase, Toshiyuki

    2007-01-01

    The concentration of neutrophils in the pulmonary microvasculature is higher than in large systemic vessels. It is thought that the high concentration of neutrophils facilitates their effective recruitment to sites of inflammation. Thus, in order to understand the role of neutrophils in the immune system, it is important to clarify their flow characteristics in the pulmonary microvasculature. In a previous study, we developed a model to simulate the flow of neutrophils in a capillary network, in which the cells were modeled as spheres of a Maxwell material with a cortical tension and the capillary segments were modeled as arc-shaped constrictions in straight pipes. In the present paper, the flow of neutrophils in a simplified alveolar capillary network model is investigated for various constriction shapes and cell stiffnesses. Finally, it is shown that both the coefficient of variation of the transit time of the cells, which is the standard deviation divided by the mean transit time, and the mean transit time increase as the capillary segments become steep or tight, or when the cells become hard. The mean value of the transit time exceeds the median for all of the conditions that occur in real lungs, although the difference between them is small.

  11. Expression of Iron-Related Proteins at the Neurovascular Unit Supports Reduction and Reoxidation of Iron for Transport Through the Blood-Brain Barrier.

    PubMed

    Burkhart, Annette; Skjørringe, Tina; Johnsen, Kasper Bendix; Siupka, Piotr; Thomsen, Louiza Bohn; Nielsen, Morten Schallburg; Thomsen, Lars Lykke; Moos, Torben

    2016-12-01

    The mechanisms for iron transport through the blood-brain barrier (BBB) remain a controversy. We analyzed for expression of mRNA and proteins involved in oxidation and transport of iron in isolated brain capillaries from dietary normal, iron-deficient, and iron-reverted rats. The expression was also investigated in isolated rat brain endothelial cells (RBECs) and in immortalized rat brain endothelial (RBE4) cells grown as monoculture or in hanging culture inserts with defined BBB properties. Transferrin receptor 1, ferrireductases Steap 2 and 3, divalent metal transporter 1 (DMT1), ferroportin, soluble and glycosylphosphatidylinositol (GPI)-anchored ceruloplasmin, and hephaestin were all expressed in brain capillaries in vivo and in isolated RBECs and RBE4 cells. Gene expression of DMT1, ferroportin, and soluble and GPI-anchored ceruloplasmin were significantly higher in isolated RBECs with induced BBB properties. Primary pericytes and astrocytes both expressed ceruloplasmin and hephaestin, and RBECs, pericytes, and astrocytes all exhibited ferrous oxidase activity. The coherent protein expression of these genes was demonstrated by immunocytochemistry. The data show that brain endothelial cells provide the machinery for receptor-mediated uptake of ferric iron-containing transferrin. Ferric iron can then undergo reduction to ferrous iron by ferrireductases inside endosomes followed by DMT1-mediated pumping into the cytosol and subsequently cellular export by ferroportin. The expression of soluble ceruloplasmin by brain endothelial cells, pericytes, and astrocytes that together form the neurovascular unit (NVU) provides the ferroxidase activity necessary to reoxidize ferrous iron once released inside the brain.

  12. Mannose 6-Phosphate Receptor–mediated Transport of Sulfamidase Across the Blood–brain Barrier in the Newborn Mouse

    PubMed Central

    Urayama, Akihiko; Grubb, Jeffrey H; Sly, William S; Banks, William A

    2010-01-01

    Mucopolysaccharidosis type IIIA (MPS IIIA), which is a lysosomal storage disorder (LSD) caused by inherited deficiency of sulfamidase, is characterized by severe, progressive central nervous system (CNS) dysfunction. Enzyme replacement therapy (ERT) to treat CNS storage is challenging, because the access of enzymes to the brain is restricted by the blood–brain barrier (BBB). In a prior study, we found that phosphorylated β-glucuronidase (P-GUS) could be transcytosed across the BBB in newborn mice by the mannose 6-phosphate (M6P) receptor. In order to determine whether sulfamidase can utilize this pathway, we examined brain influx and the specificity of uptake of sulfamidase after intravenous (IV) injection in 2-day-old and 8-week-old mice. [131I]Sulfamidase was transported across the BBB in neonates at rates higher than that of simultaneously injected [125I]albumin. In contrast, the transport of [131I]sulfamidase was negligible in 8-week-old mice, thereby showing that the BBB transport mechanism is developmentally downregulated. Capillary depletion revealed that 83.7% of the [131I]sulfamidase taken up by the brain was in the parenchyma, demonstrating transfer across the capillary wall. The uptake of [131I]sulfamidase into the brain was significantly reduced by co-injections of M6P and P-GUS. That is, the transport of sulfamidase into the brain parenchyma in early postnatal life is mediated by the M6P receptor, which is shared with P-GUS and is likely accessible to other M6P-containing lysosomal enzymes. PMID:18443601

  13. Capillary waves with surface viscosity

    NASA Astrophysics Data System (ADS)

    Shen, Li; Denner, Fabian; Morgan, Neal; van Wachem, Berend; Dini, Daniele

    2017-11-01

    Experiments over the last 50 years have suggested a correlation between the surface (shear) viscosity and the stability of a foam or emulsion. With recent techniques allowing more accurate measurements of the elusive surface viscosity, we examine this link theoretically using small-amplitude capillary waves in the presence of the Marangoni effect and surface viscosity modelled via the Boussinesq-Scriven model. The surface viscosity effect is found to contribute a damping effect on the amplitude of the capillary wave with subtle differences to the effect of the convective-diffusive Marangoni transport. The general wave dispersion is augmented to take into account the Marangoni and surface viscosity effects, and a first-order correction to the critical damping wavelength is derived. The authors acknowledge the financial support of the Shell University Technology Centre for fuels and lubricants.

  14. Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.

    PubMed

    Atallah, Afnan; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

    2017-09-01

    A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.

  15. Effect of dispersion forces on the capillary-wave fluctuations of liquid surfaces.

    PubMed

    Chacón, Enrique; Fernández, Eva M; Tarazona, Pedro

    2014-04-01

    We present molecular dynamics evidence for the nonanalytic effects of the long-range dispersion forces on the capillary waves fluctuations of a Lennard-Jones liquid surface. The results of the intrinsic sampling method, for the analysis of the instantaneous interfacial shape, are obtained in large systems for several cut-off distances of the potential tail, and they show good agreement with the theoretical prediction by Napiórkowski and Dietrich, based on a density functional analysis. The enhancement of the capillary waves is quantified to be within 1% for a simple liquid near its triple point.

  16. Viscosity of particulate soap films: approaching the jamming of 2D capillary suspensions.

    PubMed

    Timounay, Yousra; Rouyer, Florence

    2017-05-14

    We compute the effective viscosity of particulate soap films thanks to local velocity fields obtained by Particle Image Velocimetry (PIV) during film retraction experiments. We identify the jamming of these 2D capillary suspensions at a critical particle surface fraction (≃0.84) where effective viscosity diverges. Pair correlation function and number of neighbors in contact or close to contact reveal the cohesive nature of this 2D capillary granular media. The experimental 2D dynamic viscosities can be predicted by a model considering viscous dissipation at the liquid interfaces induced by the motion of individual particles.

  17. Modeling oxygen transport in human placental terminal villi.

    PubMed

    Gill, J S; Salafia, C M; Grebenkov, D; Vvedensky, D D

    2011-12-21

    Oxygen transport from maternal blood to fetal blood is a primary function of the placenta. Quantifying the effectiveness of this exchange remains key in identifying healthy placentas because of the great variability in capillary number, caliber and position within the villus-even in placentas deemed clinically "normal". By considering villous membrane to capillary membrane transport, stationary oxygen diffusion can be numerically solved in terminal villi represented by digital photomicrographs. We aim to provide a method to determine whether and if so to what extent diffusional screening may operate in placental villi. Segmented digital photomicrographs of terminal villi from the Pregnancy, Infection and Nutrition study in North Carolina 2002 are used as a geometric basis for solving the stationary diffusion equation. Constant maternal villous oxygen concentration and perfect fetal capillary membrane absorption are assumed. System efficiency is defined as the ratio of oxygen flux into a villus and the sum of the capillary areas contained within. Diffusion screening is quantified by comparing numerical and theoretical maximum oxygen fluxes. A strong link between various measures of villous oxygen transport efficiency and the number of capillaries within a villus is established. The strength of diffusional screening is also related to the number of capillaries within a villus. Our measures of diffusional efficiency are shown to decrease as a function of the number of capillaries per villus. This low efficiency, high capillary number relationship supports our hypothesis that diffusional screening is present in this system. Oxygen transport per capillary is reduced when multiple capillaries compete for diffusing oxygen. A complete picture of oxygen fluxes, capillary and villus areas is obtainable and presents an opportunity for future work. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Subtle exchange model of flow depended on the blood cell shape to enhance the micro-circulation in capillary

    NASA Astrophysics Data System (ADS)

    Chan, Iatneng

    2012-02-01

    In general the exchange of gases or other material in capillary system is conceptualized by the diffusion effect. But in this model, we investigate a micro-flow pattern by simulation and computation on a micro-exchange model in which the blood cell is a considered factor, especially on its shape. It shows that the cell benefits the circulation while it is moving in the capillary. In the study, the flow detail near the cell surface is mathematically analyzed, such that the Navier-Stokes equations are applied and the viscous factor is also briefly considered. For having a driven force to the motion of micro-circulation, a breathing mode is suggested to approximately compute on the flow rate in the blood capillary during the transfer of cell. The rate is also used to estimate the enhancement to the circulation in additional to the outcome of diffusion. Moreover in the research, the shape change of capillary wall under pressure influence is another element in the beginning calculation for the effect in the assistance to cell motion.

  19. Effect of sieving polymer concentration on separation of 100 bp DNA Ladder by capillary gel electrophoresis

    NASA Astrophysics Data System (ADS)

    Nakazumi, T.; Hara, Y.

    2017-09-01

    We studied the effect of sieving polymer concentration on separation of a 100 bp DNA Ladder by capillary gel electrophoresis (CGE) using hydroxyethyl cellulose (HEC) with a molecular size of 1000 k. For measurement purposes, we selected a fused silica capillary with total length of 15 cm and effective length of 7.5 cm; this was applied to compact CGE equipment for a Point-Care-Testing (POCT) system. Measurement results of the 100 bp DNA Ladder sample indicated that small DNA separation was significantly affected by HEC sieving polymer concentration. This was due to the level of entanglement between small DNA molecules and the sieving polymer chain significantly influencing migration time, mobility, and resolution length of the CGE process. We concluded that 1.0 w/v % HEC sieving polymer concentration was optimal for CGE separation of DNA ≥1000bp in the 100 bp DNA Ladder (100-1500 bp) when using the short-length capillary.

  20. Capillary whole blood testing by a new portable monitor. Comparison with standard determination of the international normalized ratio.

    PubMed

    de Miguel, Dunia; Burgaleta, Carmen; Reyes, Eduardo; Pascual, Teresa

    2003-07-01

    We evaluated a new portable monitor (AvoSure PT PRO, Menarini Diagnostics, Firenze, Italy) developed to test the prothrombin time in capillary blood and plasma by comparing it with the standard laboratory determination. We studied 62 patients receiving acenocoumarol therapy. The international normalized ratio (INR) in capillary blood was analyzed by 2 methods: AvoSure PT PRO and Thrombotrack Nycomed Analyzer (Axis-Shield, Dundee, Scotland). Parallel studies were performed in plasma samples by a reference method using the Behring Coagulation Timer (Behring Diagnostics, Marburg, Germany). Plasma samples also were tested with the AvoSure PT PRO. Correlation was good for INR values for capillary blood and plasma samples by AvoSure PT PRO and our reference method (R2 = 0.8596) and for capillary blood samples tested by the AvoSure PT PRO and Thrombotrack Nycomed Analyzer (R2 = 0.8875). The correlation for INR in capillary blood and plasma samples by AvoSure PT PRO was 0.6939 (P < .0004). Capillary blood determinations are rapid and effective for monitoring oral anticoagulation therapy and have a high correlation to plasma determinations. AvoSure PT PRO is accurate for controlling INR in plasma and capillary blood samples, may be used in outpatient clinics, and has advantages over previous portable monitors.

  1. Vapor bridges between solid substrates in the presence of the contact line pinning effect: Stability and capillary force

    NASA Astrophysics Data System (ADS)

    Liu, Yawei; Zhang, Xianren

    2016-12-01

    In this work, we focus on investigating how nanobubbles mediate long-range interaction between neighboring solid substrates in the presence of the contact line pinning effect caused by surface heterogeneities. Using the constrained lattice density functional theory (LDFT), we prove that the nanobubbles, which take the form of vapor bridges here, are stabilized by the pinning effect if the separation between two substrates is less than a critical distance. The critical distance strongly depends on the chemical potential (i.e., the degree of saturation) and could become extremely long at a special chemical potential. Moreover, under the pinning effect, the substrate chemistry only determines the stability of the vapor bridges and the range of the capillary force, but has less influences on the magnitude of the capillary force, indicating that the substrate chemistry or the apparent contact angle for droplets or bubbles on the substrates is no longer a direct parameter to determine the magnitude of capillary force. A qualitative analysis for the two dimensional vapor bridges by considering the feedback mechanism can explain the results from the LDFT calculations.

  2. Effects of increased inspired oxygen concentration on tissue oxygenation: theoretical considerations.

    PubMed

    Lumb, Andrew B; Nair, Sindhu

    2010-03-01

    Breathing increased fractional oxygen concentration (FiO2) is recommended for the treatment of tissue ischaemia. The theoretical benefits of increasing FiO2 on tissue oxygenation were evaluated using standard physiological equations. Assuming constant oxygen consumption by tissues throughout the length of a capillary, the oxygen content at 20 arbitrary points along a capillary was calculated. Using mathematical representations of the haemoglobin dissociation curve and an iterative approach to include the dissolved oxygen component of oxygen content, the oxygen partial pressure (PO2) profile along a capillary was estimated. High FiO2 concentrations cause large increases in PO2 at the arteriolar end of capillaries but these large PO2 values, caused by the extra dissolved oxygen, rapidly decline along the capillary. At the venular end of the capillary (the area of tissue most likely to be hypoxic), breathing oxygen causes only a modest improvement in PO2. Increasing FiO2 to treat tissue hypoxia has clear benefits, but a multimodal approach to management is required.

  3. Recent advances in capillary ultrahigh pressure liquid chromatography.

    PubMed

    Blue, Laura E; Franklin, Edward G; Godinho, Justin M; Grinias, James P; Grinias, Kaitlin M; Lunn, Daniel B; Moore, Stephanie M

    2017-11-10

    In the twenty years since its initial demonstration, capillary ultrahigh pressure liquid chromatography (UHPLC) has proven to be one of most powerful separation techniques for the analysis of complex mixtures. This review focuses on the most recent advances made since 2010 towards increasing the performance of such separations. Improvements in capillary column preparation techniques that have led to columns with unprecedented performance are described. New stationary phases and phase supports that have been reported over the past decade are detailed, with a focus on their use in capillary formats. A discussion on the instrument developments that have been required to ensure that extra-column effects do not diminish the intrinsic efficiency of these columns during analysis is also included. Finally, the impact of these capillary UHPLC topics on the field of proteomics and ways in which capillary UHPLC may continue to be applied to the separation of complex samples are addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Fatigue Performance of Ti-6Al-4V Additively Manufactured Specimens with Integrated Capillaries of an Embedded Structural Health Monitoring System

    PubMed Central

    Hinderdael, Michaël; Strantza, Maria; De Baere, Dieter; Devesse, Wim; De Graeve, Iris; Terryn, Herman; Guillaume, Patrick

    2017-01-01

    Additive manufacturing (AM) of metals offers new possibilities for the production of complex structures. Up to now, investigations on the mechanical response of AM metallic parts show a significant spread and unexpected failures cannot be excluded. In this work, we focus on the detection of fatigue cracks through the integration of a Structural Health Monitoring (SHM) system in Ti-6Al-4V specimens. The working principle of the presented system is based on the integration of small capillaries that are capable of detecting fatigue cracks. Four-point bending fatigue tests have been performed on Ti-6Al-4V specimens with integrated capillaries and compared to the reference specimenswithout capillaries. Specimens were produced by conventional subtractive manufacturing of wrought material and AM, using the laser based Directed Energy Deposition (DED) process. In this study, we investigated the effect of the presence of the capillary on the fatigue strength and fatigue initiation location. Finite element (FEM) simulations were performed to validate the experimental test results. The presence of a drilled capillary in the specimens did not alter the fatigue initiation location. However, the laser based DED production process introduced roughness on the capillary surface that altered the fatigue initiation location to the capillary surface. The fatigue performance was greatly reduced when considering a printed capillary. It is concluded that the surface quality of the integrated capillary is of primary importance in order not to influence the structural integrity of the component to be monitored. PMID:28841186

  5. Fatigue Performance of Ti-6Al-4V Additively Manufactured Specimens with Integrated Capillaries of an Embedded Structural Health Monitoring System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hinderdael, Michaël; Strantza, Maria; De Baere, Dieter

    Additive manufacturing (AM) of metals offers new possibilities for the production of complex structures. Up to now, investigations on the mechanical response of AM metallic parts show a significant spread and unexpected failures cannot be excluded. In this work, we focus on the detection of fatigue cracks through the integration of a Structural Health Monitoring (SHM) system in Ti-6Al-4V specimens. The working principle of the presented system is based on the integration of small capillaries that are capable of detecting fatigue cracks. Four-point bending fatigue tests have been performed on Ti-6Al-4V specimens with integrated capillaries and compared to the referencemore » specimenswithout capillaries. Specimens were produced by conventional subtractive manufacturing of wrought material and AM, using the laser based Directed Energy Deposition (DED) process. In this study, we investigated the effect of the presence of the capillary on the fatigue strength and fatigue initiation location. Finite element (FEM) simulations were performed to validate the experimental test results. The presence of a drilled capillary in the specimens did not alter the fatigue initiation location. However, the laser based DED production process introduced roughness on the capillary surface that altered the fatigue initiation location to the capillary surface. The fatigue performance was greatly reduced when considering a printed capillary. It is concluded that the surface quality of the integrated capillary is of primary importance in order not to influence the structural integrity of the component to be monitored.« less

  6. Fatigue Performance of Ti-6Al-4V Additively Manufactured Specimens with Integrated Capillaries of an Embedded Structural Health Monitoring System

    DOE PAGES

    Hinderdael, Michaël; Strantza, Maria; De Baere, Dieter; ...

    2017-08-25

    Additive manufacturing (AM) of metals offers new possibilities for the production of complex structures. Up to now, investigations on the mechanical response of AM metallic parts show a significant spread and unexpected failures cannot be excluded. In this work, we focus on the detection of fatigue cracks through the integration of a Structural Health Monitoring (SHM) system in Ti-6Al-4V specimens. The working principle of the presented system is based on the integration of small capillaries that are capable of detecting fatigue cracks. Four-point bending fatigue tests have been performed on Ti-6Al-4V specimens with integrated capillaries and compared to the referencemore » specimenswithout capillaries. Specimens were produced by conventional subtractive manufacturing of wrought material and AM, using the laser based Directed Energy Deposition (DED) process. In this study, we investigated the effect of the presence of the capillary on the fatigue strength and fatigue initiation location. Finite element (FEM) simulations were performed to validate the experimental test results. The presence of a drilled capillary in the specimens did not alter the fatigue initiation location. However, the laser based DED production process introduced roughness on the capillary surface that altered the fatigue initiation location to the capillary surface. The fatigue performance was greatly reduced when considering a printed capillary. It is concluded that the surface quality of the integrated capillary is of primary importance in order not to influence the structural integrity of the component to be monitored.« less

  7. Capillary Rise: Validity of the Dynamic Contact Angle Models.

    PubMed

    Wu, Pingkeng; Nikolov, Alex D; Wasan, Darsh T

    2017-08-15

    The classical Lucas-Washburn-Rideal (LWR) equation, using the equilibrium contact angle, predicts a faster capillary rise process than experiments in many cases. The major contributor to the faster prediction is believed to be the velocity dependent dynamic contact angle. In this work, we investigated the dynamic contact angle models for their ability to correct the dynamic contact angle effect in the capillary rise process. We conducted capillary rise experiments of various wetting liquids in borosilicate glass capillaries and compared the model predictions with our experimental data. The results show that the LWR equations modified by the molecular kinetic theory and hydrodynamic model provide good predictions on the capillary rise of all the testing liquids with fitting parameters, while the one modified by Joos' empirical equation works for specific liquids, such as silicone oils. The LWR equation modified by molecular self-layering model predicts well the capillary rise of carbon tetrachloride, octamethylcyclotetrasiloxane, and n-alkanes with the molecular diameter or measured solvation force data. The molecular self-layering model modified LWR equation also has good predictions on the capillary rise of silicone oils covering a wide range of bulk viscosities with the same key parameter W(0), which results from the molecular self-layering. The advantage of the molecular self-layering model over the other models reveals the importance of the layered molecularly thin wetting film ahead of the main meniscus in the energy dissipation associated with dynamic contact angle. The analysis of the capillary rise of silicone oils with a wide range of bulk viscosities provides new insights into the capillary dynamics of polymer melts.

  8. Fatigue Performance of Ti-6Al-4V Additively Manufactured Specimens with Integrated Capillaries of an Embedded Structural Health Monitoring System.

    PubMed

    Hinderdael, Michaël; Strantza, Maria; De Baere, Dieter; Devesse, Wim; De Graeve, Iris; Terryn, Herman; Guillaume, Patrick

    2017-08-25

    Additive manufacturing (AM) of metals offers new possibilities for the production of complex structures. Up to now, investigations on the mechanical response of AM metallic parts show a significant spread and unexpected failures cannot be excluded. In this work, we focus on the detection of fatigue cracks through the integration of a Structural Health Monitoring (SHM) system in Ti-6Al-4V specimens. The working principle of the presented system is based on the integration of small capillaries that are capable of detecting fatigue cracks. Four-point bending fatigue tests have been performed on Ti-6Al-4V specimens with integrated capillaries and compared to the reference specimenswithout capillaries. Specimens were produced by conventional subtractive manufacturing of wrought material and AM, using the laser based Directed Energy Deposition (DED) process. In this study, we investigated the effect of the presence of the capillary on the fatigue strength and fatigue initiation location. Finite element (FEM) simulations were performed to validate the experimental test results. The presence of a drilled capillary in the specimens did not alter the fatigue initiation location. However, the laser based DED production process introduced roughness on the capillary surface that altered the fatigue initiation location to the capillary surface. The fatigue performance was greatly reduced when considering a printed capillary. It is concluded that the surface quality of the integrated capillary is of primary importance in order not to influence the structural integrity of the component to be monitored.

  9. Capillary-Driven Flow in Liquid Filaments Connecting Orthogonal Channels

    NASA Technical Reports Server (NTRS)

    Allen, Jeffrey S.

    2005-01-01

    Capillary phenomena plays an important role in the management of product water in PEM fuel cells because of the length scales associated with the porous layers and the gas flow channels. The distribution of liquid water within the network of gas flow channels can be dramatically altered by capillary flow. We experimentally demonstrate the rapid movement of significant volumes of liquid via capillarity through thin liquid films which connect orthogonal channels. The microfluidic experiments discussed provide a good benchmark against which the proper modeling of capillarity by computational models may be tested. The effect of surface wettability, as expressed through the contact angle, on capillary flow will also be discussed.

  10. Effect of using polyimide capillaries during thermal experiments on the particle size distribution of supported Pt nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gámez-Mendoza, Liliana; Resto, Oscar; Martínez-Iñesta, María

    2015-09-20

    Kapton HN-type polyimide capillaries are commonly used as sample holders for transmission X-ray experiments at temperatures below 673 K because of their thermal stability, high X-ray transmittance and low cost. Using high-angle annular dark field scanning high-resolution transmission electron microscopy and thermogravimetric analysis, this work shows that using polyimide capillaries leads to the overgrowth of supported Pt nanoparticles during reduction at temperatures below the glass transition temperature (T g= 658 K) owing to an outgassing of water from the polyimide. Quartz capillaries were also studied and this overgrowth was not observed.

  11. [Advances of the coatings used in columns for capillary electrophoresis and in nanochannels of chips].

    PubMed

    Liu, Chunye; Chen, Jierong

    2005-01-01

    An overview is provided on the advancement and development of coating preparation methodology and materials used in capillaries and channels in microfluidic chip. Discussion is also given on the effects of coatings in the resolutions of separation and the reproducibility of separations. Dynamic coatings and linked coatings, classified as homo-polymers, copolymers and heterocyclic compounds, are further discussed, and so are the methods for the preparation of the coatings by cross-linked reaction, sol-gel process, photomodification and chemical deposition, etc. The discussion will be useful for the optimization of capillary columns that are used in capillary electrophoresis and nanochannels of chip.

  12. Dual-opposite injection capillary electrophoresis: Principles and misconceptions.

    PubMed

    Blackney, Donna M; Foley, Joe P

    2017-03-01

    Dual-opposite injection capillary electrophoresis (DOI-CE) is a separation technique that utilizes both ends of the capillary for sample introduction. The electroosmotic flow (EOF) is suppressed to allow all ions to reach the detector quickly. Depending on the individual electrophoretic mobilities of the analytes of interest and the effective length that each analyte travels to the detection window, the elution order of analytes in a DOI-CE separation can vary widely. This review discusses the principles, applications, and limitations of dual-opposite injection capillary electrophoresis. Common misconceptions regarding DOI-CE are clarified. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Role of the sedimentary structure of the urban vadose zone (URVAZO) on the transfer of heavy metals of an urban stormwater basin

    NASA Astrophysics Data System (ADS)

    Angulo-Jaramillo, R.; Winiarski, T.; Goutaland, D.; Lassabatere, L.

    2009-12-01

    Stormwater infiltration basins have become a common alternative practice to traditional stormwater pipe networks in urban areas. They are often built in permeable subsurface soils (Urban Vadose Zone, URVAZO), such as alluvial deposits. These sedimentary deposits are highly heterogeneous and generate preferential flow paths that may cause either rapid or non-uniform transport of contaminants at great depths. The understanding of how subsurface vadose zone heterogeneities transfer contaminant and fluid flow to the aquifer still remains a challenge in urban hydrology. Indeed, urban stormwater may contain pollutants that can contaminate either soil or groundwater. The aim of this study is to evaluate the role of the lithological heterogeneity of a glaciofluvial deposit underlying an urban infiltration basin on the link between water flow and heavy metals retention. A trench wall (14m length x 3m depth) was exposed by excavating the glaciofluvial formation. By a hydrogeophysical approach based on a sedimentary structural units and in situ hydraulic characterization (Beerkan tests), a realistic hydrostratigraphic 2D model was defined. The trench was sampled on nine vertical sections of 1.5m length, with ten samples per vertical section following each lithofacies. A total of 90 samples were analyzed. Coarse (mechanical sieving) and fine (laser diffraction) particle size distribution analysis, as well as the concentration of three replicates of Pb, Cu, Zn and organic matter (OM) was measured for each sample. The principal component analysis shows a strong correlation between metal concentration and the lithofacies. This hydrostratigraphic model was implemented in the finite element program Hydrus2D. The soil heterogeneity exerts an impact on the heterogeneity of the water content field under slightly saturated conditions, as they induce capillary barrier effects. These capillary barrier effects may generate water accumulation in some lithofacies overlying matrix-free gravel; they lead to lateral flow patterns known as funneled flows. Knowledge of the geometry (orientation, dip) at the structural scale is therefore a prerequisite for evaluating the preferential flow paths. They can explain that the silt fraction may come from colloidal migration through the vadose zone. The use of coupled water-geochemical transfer models enables us to advance assumptions helping the comprehension of principal hydrogeochemical process in the urban vadose zone.

  14. Determination of Nitrate Carry-Over on Bytac(registered) Strips Via Capillary Electrophoresis

    DTIC Science & Technology

    2012-01-19

    Beckman Coulter P/ ACE MDQ capillary electrophoresis instrument. A 60 cm long (10 cm effective length), 75 µm i.d. bare fused-silica capillary was used...the separation. Due to the high concentration of the BGE, electroosmotic flow (EOF) is significantly reduced allowing for the application of a...bromide) are not seen in the electropherogram due to the reversed polarity; electroosmotic flow suppression is sufficient to cause the ammonium and

  15. Mass-controlled capillary viscometer for a Newtonian liquid: Viscosity of water at different temperatures

    NASA Astrophysics Data System (ADS)

    Digilov, Rafael M.; Reiner, M.

    2007-03-01

    The operation principle of the mass-controlled capillary viscometer is presented for a Newtonian liquid. The derived equation for the temporal changes of the mass in a liquid column draining under gravity through a discharge capillary tube accounts self-consistently for the inertial convective term associated with the acceleration effect. The viscosity of water measured at different temperatures using the new approach is in good agreement with literature data.

  16. The effects of capillary transit time heterogeneity (CTH) on brain oxygenation

    PubMed Central

    Angleys, Hugo; Østergaard, Leif; Jespersen, Sune N

    2015-01-01

    We recently extended the classic flow–diffusion equation, which relates blood flow to tissue oxygenation, to take capillary transit time heterogeneity (CTH) into account. Realizing that cerebral oxygen availability depends on both cerebral blood flow (CBF) and capillary flow patterns, we have speculated that CTH may be actively regulated and that changes in the capillary morphology and function, as well as in blood rheology, may be involved in the pathogenesis of conditions such as dementia and ischemia-reperfusion injury. The first extended flow–diffusion equation involved simplifying assumptions which may not hold in tissue. Here, we explicitly incorporate the effects of oxygen metabolism on tissue oxygen tension and extraction efficacy, and assess the extent to which the type of capillary transit time distribution affects the overall effects of CTH on flow–metabolism coupling reported earlier. After incorporating tissue oxygen metabolism, our model predicts changes in oxygen consumption and tissue oxygen tension during functional activation in accordance with literature reports. We find that, for large CTH values, a blood flow increase fails to cause significant improvements in oxygen delivery, and can even decrease it; a condition of malignant CTH. These results are found to be largely insensitive to the choice of the transit time distribution. PMID:25669911

  17. C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal.

    PubMed

    Feng, Hua; Wang, Fang; Wang, Changmiao

    2016-07-01

    To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips.

  18. Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I

    PubMed Central

    2014-01-01

    Background Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. Results Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood–brain barrier breakdown was associated with displacement of tight-junction protein Occludin. Conclusion Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke. PMID:24468193

  19. Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I.

    PubMed

    Zinnanti, William J; Lazovic, Jelena; Housman, Cathy; Antonetti, David A; Koeller, David M; Connor, James R; Steinman, Lawrence

    2014-01-27

    Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood-brain barrier breakdown was associated with displacement of tight-junction protein Occludin. Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.

  20. Estimation of structural film viscosity based on the bubble rise method in a nanofluid.

    PubMed

    Cho, Heon Ki; Nikolov, Alex D; Wasan, Darsh T

    2018-04-15

    When a single bubble moves at a very low capillary number (10 -7 ) through a liquid with dispersed nanoparticles (nanofluid) inside a vertical tube/capillary, a film is formed between the bubble surface and the tube wall and the nanoparticles self-layer inside the confined film. We measured the film thickness using reflected light interferometry. We calculated the film structural energy isotherm vs. the film thickness from the film-meniscus contact angle measurements using the reflected light interferometric method. Based on the experimental measurement of the film thickness and the calculated values of the film structural energy barrier, we estimated the structural film viscosity vs. the film thickness using the Frenkel approach. Because of the nanoparticle film self-layering phenomenon, we observed a gradual increase in the film viscosity with the decreasing film thickness. However, we observed a significant increase in the film viscosity accompanied by a step-wise decrease in the bubble velocity when the film thickness decreased from 3 to 2 particle layers due to the structural transition in the film. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Development of a rate model to investigate contributions of anatomic and physiologic determinants of in vivo skin permeation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fleischer, N.M.

    The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. The objective of the present research was to investigate an in vivo skin permeation model system thatmore » was sensitive to perturbations of skin capillary physiology and stratum corneum. A [open quotes]fuzzy[close quotes] rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (K[sub p]) of isolflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D[sub 4]-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively. Minoxidil, leukotriene D[sub 4], tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to 193%) in the K[sub p's], while phenylephrine had no significant effect on isoflurane permeation.« less

  2. Visualization and quantification of two-phase flow in transparent miniature packed beds

    NASA Astrophysics Data System (ADS)

    Zhu, Peixi; Papadopoulos, Kyriakos D.

    2012-10-01

    Optical microscopy was used to visualize the flow of two phases [British Petroleum (BP) oil and an aqueous surfactant phase] in confined space, three-dimensional, transparent, natural porous media. The porous media consisted of water-wet cryolite grains packed inside cylindrical, glass microchannels, thus producing microscopic packed beds. Primary drainage of BP oil displacing an aqueous surfactant phase was studied at capillary numbers that varied between 10-6 and 10-2. The confinement space had a significant effect on the flow behavior. Phenomena of burst motion and capillary fingering were observed for low capillary numbers due to the domination of capillary forces. It was discovered that breakthrough time and capillary number bear a log-log scale linear relationship, based on which a generalized correlation between oil travel distance x and time t was found empirically.

  3. Visualization and quantification of two-phase flow in transparent miniature packed beds.

    PubMed

    Zhu, Peixi; Papadopoulos, Kyriakos D

    2012-10-01

    Optical microscopy was used to visualize the flow of two phases [British Petroleum (BP) oil and an aqueous surfactant phase] in confined space, three-dimensional, transparent, natural porous media. The porous media consisted of water-wet cryolite grains packed inside cylindrical, glass microchannels, thus producing microscopic packed beds. Primary drainage of BP oil displacing an aqueous surfactant phase was studied at capillary numbers that varied between 10(-6) and 10(-2). The confinement space had a significant effect on the flow behavior. Phenomena of burst motion and capillary fingering were observed for low capillary numbers due to the domination of capillary forces. It was discovered that breakthrough time and capillary number bear a log-log scale linear relationship, based on which a generalized correlation between oil travel distance x and time t was found empirically.

  4. Blood-brain barrier (BBB) toxicity and permeability assessment after L-(4-¹⁰Boronophenyl)alanine, a conventional B-containing drug for boron neutron capture therapy, using an in vitro BBB model.

    PubMed

    Roda, E; Nion, S; Bernocchi, G; Coccini, T

    2014-10-02

    Since brain tumours are the primary candidates for treatment by Boron Neutron Capture Therapy, one major challenge in the selective drug delivery to CNS is the crossing of the blood-brain barrier (BBB). The present pilot study investigated (i) the transport of a conventional B-containing product (i.e., L-(4-(10)Boronophenyl)alanine, L-(10)BPA), already used in medicine but still not fully characterized regarding its CNS interactions, as well as (ii) the effects of the L-(10)BPA on the BBB integrity using an in vitro model, consisting of brain capillary endothelial cells co-cultured with glial cells, closely mimicking the in vivo conditions. The multi-step experimental strategy (i.e. Integrity test, Filter study, Transport assay) checked L-(10)BPA toxicity at 80 µg Boron equivalent/ml, and its ability to cross the BBB, additionally by characterizing the cytoskeletal and TJ's proteins by immunocytochemistry and immunoblotting. In conclusion, a lack of toxic effects of L-(10)BPA was demonstrated, nevertheless accompanied by cellular stress phenomena (e.g. vimentin expression modification), paralleled by a low permeability coefficient (0.39 ± 0.01 × 10(-3)cm min(-1)), corroborating the scarce probability that L-(10)BPA would reach therapeutically effective cerebral concentration. These findings emphasized the need for novel strategies aimed at optimizing boron delivery to brain tumours, trying to ameliorate the compound uptake or developing new targeted products suitable to safely and effectively treat head cancer. Thus, the use of in vitro BBB model for screening studies may provide a useful early safety assessment for new effective compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood–brain barrier

    PubMed Central

    Chaturvedi, Mayank; Molino, Yves; Sreedhar, Bojja; Khrestchatisky, Michel; Kaczmarek, Leszek

    2014-01-01

    Aim The aim of this study was to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for delivery of a protein – tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) – across the blood–brain barrier (BBB) to inhibit deleterious matrix metalloproteinases (MMPs). Materials and methods The NPs were formulated by multiple-emulsion solvent-evaporation, and for enhancing BBB penetration, they were coated with polysorbate 80 (Ps80). We compared Ps80-coated and uncoated NPs for their toxicity, binding, and BBB penetration on primary rat brain capillary endothelial cell cultures and the rat brain endothelial 4 cell line. These studies were followed by in vivo studies for brain delivery of these NPs. Results Results showed that neither Ps80-coated nor uncoated NPs caused significant opening of the BBB, and essentially they were nontoxic. NPs without Ps80 coating had more binding to endothelial cells compared to Ps80-coated NPs. Penetration studies showed that TIMP-1 NPs + Ps80 had 11.21%±1.35% penetration, whereas TIMP-1 alone and TIMP-1 NPs without Ps80 coating did not cross the endothelial monolayer. In vivo studies indicated BBB penetration of intravenously injected TIMP-1 NPs + Ps80. Conclusion The study demonstrated that Ps80 coating of NPs does not cause significant toxic effects to endothelial cells and that it can be used to enhance the delivery of protein across endothelial cell barriers, both in vitro and in vivo. PMID:24531257

  6. Separation of profen enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors.

    PubMed

    Blanco, M; Coello, J; Iturriaga, H; Maspoch, S; Pérez-Maseda, C

    1998-01-09

    A method for resolving the enantiomers of various 2-arylpropionic acids (viz. ketoprofen, ibuprofen and fenoprofen) by capillary zone electrophoresis (CZE) using a background electrolyte (BGE) containing a cyclodextrin as chiral selector is proposed. The effects of the type of cyclodextrin used and its concentration on resolution were studied and heptakis-2,3,6-tri- O-methyl-beta-cyclodextrin was found to be the sole effective choice for the quantitative enantiomeric resolution of all the compounds tested. The influence of pH, BGE concentration, capillary temperature and addition of methanol to the BGE on resolution and other separation-related parameters was also studied. The three compounds studied can be enantiomerically resolved with a high efficiency in a short time (less than 20 min) with no capillary treatment. This makes the proposed method suitable for assessing the enantiomeric purity of commercially available pharmaceuticals.

  7. Effects of capillary heterogeneity on vapor-liquid counterflow in porous media

    NASA Astrophysics Data System (ADS)

    Stubos, A. K.; Satik, C.; Yortsos, Y. C.

    1992-06-01

    Based on a continuum description, the effect of capillary heterogeneity, induced by variation in permeability, on the steady state, countercurrent, vapor-liquid flow in porous media is analyzed. It is shown that the heterogeneity acts as a body force that may enhance or diminish gravity effects on heat pipes. Selection rules that determine the steady states reached in homogeneous, gravity-driven heat pipes are also formulated. It is shown that the 'infinite' two-phase zone may terminate by a substantial change in the permeability somewhere in the medium. The two possible sequences, liquid-liquid dominated-dry, or liquid-vapor dominated-dry find applications in geothermal systems. Finally, it is shown that although weak heterogeneity affects only gravity controlled flows, stronger variations in permeability can give rise to significant capillary effects.

  8. Symmetric and asymmetric capillary bridges between a rough surface and a parallel surface.

    PubMed

    Wang, Yongxin; Michielsen, Stephen; Lee, Hoon Joo

    2013-09-03

    Although the formation of a capillary bridge between two parallel surfaces has been extensively studied, the majority of research has described only symmetric capillary bridges between two smooth surfaces. In this work, an instrument was built to form a capillary bridge by squeezing a liquid drop on one surface with another surface. An analytical solution that describes the shape of symmetric capillary bridges joining two smooth surfaces has been extended to bridges that are asymmetric about the midplane and to rough surfaces. The solution, given by elliptical integrals of the first and second kind, is consistent with a constant Laplace pressure over the entire surface and has been verified for water, Kaydol, and dodecane drops forming symmetric and asymmetric bridges between parallel smooth surfaces. This solution has been applied to asymmetric capillary bridges between a smooth surface and a rough fabric surface as well as symmetric bridges between two rough surfaces. These solutions have been experimentally verified, and good agreement has been found between predicted and experimental profiles for small drops where the effect of gravity is negligible. Finally, a protocol for determining the profile from the volume and height of the capillary bridge has been developed and experimentally verified.

  9. Enhanced laser radiation pressure acceleration of protons with a gold cone-capillary

    NASA Astrophysics Data System (ADS)

    Lv, Chong; Xie, Bai-Song; Wan, Feng; Hou, Ya-Juan; Jia, Mo-Ran; Sang, Hai-Bo; Hong, Xue-Ren; Liu, Shi-Bing

    2017-03-01

    A scheme with a gold cone-capillary is proposed to improve the protons acceleration, and involved problems are investigated by using the two-dimensional particle-in-cell simulations. It is demonstrated that the cone-capillary can efficiently guide and collimate the protons to a longer distance and result in a better beam quality with a dense density ≥ 10 n c , monoenergetic peak energy E k ˜ 1.51 GeV , spatial emittance ˜ 0.0088 mm mrad with divergence angle θ ˜ 1.0 ° and diameter ˜ 0.5 μ m . The enhancement is mainly attributed to the focusing effect by the transverse electric field generated by the cone as well as the capillary, which can prevent greatly the protons from expanding in the transverse direction. Comparable to without the capillary, the protons energy spectra have a stable monoenergetic peak and divergence angle nearby 1.0 ° in longer time. Besides, the efficiency of acceleration depending on the capillary length is explored, and the optimal capillary length is also achieved. Such a target may be beneficial to many applications such as ion fast ignition in inertial fusion, proton therapy and so on.

  10. Connective Tissue Growth Factor Is Involved in Structural Retinal Vascular Changes in Long-Term Experimental Diabetes

    PubMed Central

    Van Geest, Rob J.; Leeuwis, Jan Willem; Dendooven, Amélie; Pfister, Frederick; Bosch, Klazien; Hoeben, Kees A.; Vogels, Ilse M.C.; Van der Giezen, Dionne M.; Dietrich, Nadine; Hammes, Hans-Peter; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J.F.

    2014-01-01

    Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF+/−) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF+/− mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF+/− mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR. PMID:24217924

  11. Gas/oil capillary pressure at chalk at elevated pressures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Christoffersen, K.R.; Whitson, C.H.

    1995-09-01

    Accurate capillary pressure curves are essential for studying the recovery of oil by gas injection in naturally fractured chalk reservoirs. A simple and fast method to determine high-pressure drainage capillary pressure curves has been developed. The effect of gas/oil interfacial tension (IFT) on the capillary pressure of chalk cores has been determined for a methane/n-pentane system. Measurements on a 5-md outcrop chalk core were made at pressures of 70, 105, and 130 bar, with corresponding IFT`s of 6.3, 3.2, and 1.5 mN/m. The results were both accurate and reproducible. The measured capillary pressure curves were not a linear function ofmore » IFT when compared with low-pressure centrifuge data. Measured capillary pressures were considerably lower than IFT-scaled centrifuge data. It appears that the deviation starts at an IFT of about 5 mN/m. According to the results of this study, the recovery of oil by gravity drainage in naturally fractured chalk reservoirs may be significantly underestimated if standard laboratory capillary pressure curves are scaled by IFT only. However, general conclusions cannot be made on the basis on only this series of experiments on one chalk core.« less

  12. Mach-like capillary-gravity wakes.

    PubMed

    Moisy, Frédéric; Rabaud, Marc

    2014-08-01

    We determine experimentally the angle α of maximum wave amplitude in the far-field wake behind a vertical surface-piercing cylinder translated at constant velocity U for Bond numbers Bo(D)=D/λ(c) ranging between 0.1 and 4.2, where D is the cylinder diameter and λ(c) the capillary length. In all cases the wake angle is found to follow a Mach-like law at large velocity, α∼U(-1), but with different prefactors depending on the value of Bo(D). For small Bo(D) (large capillary effects), the wake angle approximately follows the law α≃c(g,min)/U, where c(g,min) is the minimum group velocity of capillary-gravity waves. For larger Bo(D) (weak capillary effects), we recover a law α∼√[gD]/U similar to that found for ship wakes at large velocity [Rabaud and Moisy, Phys. Rev. Lett. 110, 214503 (2013)]. Using the general property of dispersive waves that the characteristic wavelength of the wave packet emitted by a disturbance is of order of the disturbance size, we propose a simple model that describes the transition between these two Mach-like regimes as the Bond number is varied. We show that the new capillary law α≃c(g,min)/U originates from the presence of a capillary cusp angle (distinct from the usual gravity cusp angle), along which the energy radiated by the disturbance accumulates for Bond numbers of order of unity. This model, complemented by numerical simulations of the surface elevation induced by a moving Gaussian pressure disturbance, is in qualitative agreement with experimental measurements.

  13. Flow Modification Induced by Quincke Rotation in a Capillary

    NASA Astrophysics Data System (ADS)

    Cebers, A.; Lemaire, E.; Lobry, L.

    When particles immersed in a semi-insulating liquid are submitted to a sufficiently high DC field, they can rotate spontaneously around any axis perpendicular to the field (Quincke rotation). Recently we have shown that due to Quincke effect the effective viscosity of a colloidal suspension could be reduced. When the suspension is submitted to a shear, the particles rotation is amplified by the electric torque and drives the suspending liquid. For a flow in a capillary, this effect manifests itself by an increase of the flow rate. We present the results of our experiments carried out with a rectangular cross section capillary. These results are compared with the direct determination of the apparent viscosity in a Couette flow rheometer.

  14. Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole-body glucose uptake.

    PubMed

    Meijer, Rick I; De Boer, Michiel P; Groen, Martine R; Eringa, Etto C; Rattigan, Stephen; Barrett, Eugene J; Smulders, Yvo M; Serne, Erik H

    2012-08-01

    Insulin-induced capillary recruitment is considered a determinant of insulin-mediated glucose uptake. Insulin action on the microvasculature has been assessed in skin; however, there is concern as to whether the vascular responses observed in skin reflect those in the muscle. We hypothesized that insulin-induced capillary recruitment in skin would correlate with microvascular recruitment in muscle in a group of subjects displaying a wide variation in insulin sensitivity. Capillary recruitment in skin was assessed using capillary videomicroscopy, and skeletal muscle microvascular recruitment (i.e., increase in MBV) was studied using CEU in healthy volunteers (n = 18, mean age: 30.6 ± 11.1 years). Both microvascular measurements were performed during saline infusion, and during a hyperinsulinemic euglycemic clamp. During hyperinsulinemia, capillary recruitment in skin was augmented from 58.1 ± 18.2% to 81.0 ± 23.9% (p < 0.0001). Hyperinsulinemia increased MBV in muscle from 7.00 (2.66-17.67) to 10.06 (2.70-41.81) units (p = 0.003). Insulin's vascular effect in skin and muscle was correlated (r = 0.57). Insulin's microvascular effects in skin and muscle showed comparable strong correlations with insulin-mediated glucose uptake (r = 0.73 and 0.68, respectively). Insulin-augmented capillary recruitment in skin parallels insulin-mediated microvascular recruitment in muscle and both are related to insulin-mediated glucose uptake. © 2012 John Wiley & Sons Ltd.

  15. Cheerios Effect Controlled by Electrowetting.

    PubMed

    Yuan, Junqi; Feng, Jian; Cho, Sung Kwon

    2015-08-04

    The Cheerios effect is a common phenomenon in which small floating objects are either attracted or repelled by the sidewall due to capillary interaction. This attractive or repulsive behavior is highly dependent on the slope angles (angles of the interface on the wall or floating object with respect to a horizontal line) that can be mainly controlled by the wettability of the wall and floating object and the density of the object. In this paper, electrowetting on dielectric (EWOD) is implemented to the wall or floating object in order to actively control the wettability and thus capillary interaction. As such, the capillary force on buoyant and dense floating objects can be easily switched between repulsion and attraction by simply applying an electrical input. In addition, the theoretical prediction for the capillary force is verified experimentally by measuring the motion of floating particle and the critical contact angle on the wall at which the capillary force changes from attraction to repulsion. This successive verification is enabled by the merit of EWOD that allows for continuous change in the contact angle. Finally, the control method is extended to continuously move a floating object along a linear path and to continuously rotate a dumbbell-like floating object in centimeter scales using arrays of EWOD electrodes. A continuous linear motion is also accomplished in a smaller scale where the channel width (3 mm) is comparable to the capillary length.

  16. Running exercise protects the capillaries in white matter in a rat model of depression.

    PubMed

    Chen, Lin-Mu; Zhang, Ai-Pin; Wang, Fei-Fei; Tan, Chuan-Xue; Gao, Yuan; Huang, Chun-Xia; Zhang, Yi; Jiang, Lin; Zhou, Chun-Ni; Chao, Feng-Lei; Zhang, Lei; Tang, Yong

    2016-12-01

    Running has been shown to improve depressive symptoms when used as an adjunct to medication. However, the mechanisms underlying the antidepressant effects of running are not fully understood. Changes of capillaries in white matter have been discovered in clinical patients and depression model rats. Considering the important part of white matter in depression, running may cause capillary structural changes in white matter. Chronic unpredictable stress (CUS) rats were provided with a 4-week running exercise (from the fifth week to the eighth week) for 20 minutes each day for 5 consecutive days each week. Anhedonia was measured by a behavior test. Furthermore, capillary changes were investigated in the control group, the CUS/Standard group, and the CUS/Running group using stereological methods. The 4-week running increased sucrose consumption significantly in the CUS/Running group and had significant effects on the total volume, total length, and total surface area of the capillaries in the white matter of depression rats. These results demonstrated that exercise-induced protection of the capillaries in white matter might be one of the structural bases for the exercise-induced treatment of depression. It might provide important parameters for further study of the vascular mechanisms of depression and a new research direction for the development of clinical antidepressant means. J. Comp. Neurol. 524:3577-3586, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Thermal and capillary effects on the caprock mechanical stability at In Salah, Algeria

    DOE PAGES

    Vilarrasa, Víctor; Rutqvist, Jonny; Rinaldi, Antonio Pio

    2015-04-20

    Thermo-mechanical effects are important in geologic carbon storage because CO 2 will generally reach the storage formation colder than the rock, inducing thermal stresses. Capillary functions, i.e., retention and relative permeability curves, control the CO 2 plume shape, which may affect overpressure and thus, caprock stability. To analyze these thermal and capillary effects, we numerically solve non-isothermal injection of CO 2 in deformable porous media considering the In Salah, Algeria, CO 2 storage site. Here, we find that changes in the capillary functions have a negligible effect on overpressure and thus, caprock stability is not affected by capillary effects. But,more » we show that for the strike slip stress regime prevalent at In Salah, stability decreases in the lowest parts of the caprock during injection due to cooling-induced thermal stresses. Simulations show that shear slip along pre-existing fractures may take place in the cooled region, whereas tensile failure is less likely to occur. Indeed, only the injection zone and the lowest tens of meters of the 900-m-thick caprock at In Salah might be affected by cooling effects, which would thus not jeopardize the overall sealing capacity of the caprock. Furthermore, faults are likely to remain stable far away from the injection well because outside the cooled region the injection-induced stress changes are not sufficient to exceed the anticipated shear strength of minor faults. Nonetheless, we recommend that thermal effects should be considered in the site characterization and injection design of future CO 2 injection sites to assess caprock stability and guarantee a permanent CO 2 storage.« less

  18. Modification of narrow ablating capillaries under the influence of multiple femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Gubin, K. V.; Lotov, K. V.; Trunov, V. I.; Pestryakov, E. V.

    2016-09-01

    Powerful femtosecond laser pulses that propagate through narrow ablating capillaries cause modification of capillary walls, which is studied experimentally and theoretically. At low intensities, the laser-induced periodic surface structures and porous coating composed of sub-micron particles appear on the walls. At higher intensities, the surface is covered by deposited droplets of the size up to 10 μm. In both cases, the ablated material forms a solid plug that completely blocks the capillary after several hundreds or thousands of pulses. The suggested theoretical model indicates that the plug formation is a universal effect. It must take place in any narrow tube subject to ablation under the action of short laser pulses.

  19. Capillary filtration in venous hypertension. Comparison between the vacuum suction chamber (VSC) device and straingauge phlethysmography.

    PubMed

    Belcaro, G; Rulo, A; Renton, S

    1992-01-01

    To evaluate capillary filtration a group of normal subjects and two groups of subjects with venous incompetence (50 with deep and 50 with superficial incompetence) were studied with the vacuum suction chamber (VSC) device applied onto the internal perimalleolar region. This method was compared with straingauge plethysmography rate of ankle swelling (RAS). By the VSC the time taken for the weal to disappear (VSC time) was considered indicative of capillary filtration. The values obtained with the two methods were well related (r < 0.742) and there was a good separation between patients and normals. The separation between the two groups of patients was significantly better (p < 0.05) with the VSC time. In conclusion VSC time is a good indication of capillary filtration in comparison with straingauge plethysmography RAS. It may be used to assess variations in capillary filtration in venous hypertension and possibly to follow up the effects of treatments.

  20. Geometric control of capillary architecture via cell-matrix mechanical interactions.

    PubMed

    Sun, Jian; Jamilpour, Nima; Wang, Fei-Yue; Wong, Pak Kin

    2014-03-01

    Capillary morphogenesis is a multistage, multicellular activity that plays a pivotal role in various developmental and pathological situations. In-depth understanding of the regulatory mechanism along with the capability of controlling the morphogenic process will have direct implications on tissue engineering and therapeutic angiogenesis. Extensive research has been devoted to elucidate the biochemical factors that regulate capillary morphogenesis. The roles of geometric confinement and cell-matrix mechanical interactions on the capillary architecture, nevertheless, remain largely unknown. Here, we show geometric control of endothelial network topology by creating physical confinements with microfabricated fences and wells. Decreasing the thickness of the matrix also results in comparable modulation of the network architecture, supporting the boundary effect is mediated mechanically. The regulatory role of cell-matrix mechanical interaction on the network topology is further supported by alternating the matrix stiffness by a cell-inert PEG-dextran hydrogel. Furthermore, reducing the cell traction force with a Rho-associated protein kinase inhibitor diminishes the boundary effect. Computational biomechanical analysis delineates the relationship between geometric confinement and cell-matrix mechanical interaction. Collectively, these results reveal a mechanoregulation scheme of endothelial cells to regulate the capillary network architecture via cell-matrix mechanical interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. The relative influence of hematocrit and red blood cell velocity on oxygen transport from capillaries to tissue.

    PubMed

    Lücker, Adrien; Secomb, Timothy W; Weber, Bruno; Jenny, Patrick

    2017-04-01

    Oxygen transport to parenchymal cells occurs mainly at the microvascular level and depends on convective RBC flux, which is proportional in an individual capillary to the product of capillary hematocrit and RBC velocity. This study investigates the relative influence of these two factors on tissue PO 2 . A simple analytical model is used to quantify the respective influences of hematocrit, RBC velocity, and RBC flow on tissue oxygenation around capillaries. Predicted tissue PO 2 levels are compared with a detailed computational model. Hematocrit is shown to have a larger influence on tissue PO 2 than RBC velocity. The effect of RBC velocity increases with distance from the arterioles. Good agreement between analytical and numerical results is obtained, and the discrepancies are explained. Significant dependence of MTCs on RBC velocity at low hematocrit is demonstrated. For a given RBC flux in a capillary, the PO 2 in the surrounding tissue increases with increasing hematocrit, as a consequence of decreasing IVR to diffusive oxygen transport from RBCs to tissue. These results contribute to understanding the effects of blood flow changes on oxygen transport, such as those that occur in functional hyperemia in the brain. © 2016 John Wiley & Sons Ltd.

  2. Endothelial glycocalyx: permeability barrier and mechanosensor.

    PubMed

    Curry, F E; Adamson, R H

    2012-04-01

    Endothelial cells are covered with a polysaccharide rich layer more than 400 nm thick, mechanical properties of which limit access of circulating plasma components to endothelial cell membranes. The barrier properties of this endothelial surface layer are deduced from the rate of tracer penetration into the layer and the mechanics of red and white cell movement through capillary microvessels. This review compares the mechanosensor and permeability properties of an inner layer (100-150 nm, close to the endothelial membrane) characterized as a quasi-periodic structure which accounts for key aspects of transvascular exchange and vascular permeability with those of the whole endothelial surface layers. We conclude that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange. The differences between the properties of the whole layer and the inner glycocalyx structures likely reflect dynamic aspects of the endothelial surface layer including tracer binding to specific components, synthesis and degradation of key components, activation of signaling pathways in the endothelial cells when components of the surface layer are lost or degraded, and the spatial distribution of adhesion proteins in microdomains of the endothelial cell membrane.

  3. Congenital nephrotic syndrome.

    PubMed

    Hamed, Radi Ma

    2003-01-01

    The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

  4. Evaluation of the interaction between hydroxyapatite and bisphosphonate by nonlinear capillary electrochromatography.

    PubMed

    Kong, Deying; Chen, Zilin

    2017-05-01

    Bisphosphonates are a class of chemical compounds used to treat diseases caused by increased bone resorption. Zoledronate is a third-generation bisphosphonate drug. Hydroxyapatite is main mineral constituent of bones, which can be bound by bisphosphonates in vivo. In this work, we report a method of nonlinear capillary electrochromatography for study on the interaction between hydroxyapatite and bisphosphonate. Hydroxyapatite was modified on the inner wall of capillary by a biomimetic-mineralization method. Then nonlinear chromatography was used to fit and analyze the interaction between zoledronate and hydroxyapatite. The association rate constants of zoledronate in hydroxyapatite-modified capillary and bare capillary are 642.3 and 195/M/min, respectively. This indicates that there is strong binding interactions and affinity between zoledronate and hydroxyapatite. Besides, the interaction between zoledronate and hydroxyapatite was confirmed further by ultraviolet spectroscopy. The method of nonlinear capillary electrochromatography provides a fast and effect approach for studying of bone metabolism disease by evaluation of interaction between hydroxyapatite and bisphosphonates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Integrated on-line system for DNA sequencing by capillary electrophoresis: From template to called bases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ton, H.; Yeung, E.S.

    1997-02-15

    An integrated on-line prototype for coupling a microreactor to capillary electrophoresis for DNA sequencing has been demonstrated. A dye-labeled terminator cycle-sequencing reaction is performed in a fused-silica capillary. Subsequently, the sequencing ladder is directly injected into a size-exclusion chromatographic column operated at nearly 95{degree}C for purification. On-line injection to a capillary for electrophoresis is accomplished at a junction set at nearly 70{degree}C. High temperature at the purification column and injection junction prevents the renaturation of DNA fragments during on-line transfer without affecting the separation. The high solubility of DNA in and the relatively low ionic strength of 1 x TEmore » buffer permit both effective purification and electrokinetic injection of the DNA sample. The system is compatible with highly efficient separations by a replaceable poly(ethylene oxide) polymer solution in uncoated capillary tubes. Future automation and adaptation to a multiple-capillary array system should allow high-speed, high-throughput DNA sequencing from templates to called bases in one step. 32 refs., 5 figs.« less

  6. Separation of delta-, gamma- and alpha-tocopherols by CEC.

    PubMed

    Fanali, Salvatore; Catarcini, Paolo; Quaglia, Maria Giovanna; Camera, Emanuela; Rinaldi, Mariarosa; Picardo, Mauro

    2002-08-01

    In this study capillary electrochromatography (CEC) was used for the separation of three tocopherols (TOHs), namely delta-, gamma- and alpha-TOH and the antioxidant compound, butylated hydroxytoluene (BHT). The CEC experiments were carried out using an octadecylsilica (ODS) stationary phase packed, in our laboratory, in a fused-silica capillary (100 microm I.D., 365 microm O.D. x 33 cm of total length and 24.6 or 8.4 cm effective length). The mobile phase was composed by a mixture of methanol (MeOH) and acetonitrile (ACN), at different concentrations and 0.01% (w/v) of ammonium acetate. Retention time (t(R)), retention factor (k), resolution (R(s)) of the three TOHs were strongly influenced by the organic solvent composition of the run buffer and by the effective length of the capillary. Optimum experimental conditions were found even employing the short effective length of the capillary achieving the baseline separation of the studied analytes in a relatively short time (less than 5 min). The optimized method was applied to the qualitative analysis of vitamin E (alpha-TOH) present in a human serum extract.

  7. A new structure of permeable pavement for mitigating urban heat island.

    PubMed

    Liu, Yong; Li, Tian; Peng, Hangyu

    2018-09-01

    The urban heat island (UHI) effect has been a great threat to human habitation, and how to mitigate this problem has been a global concern over decades. This paper addresses the cooling effect of a novel permeable pavement called evaporation-enhancing permeable pavement, which has capillary columns in aggregate and a liner at the bottom. To explore the efficiency of mitigating the UHI, bench-scale permeable pavement units with capillary columns were developed and compared with conventional permeable pavement. Criteria of capillary capacities of the column, evaporation rates, and surface temperature of the pavements were monitored under simulated rainfall and Shanghai local weather conditions. Results show the capillary column was important in increasing evaporation by lifting water from the bottom to the surface, and the evaporation-enhancing permeable pavement was cooler than a conventional permeable pavement by as much as 9.4°C during the experimental period. Moreover, the cooling effect of the former pavement could persist more than seven days under the condition of no further rainfall. Statistical analysis result reveals that evaporation-enhancing permeable pavement can mitigate the UHI effect significantly more than a conventional permeable pavement. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury.

    PubMed

    Tong, Nianting; Zhang, Zhenzhen; Zhang, Wei; Qiu, Yating; Gong, Yuanyuan; Yin, Lili; Qiu, Qinghua; Wu, Xingwei

    2013-01-01

    Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

  9. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.

    PubMed

    McDannold, Nathan; Vykhodtseva, Natalia; Raymond, Scott; Jolesz, Ferenc A; Hynynen, Kullervo

    2005-11-01

    Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

  10. Effects of exercise on capillaries in the white matter of transgenic AD mice

    PubMed Central

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-01-01

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer’s disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD. PMID:29029478

  11. Effects of exercise on capillaries in the white matter of transgenic AD mice.

    PubMed

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-09-12

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

  12. Modeling steady state SO2-dependent changes in capillary ATP concentration using novel O2 micro-delivery methods

    PubMed Central

    Ghonaim, Nour W.; Fraser, Graham M.; Ellis, Christopher G.; Yang, Jun; Goldman, Daniel

    2013-01-01

    Adenosine triphosphate (ATP) is known to be released from the erythrocyte in an oxygen (O2) dependent manner. Since ATP is a potent vasodilator, it is proposed to be a key regulator in the pathway that mediates micro-vascular response to varying tissue O2 demand. We propose that ATP signaling mainly originates in the capillaries due to the relatively long erythrocyte transit times in the capillary and the short ATP diffusion distance to the electrically coupled endothelium. We have developed a computational model to investigate the effect of delivering or removing O2 to limited areas at the surface of a tissue with an idealized parallel capillary array on total ATP concentration. Simulations were conducted when exposing full surface to perturbations in tissue O2 tension (PO2) or locally using a circular micro-outlet (~100 μm in diameter), a square micro-slit (200 × 200 μm), or a rectangular micro-slit (1000 μm wide × 200 μm long). Results indicated the rectangular micro-slit has the optimal dimensions for altering hemoglobin saturations (SO2) in sufficient number capillaries to generate effective changes in total [ATP]. This suggests a threshold for the minimum number of capillaries that need to be stimulated in vivo by imposed tissue hypoxia to induce a conducted micro-vascular response. SO2 and corresponding [ATP] changes were also modeled in a terminal arteriole (9 μm in diameter) that replaces 4 surface capillaries in the idealized network geometry. Based on the results, the contribution of terminal arterioles to the net change in [ATP] in the micro-vascular network is minimal although they would participate as O2 sources thus influencing the O2 distribution. The modeling data presented here provide important insights into designing a novel micro-delivery device for studying micro-vascular O2 regulation in the capillaries in vivo. PMID:24069001

  13. Wettability Control on Fluid-Fluid Displacements in Patterned Microfluidics

    NASA Astrophysics Data System (ADS)

    Zhao, B.; Trojer, M.; Cueto-Felgueroso, L.; Juanes, R.

    2014-12-01

    Two-phase flow in porous media is important in many natural and industrial processes like geologic CO2 sequestration, enhanced oil recovery, and water infiltration in soil. While it is well known that the wetting properties of porous media can vary drastically depending on the type of media and the pore fluids, the effect of wettability on fluid displacement continues to challenge our microscopic and macroscopic descriptions. Here we study this problem experimentally, starting with the classic experiment of two-phase flow in a capillary tube. We image the shape of the meniscus and measure the associated capillary pressure for a wide range of capillary numbers. We confirm that wettability exerts a fundamental control on meniscus deformation, and synthesize new observations on the dependence of the dynamic capillary pressure on wetting properties (contact angle) and flow conditions (viscosity contrast and capillary number). We compare our experiments to a macroscopic phase-field model of two-phase flow. We use the insights gained from the capillary tube experiments to explore the viscous fingering instability in the Hele-Shaw geometry in the partial-wetting regime. A key difference between a Hele-Shaw cell and a porous medium is the existence of micro-structures (i.e. pores and pore throats). To investigate how these micro-structrues impact fluid-fluid displacement, we conduct experiments on a planar microfluidic device patterned with vertical posts. We track the evolution of the fluid-fluid interface and elucidate the impact of wetting on the cooperative nature of fluid displacement during pore invasion events. We use the insights gained from the capillary tube and patterned microfluidics experiments to elucidate the effect of wetting properties on viscous fingering and capillary fingering in a Hele-Shaw cell filled with glass beads, where we observe a contact-angle-dependent stabilizing behavior for the emerging flow instabilities, as the system transitions from drainage to imbibition.

  14. Pharmacologic manipulation of the microcirculation in cutaneous and myocutaneous flaps in pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pang, C.Y.; Neligan, P.C.; Nakatsuka, T.

    1985-04-01

    The vascular effects of isoxsuprine, diazoxide, and isoproterenol were studied in arterial buttock flaps and latissimus dorsi myocutaneous flaps in pigs. Capillary blood flow to the skin and muscles of these flaps was measured by the radioactive microsphere (15-mu diameter) technique 6 hours postoperatively under pentobarbital anesthesia. It was observed that isoproterenol, a beta-adrenergic receptor agonist, was not effective in augmentation of skin blood flow in the arterial buttock flaps. However, isoproterenol significantly increased capillary blood flow to the arterialized portion of latissimus dorsi myocutaneous flaps compared with controls. Isoxsuprine and diazoxide (vascular smooth muscle relaxants) significantly (p less thanmore » 0.05) increased total capillary blood flow to the skin of arterial buttock flaps and to the skin and muscles of the latissimus dorsi myocutaneous flaps. However, the increase in capillary blood flow occurred mainly in the arterialized portion of these flaps. The capillary blood flow, which was supplied by the small arteries in the distal portion of the arterial buttock and latissimus dorsi flaps, was not increased by treatment with isoxsuprine or diazoxide. Therefore, there was also no increase in the maximum distance of capillary blood flow from the pedicle to the distal end of the flaps. These observations led the authors to hypothesize that different sizes (diameters) of arteries in the skin and muscle have different reactivity (or sensitivity) to vasodilatory drugs. In the present experiment, the large dominant artery of the arterial buttock and latissimus dorsi flaps responded to isoxsuprine or diazoxide (vascular smooth-muscle relaxants), resulting in an increase in blood supply to the capillaries in the proximal portion of the flaps.« less

  15. Determination of vanillin in vanilla perfumes and air by capillary electrophoresis.

    PubMed

    Minematsu, Saaya; Xuan, Guang-Shan; Wu, Xing-Zheng

    2013-12-01

    The present study investigated capillary electrophoretic detection of vanillin in vanilla perfume and air. An UV-absorbance detector was used in a home-made capillary electrophoretic instrument. A fused silica capillary (outer diameter: 364 μm, inner diameter: 50 μm) was used as a separation capillary, and a high electric voltage (20 kV) was applied across the two ends of the capillary. Total length of the capillary was 70 cm, and the effective length was 55 cm. Experimental results showed that the vanillin peak was detected at about 600, 450, and 500 seconds when pH of running buffers in CE were 7.2, 9.3, and 11.5, respectively. The peak area of vanillin was proportional to its concentration in the range of 0-10(-2) mol/L. The detection limit was about 10(-5) mol/L. Vanillin concentration in a 1% vanilla perfume sample was determined to be about 3×10(-4) mol/L, agreed well with that obtained by a HPLC method. Furthermore, determination of vanillin in air by combination of CE and active carbon adsorption method was investigated. Copyright © 2013 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  16. Cell adhesion during bullet motion in capillaries.

    PubMed

    Takeishi, Naoki; Imai, Yohsuke; Ishida, Shunichi; Omori, Toshihiro; Kamm, Roger D; Ishikawa, Takuji

    2016-08-01

    A numerical analysis is presented of cell adhesion in capillaries whose diameter is comparable to or smaller than that of the cell. In contrast to a large number of previous efforts on leukocyte and tumor cell rolling, much is still unknown about cell motion in capillaries. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram was obtained for various values of capillary diameter and receptor density. We found that bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis. Copyright © 2016 the American Physiological Society.

  17. Hydrophilic solute transport across the rat blood-brain barrier

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lucchesi, K.J.

    1987-01-01

    Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB)more » was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.« less

  18. Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton.

    PubMed

    Liu, Li-Bo; Xue, Yi-Xue; Liu, Yun-Hui; Wang, Yi-Bao

    2008-04-01

    Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and claudin-5 are attenuated by BK induction. Immunohistochemistry and immunofluorescence assays show that the attenuated expression of ZO-1, occludin, and claudin-5 and F-actin is most obvious in the smaller tumor capillaries (<20 microm) after BK infusion, and there is no change in the larger tumor capillaries (>20 microm). The redistribution of ZO-1, occludin, and claudin-5 and rearrangement of F-actin in brain microvascular endothelial cells are observed at the same time. Meanwhile, Evans blue assay shows that the permeability of BTB increases after BK infusion. Transmission electron microscopy indicates that TJ is opened and that pinocytotic vesicular density is increased. Transendothelial electrical resistance (TEER) and horseradish peroxidase flux assays also reveal that TJ is opened by BK induction. In addition, radioimmunity and Western blot assay reveal a significant decrease in expression levels of cAMP and catalytic subunit of protien kinase A (PKAcs) of tumor tissue. This study demonstrates that the increase of BK-mediated BTB permeability is associated with the down-regulation of ZO-1, occludin, and claudin-5 and the rearrangement of F-actin and that cAMP/PKA signal transduction system might be involved in the modulating process.

  19. Cultured bovine brain capillary endothelial cells (BBCEC) - a blood-brain barrier model for studying the binding and internalization of insulin and insulin-like growth factor 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Keller, B.T.; Borchardt, R.T.

    1987-05-01

    Cultured bovine brain capillary endothelial cells (BBCEC) have previously been reported by their laboratory as a working model for studying nutrient and drug transport and metabolism at the blood-brain barrier. In the present study, they have utilized this culture system to investigate the binding and internalization of (/sup 125/I)-labelled insulin (INS) and insulin-like growth factor 1(IGF-1) by BBCEC. After 2 hrs at 23/sup 0/C, the specific binding of INS and IGF-1 was 1.6% and 13.6%, respectively. At 37/sup 0/C, the maximum specific binding was 0.9% for INS and 5.8% for IGF-1. Using an acid-wash technique to assess peptide internalization, itmore » was observed that, at 37/sup 0/C, approximately 60% of the bound INS rapidly became resistant to acid treatment, a value which was constant over 2 hr. With IGF-1, a similar proportion of the bound material, 62%, became resistant by 30 min, but subsequently decreased to 45% by 2 hr. Scatchard analysis of competitive binding studies indicated the presence of two binding sites for each protein, having K/sub d/'s of 0.82 nM and 19.2 nM for INS and 0.39 nM and 3.66 nM for IGF-1. Little change in the amount of INS binding was observed over a four-day interval as the cultures became a confluent monolayer. The present report of binding and internalization of these proteins suggests that the BBCEC may utilize a receptor-mediated process to internalize and/or transport (transcytosis) INS and IGF-1 from the circulation.« less

  20. Blood-brain barrier transport machineries and targeted therapy of brain diseases

    PubMed Central

    Barar, Jaleh; Rafi, Mohammad A.; Pourseif, Mohammad M.; Omidi, Yadollah

    2016-01-01

    Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB), drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases must adequately cross the BBB to provide their therapeutic properties on biological targets within the central nervous system (CNS). However, most of these pharmaceuticals do not sufficiently penetrate into CNS, failing to meet the intended therapeutic outcomes. Most lipophilic drugs capable of penetrating BBB are prone to the efflux functionality of BBB. In contrast, all hydrophilic drugs are facing severe infiltration blockage imposed by the tight cellular junctions of the BBB. Hence, a number of strategies have been devised to improve the efficiency of brain drug delivery and targeted therapy of CNS disorders using multimodal nanosystems (NSs). Conclusions: In order to improve the therapeutic outcomes of CNS drug transfer and targeted delivery, the discriminatory permeability of BBB needs to be taken under control. The carrier-mediated transport machineries of brain capillary endothelial cells (BCECs) can be exploited for the discovery, development and delivery of small molecules into the brain. Further, the receptor-mediated transport systems can be recruited for the delivery of macromolecular biologics and multimodal NSs into the brain. PMID:28265539

  1. Oxysterols decrease apical-to-basolateral transport of Aß peptides via an ABCB1-mediated process in an in vitro Blood-brain barrier model constituted of bovine brain capillary endothelial cells.

    PubMed

    Saint-Pol, Julien; Candela, Pietra; Boucau, Marie-Christine; Fenart, Laurence; Gosselet, Fabien

    2013-06-23

    It is known that activation of the liver X receptors (LXRs) by natural or synthetic agonists decreases the amyloid burden and enhances cognitive function in transgenic murine models of Alzheimer's disease (AD). Recent evidence suggests that LXR activation may affect the transport of amyloid ß (Aß) peptides across the blood-brain barrier (the BBB, which isolates the brain from the peripheral circulation). By using a well-characterized in vitro BBB model, we demonstrated that LXR agonists (24S-hydroxycholesterol, 27-hydroxycholesterol and T0901317) modulated the expression of target genes involved in cholesterol homeostasis (such as ATP-binding cassette sub-family A member 1 (ABCA1)) and promoted cellular cholesterol efflux to apolipoprotein A-I and high density lipoproteins. Interestingly, we also observed a decrease in Aß peptide influx across brain capillary endothelial cells, although ABCA1 did not appear to be directly involved in this process. By focusing on others receptors and transporters that are thought to have major roles in Aß peptide entry into the brain, we then demonstrated that LXR stimulation provoked an increase in expression of the ABCB1 transporter (also named P-glycoprotein (P-gp)). Further investigations confirmed ABCB1's involvement in the restriction of Aß peptide influx. Taken as a whole, our results not only reinforce the BBB's key role in cerebral cholesterol homeostasis but also demonstrate the importance of the LXR/ABCB1 axis in Aß peptide influx-highlighting an attractive new therapeutic approach whereby the brain could be protected from peripheral Aß peptide entry. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Blood-brain barrier transport machineries and targeted therapy of brain diseases.

    PubMed

    Barar, Jaleh; Rafi, Mohammad A; Pourseif, Mohammad M; Omidi, Yadollah

    2016-01-01

    Introduction: Desired clinical outcome of pharmacotherapy of brain diseases largely depends upon the safe drug delivery into the brain parenchyma. However, due to the robust blockade function of the blood-brain barrier (BBB), drug transport into the brain is selectively controlled by the BBB formed by brain capillary endothelial cells and supported by astrocytes and pericytes. Methods: In the current study, we have reviewed the most recent literature on the subject to provide an insight upon the role and impacts of BBB on brain drug delivery and targeting. Results: All drugs, either small molecules or macromolecules, designated to treat brain diseases must adequately cross the BBB to provide their therapeutic properties on biological targets within the central nervous system (CNS). However, most of these pharmaceuticals do not sufficiently penetrate into CNS, failing to meet the intended therapeutic outcomes. Most lipophilic drugs capable of penetrating BBB are prone to the efflux functionality of BBB. In contrast, all hydrophilic drugs are facing severe infiltration blockage imposed by the tight cellular junctions of the BBB. Hence, a number of strategies have been devised to improve the efficiency of brain drug delivery and targeted therapy of CNS disorders using multimodal nanosystems (NSs). Conclusions: In order to improve the therapeutic outcomes of CNS drug transfer and targeted delivery, the discriminatory permeability of BBB needs to be taken under control. The carrier-mediated transport machineries of brain capillary endothelial cells (BCECs) can be exploited for the discovery, development and delivery of small molecules into the brain. Further, the receptor-mediated transport systems can be recruited for the delivery of macromolecular biologics and multimodal NSs into the brain.

  3. Fluid mechanics of electroosmotic flow and its effect on band broadening in capillary electrophoresis.

    PubMed

    Ghosal, Sandip

    2004-01-01

    Electroosmotic flow (EOF) usually accompanies electrophoretic migration of charged species in capillary electrophoresis unless special precautions are taken to suppress it. The presence of the EOF provides certain advantages in separations. It is an alternative to mechanical pumps, which are inefficient and difficult to build at small scales, for transporting reagents and analytes on microfluidic chips. The downside is that any imperfection that distorts the EOF profile reduces the separation efficiency. In this paper, the basic facts about EOF are reviewed from the perspective of fluid mechanics and its effect on separations in free solution capillary zone electrophoresis is discussed in the light of recent advances.

  4. A model and numerical method for compressible flows with capillary effects

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmidmayer, Kevin, E-mail: kevin.schmidmayer@univ-amu.fr; Petitpas, Fabien, E-mail: fabien.petitpas@univ-amu.fr; Daniel, Eric, E-mail: eric.daniel@univ-amu.fr

    2017-04-01

    A new model for interface problems with capillary effects in compressible fluids is presented together with a specific numerical method to treat capillary flows and pressure waves propagation. This new multiphase model is in agreement with physical principles of conservation and respects the second law of thermodynamics. A new numerical method is also proposed where the global system of equations is split into several submodels. Each submodel is hyperbolic or weakly hyperbolic and can be solved with an adequate numerical method. This method is tested and validated thanks to comparisons with analytical solutions (Laplace law) and with experimental results onmore » droplet breakup induced by a shock wave.« less

  5. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

    PubMed Central

    Sun, Kai; Fan, Jingyu; Han, Jingyan

    2015-01-01

    Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

  6. On Thermocapillary Mechanism of Spatial Separation of Metal Melts

    NASA Astrophysics Data System (ADS)

    Demin, V. A.; Mizev, A. I.; Petukhov, M. I.

    2018-02-01

    Theoretical research has been devoted to the study of binary metal melts behavior in a thin capillary. Earlier it has been found experimentally that unusually significant and quick redistribution of melts components takes place along capillary after the cooling. Numerical simulation of concentration-induced convection has been carried out to explain these experimental data. Two-component melt of both liquid metals filling vertical thin capillary with non-uniform temperature distribution on the boundaries is considered. It is assumed that the condition of absolute non-wetting is valid on the sidewalls. Because of this effect there is a free surface on vertical boundaries, where thermocapillary force is appeared due to the external longitudinal temperature gradient. It makes to move liquid elements at a big distance, compared with axial size of capillary. Effects of adsorption-desorption on the surface, thermal and concentration-capillary forces, convective motion in a volume and diffusion generate the large-scale circulation. This process includes the admixture carrying-out on the surface in the more hot higher part of the channel, its following transfer down along the boundary due to the thermocapillary force and its return in the volume over the desorption in the lower part of capillary. Intensity of motion and processes of adsorption-desorption on the free boundary have the decisive influence upon the formation of concentration fields and speed of components redistribution. Thus, one of the possible mechanisms of longitudinal division on components of liquid binary mixtures in thin channels has been demonstrated.

  7. Numerical Simulations of Crystal Growth of an Alloy Under Microgravity Conditions

    NASA Technical Reports Server (NTRS)

    Simpson, James E.; deGroh, Henry C., III; Garimella, Suresh V.; Abbaschian, Reza

    1999-01-01

    The directional solidification of a dilute binary alloy (Bi-1.0 at.%Sn)is investigated. Results are obtained at a gravity level of I pg. Computations are performed in two dimensions with a fixed, non-uniform grid. The simulation involves a solution of the species concentration equation (modified to account for solute rejection at the interface) and energy equation (modified to account for phase-change) for both the solid and liquid phases, in addition to the constitutive equations for describing convective flow in the melt. The effects of conductive heat transfer in the ampoule and in a capillary tube in the sample are included. To gauge the effects of including this growth capillary tube in the apparatus, simulations both with and without the capillary tube are presented and compared. Fully transient simulations have been performed; no simplifying steady-state approximations are used, however, the influence of solute on the melting temperature at the interface is not included. Both thermal and solutal convective cells are seen to form. Convective velocities are significantly damped inside the capillary, causing less segregation due to convection. As solidification proceeds beyond the capillary tube, longitudinal segregation arises as a result of the change in cross-sectional area of solidifying material. The magnitudes of the velocities in this cell increase significantly once the solid/liquid front passes beyond the end of the capillary tube; this causes a corresponding increase in the level of radial solute segregation in the solidified material.

  8. Synergistic Use of Gold Nanoparticles (AuNPs) and “Capillary Enzyme-Linked Immunosorbent Assay (ELISA)” for High Sensitivity and Fast Assays

    PubMed Central

    Kim, Wan-Joong; Cho, Hyo Young; Jeong, Bongjin; Byun, Sangwon; Huh, JaeDoo; Kim, Young Jun

    2017-01-01

    Using gold nanoparticles (AuNPs) on “capillary enzyme-linked immunosorbent assay (ELISA)”, we produced highly sensitive and rapid assays, which are the major attributes for point-of-care applications. First, in order to understand the size effect of AuNPs, AuNPs of varying diameters (5 nm, 10 nm, 15 nm, 20 nm, 30 nm, and 50 nm) conjugated with Horseradish Peroxidase (HRP)-labeled anti-C reactive protein (antiCRP) (AuNP•antiCRP-HRP) were used for well-plate ELISA. AuNP of 10 nm produced the largest optical density, enabling detection of 0.1 ng/mL of CRP with only 30 s of incubation, in contrast to 10 ng/mL for the ELISA run in the absence of AuNP. Then, AuNP of 10 nm conjugated with antiCRP-HRP (AuNP•antiCRP-HRP) was used for “capillary ELISA” to detect as low as 0.1 ng/mL of CRP. Also, kinetic study on both 96-well plates and in a capillary tube using antiCRP-HRP or AuNP•antiCRP-HRP showed a synergistic effect between AuNP and the capillary system, in which the fastest assay was observed from the “AuNP capillary ELISA”, with its maximum absorbance reaching 2.5 min, while the slowest was the typical well-plate ELISA with its maximum absorbance reaching in 13.5 min. PMID:29278402

  9. Metrology and Transport of Multiply Charged Ions

    NASA Astrophysics Data System (ADS)

    Kulkarni, Dhruva

    The transport and interaction of singly- and multiply-charged ions with matter has been studied. The experiments were performed in an ultra-high vacuum environment. The low- and hyperthermal-energy ion beamline was used as a source of singly charged ions, while the CUEBIT facility was used as a source of multiply charged ions. The kinetic energy of the ion beam obtained from the CUEBIT is offset from the nominal value expected from the applied electrostatic potentials. These offsets were studied by measuring the kinetic energy of the beam using a retarding field analyzer (RFA). The offset was attributed to the space charge of the electron beam that is used to create the multiply charged ions. The charge density of the electron beam was varied by changing operational parameters of the electron beam, namely the electron beam current and the energy of the electron beam. Ion beams of Ar4+ and Ar8+ were extracted from the source and the offsets observed in the kinetic energy were related to the variation in the space charge potential of the electron beam. Measurements of these offsets, ranging from 100 eV/Q to 300 eV/Q, are significant and important for experiments that aim to utilize the potential energy of slow multiply charged ions. The transport of ions using capillaries has been studied to investigate the viability of ion-guiding as a means for a novel ion delivery mechanism. Results on transport through large bore capillaries (macrocapillaries) that probe both the geometric and ionguided mechanisms are presented. The angle- and position-dependent transport properties were found to depend on the material of the capillary (specifically, whether metal or insulator) and the geometry of the capillary. Rb+ ions at a kinetic energy of 1 keV were transmitted through metal and glass capillaries that were a few centimeters in length and a few millimeters in diameter. Oscillations were observed in the capillaries made of glass which were absent in the metal capillaries. Calculations based on the geometry of the experimental setup and kinematics of the ions showed that these oscillations could be attributed to the charge patches formed on the capillary walls. Electronic excitations in solids due to energetic ions at low kinetic energy were measured by using Schottky diodes. Hot electron currents measured at the backside of an Ag/n-Si Schottky diode due to ion bombardment on the frontside were found to depend on the kinetic energy (500 eV to 1500 eV) and angle of incidence (+/-30°) of the ion (Rb+) beam. A sharp upturn in the energy dependent yield is consistent with a kinetic emission model for electronic excitations utilizing the device Schottky barrier as determined from current-voltage characteristics. Backside currents measured for ion incident angle are strongly peaked about normal incidence. Accounting for the increased transport distance for excited charges at non-normal incidence, the mean free path for electrons in silver was found to be 5.2 +/- 1.4 nm, which is consistent with values reported in the literature.

  10. [Pharmacological study on hemostasis, analgesic and anti inflammation effects of the alcohol extract of Hibiscus tiliaceus].

    PubMed

    Qiu, Fen; Tian, Hui; Zhang, Zhi; Yuan, Xian-Ling; Tan, Yuan-Feng; Ning, Xiao-Qing

    2013-10-01

    To study the effects of hemostasis, analgesic and anti inflammation of the alcohol extract of Hibiscus tiliaceus and offer pharmacological and experimental basis for its safe and effective use in clinic. The effects of hemostasist were observed with tail breaking method, capillary tube method and slide method; Hot board and body distortion induced by acetic acid methods were applied in mice analgesia experiment, the mice model of acute auricle swelling induced by dmi ethylbenzene and capillary permeability induced by acetic acid were applied to observe the anti inflammatory effects. The alcohol extract of Hibiscus tiliaceus could significantly reduce the bleeding time and the clotting time, delay the plant reaction time and reduce the writhing times of the mice, and it also had effect on inhibiting swelling of mice ear and the permeability of the capillary. These results suggest that the alcohol extract of Hibiscus tiliaceus has the effects of hemostasis, analgesic and anti inflammation.

  11. S-Adenosylhomocysteine Assay in the Urine by Capillary Electrophoresis.

    PubMed

    Luzyanin, B P; Ivanov, A V; Viryus, E D; Kubatiev, A A

    2015-08-01

    We present a simple and effective method for measuring urine S-adenosylhomocysteine by capillary electrophoresis without using modifiers. The detection threshold of the method is 0.1 μM S-adenosylhomocysteine, the time of analysis 13 min, reproducibility at physiological concentrations within 4%.

  12. Effect of Foam on Liquid Phase Mobility in Porous Media

    NASA Astrophysics Data System (ADS)

    Eftekhari, A. A.; Farajzadeh, R.

    2017-03-01

    We investigate the validity of the assumption that foam in porous media reduces the mobility of gas phase only and does not impact the liquid-phase mobility. The foam is generated by simultaneous injection of nitrogen gas and a surfactant solution into sandstone cores and its strength is varied by changing surfactant type and concentration. We find, indeed, that the effect of foam on liquid-phase mobility is not pronounced and can be ignored. Our new experimental results and analyses resolve apparent discrepancies in the literature. Previously, some researchers erroneously applied relative permeability relationships measured at small to moderate capillary numbers to foam floods at large capillary number. Our results indicate that the water relative permeability in the absence of surfactant should be measured with the capillary pressure ranging up to values reached during the foam floods. This requires conducting a steady-state gas/water core flood with capillary numbers similar to that of foam floods or measuring the water relative-permeability curve using a centrifuge.

  13. On-demand control of microfluidic flow via capillary-tuned solenoid microvalve suction.

    PubMed

    Zhang, Qiang; Zhang, Peiran; Su, Yetian; Mou, Chunbo; Zhou, Teng; Yang, Menglong; Xu, Jian; Ma, Bo

    2014-12-21

    A simple, low-cost and on-demand microfluidic flow controlling platform was developed based on a unique capillary-tuned solenoid microvalve suction effect without any outer pressure source. The suction effect was innovatively employed as a stable and controllable driving force for the manipulation of the microfluidic system by connecting a piece of capillary between the microvalve and the microfluidic chip, which caused significant hydrodynamic resistance differences among the solenoid valve ports and changed the flowing mode inside the valve. The volume of sucked liquid could be controlled from microliters even down to picoliters either by decreasing the valve energized duration (from a maximum energized duration to the valve response time of 20 ms) or by increasing the inserted capillary length (i.e., its hydrodynamic resistance). Several important microfluidic unit operations such as cell/droplet sorting and on-demand size-controllable droplet generation have been demonstrated on the developed platform and both simulations and experiments confirmed that this platform has good controllability and stability.

  14. Viscous peeling with capillary suction

    NASA Astrophysics Data System (ADS)

    Peng, Gunnar; Lister, John

    2014-11-01

    If an elastic tape is stuck to a rigid substrate by a thin film of viscous fluid and then peeled off by pulling at a small angle to the horizontal, then both viscous and capillary forces affect the peeling speed (McEwan and Taylor, 1966). If there is no capillary meniscus (e.g. if the peeling is due to viscous fluid being injected under the tape), then the peeling speed is given by a Cox-Voinov-like law, and is an increasing function of the peeling angle. We show that, with a meniscus present, the effect of the capillary forces is to suck down the tape, reducing the effective peeling angle and hence the peeling speed. When surface tension dominates and the peeling speed tends to zero, the system transitions to a new state whose time-evolution can be described by a system of coupled ordinary differential equations. These asymptotic results are confirmed by numerical calculations. Similar results hold for the peeling-by-bending of elastic beams, with ``angle'' replaced by ``curvature'' (i.e. bending moment).

  15. Development of cost-effective plasmonic biosensor using partially embedded gold nanoparticles for detection of immunoglobulin proteins

    NASA Astrophysics Data System (ADS)

    Kumari, Sudha; Moirangthem, Rakesh S.

    2018-02-01

    This work illustrates a label-free sensing of biomolecules using a simple capillary sensor. Here, capillary biosensor was prepared by decorating inner walls of a glass capillary with gold nanoparticles that was employed to investigate the biomolecular interactions. As a demonstration, rabbit immunoglobulin G (IgG) and anti-rabbit IgG (anti-IgG) proteins were chosen as a model system to monitor the receptor-analyte interactions. A surface binding sensitivity of 409 pg mm-2 was able to achieve towards the detection of 10 nM concentration of anti-rabbit IgG. The presented plasmonic sensor provides multiple advantages over conventional LSPR sensor by lifting requirement of the flow cell, prolonged sample preparation, complicated measurement setup etc that may enable its usage in rapid diagnostic testing. We believed that our proposed plasmonic capillary sensor could represent a potential candidate for developing cost-effective, label-free and high sensitivity sensing device for detection of biological molecules at low concentration.

  16. Effect of Foam on Liquid Phase Mobility in Porous Media

    PubMed Central

    Eftekhari, A. A.; Farajzadeh, R.

    2017-01-01

    We investigate the validity of the assumption that foam in porous media reduces the mobility of gas phase only and does not impact the liquid-phase mobility. The foam is generated by simultaneous injection of nitrogen gas and a surfactant solution into sandstone cores and its strength is varied by changing surfactant type and concentration. We find, indeed, that the effect of foam on liquid-phase mobility is not pronounced and can be ignored. Our new experimental results and analyses resolve apparent discrepancies in the literature. Previously, some researchers erroneously applied relative permeability relationships measured at small to moderate capillary numbers to foam floods at large capillary number. Our results indicate that the water relative permeability in the absence of surfactant should be measured with the capillary pressure ranging up to values reached during the foam floods. This requires conducting a steady-state gas/water core flood with capillary numbers similar to that of foam floods or measuring the water relative-permeability curve using a centrifuge. PMID:28262795

  17. Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

    PubMed

    Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

    2016-02-01

    Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  18. Influence of Capillary Force and Buoyancy on CO2 Migration During CO2 Injection in a Sandstone Reservoir

    NASA Astrophysics Data System (ADS)

    Wu, H.; Pollyea, R.

    2017-12-01

    Carbon capture and sequestration (CCS) is one component of a broad carbon management portfolio designed to mitigate adverse effects of anthropogenic CO2 emissions. During CCS, capillary trapping is an important mechanism for CO2 isolation in the disposal reservoir, and, as a result, the distribution of capillary force is an important factor affecting CO2 migration. Moreover, the movement of CO2 being injected to the reservoir is also affected by buoyancy, which results from the density difference between CO2 and brine. In order to understand interactions between capillary force and buoyancy, we implement a parametric modeling experiment of CO2 injections in a sandstone reservoir for combinations of the van Genuchten capillary pressure model that bound the range of capillary pressure-saturation curves measured in laboratory experiments. We simulate ten years supercritical CO2 (scCO2) injections within a 2-D radially symmetric sandstone reservoir for five combinations of the van Genuchten model parameters λ and entry pressure (P0). Results are analyzed on the basis of a modified dimensionless ratio, ω, which is similar to the Bond number and defines the relationship between buoyancy pressure and capillary pressure. We show how parametric variability affects the relationship between buoyancy and capillary force, and thus controls CO2 plume geometry. These results indicate that when ω >1, then buoyancy governs the system and CO2 plume geometry is governed by upward flow. In contrast, when ω <1, then buoyancy is smaller than capillary force and lateral flow governs CO2 plume geometry. As a result, we show that the ω ratio is an easily implemented screening tool for qualitative assessment of reservoir performance.

  19. Combined contactless conductometric, photometric, and fluorimetric single point detector for capillary separation methods.

    PubMed

    Ryvolová, Markéta; Preisler, Jan; Foret, Frantisek; Hauser, Peter C; Krásenský, Pavel; Paull, Brett; Macka, Mirek

    2010-01-01

    This work for the first time combines three on-capillary detection methods, namely, capacitively coupled contactless conductometric (C(4)D), photometric (PD), and fluorimetric (FD), in a single (identical) point of detection cell, allowing concurrent measurements at a single point of detection for use in capillary electrophoresis, capillary electrochromatography, and capillary/nanoliquid chromatography. The novel design is based on a standard 6.3 mm i.d. fiber-optic SMA adapter with a drilled opening for the separation capillary to go through, to which two concentrically positioned C(4)D detection electrodes with a detection gap of 7 mm were added on each side acting simultaneously as capillary guides. The optical fibers in the SMA adapter were used for the photometric signal (absorbance), and another optical fiber at a 45 degrees angle to the capillary was applied to collect the emitted light for FD. Light emitting diodes (255 and 470 nm) were used as light sources for the PD and FD detection modes. LOD values were determined under flow-injection conditions to exclude any stacking effects: For the 470 nm LED limits of detection (LODs) for FD and PD were for fluorescein (1 x 10(-8) mol/L) and tartrazine (6 x 10(-6) mol/L), respectively, and the LOD for the C(4)D was for magnesium chloride (5 x 10(-7) mol/L). The advantage of the three different detection signals in a single point is demonstrated in capillary electrophoresis using model mixtures and samples including a mixture of fluorescent and nonfluorescent dyes and common ions, underivatized amino acids, and a fluorescently labeled digest of bovine serum albumin.

  20. The combination of electrospray and flow focusing

    NASA Astrophysics Data System (ADS)

    Gañán-Calvo, Alfonso M.; López-Herrera, José M.; Riesco-Chueca, Pascual

    2006-11-01

    An ultra-fine liquid atomization procedure combining the advantages of electrospray and flow focusing is presented. Both techniques are known to produce strikingly small and steady liquid micro-jets issuing from menisci held by capillary forces. Such menisci take the form of a cusp-like drop attached to the feeding tube (flow focusing: FF) or a Taylor cone (electrospray: ES). The issuing micro-jets are forced or ‘sucked’ from the parent meniscus either by pressure or electrohydrodynamic forces. Subsequent capillary breakup of the jet leads to fine sprays of remarkable quality. Here we describe the joint effect of pressurization and electrification in a flow focusing device, and the subsequent coupling of both ES and FF phenomena. For any given liquid and flow rate, the combined procedure gives rise to significantly smaller droplet sizes than observed in any of the source techniques. The co-flowing gas stream removes space charges; in addition, the perforated plate facing the feed tube provides an electric barrier, shielding the jet-meniscus or ‘production’ area from the spray or ‘product’ area. As a result, space charges and electrified droplets are removed from the production area, thus avoiding the ambient electric saturation which becomes a limiting factor in ES-spraying: a significantly enhanced spraying stability ensues, with a much wider operation range than FF or ES. Other unexpected outcomes from the combination are also shown. A theoretical model is developed to predict the emitted droplet size: a first integral of the momentum equation yielding a generalized Bernoulli equation, and an explicit approximation for the jet diameter and droplet size, accurate within a broad parametrical band.

  1. Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain.

    PubMed

    Burkhart, Annette; Andresen, Thomas Lars; Aigner, Achim; Thomsen, Louiza Bohn; Moos, Torben

    2017-07-01

    Treatment of chronic disorders affecting the central nervous system (CNS) is complicated by the inability of drugs to cross the blood-brain barrier (BBB). Non-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion further into the brain. The present study aims to investigate the possibility of transfecting primary rat brain endothelial cells (RBECs) for recombinant protein synthesis and secretion of the neuroprotective protein erythropoietin (EPO). We previously showed that 4% of RBECs with BBB properties can be transfected without disrupting the BBB integrity in vitro, but it can be questioned whether this is sufficient to enable protein secretion at therapeutic levels. The present study examined various transfection vectors, with regard to increasing the transfection efficiency without disrupting the BBB integrity. Lipofectamine 3000™ was the most potent vector compared to polyethylenimine (PEI) and Turbofect. When co-cultured with astrocytes, the genetically modified RBECs secreted recombinant EPO into the cell culture medium both luminally and abluminally, and despite lower levels of EPO reaching the abluminal chamber, the amount of recombinant EPO was sufficient to evolve a biological effect on astrocytes cultured at the abluminal side in terms of upregulated gene expression of brain-derived neurotropic factor (BDNF). In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB.

  2. Binding of anti-basement membrane antibody to alveolar basement membrane after intratracheal gasoline instillation in rabbits.

    PubMed Central

    Yamamoto, T.; Wilson, C. B.

    1987-01-01

    A possible causal relationship has been suggested between hydrocarbon (gasoline, solvents, etc.) exposure and development of anti-basement membrane antibody-associated Goodpasture's syndrome in man. The authors evaluated the effect of hydrocarbons on pulmonary capillary permeability and binding of heterologous anti-basement membrane antibodies in the lungs after intratracheal instillation of minute amounts of unleaded gasoline into rabbits. The anti-glomerular basement membrane (GBM) antibodies used reacted with the alveolar basement membrane (ABM) in vitro by indirect immunofluorescence. The gasoline treatment altered pulmonary capillary permeability, judging from the increased accumulation of systemically administered radioiodinated bovine serum albumin in the alveolar and extravascular spaces of lungs; it also induced focal macroscopic and microscopic pulmonary histologic lesions. The gasoline caused focal in vivo binding of the anti-GBM antibodies to the ABM detectable by immunofluorescence microscopy. No binding was observed in lungs from control rabbits given saline instillations when assayed by immunofluorescence. The paired label radioisotope technique confirmed the increased antibody binding to lungs injured with gasoline (1.08 +/- 0.03 micrograms) versus 0.37 +/- 0.07 microgram after saline (P less than 0.001). These results indicate that gasoline exposure damages a pulmonary barrier that normally prevents binding of anti-GBM/ABM antibody to ABM and suggest that hydrocarbon exposure may be one of perhaps several pneumotoxic events that contribute to the episodic pulmonary hemorrhage in Goodpasture's syndrome by temporarily allowing ABM binding of anti-basement membrane antibodies. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3548409

  3. Migration And Entrapment Of Mercury In The Subsurface

    NASA Astrophysics Data System (ADS)

    M, D.; Nambi, I. M.

    2009-12-01

    Elemental mercury is an immiscible liquid with high density and high surface tension. The movement of mercury in the saturated subsurface region is therefore considered a case of two phase flow involving mercury and water and is expected to be governed by gravity, viscous and capillary forces. Fundamental investigation into the migration and capillary entrapment of mercury in the subsurface was done by controlled laboratory capillary pressure saturation experiments using mercury and water as non wetting and wetting fluid respectively. Residual mercury saturation and van Genuchten’s capillary entrapment parameters were determined independently for different sizes of porous media. Based on the experimental data, theoretical investigations were done on the role of the three predominant forces and their influence on mercury migration and entrapment. The effects of fluid density and interfacial tension and the influence of Capillary and Bond number on mercury entrapment were analyzed with the help of similar capillary pressure - saturation experiments using Tetrachloroethylene (PCE)-water fluid pair. Mercury-water systems exhibited a low residual saturation of 0.02 and 0.07 as compared to 0.16 and 0.27 for PCE-water systems. Less residual mercury saturation, lack of apparent hysteresis in capillary pressure saturation curves and large variation in van Genuchten’s parameters 'α'(inverse of displacement pressure) and ‘n’ (pore size distribution index) for mercury-water systems compared to PCE-water systems were observed. These anomalies between the two systems elucidate that the capillary trapping is equally dependent on the fluid characteristics especially for high density immiscible fluids. Gravity force nevertheless a predominant controlling factor in the migration of highly dense mercury, is counteracted by not less trivial capillary force which was 1.22x104 times higher than gravity force. The capillary forces thus surmount the gravity forces and cause entrapment of mercury in the soil pores even in homogeneous porous medium system. Bond number (Bond number relates gravity and capillary forces) for mercury-water system was found to 2.5 times higher than PCE-water systems. Large density differences between mercury and water lead to high Bond number and thus less residual saturation. Capillary number (Capillary number relates viscous and capillary forces) was found to be less for mercury-water systems. Literature review unveils that low Capillary number does not influence non wetting residual saturation. But for high density mercury with natural infiltration, even low Capillary number influences residual saturation. With the alarming increase in number of mercury spill sites, results of this study showed a better understanding of the capillary entrapment phenomena and the extent of influence of each predominant force during displacement of highly dense mercury. The fundamental inputs to NAPL entrapment models were generated in this study for mercury for the first time. This data will be used to assess the distribution of mercury in contaminated sites and design suitable remedial alternatives.

  4. Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

    PubMed

    Aragon, Mario J; Topper, Lauren; Tyler, Christina R; Sanchez, Bethany; Zychowski, Katherine; Young, Tamara; Herbert, Guy; Hall, Pamela; Erdely, Aaron; Eye, Tracy; Bishop, Lindsey; Saunders, Samantha A; Muldoon, Pretal P; Ottens, Andrew K; Campen, Matthew J

    2017-03-07

    Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

  5. Carrier-Mediated Transport of Nicotine Across the Inner Blood-Retinal Barrier: Involvement of a Novel Organic Cation Transporter Driven by an Outward H(+) Gradient.

    PubMed

    Tega, Yuma; Kubo, Yoshiyuki; Yuzurihara, Chihiro; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

    2015-09-01

    The present study was carried out to investigate the blood-to-retina transport of nicotine across the inner blood-retinal barrier (BRB). Using the in vivo vascular injection method, the blood-to-retina influx clearance of nicotine across the BRB was determined as 131 μL/(min?g retina), which is much higher than that of a nonpermeable paracellular marker, and blood-to-retina transport of nicotine was inhibited by organic cations such as pyrilamine and verapamil. The nicotine uptake by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro model of the inner BRB, exhibited time, temperature, and concentration dependence with a Km of 492 μM. These results suggest the involvement of a carrier-mediated transport process in nicotine transport in the inner BRB. The nicotine uptake by TR-iBRB2 cells was stimulated by an outwardly directed H(+) gradient, and the uptake was significantly inhibited by bulky and hydrophobic cationic drugs, whereas inhibitors of organic cation transporters did not show inhibitory effect. These results suggest that the novel organic cation transport system driven by an outwardly directed H(+) gradient is involved in the blood-to-retina transport of nicotine across the inner BRB. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. SEPARATION OF OCTYLPHENOL POLYETHER ALCOHOLS SURFACTANTS BY CAPILLARY COLUMN AND HPLC

    EPA Science Inventory

    Separation of nonionic octylphenol polyether alcohols (OPA) by supercritical fluid chromatography (SFC) and HPLC is described. sing a density programming and a 50-pm i.d. capillary column, a total of 18 group oligomers was separated. he effects of the operating parameters, such a...

  7. Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model.

    PubMed

    Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

    2018-05-01

    Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo , suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction.

  8. Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model

    PubMed Central

    Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

    2018-01-01

    Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo, suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction. PMID:29760995

  9. Rapid bio-patterning method based on the fabrication of PEG microstructures and layer-by-layer polymeric thin film

    NASA Astrophysics Data System (ADS)

    Shim, Hyun-Woo; Lee, Ji-Hye; Choi, Chang-Hyoung; Song, Hwan-Moon; Kim, Bo-Yeol; Kim, Dong-Pyo; Lee, Chang-Soo

    2007-12-01

    The patterning of biomolecules in well-defined microstructures is critical issue for the development of biosensors and biochips. However, the fabrication of microstructures with well-ordered and spatially discrete forms to provide the patterned surface for the immobilization of biomolecules is difficult because of the lack of distinct physical and chemical barriers separating patterns. This study present rapid biomolecule patterning using micromolding in capillaries (MIMIC), soft-lithographic fabrication of PEG microstructures for prevention of nonspecific binding as a biological barrier, and self assembled polymeric thin film for efficient immobilization of proteins or cells. For the proof of concept, protein (FITC-BSA), bacteria (E.coli BL21-pET23b-GFP) were used for biomolecules patterning on polyelectrolyte coated surface within PEG microstructures. The novel approach of MIMIC combined with LbL coating provides a general platform for patterning a broad range of materials because it can be easily applied to various substrates such as glass, silicon, silicon dioxide, and polymers.

  10. Study of the therapeutic benefit of cationic copolymer administration to vascular endothelium under mechanical stress

    PubMed Central

    Giantsos-Adams, Kristina; Lopez-Quintero, Veronica; Kopeckova, Pavla; Kopecek, Jindrich; Tarbell, John M.; Dull, Randal

    2015-01-01

    Pulmonary edema and the associated increases in vascular permeability continue to represent a significant clinical problem in the intensive care setting, with no current treatment modality other than supportive care and mechanical ventilation. Therapeutic compound(s) capable of attenuating changes in vascular barrier function would represent a significant advance in critical care medicine. We have previously reported the development of HPMA-based copolymers, targeted to endothelial glycocalyx that are able to enhance barrier function. In this work, we report the refinement of copolymer design and extend our physiological studies todemonstrate that the polymers: 1) reduce both shear stress and pressure-mediated increase in hydraulic conductivity, 2) reduce nitric oxide production in response to elevated hydrostatic pressure and, 3) reduce the capillary filtration coefficient (Kfc) in an isolated perfused mouse lung model. These copolymers represent an important tool for use in mechanotransduction research and a novel strategy for developing clinically useful copolymers for the treatment of vascular permeability. PMID:20932573

  11. Atomic oxygen production scaling in a nanosecond-pulsed externally grounded dielectric barrier plasma jet

    NASA Astrophysics Data System (ADS)

    Sands, Brian; Schmidt, Jacob; Ganguly, Biswa; Scofield, James

    2014-10-01

    Atomic oxygen production is studied in a capillary dielectric barrier plasma jet that is externally grounded and driven with a 20-ns risetime positive unipolar pulsed voltage at pulse repetition rates up to 25 kHz. The power coupled to the discharge can be easily increased by increasing the pulse repetition rate. At a critical turnover frequency, determined by the net energy density coupled to the discharge, the plasma chemistry abruptly changes. This is indicated by increased plasma conductance and a transition in reactive oxygen species production from an ozone-dominated production regime below the turnover frequency to atomic-oxygen-dominated production at higher pulse rates. Here, we characterize atomic oxygen production scaling using spatially- and temporally-resolved two-photon absorption laser-induced-fluorescence (TALIF). Quantitative results are obtained via calibration with xenon using a similar laser excitation and collection system. These results are compared with quantitative ozone and discharge power measurements using a helium gas flow with oxygen admixtures up to 3%.

  12. Plastic roles of pericytes in the blood-retinal barrier.

    PubMed

    Park, Do Young; Lee, Junyeop; Kim, Jaeryung; Kim, Kangsan; Hong, Seonpyo; Han, Sangyeul; Kubota, Yoshiaki; Augustin, Hellmut G; Ding, Lei; Kim, Jin Woo; Kim, Hail; He, Yulong; Adams, Ralf H; Koh, Gou Young

    2017-05-16

    The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption. However, PDGF-B/PDGFRβ signalling is expendable for maintaining BRB integrity in adult mice. Although selective pericyte loss in stable adult retinal vessels surprisingly does not cause BRB disintegration, it sensitizes retinal vascular endothelial cells (ECs) to VEGF-A, leading to upregulation of angiopoietin-2 (Ang2) in ECs through FOXO1 activation and triggering a positive feedback that resembles the pathogenesis of DR. Accordingly, either blocking Ang2 or activating Tie2 greatly attenuates BRB breakdown, suggesting potential therapeutic approaches to reduce retinal damages upon DR progression.

  13. Image Quality Improvement in Adaptive Optics Scanning Laser Ophthalmoscopy Assisted Capillary Visualization Using B-spline-based Elastic Image Registration

    PubMed Central

    Uji, Akihito; Ooto, Sotaro; Hangai, Masanori; Arichika, Shigeta; Yoshimura, Nagahisa

    2013-01-01

    Purpose To investigate the effect of B-spline-based elastic image registration on adaptive optics scanning laser ophthalmoscopy (AO-SLO)-assisted capillary visualization. Methods AO-SLO videos were acquired from parafoveal areas in the eyes of healthy subjects and patients with various diseases. After nonlinear image registration, the image quality of capillary images constructed from AO-SLO videos using motion contrast enhancement was compared before and after B-spline-based elastic (nonlinear) image registration performed using ImageJ. For objective comparison of image quality, contrast-to-noise ratios (CNRS) for vessel images were calculated. For subjective comparison, experienced ophthalmologists ranked images on a 5-point scale. Results All AO-SLO videos were successfully stabilized by elastic image registration. CNR was significantly higher in capillary images stabilized by elastic image registration than in those stabilized without registration. The average ratio of CNR in images with elastic image registration to CNR in images without elastic image registration was 2.10 ± 1.73, with no significant difference in the ratio between patients and healthy subjects. Improvement of image quality was also supported by expert comparison. Conclusions Use of B-spline-based elastic image registration in AO-SLO-assisted capillary visualization was effective for enhancing image quality both objectively and subjectively. PMID:24265796

  14. Interfacing Capillary-Based Separations to Mass Spectrometry Using Desorption Electrospray Ionization

    PubMed Central

    Barbula, Griffin K.; Safi, Samir; Chingin, Konstantin; Perry, Richard H.; Zare, Richard N.

    2014-01-01

    The powerful hybrid analysis method of capillary-based separations followed by mass spectrometric analysis gives substantial chemical identity and structural information. It is usually carried out using electrospray ionization. However, the salts and detergents used in the mobile phase for electrokinetic separations suppress ionization efficiencies and contaminate the inlet of the mass spectrometer. This report describes a new method that uses desorption electrospray ionization (DESI) to overcome these limitations. Effluent from capillary columns is deposited on a rotating Teflon disk that is covered with paper. As the surface rotates, the temporal separation of the eluting analytes (i.e., the electropherogram) is spatially encoded on the surface. Then, using DESI, surface-deposited analytes are preferentially ionized, reducing the effects of ion suppression and inlet contamination on signal. With the use of this novel approach, two capillary-based separations were performed: a mixture of the rhodamine dyes at milligram/milliliter levels in a 10 mM sodium borate solution was separated by capillary electrophoresis, and a mixture of three cardiac drugs at milligram/milliliter levels in a 12.5 mM sodium borate and 12.5 mM sodium dodecyl sulfate solution was separated by micellar electrokinetic chromatography. In both experiments, the negative effects of detergents and salts on the MS analyses were minimized. PMID:21319740

  15. Self-separation of blood plasma from whole blood during the capillary flow in microchannel

    NASA Astrophysics Data System (ADS)

    Nunna, Bharath Babu; Zhuang, Shiqiang; Lee, Eon Soo

    2017-11-01

    Self-separation of blood plasma from whole blood in microchannels is of great importance due to the enormous range of applications in healthcare and diagnostics. Blood is a multiphase complex fluid, composed of cells suspended in blood plasma. RBCs are the suspended particles whose shape changes during the flow of blood. The primary constituents of blood are erythrocytes or red blood cells (RBCs), leukocytes or white blood cells (WBCs), thrombocytes or platelets and blood plasma. The existence of RBCs in blood makes the blood a non-Newtonian fluid. The current study of separation of blood plasma from whole blood during self-driven flows in a single microchannel without bifurcation, by enhancing the capillary effects. The change in the capillary effect results in a change in contact angle which directly influences the capillary flow. The flow velocity directly influences the net force acting on the RBCs and influence the separation process. The experiments are performed on the PDMS microchannels with different contact angles by altering the surface characteristics using plasma treatment. The change in the separation length is studied during the capillary flow of blood in microchannel. Bharath Babu Nunna is a researcher in mechanical engineering and implementing the novel and innovative technologies in the biomedical devices to enhance the sensitivity of the disease diagnosis.

  16. The relative influence of hematocrit and red blood cell velocity on oxygen transport from capillaries to tissue

    PubMed Central

    Lücker, Adrien; Secomb, Timothy W.; Weber, Bruno; Jenny, Patrick

    2016-01-01

    Objective Oxygen transport to parenchymal cells occurs mainly at the microvascular level, and depends on convective red blood cell (RBC) flux, which is proportional in an individual capillary to the product of capillary hematocrit and red blood cell velocity. This study investigates the relative influence of these two factors on tissue oxygen partial pressure (Po2). Methods A simple analytical model is used to quantify the respective influences of hematocrit, RBC velocity and flow on tissue oxygenation around capillaries. Predicted tissue Po2 levels are compared with a detailed computational model. Results Hematocrit is shown to have a larger influence on tissue Po2 than RBC velocity. The effect of RBC velocity increases with distance from the arterioles. Good agreement between analytical and numerical results is obtained and the discrepancies are explained. Significant dependence of mass transfer coefficients on RBC velocity at low hematocrit is demonstrated. Conclusions For a given RBC flux in a capillary, the Po2 in the surrounding tissue increases with increasing hematocrit, as a consequence of decreasing intravascular resistance to diffusive oxygen transport from RBCs to tissue. These results contribute to understanding the effects of blood flow changes on oxygen transport, such as occur in functional hyperemia in the brain. PMID:27893186

  17. The CE-Way of Thinking: "All Is Relative!".

    PubMed

    Schmitt-Kopplin, Philippe; Fekete, Agnes

    2016-01-01

    Over the last two decades the development of capillary electrophoresis instruments lead to systems with programmable sampler, separation column, separation buffer, and detection devices comparable visually in many aspects to the setup of classical chromatography.Two processes make capillary electrophoresis essentially different from chromatography and are the basis of the CE-way of thinking, namely, the injection type and the liquid flow within the capillary. (1) When the injection is made hydrodynamically (such as in most of the found applications in the literature), the injected volumes are directly dependent on the type and size of the separation capillary. (2) The buffer velocity is not pressure driven as in liquid chromatography but electrokinetically governed by the quality of the capillary surface (separation buffer dependant surface charge) inducing an electroosmotic flow (EOF). The EOF undergoes small variations and is not necessarily identical from one separation or day to the other. The direct consequence is an apparent nonreproducible migration time of the analytes, even though the own velocity of the ions is the same.The effective mobility (field strength normalized velocity) of the ions is a possible parameterization from acquired timescale to effective mobility-scale electropherograms leading to a reproducible visualization and better quantification with a direct relation to structural characters of the analytes (i.e., charge and size-see chapter on semiempirical modelization).

  18. Drag reducing properties of microalgal exopolymers.

    PubMed

    Ramus, J; Kenney, B E; Shaughnessy, E J

    1989-01-25

    Dilute aqueous solutions of polymers released by marine phytoplankton (microalgae) were shown to effectively reduce drag in capillary pipe flow. Tests were performed in a capillary turbulent flow viscometer which extruded small samples under high pressures. In all, 22 species were screened, and the products of one chlorophyte and four rhodophyte species proved especially effective. The viscoelastic polymers produced by these species delayed the transition from laminar to turbulent flow to significantly higher Re. In general, polymeric regime segments come off the maximum drag reduction asymptote at characteristic retro-onset points, and come to lie approximately parallel to, but displaced upwards from the Prandtl-von Karman line. The delay to transition was shown to be dependent on additive polymer concentration, capillary diameter, and temperature. Ionic concentration, ionic composition, or pH had little effect on drag reducing properties.

  19. Simultaneous determination of rifabutin and human serum albumin in pharmaceutical formulations by capillary electrophoresis.

    PubMed

    Ermolenko, Yu; Anshakova, A; Osipova, N; Kamentsev, M; Maksimenko, O; Balabanyan, V; Gelperina, S

    Capillary zone electrophoresis (CZE) was used for determination of rifabutin (RFB), an anti-tuberculosis antibiotic drug, in various pharmaceutical formulations. Apart from that, simultaneous determination of RFB and human serum albumin (HSA) was performed. Electrophoretic behaviour of RFB was examined at various pH levels. CE conditions: a quartz capillary tube (internal diameter 75mm, effective length 50cm, total length 60cm), the capillary temperature was 25°С, the voltage applied to the capillary tube was +20kV, the UV detection wavelength was 214nm, hydrodynamic injection of the sample was performed at 30mbar for 5s, tetraborate buffer solution (0.01М, рН9.2). The obtained results are characterized by high efficiency (number of theoretical plates up to 260,000) and sufficient sensitivity (LOQ starting from 0.02μg/ml for RFB). The obtained data are in good accord with both HPLC results (for RFB) and spectrophotometry (for HSA). Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A neuron-in-capillary platform for facile collection and mass spectrometric characterization of a secreted neuropeptide

    PubMed Central

    Lee, Chang Young; Fan, Yi; Rubakhin, Stanislav S.; Yoon, Sook; Sweedler, Jonathan V.

    2016-01-01

    The integration of microfluidic devices—which efficiently handle small liquid volumes—with separations/mass spectrometry (MS) is an effective approach for profiling the neurochemistry occurring in selected neurons. Interfacing the microfluidic cell culture to the mass spectrometer is challenging because of geometric and scaling issues. Here we demonstrate the hyphenation of a neuron-in-capillary platform to a solid phase extraction device and off-line MS. A primary neuronal culture of Aplysia californica neurons was established directly inside a cylindrical polyimide capillary. The approach also uses a particle-embedded monolith to condition neuropeptide releasates collected from several Aplysia neurons cultured in the capillary, with the subsequent characterization of released peptides via MS. This system presents a number of advances compared to more traditional microfluidic devices fabricated with polydimethylsiloxane. These include low cost, easy access to cell culture, rigidity, ease of transport, and minimal fluid handling. The cylindrical geometry of the platform allows convenient interface with a wide range of analytical tools that utilize capillary columns. PMID:27245782

  1. Occlusion and rupture of ex vivo capillary bifurcation due to acoustic droplet vaporization

    NASA Astrophysics Data System (ADS)

    Feng, Yi; Qin, Dui; Zhang, Jun; Zhang, Lei; Bouakaz, Ayache; Wan, Mingxi

    2018-06-01

    Gas embolotherapy (GE) consists in the occlusion of tumor blood vessels using gas emboli induced by acoustic droplet vaporization (ADV), to create tumor starvation and localized drug delivery. Therefore, the occlusion and rupture of capillary bifurcation due to ADV was investigated in an ex vivo rat mesentery model using a confocal acousto-optical high-speed microscope system. Following ADV bubble formation, coalescence, and translational movement, the growing bubbles lodged in and then occluded two different capillary bifurcations. Capillary rupture was induced at the bubble lodging area, immediately followed by gas extravasation and bubble dislodging. Before and after bubble lodgment/occlusion, a local microvessel invagination was observed due to the interactions between ADV bubbles and the microvessel itself, indicating a contribution to the capillary rupture. Understanding the transient dynamics of ADV bubble, the bubble-microvessel interaction and the consequent mechanical bio-effects in GE is of the paramount importance for developing and applying this approach in clinical practice.

  2. Microfluidic devices connected to fused-silica capillaries with minimal dead volume.

    PubMed

    Bings, N H; Wang, C; Skinner, C D; Colyer, C L; Thibault, P; Harrison, D J

    1999-08-01

    Fused-silica capillaries have been connected to microfluidic devices for capillary electrophoresis by drilling into the edge of the device using 200-μm tungsten carbide drills. The standard pointed drill bits create a hole with a conical-shaped bottom that leads to a geometric dead volume of 0.7 nL at the junction, and significant band broadening when used with 0.2-nL sample plugs. The plate numbers obtained on the fused-silica capillary connected to the chip were about 16-25% of the predicted numbers. The conical area was removed with a flat-tipped drill bit and the band broadening was substantially eliminated (on average 98% of the predicted plate numbers were observed). All measurements were made while the device was operating with an electrospray from the end of the capillary. The effective dead volume of the flat-bottom connection is minimal and allows microfluidic devices to be connected to a wide variety of external detectors.

  3. Drag reducing polymers improve coronary flow reserve through modulation of capillary resistance.

    PubMed

    Pacella, John J; Kameneva, Marina V; Villanueva, Flordeliza S

    2009-01-01

    We have shown that drag-reducing polymers (DRP) reduce microvascular resistance and improve myocardial perfusion during coronary stenosis. We used myocardial contrast echocardiography (MCE) and mathematical modeling to define the DRP microvascular effects. A non-flow-limiting left anterior descending (LAD) stenosis was created in 8 dogs. Intramyocardial blood volume, RBC velocity and flow in the LAD and circumflex (CX) beds were obtained from MCE at baseline, and in hyperemia, stenosis, hyperemia + stenosis, and hyperemia + stenosis + DRP. Microvascular resistances were calculated from a lumped-parameter model. During stenosis + hyperemia, LAD bed microvascular resistance increased (p<0.015), and capillary volume (p<0.002) and red cell velocity (p<0.0004) decreased relative to baseline. With DRP, during stenosis and hyperemia, LAD bed microvascular resistance decreased (p<0.04); there was an increase in capillary volume (p<0.007), RBC velocity (p<0.006), and flow (p<0.05). Decreased model-computed capillary resistance accounted for the reduction in LAD bed resistance after DRP. We conclude that DRP improve flow reserve during coronary stenosis by modulating capillary resistance. Primary modification of the rheological properties of blood to affect capillary resistance is a novel approach for the treatment of acute coronary syndromes.

  4. Powerless tunable photonic crystal with bistable color and millisecond switching.

    PubMed

    Chan, Chia-Tsung; Yeh, J Andrew

    2011-07-04

    This study demonstrated a tunable photonic crystal (PhC) with 70 nm-wide spectral tuning (535 nm to 605 nm) and 3 ms of response time. The tunable PhC is based on reciprocal capillary action of liquid in the nanoscale PhC voids. By wetting the porous silicon PhC with ethanol and water, the PhC can be bistably switched respectively between liquid-filled state (orange color) and vapor-filled state (yellow color). Owing to the energy barrier between the two wetting states, the tunable PhC can remain at either of the two states with no external power consumption.

  5. Ultrastructural pathology of cortical capillary pericytes in human traumatic brain oedema.

    PubMed

    Castejón, Orlando J

    2011-01-01

    In human traumatic brain oedema pericytes exhibit remarkable oedematous changes, increased vacuolar and vesicular transport, transient transpericytal channels, and tubular structures demonstrating pericyte brain barrier dysfunction. They show nuclear invaginations, actin and myosin-like filaments, and coupled interaction with endothelial cells through the macula occludens. Some pericytes display hypertrophic and necrotic changes, and phagocytic capacity. Hypertrophic pericytes induce basement membrane splitting. Degenerated pericytes exhibit lacunar enlargement of endoplasmic reticulum, dense osmiophilic bodies, glycogen granules, vacuolization, oedematous Golgi apparatus, and pleomorphic mitochondria. Certain micropinocytotic vesicles are orientated to the Golgi complex and multivesicular bodies, suggesting that pericytes play some role in oedema resolution.

  6. In Situ Measurement of Permeability in the Vicinity of Faulted Nonwelded Bishop Tuff, Bishop, CA

    NASA Astrophysics Data System (ADS)

    Dinwiddie, C. L.; Fedors, R. W.; Ferrill, D. A.; Bradbury, K. K.

    2002-12-01

    The nonwelded Bishop Tuff includes matrix-supported massive ignimbrites and clast-supported bedded deposits. Fluid flow through such faulted nonwelded tuff is likely to be influenced by a combination of host rock properties and the presence of deformation features, such as open fractures, mineralized fractures, and fault zones that exhibit comminuted fault rock and clays. Lithologic contacts between fine- and coarse-grained sub-units of nonwelded tuff may induce formation of capillary and/or permeability barriers within the unsaturated zone, potentially leading to down-dip lateral diversion of otherwise vertically flowing fluid. However, discontinuities (e.g., fractures and faults) may lead to preferential sub-vertical fast flow paths in the event of episodic infiltration rates, thus disrupting the potential for both (1) large-scale capillary and/or permeability barriers to form and for (2) redirection of water flow over great lateral distances. This study focuses on an innovative technique for measuring changes in matrix permeability near faults in situ--changes that may lead to enhancement of vertical fluid flow and disruption of lateral fluid flow. A small-drillhole minipermeameter probe provides a means to eliminate extraction of fragile nonwelded tuffs as a necessity for permeability measurement. Advantages of this approach include (1) a reduction of weathering-effects on measured permeability, and (2) provision of a superior sealing mechanism around the gas injection zone. In order to evaluate the effect of faults and fault zone deformation on nonwelded tuff matrix permeability, as well as to address the potential for disruption of lithologic barrier-induced lateral diversion of flow, data were collected from two fault systems and from unfaulted host rock. Two hundred and sixty-seven gas-permeability measurements were made at 89 locations; i.e. permeability measurements were made in triplicate at each location with three flow rates. Data were collected at the first fault and perpendicularly away from it within the hanging wall to a distance of 6 m [20 ft] along one transect, and perpendicular to the fault from the foot wall to the hanging wall for a distance of 6 m [20 ft] along a second transect. Additionally, eight water-permeameter tests were conducted in order to augment the gas-permeability data. Gas-permeability measurements were collected along two transects at the main fault of the second fault system and perpendicularly away from it within the foot wall to a distance of 10.5 m [34 ft], crossing several secondary faults in the process. Data were also collected within the fault gouge of the main fault, and were found to vary therein by an order of magnitude. This Bishop Tuff study supports the U.S. Nuclear Regulatory Commission (NRC) review of hydrologic property studies at Yucca Mountain, Nevada, which are conducted by the U.S. Department of Energy. This abstract is an independent product of the CNWRA and does not necessarily reflect the views or regulatory position of the NRC.

  7. Numerical investigations of two-phase flow with dynamic capillary pressure in porous media via a moving mesh method

    NASA Astrophysics Data System (ADS)

    Zhang, Hong; Zegeling, Paul Andries

    2017-09-01

    Motivated by observations of saturation overshoot, this paper investigates numerical modeling of two-phase flow in porous media incorporating dynamic capillary pressure. The effects of the dynamic capillary coefficient, the infiltrating flux rate and the initial and boundary values are systematically studied using a traveling wave ansatz and efficient numerical methods. The traveling wave solutions may exhibit monotonic, non-monotonic or plateau-shaped behavior. Special attention is paid to the non-monotonic profiles. The traveling wave results are confirmed by numerically solving the partial differential equation using an accurate adaptive moving mesh solver. Comparisons between the computed solutions using the Brooks-Corey model and the laboratory measurements of saturation overshoot verify the effectiveness of our approach.

  8. Microgravity Effects on Transendothelial Transport

    NASA Technical Reports Server (NTRS)

    Tarbell, John M.

    1996-01-01

    The Endothelial Cell (EC) layer which lines blood vessels from the aorta to the capillaries provides the principal barrier to transport of water and solutes between blood and underlying tissue. Endothelial cells are continuously exposed to the mechanical shearing force (shear stress) and normal force (pressure) imposed by flowing blood on their surface, and they are adapted to this mechanical environment. When the cardiovascular system is exposed to microgravity, the mechanical environmental of endothelial cells is perturbed drastically and the transport properties of EC layers are altered in response. We have shown recently that step changes in shear stress have an acute effect on transport properties of EC layers in a cell culture model, and several recent studies in different vessels of live animals have confirmed the shear-dependent transport properties of the endothelium. We hypothesize that alterations in mechanical forces induced by microgravity and their resultant influence on transendothelial transport of water and solutes are, in large measure, responsible for the characteristic cephalad fluid shift observed in humans experiencing microgravity. To study the effects of altered mechanical forces on transendothelial transport and to test pharmacologic agents as counter measures to microgravity induced fluid shifts we have proposed ground-based studies using well defined cell culture models.

  9. Investigation of the role of the micro-porous layer in polymer electrolyte fuel cells with hydrogen deuterium contrast neutron radiography.

    PubMed

    Cho, Kyu Taek; Mench, Matthew M

    2012-03-28

    In this study, the high resolution hydrogen-deuterium contrast radiography method was applied to elucidate the impact of the micro-porous layer (MPL) on water distribution in the porous fuel cell media. At the steady state, deuterium replaced hydrogen in the anode stream, and the large difference in neutron attenuation of the D(2)O produced at the cathode was used to track the produced water. It was found that the water content peaked in the cathode-side diffusion media (DM) for the cell without MPL, but with an MPL on the anode and cathode DM, the peak water amount was pushed toward the anode, resulting in a relatively flattened water profile through components and demonstrating a liquid barrier effect. Additionally, the dynamic water behavior in diffusion media was analyzed to understand the effect of a MPL and operating conditions. The water content in the DM changed with applied current, although there is a significant amount of residual liquid content that does not appear to be part of capillary channels. The effect of the MPL on irreducible saturation in DM and cell performance was also investigated.

  10. A comparison of capillary and venous blood haematocrits of pregnant women in Nigeria: the impact on diagnosis and prevalence of anaemia in pregnancy.

    PubMed

    Dim, Cyril Chukwudi; Ugwu, Emmanuel Onyebuchi; Anyaehie, Ugochukwu Bond; Obioha, Kingsley Chukwu

    2014-01-01

    Volume of red cells in capillary blood varies from that of venous blood. The magnitude of this variation as well as its impact on the diagnosis of anaemia in pregnancy needs to be studied. This study demonstrates the disparity between capillary and venous PCV in pregnancy. To determine whether capillary blood PCV (cPCV) differed from venous blood PCV (vPCV) of normal pregnant women in Enugu, Nigeria, and its effect on diagnosis and prevalence of anaemia. PCV was estimated using pairs of venous and capillary blood samples from 200 consecutive pregnant women at the Antenatal Clinic of University of Nigeria Teaching Hospital, Enugu, Nigeria. Participants' cPCV (median = 34.0%, IQR = 31.0-35.8) was significantly lower than their vPCV (median = 34.0%, IQR = 32.0-37.0) (Z = -6.85, P < 0.001). However, women's cPCV had strong positive correlation with their vPCV (r = 0.883, P < 0.001). The prevalence of anaemia among participants using capillary and venous blood was 33.5% (67/200) and 28.0% (56/200), respectively (O.R = 1.3 (CI 95%: 0.85, 1.98),  P = 0.233). Capillary blood PCV was lower than vPCV among pregnant women in Enugu, Nigeria. Nevertheless, the prevalence of anaemia derived from cPCV did not differ significantly from that of vPCV.

  11. Exploring the effect of nested capillaries on core-cladding mode resonances in hollow-core antiresonant fibers

    NASA Astrophysics Data System (ADS)

    Provino, Laurent; Taunay, Thierry

    2018-02-01

    Optimal suppression of higher-order modes (HOMs) in hollow-core antiresonant fibers comprising a single ring of thin-walled capillaries was previously studied, and can be achieved when the condition on the capillary-tocore diameter ratio is satisfied (d/D ≍ 0.68). Here we report on the conditions for maximizing the leakage losses of HOMs in hollow-core nested antiresonant node-less fibers, while preserving low confinement loss for the fundamental mode. Using an analytical model based on coupled capillary waveguides, as well as full-vector finite element modeling, we show that optimal d/D value leading to high leakage losses of HOMs, is strongly correlated to the size of nested capillaries. We also show that extremely high value of degree of HOM suppression (˜1200) at the resonant coupling is almost unchanged on a wide range of nested capillary diameter dN ested values. These results thus suggest the possibility of designing antiresonant fibers with nested elements, which show optimal guiding performances in terms of the HOM loss compared to that of the fundamental mode, for clearly defined paired values of the ratios dN ested/d and d/D. These can also tend towards a single-mode behavior only when the dimensionless parameter dN ested/d is less than 0.30, with identical wall thicknesses for all of the capillaries.

  12. Numerical analysis of cell adhesion in capillary flow

    NASA Astrophysics Data System (ADS)

    Takeishi, Naoki; Imai, Yohsuke; Ishida, Shunichi; Omori, Toshihiro; Kamm, Roger; Ishikawa, Takuji

    2016-11-01

    Numerical simulation of cell adhesion was performed for capillaries whose diameter is comparable to or smaller than that of the cell. Despite a lot of works about leukocyte and tumor cell rolling, cell motion in capillaries has remained unclear. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram is obtained for various values of capillary diameter and receptor density. According to our numerical results, bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between PSGL-1 and P-selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis. This research was supported by JSPS KAKENHI Grant Numbers 25000008, 26107703, 14J03967. We also acknowledge support from the Tohoku University Division for International Advanced Research and Education Organization.

  13. SEPARATION OF OCTYLPHENOL POLYETHER ALCOHOLS SURFACTANTS BY CAPILLARY COLUMN SFC AND HPLC

    EPA Science Inventory

    Separation of nonionic octylphenol polyether alcohols (OPA) by supercritical fluid chromatography (SFC) and HPLC is described. Using a density programming and a 50-μm i.d. capillary column, a total of 18 group oligomers was separated. The effects of the operating parameters, such...

  14. [Magnetotherapy in obliterating vascular diseases of the lower extremities].

    PubMed

    Kirillov, Iu B; Shval'b, P G; Lastushkin, A V; Baranov, V M; Sigaev, A A; Zueva, G V; Karpov, E I

    1992-01-01

    The investigators have developed a polymagnetic system "Avrora-MK-01" employing running impulse magnetic field to treat diseases of the leg vessels by the action on peripheral capillary bed. At a pregangrene stage a positive effect on peripheral capillaries was achieved in 75-82% of the patients treated.

  15. Capillary-Effect Root-Environment System

    NASA Technical Reports Server (NTRS)

    Wright, Bruce D.

    1991-01-01

    Capillary-effect root-environment system (CERES) is experimental apparatus for growing plants in nutrient solutions. Solution circulated at slight tension in cavity filled with plastic screen and covered by porous plastic membrane. By adsorptive attraction, root draws solution through membrane. Conceived for use in microgravity of space, also finds terrestrial application in germinating seedlings, because it protects them from extremes of temperature, moisture, and soil pH and from overexposure to fertilizers and herbicides.

  16. Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium

    PubMed Central

    Wilson, John X.

    2009-01-01

    Circulating levels of vitamin C (ascorbate) are low in patients with sepsis. Parenteral administration of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of sepsis, intravenous ascorbate injection increases survival and protects several microvascular functions, namely, capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators. The effects of parenteral ascorbate on microvascular function are both rapid and persistent. Ascorbate quickly accumulates in microvascular endothelial cells, scavenges reactive oxygen species, and acts through tetrahydrobiopterin to stimulate nitric oxide production by endothelial nitric oxide synthase. A major reason for the long duration of the improvement in microvascular function is that cells retain high levels of ascorbate, which alter redox-sensitive signaling pathways to diminish septic induction of NADPH oxidase and inducible nitric oxide synthase. These observations are consistent with the hypothesis that microvascular function in sepsis may be improved by parenteral administration of ascorbate as an adjuvant therapy. PMID:19319840

  17. Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.

    PubMed

    Proia, Patrizia; Schiera, Gabriella; Salemi, Giuseppe; Ragonese, Paolo; Savettieri, Giovanni; Di Liegro, Italia

    2009-12-01

    An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB model, as indicated by the decrease of the transendothelial electrical resistance (TEER). Moreover, as shown by both immunofluorescence and Western blot analyses, BBB breaking is accompanied by a decrease of the synthesis as well as the peripheral localization of occludin, a structural protein of the tight junctions that are responsible for BBB properties.

  18. Paramecium swimming in capillary tube

    NASA Astrophysics Data System (ADS)

    Jana, Saikat; Um, Soong Ho; Jung, Sunghwan

    2012-04-01

    Swimming organisms in their natural habitat need to navigate through a wide range of geometries and chemical environments. Interaction with boundaries in such situations is ubiquitous and can significantly modify the swimming characteristics of the organism when compared to ideal laboratory conditions. We study the different patterns of ciliary locomotion in glass capillaries of varying diameter and characterize the effect of the solid boundaries on the velocities of the organism. Experimental observations show that Paramecium executes helical trajectories that slowly transition to straight lines as the diameter of the capillary tubes decreases. We predict the swimming velocity in capillaries by modeling the system as a confined cylinder propagating longitudinal metachronal waves that create a finite pressure gradient. Comparing with experiments, we find that such pressure gradient considerations are necessary for modeling finite sized ciliary organisms in restrictive geometries.

  19. A FORTRAN program for interpretation of relative permeability from unsteady-state displacements with capillary pressure included

    USGS Publications Warehouse

    Udegbunam, E.O.

    1991-01-01

    This paper presents a FORTRAN program for the determination of two-phase relative permeabilities from unsteady-state displacement data with capillary pressure terms included. The interpretative model employed in this program combines the simultaneous solution of a variant of the fractional flow equation which includes a capillary pressure term and an integro-differential equation derived from Darcy's law without assuming the simplified Buckley-Leverett flow. The incorporation of capillary pressure in the governing equations dispenses with the high flowrate experimental requirements normally employed to overcome capillarity effects. An illustrative example is presented herein which implements this program for the determination of oil/water relative permeabilities from a sandstone core sample. Results obtained compares favorably with results previously given in the literature. ?? 1991.

  20. Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline.

    PubMed

    Hecht, Moritz; Krämer, Lara Maria; von Arnim, Christine A F; Otto, Markus; Thal, Dietmar Rudolf

    2018-05-01

    Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.

  1. Effects of intermediate wettability on entry capillary pressure in angular pores.

    PubMed

    Rabbani, Harris Sajjad; Joekar-Niasar, Vahid; Shokri, Nima

    2016-07-01

    Entry capillary pressure is one of the most important factors controlling drainage and remobilization of the capillary-trapped phases as it is the limiting factor against the two-phase displacement. It is known that the entry capillary pressure is rate dependent such that the inertia forces would enhance entry of the non-wetting phase into the pores. More importantly the entry capillary pressure is wettability dependent. However, while the movement of a meniscus into a strongly water-wet pore is well-defined, the invasion of a meniscus into a weak or intermediate water-wet pore especially in the case of angular pores is ambiguous. In this study using OpenFOAM software, high-resolution direct two-phase flow simulations of movement of a meniscus in a single capillary channel are performed. Interface dynamics in angular pores under drainage conditions have been simulated under constant flow rate boundary condition at different wettability conditions. Our results shows that the relation between the half corner angle of pores and contact angle controls the temporal evolution of capillary pressure during the invasion of a pore. By deviating from pure water-wet conditions, a dip in the temporal evolution of capillary pressure can be observed which will be pronounced in irregular angular cross sections. That enhances the pore invasion with a smaller differential pressure. The interplay between the contact angle and pore geometry can have significant implications for enhanced remobilization of ganglia in intermediate contact angles in real porous media morphologies, where pores are very heterogeneous with small shape factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. A coupling modulation model of capillary waves from gravity waves: Theoretical analysis and experimental validation

    NASA Astrophysics Data System (ADS)

    Chen, Pengzhen; Wang, Xiaoqing; Liu, Li; Chong, Jinsong

    2016-06-01

    According to Bragg theory, capillary waves are the predominant scatterers of high-frequency band (such as Ka-band) microwave radiation from the surface of the ocean. Therefore, understanding the modulation mechanism of capillary waves is an important foundation for interpreting high-frequency microwave remote sensing images of the surface of the sea. In our experiments, we discovered that modulations of capillary waves are significantly larger than the values predicted by the classical theory. Further, analysis shows that the difference in restoring force results in an inflection point while the phase velocity changes from gravity waves region to capillary waves region, and this results in the capillary waves being able to resonate with gravity waves when the phase velocity of the gravity waves is equal to the group velocity of the capillary waves. Consequently, we propose a coupling modulation model in which the current modulates the capillary wave indirectly by modulating the resonant gravity waves, and the modulation of the former is approximated by that of the latter. This model very effectively explains the results discovered in our experiments. Further, based on Bragg scattering theory and this coupling modulation model, we simulate the modulation of normalized radar cross section (NRCS) of typical internal waves and show that the high-frequency bands are superior to the low-frequency bands because of their greater modulation of NRCS and better radiometric resolution. This result provides new support for choice of radar band for observation of wave-current modulation oceanic phenomena such as internal waves, fronts, and shears.

  3. Nano carriers for drug transport across the blood-brain barrier.

    PubMed

    Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

    2017-01-01

    Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

  4. Modifying effect of dynamic space flight factors on radiation damage of air-dry seeds of Crepis capillaris (L) Wallr.

    PubMed

    Vaulina, E N; Kostina, L N

    1975-01-01

    The influence of dynamic factors (vibration and linear acceleration) on the rate of chromosome aberrations in Crepis capillaris was studied. The vibrational process simulated was similar in its characteristics to that occurring at the launch of spaceships. In combination with linear acceleration it caused a statistically significant increase in the rate of chromosome aberrations compared with the control (R=7.70). The dynamic factors modified the effect of radiation damage induced by acute gamma-irradiation (3 krad). Pre-radiation treatment with vibration and acceleration on the seeds caused a significant decrease (R=10.23) of the effect of radiation damage, from 15.57% to 9.74%. The post-radiation treatment of C. capillaris seeds with the dynamic factors did not change the rate of chromosome aberrations significantly (from 15.57% to 15.90%).

  5. Surface Chemistry and Structural Effects in the Stress Corrosion of Glass and Ceramic Materials.

    DTIC Science & Technology

    1986-03-31

    capillary can be improved for (GC)2 by passing S sulfur dioxide or difluoroethane through the preform and capillary during the fabrication 27 . The...hydration resistance of the glass surface. In fact, it was recently shown that the combined use of sulfur dioxide and * difluoroethane could further

  6. Ultra-High-Speed DNA Fragment Separations Using Microfabricated Capillary Array Electrophoresis Chips

    NASA Astrophysics Data System (ADS)

    Woolley, Adam T.; Mathies, Richard A.

    1994-11-01

    Capillary electrophoresis arrays have been fabricated on planar glass substrates by photolithographic masking and chemical etching techniques. The photolithographically defined channel patterns were etched in a glass substrate, and then capillaries were formed by thermally bonding the etched substrate to a second glass slide. High-resolution electrophoretic separations of φX174 Hae III DNA restriction fragments have been performed with these chips using a hydroxyethyl cellulose sieving matrix in the channels. DNA fragments were fluorescently labeled with dye in the running buffer and detected with a laser-excited, confocal fluorescence system. The effects of variations in the electric field, procedures for injection, and sizes of separation and injection channels (ranging from 30 to 120 μm) have been explored. By use of channels with an effective length of only 3.5 cm, separations of φX174 Hae III DNA fragments from ≈70 to 1000 bp are complete in only 120 sec. We have also demonstrated high-speed sizing of PCR-amplified HLA-DQα alleles. This work establishes methods for high-speed, high-throughput DNA separations on capillary array electrophoresis chips.

  7. Heat of capillary condensation in nanopores: new insights from the equation of state.

    PubMed

    Tan, Sugata P; Piri, Mohammad

    2017-02-15

    Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) coupled with the Young-Laplace equation is a recently developed equation of state (EOS) that successfully presents not only the capillary condensation but also the pore critical phenomena. The development of this new EOS allows further investigation of the heats involved in condensation. Compared to the conventional approaches, the EOS calculations present the temperature-dependent behavior of the heat of capillary condensation as well as that of the contributing effects. The confinement effect was found to be the strongest at the pore critical point. Therefore, contrary to the bulk heat condensation that vanishes at the critical point, the heat of capillary condensation in small pores shows a minimum and then increases with temperature when approaching the pore critical temperature. Strong support for the existence of the pore critical point is also discussed as the volume expansivity of the condensed phase in confinement was found to increase dramatically near the pore critical temperature. At high reduced temperatures, the Clausius-Clapeyron equation was found to apply better for confined fluids than it does for bulk fluids.

  8. Multi-capillary based optical sensors for highly sensitive protein detection

    NASA Astrophysics Data System (ADS)

    Okuyama, Yasuhira; Katagiri, Takashi; Matsuura, Yuji

    2017-04-01

    A fluorescence measuring method based on glass multi-capillary for detecting trace amounts of proteins is proposed. It promises enhancement of sensitivity due to effects of the adsorption area expansion and the longitudinal excitation. The sensitivity behavior of this method was investigated by using biotin-streptavidin binding. According to experimental examinations, it was found that the sensitivity was improved by a factor of 70 from common glass wells. We also confirmed our measuring system could detect 1 pg/mL of streptavidin. These results suggest that multi-capillary has a potential as a high-sensitive biosensor.

  9. Optimization of Capillary Electrophoresis With Laser Induced Fluorescent (CE-LIF) Detection for the Analysis of Double Standed DNA Polymerase Chain Reaction Products from the Telomeric Repeat Amplification Protocol

    DTIC Science & Technology

    2000-12-06

    Fluorescent Milligram (10ŗ) Milliliter (10ŗ) vm ^g Microgram (10") 1*1 Microliter (10" 6) MMA Master Mix A MMB Master Mix B NSCLC Non-Small-Cell...little effect on heat dissipation, the mixing helped to smooth out the convection gradients (see Weinberger 1993). The use of smaller i.d...clogging may occur (Heller 1998a). The gels must be covalently bound to the capillary wall to avoid extrusion from the capillary by electroosmotic flow

  10. The effect of a microscale fracture on dynamic capillary pressure of two-phase flow in porous media

    NASA Astrophysics Data System (ADS)

    Tang, Mingming; Lu, Shuangfang; Zhan, Hongbin; Wenqjie, Guo; Ma, Huifang

    2018-03-01

    Dynamic capillary pressure (DCP) effects, which is vital for predicting multiphase flow behavior in porous media, refers to the injection rate dependence capillary pressure observed during non-equilibrium displacement experiments. However, a clear picture of the effects of microscale fractures on DCP remains elusive. This study quantified the effects of microscale fractures on DCP and simulated pore-scale force and saturation change in fractured porous media using the multiphase lattice Boltzmann method (LBM). Eighteen simulation cases were carried out to calculate DCP as a function of wetting phase saturation. The effects of viscosity ratio and fracture orientation, aperture and length on DCP and DCP coefficient τ were investigated, where τ refers to the ratio of the difference of DCP and static capillary pressure (SCP) over the rate of wetting-phase saturation change versus time. Significant differences in τ values were observed between unfractured and fractured porous media. The τ values of fractured porous media were 1.1  × 104 Pa ms to 5.68 × 105 Pa ms, which were one or two orders of magnitude lower than those of unfractured porous media with a value of 4 × 106 Pa. ms. A horizontal fracture had greater effects on DCP and τ than a vertical fracture, given the same fracture aperture and length. This study suggested that a microscale fracture might result in large magnitude changes in DCP for two-phase flow.

  11. Process-morphology scaling relations quantify self-organization in capillary densified nanofiber arrays.

    PubMed

    Kaiser, Ashley L; Stein, Itai Y; Cui, Kehang; Wardle, Brian L

    2018-02-07

    Capillary-mediated densification is an inexpensive and versatile approach to tune the application-specific properties and packing morphology of bulk nanofiber (NF) arrays, such as aligned carbon nanotubes. While NF length governs elasto-capillary self-assembly, the geometry of cellular patterns formed by capillary densified NFs cannot be precisely predicted by existing theories. This originates from the recently quantified orders of magnitude lower than expected NF array effective axial elastic modulus (E), and here we show via parametric experimentation and modeling that E determines the width, area, and wall thickness of the resulting cellular pattern. Both experiments and models show that further tuning of the cellular pattern is possible by altering the NF-substrate adhesion strength, which could enable the broad use of this facile approach to predictably pattern NF arrays for high value applications.

  12. The use of experimental design for the development of a capillary zone electrophoresis method for the quantitation of captopril.

    PubMed

    Mukozhiwa, S Y; Khamanga, S M M; Walker, R B

    2017-09-01

    A capillary zone electrophoresis (CZE) method for the quantitation of captopril (CPT) using UV detection was developed. Influence of electrolyte concentration and system variables on electrophoretic separation was evaluated and a central composite design (CCD) was used to optimize the method. Variables investigated were pH, molarity, applied voltage and capillary length. The influence of sodium metabisulphite on the stability of test solutions was also investigated. The use of sodium metabisulphite prevented degradation of CPT over 24 hours. A fused uncoated silica capillary of 67.5cm total and 57.5 cm effective length was used for analysis. The applied voltage and capillary length affected the migration time of CPT significantly. A 20 mM phosphate buffer adjusted to pH 7.0 was used as running buffer and an applied voltage of 23.90 kV was suitable to effect a separation. The optimized electrophoretic conditions produced sharp, well-resolved peaks for CPT and sodium metabisulphite. Linear regression analysis of the response for CPT standards revealed the method was linear (R2 = 0.9995) over the range 5-70 μg/mL. The limits of quantitation and detection were 5 and 1.5 μg/mL. A simple, rapid and reliable CZE method has been developed and successfully applied to the analysis of commercially available CPT products.

  13. Circumventing Imprecise Geometric Information and Development of a Unified Modeling Technique for Various Flow Regimes in Capillary Tubes

    NASA Astrophysics Data System (ADS)

    Abbasi, Bahman

    2012-11-01

    Owing to their manufacturability and reliability, capillary tubes are the most common expansion devices in household refrigerators. Therefore, investigating flow properties in the capillary tubes is of immense appeal in the said business. The models to predict pressure drop in two-phase internal flows invariably rely upon highly precise geometric information. The manner in which capillary tubes are manufactured makes them highly susceptible to geometric imprecisions, which renders geometry-based models unreliable to the point of obsoleteness. Aware of the issue, manufacturers categorize capillary tubes based on Nitrogen flow rate through them. This categorization method presents an opportunity to substitute geometric details with Nitrogen flow data as the basis for customized models. The simulation tools developed by implementation of this technique have the singular advantage of being applicable across flow regimes. Thus the error-prone process of identifying compatible correlations is eliminated. Equally importantly, compressibility and chocking effects can be incorporated in the same model. The outcome is a standalone correlation that provides accurate predictions, regardless of any particular fluid or flow regime. Thereby, exploratory investigations for capillary tube design and optimization are greatly simplified. Bahman Abbasi, Ph.D., is Lead Advanced Systems Engineer at General Electric Appliances in Louisville, KY. He conducts research projects across disciplines in the household refrigeration industry.

  14. Do high fasting glucose levels suggest nocturnal hypoglycaemia? The Somogyi effect-more fiction than fact?

    PubMed

    Choudhary, P; Davies, C; Emery, C J; Heller, S R

    2013-08-01

    The Somogyi effect postulates that nocturnal hypoglycaemia causes fasting hyperglycaemia attributable to counter-regulatory hormone release. Although most published evidence has failed to support this hypothesis, this concept remains firmly embedded in clinical practice and often prevents patients and professionals from optimizing overnight insulin. Previous observational data found lower fasting glucose was associated with nocturnal hypoglycaemia, but did not assess the probability of infrequent individual episodes of rebound hypoglycaemia. We analysed continuous glucose monitoring data to explore its prevalence. We analysed data from 89 patients with Type 1 diabetes who participated in the UK Hypoglycaemia study. We compared fasting capillary glucose following nights with and without nocturnal hypoglycaemia (sensor glucose < 3.5 mmol/l). Fasting capillary blood glucose was lower after nights with hypoglycaemia than without [5.5 (3.0) vs. 14.5 (4.5) mmol/l, P < 0.0001], and was lower on nights with more severe nocturnal hypoglycaemia [5.5 (3.0) vs. 8.2 (2.3) mmol/l; P = 0.018 on nights with nadir sensor glucose of < 2.2 mmol/l vs. 3.5 mmol/l]. There were only two instances of fasting capillary blood glucose > 10 mmol/l after nocturnal hypoglycaemia, both after likely treatment of the episode. When fasting capillary blood glucose is < 5 mmol/l, there was evidence of nocturnal hypoglycaemia on 94% of nights. Our data indicate that, in clinical practice, the Somogyi effect is rare. Fasting capillary blood glucose ≤ 5 mmol/l appears an important indicator of preceding silent nocturnal hypoglycaemia. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  15. Solvent-resistant sol-gel polydimethyldiphenylsiloxane coating for on-line hyphenation of capillary microextraction with high-performance liquid chromatography.

    PubMed

    Segro, Scott S; Malik, Abdul

    2008-09-26

    A sol-gel polydimethyldiphenylsiloxane (PDMDPS) coating was developed for capillary microextraction on-line hyphenated with high-performance liquid chromatography (HPLC). This coating was created using methyltrimethoxysilane (MTMS) as the sol-gel precursor and di-hydroxy-terminated PDMDPS as the sol-gel active polymer. The methyl and phenyl groups on the sol-gel active polymer and the methyl groups on the sol-gel precursor ultimately turned into pendant groups providing the ability to extract non-polar analytes. A 40-cm segment of 0.25 mm I.D. fused silica capillary containing the sol-gel PDMDPS coating was installed as an external sampling loop in an HPLC injection port. Aqueous samples containing polycyclic aromatic hydrocarbons (PAHs), aromatic compounds, ketones, and aldehydes were passed through this capillary wherein the analytes were extracted by the sol-gel coating. The extracted analytes were then transferred to the HPLC column using isocratic or gradient elution with an acetonitrile/water mobile phase. This capillary demonstrated excellent extraction capability for non-polar (e.g., polycyclic aromatic hydrocarbons and aromatic compounds) as well as moderately polar compounds, such as aromatic amines, ketones, and aldehydes. The test results indicate that PDMDPS can be successfully immobilized into a sol-gel network and that the resulting solvent-resistant sol-gel organic-inorganic hybrid coating can be effectively used for on-line hyphenation of capillary microextraction with high-performance liquid chromatography. The test results also indicate that the sol-gel PDMDPS coated capillary is resistant to high-temperature solvents, making it suitable for applications in high-temperature HPLC. To the best of our knowledge, this is the first report on the creation of a silica-based sol-gel PDMDPS coating used in capillary microextraction on-line hyphenated to HPLC.

  16. Numerical simulation of oxygen delivery to muscle tissue in the presence of hemoglobin-based oxygen carriers.

    PubMed

    Patton, Jaqunda N; Palmer, Andre F

    2006-01-01

    This work represents a culmination of research on oxygen transport to muscle tissue, which takes into account oxygen transport due to convection, diffusion, and the kinetics of simultaneous reactions between oxygen and hemoglobin and myoglobin. The effect of adding hemoglobin-based oxygen carriers (HBOCs) to the plasma layer of blood in a single capillary surrounded by muscle tissue based on the geometry of the Krogh tissue cylinder is examined for a range of HBOC oxygen affinity, HBOC concentration, capillary inlet oxygen tension (pO(2)), and hematocrit. The full capillary length of the hamster retractor muscle was modeled under resting (V(max) = 1.57 x 10(-4) mLO(2) mL(-1) s(-1), cell velocity (v(c)) = 0.015 cm/s) and working (V(max) = 1.57 x 10(-3) mLO(2) mL(-1) s(-1), v(c) = 0.075 cm/s) conditions. Two spacings between the red blood cell (RBC) and the capillary wall were examined, corresponding to a capillary with and without an endothelial surface layer. Simulations led to the following conclusions, which lend physiological insight into oxygen transport to muscle tissue in the presence of HBOCs: (1) The reaction kinetics between oxygen and myoglobin in the tissue region, oxygen and HBOCs in the plasma, and oxygen and RBCs in the capillary lumen should not be neglected. (2) Simulation results yielded new insight into possible mechanisms of oxygen transport in the presence of HBOCs. (3) HBOCs may act as a source or sink for oxygen in the capillary and may compete with RBCs for oxygen. (4) HBOCs return oxygen delivery to muscle tissue to normal for varying degrees of hypoxia (inlet capillary pO(2) < 30 mmHg) and anemia (hematocrit < 46%) for the hamster model.

  17. Evaluation of capillary permeability and microcirculation in patients with chronic venous hypertension treated with venoruton by the vacuum suction chamber (VSC) device and laser-Doppler flowmetry.

    PubMed

    Belcaro, G; D'Aulerio, A; Rulo, A; Candiani, C

    1988-01-01

    A new system to study capillary permeability, the VSC (vacuum suction chamber) device has been developed to evaluate the variations of capillary permeability in postphlebitic limbs. The VSC device produces by negative pressure [obtained in a plastic chamber applied to the skin at the perimalleolar region] a wheal which disappears in normals in less than one hour. In twelve patients with moderate [superficial] venous hypertension and in twelve patients with postphlebitic limbs the time of disappearance of the wheals was significantly longer in comparison with ten normal limbs. There was also a significantly increased time of disappearance of the wheals in postphlebitic legs in comparison with those with superficial incompetence. The validation of the VSC technique with venous occlusion plethysmography (VOP) showed that the increase of time of disappearance of the wheals is well correlated with the increase of capillary permeability demonstrated by VOP. After 2 weeks treatment with Venoruton (at the dosage of 1000 mg t.i.d.) the time of disappearance of the wheal was significantly reduced in both groups of patients (while it was unchanged in normals). Laser-Doppler parameters used together with the VSC device to evaluate the microcirculatory changes associated with an altered capillary permeability also showed a significant improvement of the laser-Doppler parameters after treatment. In conclusion there is evidence by the VSC device that capillary permeability [which is abnormally increased] in chronic venous hypertension is improved [decreased] after treatment for two weeks with Venoruton. This study demonstrated also the efficacy of the VSC device to study capillary permeability and the effects of drugs active on capillary permeability.

  18. Liquid film drag out in the presence of molecular forces

    NASA Astrophysics Data System (ADS)

    Schmidhalter, I.; Cerro, R. L.; Giavedoni, M. D.; Saita, F. A.

    2013-03-01

    From a practical as well as a conceptual point of view, one of the most interesting problems of physicochemical hydrodynamics is the drag out of a liquid film by a moving solid out of a pool of liquid. The basic problem, sometimes denoted the Landau-Levich problem [L. Landau and B. Levich, "Dragging of a liquid by a moving plate," Acta Physicochim. USSR 17, 42-54 (1942)], involves an interesting blend of capillary and viscous forces plus a matching of the static solution for capillary rise with a numerical solution of the film evolution equation, neglecting gravity, on the downstream region of the flow field. The original solution describes experimental data for a wide range of Capillary numbers but fails to match results for large and very small Capillary numbers. Molecular level forces are introduced to create an augmented version of the film evolution equation to show the effect of van der Waals forces at the lower range of Capillary numbers. A closed form solution for static capillary rise, including molecular forces, was matched with a numerical solution of the augmented film evolution equation in the dynamic meniscus region. Molecular forces do not sensibly modify the static capillary rise region, since film thicknesses are larger than the range of influence of van der Waals forces, but are determinant in shaping the downstream dynamic meniscus of the very thin liquid films. As expected, a quantitatively different level of disjoining pressure for different values of molecular constants remains in the very thin liquid film far downstream. Computational results for a wide range of Capillary numbers and Hamaker constants show a clear transition towards a region where the film thickness becomes independent of the coating speed.

  19. Effect of wave action on near-well zone cleaning

    NASA Astrophysics Data System (ADS)

    Pen'kovskii, V. I.; Korsakova, N. K.

    2017-10-01

    Drilling filtrate invasion into the producing formation and native water accumulating of the near-well zone in well operation reduce the well productivity. As a result of that, depending on characteristic capillary pressure scale and differential pressure drawdown, oil production rate may become lower than expected one. In this paper, it is considered the hysteresis effects of capillary pressure after reversion of displacement. As applied to laboratory experiment conditions, the solution of problem of oil flow in formation model with a pressure drop on the model sides harmonically varied with time is presented. It was estimated a range of fluid vibration effective action on the near-well zone cleaning from capillary locking water. The plant simulating extraction of oil from formation using widely practised sucker-rod pump has been created. Formation model is presented as a slot filled with broken glass between two plates. In the process, natural oil and sodium chloride solution were used as working fluids. The experiments qualitatively confirm a positive effect of jack pumps on the near-well zone cleaning.

  20. Effect of surfactant on kinetics of thinning of capillary bridges

    NASA Astrophysics Data System (ADS)

    Nowak, Emilia; Kovalchuk, Nina; Simmons, Mark

    2015-11-01

    Kinetics of thinning of capillary bridges is of great scientific and industrial interest being of vital importance for example in various emulsification and microfluidic processes. It is well known that the rate of bridge thinning is proportional to the interfacial tension. Therefore it is expected that the process should slow down by addition of surfactant. The kinetics of capillary bridges in the presence of surfactant was studied by the dripping of liquid from a capillary tip under conditions of nearly zero flow rate (We << 1). The tested liquids were aqueous solutions of sodium lauryl ether sulphate (SLES), which is broadly used in personal care products. The viscosity, surfactant activity and adsorption kinetics have been controlled by addition of glycerol and sodium chloride. The study has shown that the kinetics of capillary bridges are determined by dynamic surface tension rather than by its equilibrium value. In particular, the kinetics of the bridge thinning for the 0.1 g L-1 aqueous SLES solution is practically the same as that of pure water despite twice lower equilibrium surface tension. EPSRC Programme Grant, MEMPHIS, EP/K0039761/1.

  1. Experimental study on nonmonotonicity of capillary desaturation curves in a 2-D pore-network

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodriquez de Castro, Antonio; Shokri, Nima; Karadimitriou, Nikolaos

    2015-10-28

    Immiscible displacement in a porous medium is important in many applications such as soil remediation and enhanced oil recovery. When gravitational forces are negligible, two-phase immiscible displacement at the pore level is controlled by capillary and viscous forces whose relative importance is quantified through the dimensionless capillary number Ca and the viscosity ratio M between liquid phases. Depending on the values of Ca and M, capillary fingering, viscous fingering, or stable displacement may be observed resulting in a variety of patterns affecting the phase entrapment. The Capillary Desaturation Curve (CDC), which represents the relationship between the residual oils saturation andmore » Ca, is an important relation to describe the phase entrapment at a given Ca. In the present study, we investigate the CDC as influenced by the viscosity ratio. A comprehensive series of experiments using a high-resolution microscope and state-of-the-art micromodels were conducted. The CDCs were calculated and the effects of Ca and M on phase entrapments were quantified. The results show that CDCs are not necessarily monotonic for all M.« less

  2. Effect of hindpaw electrical stimulation on capillary flow heterogeneity and oxygen delivery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Li, Yuandong; Wei, Wei; Li, Chenxi; Wang, Ruikang K.

    2017-02-01

    We report a novel use of optical coherence tomography (OCT) based angiography to visualize and quantify dynamic response of cerebral capillary flow pattern in mice upon hindpaw electrical stimulation through the measurement of the capillary transit-time heterogeneity (CTH) and capillary mean transit time (MTT) in a wide dynamic range of a great number of vessels in vivo. The OCT system was developed to have a central wavelength of 1310 nm, a spatial resolution of 8 µm and a system dynamic range of 105 dB at an imaging rate of 92 kHz. The mapping of dynamic cerebral microcirculations was enabled by optical microangiography protocol. From the imaging results, the spatial homogenization of capillary velocity (decreased CTH) was observed in the region of interest (ROI) corresponding to the stimulation, along with an increase in the MTT in the ROI to maintain sufficient oxygen exchange within the brain tissue during functional activation. We validated the oxygen consumption due to an increase of the MTT through demonstrating an increase in the deoxygenated hemoglobin (HbR) during the stimulation by the use of laser speckle contrast imaging.

  3. Field-Scale Modeling of Local Capillary Trapping During CO2 Injection into a Saline Aquifer

    NASA Astrophysics Data System (ADS)

    Ren, B.; Lake, L. W.; Bryant, S. L.

    2015-12-01

    Local capillary trapping is the small-scale (10-2 to 10+1 m) CO2 trapping that is caused by the capillary pressure heterogeneity. The benefit of LCT, applied specially to CO2 sequestration, is that saturation of stored CO2 is larger than the residual gas, yet these CO2 are not susceptible to leakage through failed seals. Thus quantifying the extent of local capillary trapping is valuable in design and risk assessment of geologic storage projects. Modeling local capillary trapping is computationally expensive and may even be intractable using a conventional reservoir simulator. In this paper, we propose a novel method to model local capillary trapping by combining geologic criteria and connectivity analysis. The connectivity analysis originally developed for characterizing well-to-reservoir connectivity is adapted to this problem by means of a newly defined edge weight property between neighboring grid blocks, which accounts for the multiphase flow properties, injection rate, and gravity effect. Then the connectivity is estimated from shortest path algorithm to predict the CO2 migration behavior and plume shape during injection. A geologic criteria algorithm is developed to estimate the potential local capillary traps based only on the entry capillary pressure field. The latter is correlated to a geostatistical realization of permeability field. The extended connectivity analysis shows a good match of CO2 plume computed by the full-physics simulation. We then incorporate it into the geologic algorithm to quantify the amount of LCT structures identified within the entry capillary pressure field that can be filled during CO2 injection. Several simulations are conducted in the reservoirs with different level of heterogeneity (measured by the Dykstra-Parsons coefficient) under various injection scenarios. We find that there exists a threshold Dykstra-Parsons coefficient, below which low injection rate gives rise to more LCT; whereas higher injection rate increases LCT in heterogeneous reservoirs. Both the geologic algorithm and connectivity analysis are very fast; therefore, the integrated methodology can be used as a quick tool to estimate local capillary trapping. It can also be used as a potential complement to the full-physics simulation to evaluate safe storage capacity.

  4. Lattice Boltzmann simulations of liquid CO2 displacing water in a 2D heterogeneous micromodel at reservoir pressure conditions.

    PubMed

    Chen, Yu; Li, Yaofa; Valocchi, Albert J; Christensen, Kenneth T

    2018-05-01

    We employed the color-fluid lattice Boltzmann multiphase model to simulate liquid CO 2 displacing water documented in experiments in a 2D heterogeneous micromodel at reservoir pressure conditions. The main purpose is to investigate whether lattice Boltzmann simulation can reproduce the CO 2 invasion patterns observed in these experiments for a range of capillary numbers. Although the viscosity ratio used in the simulation matches the experimental conditions, the viscosity of the fluids in the simulation is higher than that of the actual fluids used in the experiments. Doing so is required to enhance numerical stability, and is a common strategy employed in the literature when using the lattice Boltzmann method to simulate CO 2 displacing water. The simulations reproduce qualitatively similar trends of changes in invasion patterns as the capillary number is increased. However, the development of secondary CO 2 pathways, a key feature of the invasion patterns in the simulations and experiments, is found to occur at a much higher capillary number in the simulations compared with the experiments. Additional numerical simulations were conducted to investigate the effect of the absolute value of viscosity on the invasion patterns while maintaining the viscosity ratio and capillary number fixed. These results indicate that the use of a high viscosity (which significantly reduces the inertial effect in the simulations) suppresses the development of secondary CO 2 pathways, leading to a different fluid distribution compared with corresponding experiments at the same capillary number. Therefore, inertial effects are not negligible in drainage process with liquid CO 2 and water despite the low Reynolds number based on the average velocity, as the local velocity can be much higher due to Haines jump events. These higher velocities, coupled with the low viscosity of CO 2 , further amplifies the inertial effect. Therefore, we conclude that caution should be taken when using proxy fluids that only rely on the capillary number and viscosity ratio in both experiment and simulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Inhibition of Chlorine-Induced Lung Injury by the Type 4 Phosphodiesterase Inhibitor Rolipram

    PubMed Central

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-01-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. PMID:22763362

  6. Uniform Laser Excitation And Detection In Capillary Array Electrophoresis System And Method.

    DOEpatents

    Li, Qingbo; Zhou, Songsan; Liu, Changsheng

    2003-10-07

    A capillary electrophoresis system comprises capillaries positioned in parallel to each other forming a plane. The capillaries are configured to allow samples to migrate. A light source is configured to illuminate the capillaries and the samples therein. This causes the samples to emit light. A lens is configured to receive the light emitted by the samples and positioned directly over a first group of the capillaries and obliquely over a second group of the capillaries. The light source is further configured to illuminate the second group of capillaries more than the first group of the capillaries such that amount of light received by the lens from the first group of capillaries is substantially identical to amount of light received from the second group of capillaries when an identical amount of the samples is migrating through the first and second group capillaries.

  7. Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells.

    PubMed

    Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

    2012-08-15

    Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 μM and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Transferrin Receptor 1 Facilitates Poliovirus Permeation of Mouse Brain Capillary Endothelial Cells.

    PubMed

    Mizutani, Taketoshi; Ishizaka, Aya; Nihei, Coh-Ichi

    2016-02-05

    As a possible route for invasion of the CNS, circulating poliovirus (PV) in the blood is believed to traverse the blood-brain barrier (BBB), resulting in paralytic poliomyelitis. However, the underlying mechanism is poorly understood. In this study, we demonstrated that mouse transferrin receptor 1 (mTfR1) is responsible for PV attachment to the cell surface, allowing invasion into the CNS via the BBB. PV interacts with the apical domain of mTfR1 on mouse brain capillary endothelial cells (MBEC4) in a dose-dependent manner via its capsid protein (VP1). We found that F-G, G-H, and H-I loops in VP1 are important for this binding. However, C-D, D-E, and E-F loops in VP1-fused Venus proteins efficiently penetrate MBEC4 cells. These results imply that the VP1 functional domain responsible for cell attachment is different from that involved in viral permeation of the brain capillary endothelium. We observed that co-treatment of MBEC4 cells with excess PV particles but not dextran resulted in blockage of transferrin transport into cells. Using the Transwell in vitro BBB model, transferrin co-treatment inhibited permeation of PV into MBEC4 cells and delayed further viral permeation via mTfR1 knockdown. With mTfR1 as a positive mediator of PV-host cell attachment and PV permeation of MBEC4 cells, our results indicate a novel role of TfR1 as a cellular receptor for human PV receptor/CD155-independent PV invasion of the CNS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Up-regulation of K{sub ir}2.1 by ER stress facilitates cell death of brain capillary endothelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kito, Hiroaki; Yamazaki, Daiju; Department of Biological Chemistry, Kyoto University, Graduate School of Pharmaceutical Sciences, Kyoto

    Highlights: {yields} We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. {yields} The ER stress facilitated the expression of inward rectifier K{sup +} channel (K{sub ir}2.1) and induced sustained membrane hyperpolarization. {yields} The membrane hyperpolarization induced sustained Ca{sup 2+} entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. {yields} The K{sub ir}2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cellmore » turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K{sup +} channel (K{sub ir}2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K{sub ir} channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca{sup 2+} concentration due to Ca{sup 2+} influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K{sub ir}2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.« less

  10. Nanowicks

    NASA Technical Reports Server (NTRS)

    Noca, Flavio; Bronikowski, Michael; Sansom, Elijah; Zhou, Jijie; Gharib, Morteza

    2007-01-01

    Nanowicks are dense mats of nanoscale fibers that are expected to enable the development of a variety of novel capillary pumps, filters, and fluidic control devices. Nanowicks make it possible obtain a variety of novel effects, including capillary pressures orders of magnitude greater than those afforded by microscale and conventional macroscale wicks. While wicking serves the key purpose of transporting fluid, the nanofiber geometry of a nanowick makes it possible to exploit additional effects -- most notably, efficient nanoscale mixing, fluidic effects for logic or control, and ultrafiltration (in which mats of nanofibers act as biomolecular sieves).

  11. Electropherogram of capillary zone electrophoresis with effective mobility axis as a transverse axis and its analytical utility. I. Transformation applying the hypothetical electroosmotic flow.

    PubMed

    Ikuta, N; Yamada, Y; Hirokawa, T

    2000-01-01

    For capillary zone electrophoresis, a new method of transformation from migration time to effective mobility was proposed, in which the mobility increase due to Joule heating and the relaxation effect of the potential gradient were eliminated successfully. The precision of the mobility evaluated by the proposed transformation was discussed in relation to the analysis of rare earth ions. By using the transformation, almost the same pherograms could be obtained even from the pherograms obtained originally at different applied voltages.

  12. Field tracer investigation of unsaturated zone flow paths and mechanisms in agricultural soils of northwestern Mississippi, USA

    USGS Publications Warehouse

    Perkins, K.S.; Nimmo, J.R.; Rose, C.E.; Coupe, R.H.

    2011-01-01

    In many farmed areas, intensive application of agricultural chemicals and withdrawal of groundwater for irrigation have led to water quality and supply issues. Unsaturated-zone processes, including preferential flow, play a major role in these effects but are not well understood. In the Bogue Phalia basin, an intensely agricultural area in the Delta region of northwestern Mississippi, the fine-textured soils often exhibit surface ponding and runoff after irrigation and rainfall as well as extensive surface cracking during prolonged dry periods. Fields are typically land-formed to promote surface flow into drainage ditches and streams that feed into larger river ecosystems. Downward flow of water below the root zone is considered minimal; regional groundwater models predict only 5% or less of precipitation recharges the heavily used alluvial aquifer. In this study transport mechanisms within and below the root zone of a fallow soybean field were assessed by performing a 2-m ring infiltration test with tracers and subsurface monitoring instruments. Seven months after tracer application, 48 continuous cores were collected for tracer extraction to define the extent of water movement and quantify preferential flow using a mass-balance approach. Vertical water movement was rapid below the pond indicating the importance of vertical preferential flow paths in the shallow unsaturated zone, especially to depths where agricultural disturbance occurs. Lateral flow of water at shallow depths was extensive and spatially non-uniform, reaching up to 10. m from the pond within 2. months. Within 1. month, the wetting front reached a textural boundary at 4-5. m between the fine-textured soil and sandy alluvium, now a potential capillary barrier which, prior to extensive irrigation withdrawals, was below the water table. Within 10. weeks, tracer was detectable at the water table which is presently about 12. m below land surface. Results indicate that 43% of percolation may be through preferential flow paths and that any water breaking through the capillary barrier (as potential recharge) likely does so in fingers which are difficult to detect with coring methods. In other areas where water levels have declined and soils have similar properties, the potential for transport of agricultural chemicals to the aquifer may be greater than previously assumed. ?? 2010 .

  13. Velocity dependence of biphasic flow structuration: steady-state and oscillating flow effects

    NASA Astrophysics Data System (ADS)

    Tore Tallakstad, Ken; Jankov, Mihailo; Løvoll, Grunde; Toussaint, Renaud; Jørgen Mâløy, Knut; Grude Flekkøy, Eirik; Schmittbuhl, Jean; Schäfer, Gerhard; Méheust, Yves; Arendt Knudsen, Henning

    2010-05-01

    We study various types of biphasic flows in quasi-two-dimensional transparent porous models. These flows imply a viscous wetting fluid, and a lowly viscous one. The models are transparent, allowing the displacement process and structure to be monitored in space and time. Three different aspects will be presented: 1. In stationary biphasic flows, we study the relationship between the macroscopic pressure drop (related to relative permeability) and the average flow rate, and how this arises from the cluster size distribution of the lowly viscous fluid [1]. 2. In drainage situations, we study how the geometry of the invader can be explained, and how it gives rise to apparent dynamic capillary effects. We show how these can be explained by viscous effects on evolving geometries of invading fluid [2]. 3. We study the impact of oscillating pressure fields superimposed to a background flow over the flow regimes patterns [3]. Steady-State Two-Phase Flow in Porous Media: Statistics and Transport Properties. First, in stationary flow with a control of the flux of both fluids, we show how the pressure drop depends on the flow rate. We will show that the dynamics is dominated by the interplay between a viscous pressure field from the wetting fluid and bubble transport of a less viscous, nonwetting phase. In contrast with more studied displacement front systems, steady-state flow is in equilibrium, statistically speaking. The corresponding theoretical simplicity allows us to explain a data collapse in the cluster size distribution of lowly viscous fluid in the system, as well as the relation |?P|∞√Ca--. This allows to explain so called relative permeability effects by the morphological changes of the cluster size distribution. Influence of viscous fingering on dynamic saturation-pressure curves in porous media. Next, we study drainage in such models, and investigate the relationship between the pressure field and the morphology of the invading fluid. This allows to model the impact of the saturation changes in the system over the pressure difference between the wetting and non wetting phase. We show that the so-called dynamic effects referred in the hydrology literature of experimentally measured capillary pressure curves might be explained by the combined effect of capillary pressure along the invasion front of the gaseous phase and pressure changes caused by viscous effects. A detailed study of the structure optically followed shows that the geometry of the invader is self-similar with two different behaviors at small and large scales: the structure corresponds to the ones of invasion percolation models at small scales (capillary fingering structures with fractal dimension D=1.83), whereas at large scales, viscous pressure drops dominate over the capillary threshold variations, and the structures are self-similar fingering structures with a fractal dimension corresponding to Dielectric Breakdown Models (variants of the DLA model), with D ≠ƒ 1.5. The cross-over scale is set by the scale at which capillary fluctuations are of the order of the viscous pressure drops. This leads physically to the fact that cross-over scale between the two fingering dimensions, goes like the inverse of the capillary number. This study utilizes these geometrical characteristics of the viscous fingers forming in dynamic drainage, to obtain a meaningfull scaling law for the saturation-pressure curve at finite speed, i.e. the so-called dynamic capillary pressure relations. We thus show how the micromechanical interplay between viscous and capillary forces leads to some pattern formation, which results in a general form of dynamic capillary pressure relations. By combining these detailed informations on the displacement structure with global measures of pressure, saturation and controlling the capillary number Ca, a scaling relation relating pressure, saturation, system size and capillary number is developed. By applying this scaling relation, pressure-saturation curves for a wide range of capillary numbers can be collapsed. Effects of pressure oscillations on drainage in an elastic porous medium: The effects of seismic stimulation on the flow of two immiscible fluids in an elastic synthetic porous medium is experimentally investigated. A wetting fluid is slowly evacuated from the medium, while a pressure oscillation is applied on the injected non-wetting fluid. The amplitude and frequency of the pressure oscillations as well as the evacuation speed are kept constant throughout an experiment. The resulting morphology of the invading structure is found to be strongly dependent on the interplay between the amplitude and the frequency of the applied pressure oscillations and the elasticity of the porous medium. Different combinations of these properties yield morphologically similar structures, allowing a classification of structures that is found to depend on a proposed dimensionless number. [1] Tallakstad, K.T., H.A. Knudsen, T. Ramstad, G. Løvoll, K.J. Maløy, R. Toussaint and E.G. Flekkøy , Steady-state two-phase flow in porous media: statistics and transport properties, Phys. Rev. Lett. 102, 074502 (2009). doi:10.1103/PhysRevLett.102.074502 [2] Løvoll, G., M. Jankov, K.J. Maløy, R. Toussaint, J. Schmittbuhl, G. Schaefer and Y. Ḿ eheust, Influence of viscous fingering on dynamic saturation-pressure curves in porous media, submitted to Transport In Porous Media, (2010) [3] Jankov, M., G. Løvoll, H.A. Knudsen, K.J. Maløy, R. Planet, R. Toussaint and E.G. Flekkøy; Effects of pressure oscillations on drainage in an elastic porous medium, Transport In Porous Media, in press (2010).

  14. Effect of Variable Gravity on Evaporation of Binary Fluids in a Capillary Pore Evaporator

    NASA Technical Reports Server (NTRS)

    Girgis, Morris M.; Matta, Nabil S.; Kolli, Kiran; Brown, Leon; Bain, James, Jr.; McGown, Juantonio

    1996-01-01

    The research project focuses on experimental investigation of the capillary-pumped evaporative heat transfer phenomenon. The objective is to examine whether the heat transfer and stability of a heated meniscus in a capillary pore can be enhanced by adding trace amounts of a non-volatile solute to a solvent and to understand the changes that occur. The experimental setup consists of a single pore evaporator connected to a reservoir which supplies liquid to the evaporator. In addition to the experiments of capillary-pumped evaporation, a parallel experimental study has been conducted to systematically investigate the effects of gravity as well as the effects of bulk composition on the heat transfer characteristics of evaporating binary thin films near the contact line region along an inclined heated surface. To investigate the buoyancy effects on evaporation along an inclined heated surface, the angle of inclination from a horizontal plane was varied fro 15 C to 90 C. An optimum concentration between 0.5% and 1% decane in pentane/decane solutions has been demonstrated at different angles of inclination. Improved heat transfer was found for the geometry with the smallest angle of inclination of 15 degrees. In addition, flow visualization has revealed that at low inclination angles effective heat transfer takes place primarily due to an extension of the thin film near the contact line. At these low inclination angles, the optimum concentration is associated with enhanced wetting characteristics and reduced thermocapillary stresses along the interface.

  15. The hydrological response to precipitations of a layered shallow sloping deposit: physical experiments and mathematical modeling

    NASA Astrophysics Data System (ADS)

    Damiano, Emilia; Greco, Roberto; Guida, Andrea; Olivares, Lucio; Picarelli, Luciano

    2016-04-01

    Although rainfall-induced landslides are frequent, so that they can be probably considered the most widespread natural hazards, fortunately the occurrence of an extreme rainfall event only rarely corresponds to the triggering of landslides. This is due to the fact that slopes, although often considered as separated systems in the stability analyses, are actually part of a larger, more complex hydrological system, with which continuously exchange water. Indeed, most of the slopes do not fail, and when they are subjected to heavy precipitation, effective draining mechanisms spontaneously develop, such as overland and subsurface runoff, and sometimes even new preferential flow paths originated by mechanical processes, such as piping erosion or deformation cracks. Hence, the triggering of a rainfall-induced landslide requires these dynamically evolving (non-linear) drainage processes to be incapable of releasing the excess of water (and pressure) accumulating within the slope. For the case of shallow sloping covers, the capability of the slope to effectively drain the infiltrating water depends on the hydraulic properties of the involved soils (hydraulic conductivity and water retention curves) and on the hydraulic boundary conditions (at the base of the cover, where it lays upon the bedrock, and at the foot of the slope), which are in turn strongly influenced by the initial moisture state (often indicated as a predisposing cause), owing to the non-linearity of the hydraulic processes. Such an already complex picture is furthermore complicated by heterogeneity. In this study, we focus our attention onto the effects of a layered soil cover with contrasting hydraulic properties on the infiltration and drainage processes in a shallow pyroclastic deposit. This is a typical situation along many pyroclastic-covered slopes of Campania (southern Italy), which present alternations of ashes (silty sands) and pumices (sands with gravel) deposited by volcanic eruptions, and where shallow landslides are sometimes triggered by intense and long-lasting precipitations. Several studies have already pointed out that layering may play a crucial role in the development of the infiltration process, as the coarse-grained pumice layers may behave as capillary barriers, leading to the formation of perched saturated zones. The hydrological behavior of such kind of layered slopes is investigated by means of small-scale infiltration experiments carried out in an instrumented flume in the laboratory. The interpretation of the experimental results is made with the help of a mathematical model of 2-D Richards equation, which allows shedding some light in the hydraulic properties of the pumices, which are hardly measurable with standard laboratory techniques. The obtained results show how, depending on initial moisture conditions, slope inclination angle and applied rainfall intensity, the response of the slope may be very different, and that the formation of a capillary barrier is not always observed.

  16. GLP-1-Based Therapies Have No Microvascular Effects in Type 2 Diabetes Mellitus: An Acute and 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Diamant, Michaela; Serné, Erik H; van Raalte, Daniël H

    2016-10-01

    To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. We studied 57 patients with type 2 diabetes mellitus (mean±SD age: 62.8±6.9 years; body mass index: 31.8±4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3±0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center. In the acute study, the GLP-1 receptor agonist exenatide (therapeutic concentrations) or placebo (saline 0.9%) was administered intravenously. During the 12-week study, patients received the GLP-1 receptor agonist liraglutide (1.8 mg daily), the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg daily), or matching placebos. Capillary perfusion was assessed by nailfold skin capillary videomicroscopy and vasomotion by laser Doppler fluxmetry, in the fasting state and after a high-fat mixed meal. In neither study, treatment affected fasting or postprandial capillary perfusion compared with placebo (P>0.05). In the fasting state, acute exenatide infusion increased neurogenic vasomotion domain power, while reducing myogenic domain power (both P<0.05). After the meal, exenatide increased endothelial domain power (P<0.05). In the 12-week study, no effects on vasomotion were observed. Despite modest changes in vasomotion, suggestive of sympathetic nervous system activation and improved endothelial function, acute exenatide infusion does not affect skin capillary perfusion in type 2 diabetes mellitus. Twelve-week treatment with liraglutide or sitagliptin has no effect on capillary perfusion or vasomotion in these patients. Our data suggest that the effects of GLP-1-based therapies on glucose are not mediated through microvascular responses. © 2016 American Heart Association, Inc.

  17. Molar volume and adsorption isotherm dependence of capillary forces in nanoasperity contacts.

    PubMed

    Asay, David B; Kim, Seong H

    2007-11-20

    The magnitude of the capillary force at any given temperature and adsorbate partial pressure depends primarily on four factors: the surface tension of the adsorbate, its liquid molar volume, its isothermal behavior, and the contact geometry. At large contacting radii, the adsorbate surface tension and the contact geometry are dominating. This is the case of surface force apparatus measurements and atomic force microscopy (AFM) experiments with micrometer-size spheres. However, as the size of contacting asperities decreases to the nanoscale as in AFM experiments with sharp tips, the molar volume and isotherm of the adsorbate become very important to capillary formation as well as capillary adhesion. This effect is experimentally and theoretically explored with simple alcohol molecules (ethanol, 1-butanol, and 1-pentanol) which have comparable surface tensions but differing liquid molar volumes. Adsorption isotherms for these alcohols on silicon oxide are also reported.

  18. Capillary assisted deposition of carbon nanotube film for strain sensing

    NASA Astrophysics Data System (ADS)

    Li, Zida; Xue, Xufeng; Lin, Feng; Wang, Yize; Ward, Kevin; Fu, Jianping

    2017-10-01

    Advances in stretchable electronics offer the possibility of developing skin-like motion sensors. Carbon nanotubes (CNTs), owing to their superior electrical properties, have great potential for applications in such sensors. In this paper, we report a method for deposition and patterning of CNTs on soft, elastic polydimethylsiloxane (PDMS) substrates using capillary action. Micropillar arrays were generated on PDMS surfaces before treatment with plasma to render them hydrophilic. Capillary force enabled by the micropillar array spreads CNT solution evenly on PDMS surfaces. Solvent evaporation leaves a uniform deposition and patterning of CNTs on PDMS surfaces. We studied the effect of the CNT concentration and micropillar gap size on CNT coating uniformity, film conductivity, and piezoresistivity. Leveraging the piezoresistivity of deposited CNT films, we further designed and characterized a device for the contraction force measurement. Our capillary assisted deposition method of CNT films showed great application potential in fabrication of flexible CNT thin films for strain sensing.

  19. Electron density measurement in gas discharge plasmas by optical and acoustic methods

    NASA Astrophysics Data System (ADS)

    Biagioni, A.; Anania, M. P.; Bellaveglia, M.; Chiadroni, E.; Cianchi, A.; Di Giovenale, D.; Di Pirro, G.; Ferrario, M.; Filippi, F.; Mostacci, A.; Pompili, R.; Shpakov, V.; Vaccarezza, C.; Villa, F.; Zigler, A.

    2016-08-01

    Plasma density represents a very important parameter for both laser wakefield and plasma wakefield acceleration, which use a gas-filled capillary plasma source. Several techniques can be used to measure the plasma density within a capillary discharge, which are mainly based on optical diagnostic methods, as for example the well-known spectroscopic method using the Stark broadening effect. In this work, we introduce a preliminary study on an alternative way to detect the plasma density, based on the shock waves produced by gas discharge in a capillary. Firstly, the measurements of the acoustic spectral content relative to the laser-induced plasmas by a solid target allowed us to understand the main properties of the acoustic waves produced during this kind of plasma generation; afterwards, we have extended such acoustic technique to the capillary plasma source in order to calibrate it by comparison with the stark broadening method.

  20. Polyvinylpyrrolidone-sodium dodecylsulfate complex is a family of pseudo-polyanions with different charge densities: Evidence from capillary electrophoresis, capillary viscosimetry and conductometry.

    PubMed

    Wu, Yefan; Chen, Jie; Fang, Yun; Zhu, Meng

    2016-10-01

    Accordance with the previously supposed polyelectrolyte-like behaviour of neutral polymer-anionic surfactant complexes, direct evidence for the formation of the pseudo-polyanions in polyvinylpyrrolidone (PVP)-sodium dodecylsulfate (SDS) solution is put forward in this paper by capillary electrophoresis (CE) experiments in assistance with capillary viscosimetry and conductometry. The contradictory phenomena of the absolute value of relative electrophoretic mobility (re) increasing while the ionization degree (α) decreasing with the increasing specific clusterization [Г] in aqueous PVP-SDS solution are explained by the finding that the PVP-SDS complex is eventually a family of PVP-SDS pseudo-polyanions with different charge densities. And it is found countercations playing an important role in the formation of the PVP-SDS pseudo-polyanions in virtue of bridge effect. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Experimental investigation of supercritical CO 2 trapping mechanisms at the Intermediate Laboratory Scale in well-defined heterogeneous porous media

    DOE PAGES

    Trevisan, Luca; Pini, Ronny; Cihan, Abdullah; ...

    2014-12-31

    The heterogeneous nature of typical sedimentary formations can play a major role in the propagation of the CO 2 plume, eventually dampening the accumulation of mobile phase underneath the caprock. From core flooding experiments, it is also known that contrasts in capillary threshold pressure due to different pore size can affect the flow paths of the invading and displaced fluids and consequently influence the build- up of non-wetting phase (NWP) at interfaces between geological facies. The full characterization of the geologic variability at all relevant scales and the ability to make observations on the spatial and temporal distribution of themore » migration and trapping of supercritical CO 2 is not feasible from a practical perspective. To provide insight into the impact of well-defined heterogeneous systems on the flow dynamics and trapping efficiency of supercritical CO 2 under drainage and imbibition conditions, we present an experimental investigation at the meter scale conducted in synthetic sand reservoirs packed in a quasi-two-dimensional flow-cell. Two immiscible displacement experiments have been performed to observe the preferential entrapment of NWP in simple heterogeneous porous media. The experiments consisted of an injection, a fluid redistribution, and a forced imbibition stages conducted in an uncorrelated permeability field and a homogeneous base case scenario. We adopted x-ray attenuation analysis as a non-destructive technique that allows a precise measurement of phase saturations throughout the entire flow domain. By comparing a homogeneous and a heterogeneous scenario we have identified some important effects that can be attributed to capillary barriers, such as dampened plume advancement, higher non-wetting phase saturations, larger contact area between the injected and displaced phases, and a larger range of non-wetting phase saturations.« less

  2. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

    PubMed

    Moazed, Farzad; Burnham, Ellen L; Vandivier, R William; O'Kane, Cecilia M; Shyamsundar, Murali; Hamid, Umar; Abbott, Jason; Thickett, David R; Matthay, Michael A; McAuley, Daniel F; Calfee, Carolyn S

    2016-12-01

    Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Interaction between blood and solid particles propagating through a capillary with slip effects.

    PubMed

    Zeeshan, A; Fatima, A; Khalid, F; Bhatti, M M

    2018-04-18

    This article describes the interaction between solid particles and blood propagating through a capillary. A slip condition is considered on the walls of the capillary. The rheological features of the blood are discussed by considering as a two-phase Newtonian fluid model, i.e., the suspension of cells in plasma. A perturbation method is successfully applied to obtain the series solution of the governing coupled differential equations. The series solution for both fluid and particle phase are presented up to second order approximation. The expressions for the velocity and pressure distributions under slip effects are determined within a tube. Furthermore, the current results are beneficial to understand the rheological features of blood which will be helpful to interpret and analyze more complex blood flow models. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Separation of 2-aminobenzoic acid-derivatized glycosaminoglycans and asparagine-linked glycans by capillary electrophoresis.

    PubMed

    Sato, Kae; Sato, Kiichi; Okubo, Akira; Yamazaki, Sunao

    2005-01-01

    A capillary electrophoresis method was developed for the analysis of oligosaccharides combined with derivatization with 2-aminobenzoic acid. Glycosaminoglycan delta-disaccharides were effectively resolved on a fused-silica capillary tube using 150 mM borate, pH 8.5, as a running electrolyte solution. This analytical method was applied to the identification of glycosaminoglycan in combination with enzymatic digestion. The separation of N-glycans or glucose-oligomers was performed with a phosphate buffer containing polyethylene glycol or borate as an electrolyte solution. This method is expected to be useful in the determination of oligosaccharide structures in a glycoprotein.

  5. Infiltration of MHD liquid into a deformable porous material

    NASA Astrophysics Data System (ADS)

    Naseem, Anum; Mahmood, Asif; Siddique, J. I.; Zhao, Lifeng

    2018-03-01

    We analyze the capillary rise dynamics for magnetohydrodynamics (MHD) fluid flow through deformable porous material in the presence of gravity effects. The modeling is performed using mixture theory approach and mathematical manipulation yields a nonlinear free boundary problem. Due to the capillary rise action, the pressure gradient in the liquid generates a stress gradient that results in the deformation of porous substrate. The capillary rise process for MHD fluid slows down as compared to Newtonian fluid case. Numerical solutions are obtained using a method of lines approach. The graphical results are presented for important physical parameters, and comparison is presented with Newtonian fluid case.

  6. A sex-specific relationship between capillary density and anaerobic threshold

    PubMed Central

    Robbins, Jennifer L.; Duscha, Brian D.; Bensimhon, Daniel R.; Wasserman, Karlman; Hansen, James E.; Houmard, Joseph A.; Annex, Brian H.; Kraus, William E.

    2009-01-01

    Although both capillary density and peak oxygen consumption (V̇o2) improve with exercise training, it is difficult to find a relationship between these two measures. It has been suggested that peak V̇o2 may be more related to central hemodynamics than to the oxidative potential of skeletal muscle, which may account for this observation. We hypothesized that change in a measure of submaximal performance, anaerobic threshold, might be related to change in skeletal muscle capillary density, a marker of oxidative potential in muscle, with training. Due to baseline differences among these variables, we also hypothesized that relationships might be sex specific. A group of 21 subjects completed an inactive control period, whereas 28 subjects (17 men and 11 women) participated in a 6-mo high-intensity exercise program. All subjects were sedentary, overweight, and dyslipidemic. Potential relationships were assessed between change in capillary density with both change in V̇o2 at peak and at anaerobic threshold with exercise training. All variables and relationships were assessed for sex-specific effects. Change in peak V̇o2 was not related to change in capillary density after exercise training in either sex. Men had a positive correlation between change in V̇o2 at anaerobic threshold and change in capillary density with exercise training (r = 0.635; P < 0.01), whereas women had an inverse relationship (r = −0.636; P < 0.05) between the change in these variables. These findings suggest that, although enhanced capillary density is associated with training-induced improvements in submaximal performance in men, this relationship is different in women. PMID:19164774

  7. A sex-specific relationship between capillary density and anaerobic threshold.

    PubMed

    Robbins, Jennifer L; Duscha, Brian D; Bensimhon, Daniel R; Wasserman, Karlman; Hansen, James E; Houmard, Joseph A; Annex, Brian H; Kraus, William E

    2009-04-01

    Although both capillary density and peak oxygen consumption (Vo(2)) improve with exercise training, it is difficult to find a relationship between these two measures. It has been suggested that peak Vo(2) may be more related to central hemodynamics than to the oxidative potential of skeletal muscle, which may account for this observation. We hypothesized that change in a measure of submaximal performance, anaerobic threshold, might be related to change in skeletal muscle capillary density, a marker of oxidative potential in muscle, with training. Due to baseline differences among these variables, we also hypothesized that relationships might be sex specific. A group of 21 subjects completed an inactive control period, whereas 28 subjects (17 men and 11 women) participated in a 6-mo high-intensity exercise program. All subjects were sedentary, overweight, and dyslipidemic. Potential relationships were assessed between change in capillary density with both change in Vo(2) at peak and at anaerobic threshold with exercise training. All variables and relationships were assessed for sex-specific effects. Change in peak Vo(2) was not related to change in capillary density after exercise training in either sex. Men had a positive correlation between change in Vo(2) at anaerobic threshold and change in capillary density with exercise training (r = 0.635; P < 0.01), whereas women had an inverse relationship (r = -0.636; P < 0.05) between the change in these variables. These findings suggest that, although enhanced capillary density is associated with training-induced improvements in submaximal performance in men, this relationship is different in women.

  8. Active and passive transport of drugs in the human placenta.

    PubMed

    Włoch, Stanisław; Pałasz, Artur; Kamiński, Marcin

    2009-10-01

    The human placenta, characterized by the processes of passive transport and facilitated diffusion, contains numerous active transport proteins, usually located in the microvilli of the syncytiotrophoblast or in the endothelium of the capillaries of the villi. These proteins use either the energy from ATP hydrolysis or other mechanisms resulting, among others, from the formation of the maternofetal ion gradient, which facilitates the transfer of various endogenous substances or xenobiotics across the body membranes. The proteins either trigger the efflux of these substances from the fetal tissues via the placenta into the maternal bloodstream, or conversely they accumulate them in the fetal tissues. Both the placenta and the fetus are equipped with independent systems of enzymes of 1st and 2nd phase of substrate metabolism, such as CYP450, glucuronyltransferase or sulphatase. An active therapy with a wide range of drugs, often at high toxicity levels, either shortly before or during pregnancy, has naturally posed a question concerning the degree of impermeability of the placental barrier and how effectively it can be crossed, including any possible negative embryotoxic or teratogenic consequences. Such hazards seem to be quite real, as many drugs are substrates for ABC transporters. Also the placenta itself, including its structure, is subject to vast transformations during pregnancy which may be observed as the thinning of the barrier separating the maternal blood from the fetal one, from 20-30 microm in the first trimester of gestation down to 2-4 microm in the third trimester of gestation.

  9. Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment

    PubMed Central

    Savige, Judy

    2014-01-01

    The glomerular filtration barrier comprises a fenestrated capillary endothelium, glomerular basement membrane and podocyte slit diaphragm. Over the past decade we have come to realise that permselectivity depends on size and not necessarily charge, that the molecular sieve depends on the podocyte contractile apparatus and is highly dynamic, and that protein uptake by proximal tubular epithelial cells stimulates signalling and the production of transcription factors and inflammatory mediators. Alport syndrome is the second commonest monogenic cause of renal failure after autosomal dominant polycystic kidney disease. Eighty per cent of patients have X-linked disease caused by mutations in the COL4A5 gene. Most of these result in the replacement of the collagen IV α3α4α5 network with the α1α1α2 heterotrimer. Affected membranes also have ectopic laminin and increased matrix metalloproteinase levels, which makes them more susceptible to proteolysis. Mechanical stress, due to the less elastic membrane and hypertension, interferes with integrin-mediated podocyte–GBM adhesion. Proteinuria occurs when urinary levels exceed tubular reabsorption rates, and initiates tubulointerstitial fibrosis. The glomerular mesangial cells produce increased TGFβ and CTGF which also contribute to glomerulosclerosis. Currently there is no specific therapy for Alport syndrome. However treatment with angiotensin converting enzyme (ACE) inhibitors delays renal failure progression by reducing intraglomerular hypertension, proteinuria, and fibrosis. Our greater understanding of the mechanisms underlying the GBM changes and their consequences in Alport syndrome have provided us with further novel therapeutic targets. PMID:25107927

  10. Hemoglobin-based O2 carrier O2 affinity and capillary inlet pO2 are important factors that influence O2 transport in a capillary.

    PubMed

    Dimino, Michael L; Palmer, Andre F

    2007-01-01

    Hemopure (Biopure; Cambridge, MA) and PolyHeme (Northfield Laboratories; Evanston, IL) are two acellular hemoglobin-based O2 carriers (HBOCs) currently in phase III clinical trials for use as red blood cell substitutes. The most common adverse side effect that these HBOCs exhibit is increased vasoconstriction. Autoregulatory theory has been presented as a possible explanation for this physiological effect, where it is hypothesized that low-affinity HBOCs over-deliver O2 to tissues surrounding arterioles, thereby eliciting vasoconstriction. In this paper, we wanted to investigate HBOC oxygenation of tissue surrounding a capillary, which is the smallest element of the circulatory system. An a priori model has been developed in which the performance of mixtures of acellular HBOCs (synthesized by our group and others) and human red blood cells (hRBCs) has been simulated using a Krogh tissue cylinder model (KTCM) comprising a capillary surrounded by a capillary membrane and skeletal muscle tissue in cylindrical coordinates with specified tissue O2 consumption rates and Michaelis-Menten kinetics. In this study, the total hemoglobin (hRBCs and HBOCs) concentration was kept constant. The HBOCs studied possessed O2 affinities that were higher and lower compared to hRBCs (P50's spanned 5-55 mmHg), and the equilibrium binding/release of oxygen to/from the HBOCs was modeled using the Adair equation. At normoxic inlet pO2's, there was no correlation between O2 flux out of the capillary and the O2 affinity of the HBOC. However, a correlation was found between the average pO2 tension in the capillary and the O2 affinity of the HBOC. Additionally, we studied the change in the O2 equilibrium curve of HBOCs with different O2 affinities over a wide range of inlet pO2's and found that changing the inlet pO2 greatly affected which HBOC, having a unique O2 affinity, best delivered O2 to the surrounding tissue. The analysis of oxygen transport presented could lead to a better prediction of which acellular HBOC is best suited for a specific transfusion application that many times depends on the capillary inlet pO2 tension.

  11. Effect of moisture on the traction-separation behavior of cellulose nanocrystal interfaces

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sinko, Robert; Keten, Sinan, E-mail: s-keten@northwestern.edu; Department of Civil and Environmental Engineering, Northwestern University, 2145 Sheridan Road, Room A136, Evanston, Illinois 60208

    2014-12-15

    Interfaces and stress transfer between cellulose nanocrystals (CNCs) dictate the mechanical properties of hierarchical cellulose materials such as neat films and nanocomposites. An interesting question that remains is how the behavior of these interfaces changes due to environmental stimuli, most notably moisture. We present analyses on the traction-separation behavior between Iβ CNC elementary fibrils, providing insight into how the presence of a single atomic layer of water at these interfaces can drastically change the mechanical behavior. We find that molecular water at the interface between hydrophilic CNC surfaces has a negligible effect on the tensile separation adhesion energy. However, whenmore » water cannot hydrogen bond easily to the surface (i.e., hydrophobic surface), it tends to maintain hydrogen bonds with other water molecules across the interface and form a capillary bridge that serves to increase the energy required to separate the crystals. Under shear loading, water lowers the energy barriers to sliding by reducing the atomic friction and consequently the interlayer shear modulus between crystals. Our simulations indicate that these nanoscale interfaces and physical phenomena such as interfacial adhesion, interlayer shear properties, and stick-slip friction behavior can be drastically altered by the presence of water.« less

  12. The use of impedance matching capillaries for reducing resonance in rosette infrasonic spatial filters.

    PubMed

    Hedlin, Michael A H; Alcoverro, Benoit

    2005-04-01

    Rosette spatial filters are used at International Monitoring System infrasound array sites to reduce noise due to atmospheric turbulence. A rosette filter consists of several clusters, or rosettes, of low-impedance inlets. Acoustic energy entering each rosette of inlets is summed, acoustically, at a secondary summing manifold. Acoustic energy from the secondary manifolds are summed acoustically at a primary summing manifold before entering the microbarometer. Although rosette filters have been found to be effective at reducing infrasonic noise across a broad frequency band, resonance inside the filters reduces the effectiveness of the filters at high frequencies. This paper presents theoretical and observational evidence that the resonance inside these filters that is seen below 10 Hz is due to reflections occuring at impedance discontinuities at the primary and secondary summing manifolds. Resonance involving reflections at the inlets amplifies noise levels at frequencies above 10 Hz. This paper further reports results from theoretical and observational tests of impedance matching capillaries for removing the resonance problem. Almost total removal of resonant energy below 5 Hz was found by placing impedance matching capillaries adjacent to the secondary summing manifolds in the pipes leading to the primary summing manifold and the microbarometer. Theory and recorded data indicate that capillaries with resistance equal to the characteristic impedance of the pipe connecting the secondary and primary summing manifolds suppresses resonance but does not degrade the reception of acoustic signals. Capillaries at the inlets can be used to remove resonant energy at higher frequencies but are found to be less effective due to the high frequency of this energy outside the frequency band of interest.

  13. Pore-scale modeling of wettability effects on CO2-brine displacement during geological storage

    NASA Astrophysics Data System (ADS)

    Basirat, Farzad; Yang, Zhibing; Niemi, Auli

    2017-11-01

    Wetting properties of reservoir rocks and caprocks can vary significantly, and they strongly influence geological storage of carbon dioxide in deep saline aquifers, during which CO2 is supposed to displace the resident brine and to become permanently trapped. Fundamental understanding of the effect of wettability on CO2-brine displacement is thus important for improving storage efficiency and security. In this study, we investigate the influence of wetting properties on two-phase flow of CO2 and brine at the pore scale. A numerical model based on the phase field method is implemented to simulate the two-phase flow of CO2-brine in a realistic pore geometry. Our focus is to study the pore-scale fluid-fluid displacement mechanisms under different wetting conditions and to quantify the effect of wettability on macroscopic parameters such as residual brine saturation, capillary pressure, relative permeability, and specific interfacial area. Our simulation results confirm that both the trapped wetting phase saturation and the normalized interfacial area increase with decreasing contact angle. However, the wetting condition does not appear to influence the CO2 breakthrough time and saturation. We also show that the macroscopic capillary pressures based on the pressure difference between inlet and outlet can differ significantly from the phase averaging capillary pressures for all contact angles when the capillary number is high (log Ca > -5). This indicates that the inlet-outlet pressure difference may not be a good measure of the continuum-scale capillary pressure. In addition, the results show that the relative permeability of CO2 can be significantly lower in strongly water-wet conditions than in the intermediate-wet conditions.

  14. Water Displacement in Oil-Wet Tight Reservoirs by Dynamic Network Simulation

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Li, M.; Chen, M.

    2017-12-01

    Pore network simulation is an effective tool for studying the multiphase flow in porous media. Based on the topological information and pore-throat size distribution obtained from the analysis of Scanning Electron Microscope (SEM) and constant-rate mercury injection (CRMI) for tight cores (composed by micro-nano scale throats and micro scale pores), a simple cubic (SC) pore-throat network was built with equilateral triangular cross-section throats and cubic bodies. Rules for oil and water movement and redistribution were devised in accordance with the physics process at pore-throat scale. Water flooding from oil-saturated under irreducible water were simulated by considering the changing displacement rate and viscosity ratio at the slightly oil-wet condition (the static contact angle ranges between π/2 to 2π/3). Different from the double pressure field algorithm, a single pressure field which solved by using successive over relaxation method was used with the flow of irreducible water in corners was ignored while its swilling was take into consideration. Dynamic of displacement fronts, relative permeability curves and residual oil saturation were obtained. It showed that there were obviously snap-off at low capillary number (Nc<10-5) and fingering at high capillary number (Nc<10-4) even at a favorable viscosity ratio (M=1). The magnitude of viscosity ratio effect on relative permeability depended largely on the capillary number, which the effect wasn't noticeable for a high capillary number. For residual oil saturation Sor, it showed that Sor decreased with the increase of capillary number at different viscosity ratio. Changing of residual oil saturation from simulation was in good agreement with the experimental results in a certain range, which indicated that this network model could be used to character the water flooding in tight reservoirs.

  15. Study on clinical effect and immunologic mechanism of infants capillary bronchitis secondary bronchial asthma treated with bacterial lysates Broncho-Vaxom.

    PubMed

    Han, R-F; Li, H-Y; Wang, J-W; Cong, X-J

    2016-05-01

    To study the clinical effects and immunologic mechanism of infant capillary bronchitis secondary bronchial asthma treated with bacterial lysates (Broncho-Vaxom OM-85BV). Between February 2013 and February 2014, 136 infant capillary bronchitis secondary bronchial asthma cases were chosen. This research was approved by Ethics Committee in our hospital and obtained the informed consent right from patients and guardians. Patients were divided into the control group (n = 62) and the observation group (n = 74) using random number table method. Patients in the control group were treated with normal glucocorticoid atomizing inhalation, aminophylline and antibiotic treatment. In the observation group besides the abovementioned treatment, we added Broncho-Vaxom OM-85BV, qd po for 10 days continuously and quitted it for 20 days. This continued for a total of 3 months. Follow-ups were set for about one year to compare the effects. The onset frequency and duration of capillary bronchitis and asthma in observation group declined remarkably compared with control group and the differences were statistically significant (p < 0.05). The level of IL-17 and IL-4 in the observation group decreased significantly, whereas, the level of IL-10 and IFN- γ increased considerably. Differences were all statistically significant (p < 0.05). Peripheral blood CD4+ T lymphocytes in the observation group patients expressed lower levels of nicotinic acetylcholine receptors α7 (α7nAChR) compared to the control group. Then difference was statistically significant (p < 0.05). Broncho-Vaxom OM-85BV reduced the onset of infant capillary bronchitis secondary bronchial asthma, relating to the reduced inflammation reaction. It also regulated the immunologic function of Th1/Th2, and lowered the α7nAChR level.

  16. Blood Vessel Adaptation with Fluctuations in Capillary Flow Distribution

    PubMed Central

    Hu, Dan; Cai, David; Rangan, Aaditya V.

    2012-01-01

    Throughout the life of animals and human beings, blood vessel systems are continuously adapting their structures – the diameter of vessel lumina, the thickness of vessel walls, and the number of micro-vessels – to meet the changing metabolic demand of the tissue. The competition between an ever decreasing tendency of luminal diameters and an increasing stimulus from the wall shear stress plays a key role in the adaptation of luminal diameters. However, it has been shown in previous studies that the adaptation dynamics based only on these two effects is unstable. In this work, we propose a minimal adaptation model of vessel luminal diameters, in which we take into account the effects of metabolic flow regulation in addition to wall shear stresses and the decreasing tendency of luminal diameters. In particular, we study the role, in the adaptation process, of fluctuations in capillary flow distribution which is an important means of metabolic flow regulation. The fluctuation in the flow of a capillary group is idealized as a switch between two states, i.e., an open-state and a close-state. Using this model, we show that the adaptation of blood vessel system driven by wall shear stress can be efficiently stabilized when the open time ratio responds sensitively to capillary flows. As micro-vessel rarefaction is observed in our simulations with a uniformly decreased open time ratio of capillary flows, our results point to a possible origin of micro-vessel rarefaction, which is believed to induce hypertension. PMID:23029014

  17. CE-MS analysis of heroin and its basic impurities using a charged polymer-protected gold nanoparticle-coated capillary.

    PubMed

    Zhang, Zhengxiang; Yan, Bo; Liu, Kelin; Liao, Yiping; Liu, Huwei

    2009-01-01

    The first application of charged polymer-protected gold nanoparticles (Au NPs) as semi-permanent capillary coating in CE-MS was presented. Poly(diallyldimethylammonium chloride) (PDDA) was the only reducing and stabilizing agent for Au NPs preparation. Stable and repeatable coating with good tolerance to 0.1 M HCl, methanol, and ACN was obtained via a simple rinsing procedure. Au NPs enhanced the coating stability toward flushing by methanol, improved the run-to-run and capillary-to-capillary repeatabilities, and improved the separation efficiency of heroin and its basic impurities for tracing geographical origins of illicit samples. Baseline resolution of eight heroin-related alkaloids was achieved on the PDDA-protected Au NPs-coated capillary under the optimum conditions: 120 mM ammonium acetate (pH 5.2) with addition of 13% methanol, separation temperature 20 degrees C, applied voltage -20 kV, and capillary effective length 60.0 cm. CE-MS analysis with run-to-run RSDs (n=5) of migration time in the range of 0.43-0.62% and RSDs (n=5) of peak area in the range of 1.49-4.68% was obtained. The established CE-MS method would offer sensitive detection and confident identification of heroin and related compounds and provide an alternative to LC-MS and GC-MS for illicit drug control.

  18. Sheath-flow electrochemical detection of amino acids with a copper wire electrode in capillary electrophoresis.

    PubMed

    Inoue, Junji; Kaneta, Takashi; Imasaka, Totaro

    2012-09-01

    Here, we report the detection of native amino acids using a sheath-flow electrochemical detector with a working electrode made of copper wire. A separation capillary that was inserted into a platinum tube in the detector acted as a grounded electrode for electrophoresis and as a flow channel for sheath liquid. Sheath liquid flowed outside the capillary to support the transport of the separated analytes to the working electrode for electrochemical detection. The copper wire electrode was aligned at the outlet of the capillary in a wall-jet configuration. Amino acids injected into the capillary were separated following elution from the end of the capillary and detection by the copper electrode. Three kinds of copper electrodes with different diameters-50, 125, and 300 μm-were examined to investigate the effect of the electrode diameter on sensitivity. The peak widths of the analytes were independent of the diameter of the working electrode, while the 300-μm electrode led to a decrease in the signal-to-noise ratio compared with the 50- and 125-μm electrodes, which showed no significant difference. The flow rate of the sheath liquid was also varied to optimize the detection conditions. The limits of detection for amino acids ranged from 4.4 to 27 μM under optimal conditions. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Effect of interfacial slip on the thin film drainage time for two equal-sized, surfactant-free drops undergoing a head-on collision: A scaling analysis

    NASA Astrophysics Data System (ADS)

    Ramachandran, A.; Leal, L. G.

    2016-10-01

    Using a scaling analysis, we assess the impact of interfacial slip on the time required for the thin liquid film between two drops undergoing a head-on collision to drain to the critical thickness for rupture by van der Waals forces. Interfacial slip is included in our continuum development using a Navier slip boundary condition, with the slip coefficient modeled using previous theories [Helfand and Tagami, J. Chem. Phys. 57, 1812 (1972), 10.1063/1.1678491; Goveas and Fredrickson, Eur. Phys. J. B 2, 79 (1998), 10.1007/s100510050228]. Slip decreases hydrodynamic resistance and speeds up film drainage. It renders the dependence of the drainage time on capillary number stronger in the spherical-film regime, but, interestingly, this dependence is altered only weakly in the dimpled-film regime. A subtle effect of slip is that it increases the range of capillary numbers in which the film remains predominantly spherical in shape during drainage (as opposed to being dimpled), leading to significantly faster drainage for these capillary numbers. Slip also leads to an increase in the critical capillary number beyond which coalescence is not possible in a head-collision.

  20. Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

    NASA Technical Reports Server (NTRS)

    Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

    1995-01-01

    Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

  1. Open tubular capillary columns with basic templates made by the generalized preparation protocol in capillary electrochromatography chiral separation and template structural effects on chiral separation capability.

    PubMed

    Zaidi, Shabi Abbas; Lee, Seung Mi; Cheong, Won Jo

    2011-03-04

    Some open tubular (OT) molecule imprinted polymer (MIP) silica capillary columns have been prepared using atenolol, sulpiride, methyl benzylamine (MBA) and (1-naphthyl)-ethylamine (NEA) as templates by the pre-established generalized preparation protocol. The four MIP thin layers of different templates showed quite different morphologies. The racemic selectivity of each MIP column for the template enantiomers was optimized by changing eluent composition and pH. The template structural effects on chiral separation performance have been examined. This work verifies the versatility of the generalized preparation protocol for OT-MIP silica capillary columns by extending its boundary toward templates with basic functional group moieties. This study is the very first report to demonstrate a generalized MIP preparation protocol that is valid for both acidic and basic templates. The chiral separation performances of atenolol and sulpiride by the MIPs of this study were found better than or comparable to those of atenolol and sulpiride obtained by non-MIP separation techniques and those of some basic template enantiomers obtained by MIP based techniques. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

    PubMed

    Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

    2015-07-01

    The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015 International Society for Neurochemistry.

  3. Blood-brain Barrier Disruption Leads to Postoperative Cognitive Dysfunction.

    PubMed

    Wang, Bin; Li, Siyuan; Cao, Xipeng; Dou, Xinghui; Li, Jingzhu; Wang, Ling; Wang, Mingshan; Bi, Yanlin

    2017-01-01

    Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation. In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM). Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope. The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Laser illumination of multiple capillaries that form a waveguide

    DOEpatents

    Dhadwal, Harbans S.; Quesada, Mark A.; Studier, F. William

    1998-08-04

    A system and method are disclosed for efficient laser illumination of the interiors of multiple capillaries simultaneously, and collection of light emitted from them. Capillaries in a parallel array can form an optical waveguide wherein refraction at the cylindrical surfaces confines side-on illuminating light to the core of each successive capillary in the array. Methods are provided for determining conditions where capillaries will form a waveguide and for assessing and minimizing losses due to reflection. Light can be delivered to the arrayed capillaries through an integrated fiber optic transmitter or through a pair of such transmitters aligned coaxially at opposite sides of the array. Light emitted from materials within the capillaries can be carried to a detection system through optical fibers, each of which collects light from a single capillary, with little cross talk between the capillaries. The collection ends of the optical fibers can be in a parallel array with the same spacing as the capillary array, so that the collection fibers can all be aligned to the capillaries simultaneously. Applicability includes improving the efficiency of many analytical methods that use capillaries, including particularly high-throughput DNA sequencing and diagnostic methods based on capillary electrophoresis.

  5. Laser illumination of multiple capillaries that form a waveguide

    DOEpatents

    Dhadwal, H.S.; Quesada, M.A.; Studier, F.W.

    1998-08-04

    A system and method are disclosed for efficient laser illumination of the interiors of multiple capillaries simultaneously, and collection of light emitted from them. Capillaries in a parallel array can form an optical waveguide wherein refraction at the cylindrical surfaces confines side-on illuminating light to the core of each successive capillary in the array. Methods are provided for determining conditions where capillaries will form a waveguide and for assessing and minimizing losses due to reflection. Light can be delivered to the arrayed capillaries through an integrated fiber optic transmitter or through a pair of such transmitters aligned coaxially at opposite sides of the array. Light emitted from materials within the capillaries can be carried to a detection system through optical fibers, each of which collects light from a single capillary, with little cross talk between the capillaries. The collection ends of the optical fibers can be in a parallel array with the same spacing as the capillary array, so that the collection fibers can all be aligned to the capillaries simultaneously. Applicability includes improving the efficiency of many analytical methods that use capillaries, including particularly high-throughput DNA sequencing and diagnostic methods based on capillary electrophoresis. 35 figs.

  6. Device to improve detection in electro-chromatography

    DOEpatents

    Garguilo, Michael G.; Paul, Phillip H.; Rakestraw, David J.

    2000-01-01

    Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.

  7. Device to improve detection in electro-chromatography

    DOEpatents

    Garguilo, Michael G.; Paul, Phillip H.; Rakestraw, David J.

    2002-01-01

    Apparatus and method for improving the resolution of non-pressure driven capillary chromatographic systems, and particularly for capillary electrochromatography (CEC) systems. By reducing the cross-sectional area of a packed capillary column by means of a second open capillary contiguous with the outlet end of a packed capillary column, where the packed capillary column has a cross sectional area of between about 2 and 5 times that of the open capillary column, the phenomenon of band broadening in the transition region between the open capillary and the packed capillary column, where the individual components of the mixture are analyzed, can be eliminated, thereby providing for a significant improvement in resolution and more accurate detection and analysis.

  8. Pivotal debates and controversies on the structure and function of the avian respiratory system: setting the record straight.

    PubMed

    Maina, John N

    2017-08-01

    Among the extant air-breathing vertebrates, the avian respiratory system is structurally the most complex and functionally the most efficient gas exchanger. Having been investigated for over four centuries, some aspects of its biology have been extremely challenging and highly contentious and others still remain unresolved. Here, while assessing the most recent findings, four notable aspects of the structure and function of the avian respiratory system are examined critically to highlight the questions, speculations, controversies and debates that have arisen from past research. The innovative techniques and experiments that were performed to answer particular research questions are emphasised. The features that are outlined here concern the arrangement of the airways, the path followed by the inspired air, structural features of the lung and the air and blood capillaries, and the level of cellular defence in the avian respiratory system. Hitherto, based on association with the proven efficiency of naturally evolved and human-made counter-current exchange systems rather than on definite experimental evidence, a counter-current gas exchange system was suggested to exist in the avian respiratory system and was used to explain its exceptional efficiency. However, by means of an elegant experiment in which the direction of the air-flow in the lung was reversed, a cross-current system was shown to be in operation instead. Studies of the arrangement of the airways and the blood vessels corroborated the existence of a cross-current system in the avian lung. While the avian respiratory system is ventilated tidally, like most other invaginated gas exchangers, the lung, specifically the paleopulmonic parabronchi, is ventilated unidirectionally and continuously in a caudocranial (back-to-front) direction by synchronized actions of the air sacs. The path followed by the inspired air in the lung-air sac system is now known to be controlled by a mechanism of aerodynamic valving and not by anatomical valves or sphincters, as was previously supposed. The structural strength of the air and blood capillaries is derived from: the interdependence between the air and blood capillaries; a tethering effect between the closely entwined respiratory units; the presence of epithelial-epithelial cell connections (retinacula or cross-bridges) that join the blood capillaries while separating the air capillaries; the abundance and intricate arrangement of the connective tissue elements, i.e. collagen, elastin, and smooth muscle fibres; the presence of type-IV collagen, especially in the basement membranes of the blood-gas barrier and the epithelial-epithelial cell connections; and a putative tensegrity state in the lung. Notwithstanding the paucity of free surface pulmonary macrophages, the respiratory surface of the avian lung is well protected from pathogens and particulates by an assortment of highly efficient phagocytic cells. In commercial poultry production, instead of weak pulmonary cellular defence, stressful husbandry practices such as overcrowding, force-feeding, and intense genetic manipulation for rapid weight gain and egg production may account for the reported susceptibility of birds to aerosol-transmitted diseases. © 2016 Cambridge Philosophical Society.

  9. Sheathless interface for coupling capillary electrophoresis with mass spectrometry

    DOEpatents

    Wang, Chenchen; Tang, Keqi; Smith, Richard D.

    2014-06-17

    A sheathless interface for coupling capillary electrophoresis (CE) with mass spectrometry is disclosed. The sheathless interface includes a separation capillary for performing CE separation and an emitter capillary for electrospray ionization. A portion of the emitter capillary is porous or, alternatively, is coated to form an electrically conductive surface. A section of the emitter capillary is disposed within the separation capillary, forming a joint. A metal tube, containing a conductive liquid, encloses the joint.

  10. Design of Capillary Flows with Spatially Graded Porous Films

    NASA Astrophysics Data System (ADS)

    Joung, Young Soo; Figliuzzi, Bruno Michel; Buie, Cullen

    2013-11-01

    We have developed a new capillary tube model, consisting of multi-layered capillary tubes oriented in the direction of flow, to predict capillary speeds on spatially graded porous films. Capillary flows through thin porous media have been widely utilized for small size liquid transport systems. However, for most media it is challenging to realize arbitrary shapes and spatially functionalized micro-structures with variable flow properties. Therefore, conventional media can only be used for capillary flows obeying Washburn's equation and the modifications thereof. Given this background, we recently developed a method called breakdown anodization (BDA) to produce highly wetting porous films. The resulting surfaces show nearly zero contact angles and fast water spreading speed. Furthermore, capillary pressure and spreading diffusivity can be expressed as functions of capillary height when customized electric fields are used in BDA. From the capillary tube model, we derived a general capillary flow equation of motion in terms of capillary pressure and spreading diffusivity. The theoretical model shows good agreement with experimental capillary flows. The study will provide novel design methodologies for paper-based microfluidic devices.

  11. Measurement of ozone production scaling in a helium plasma jet with oxygen admixture

    NASA Astrophysics Data System (ADS)

    Sands, Brian; Ganguly, Biswa

    2012-10-01

    Capillary dielectric barrier plasma jet devices that generate confined streamer-like discharges along a rare gas flow can produce significant quantities of reactive oxygen species with average input powers ranging from 100 mW to >1 W. We have measured spatially-resolved ozone production in a He plasma jet with O2 admixture concentrations up to 5% using absorption spectroscopy of the O3 Hartley band system. A 20-ns risetime, 10-13 kV positive unipolar voltage pulse train was used to power the discharge, with pulse repetition rates varied from 1-20 kHz. The discharge was operated in a transient glow mode to scale the input power by adjusting the gap width between the anode and downstream cathodic plane. Peak ozone number densities in the range of 10^16 - 10^17 cm-3 were measured. At a given voltage, the density of ozone increased monotonically up to 3% O2 admixture (6 mm gap) as the peak discharge current decreased by an order of magnitude. Ozone production increased with distance from the capillary, consistent with observations by other groups. Atomic oxygen production inferred from O-atom 777 nm emission intensity did not scale with ozone as the input power was increased. The spatial distribution of ozone and scaling with input power will be presented.

  12. Placental Growth Factor Contributes to Micro-Vascular Abnormalization and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy

    PubMed Central

    Kowalczuk, Laura; Touchard, Elodie; Omri, Samy; Jonet, Laurent; Klein, Christophe; Valamanes, Fatemeh; Berdugo, Marianne; Bigey, Pascal; Massin, Pascale; Jeanny, Jean-Claude; Behar-Cohen, Francine

    2011-01-01

    Objective There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1). Materials and Methods pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis. Results After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation. Conclusion This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease. PMID:21408222

  13. Myristic Acid-Modified DA7R Peptide for Whole-Process Glioma-Targeted Drug Delivery.

    PubMed

    Ying, Man; Wang, Songli; Zhang, Mingfei; Wang, Ruifeng; Zhu, Hangchang; Ruan, Huitong; Ran, Danni; Chai, Zhilan; Wang, Xiaoyi; Lu, Weiyue

    2018-06-13

    The clinical treatment of aggressive glioma has been a great challenge, mainly because of the complexity of the glioma microenvironment and the existence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hampers the effective accumulation of most therapeutic agents in the glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis, and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma-targeted drug delivery strategy was proposed. The D A7R peptide has effective BBTB-penetrating and notable glioma-, angiogenesis-, and VM-targeting abilities. Herein, we designed a myristic acid modified D A7R ligand (MC- D A7R), which combines tumor-homing D A7R with BBB-penetrable MC. MC- D A7R was then immobilized to PEGylated liposomes (MC- D A7R-LS) to form a whole-process glioma-targeting system. MC- D A7R-LS exhibited exceptional internalization in glioma, tumor neovascular, and brain capillary endothelial cells. Enhanced BBTB- and BBB-traversing efficiencies were also observed on MC- D A7R-LS. Ex vivo imaging on brain tumors also demonstrated the feasibility of MC- D A7R-LS in intracranial glioma-homing, whereas the immunofluorescence studies demonstrated its GSC and angiogenesis homing. Furthermore, doxorubicin-loaded MC- D A7R-LS accomplished a remarkable therapeutic outcome, as a result of a synergistic improvement on the glioma microenvironment. Our study highlights the potential of the MC-modified D A7R peptide as a great candidate for the whole-process glioma-targeted drug delivery.

  14. MRI investigation of water-oil two phase flow in straight capillary, bifurcate channel and monolayered glass bead pack.

    PubMed

    Liu, Yu; Jiang, Lanlan; Zhu, Ningjun; Zhao, Yuechao; Zhang, Yi; Wang, Dayong; Yang, Mingjun; Zhao, Jiafei; Song, Yongchen

    2015-09-01

    The study of immiscible fluid displacement between aqueous-phase liquids and non-aqueous-phase liquids in porous media is of great importance to oil recovery, groundwater contamination, and underground pollutant migration. Moreover, the attendant viscous, capillary, and gravitational forces are essential to describing the two-phase flows. In this study, magnetic resonance imaging was used to experimentally examine the detailed effects of the viscous, capillary, and gravitational forces on water-oil flows through a vertical straight capillary, bifurcate channel, and monolayered glass-bead pack. Water flooding experiments were performed at atmospheric pressure and 37.8°C, and the evolution of the distribution and saturation of the oil as well as the characteristics of the two-phase flow were investigated and analyzed. The results showed that the flow paths, i.e., the fingers of the displacing phase, during the immiscible displacement in the porous medium were determined by the viscous, capillary, and gravitational forces as well as the sizes of the pores and throats. The experimental results afford a fundamental understanding of immiscible fluid displacement in a porous medium. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Underwater locomotion in a terrestrial beetle: combination of surface de-wetting and capillary forces

    PubMed Central

    Hosoda, Naoe; Gorb, Stanislav N.

    2012-01-01

    For the first time, we report the remarkable ability of the terrestrial leaf beetle Gastrophysa viridula to walk on solid substrates under water. These beetles have adhesive setae on their feet that produce a secretory fluid having a crucial role in adhesion on land. In air, adhesion is produced by capillary forces between the fluid-covered setae and the substrate. In general, capillary forces do not contribute to adhesion under water. However, our observations showed that these beetles may use air bubbles trapped between their adhesive setae to walk on flooded, inclined substrata or even under water. Beetle adhesion to hydrophilic surfaces under water was lower than that in air, whereas adhesion to hydrophobic surfaces under water was comparable to that in air. Oil-covered hairy pads had a pinning effect, retaining the air bubbles on their feet. Bubbles in contact with the hydrophobic substrate de-wetted the substrate and produced capillary adhesion. Additional capillary forces are generated by the pad's liquid bridges between the foot and the substrate. Inspired by this idea, we designed an artificial silicone polymer structure with underwater adhesive properties. PMID:22874756

  16. Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry

    PubMed Central

    2016-01-01

    We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ∼5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of-concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected. PMID:27249533

  17. Correlation of refrigerant mass flow rate through adiabatic capillary tubes using mixture refrigerant carbondioxide and ethane for low temperature applications

    NASA Astrophysics Data System (ADS)

    Nasruddin, Syaka, Darwin R. B.; Alhamid, M. Idrus

    2012-06-01

    Various binary mixtures of carbon dioxide and hydrocarbons, especially propane or ethane, as alternative natural refrigerants to Chlorofluorocarbons (CFCs) or Hydro fluorocarbons (HFCs) are presented in this paper. Their environmental performance is friendly, with an ozone depletion potential (ODP) of zero and Global-warming potential (GWP) smaller than 20. The capillary tube performance for the alternative refrigerant HFC HCand mixed refrigerants have been widely studied. However, studies that discuss the performance of the capillary tube to a mixture of natural refrigerants, in particular a mixture of azeotrope carbon dioxide and ethane is still undeveloped. A method of empirical correlation to determine the mass flow rate and pipe length has an important role in the design of the capillary tube for industrial refrigeration. Based on the variables that effect the rate of mass flow of refrigerant in the capillary tube, the Buckingham Pi theorem formulated eight non-dimensional parameters to be developed into an empirical equations correlation. Furthermore, non-linear regression analysis used to determine the co-efficiency and exponent of this empirical correlation based on experimental verification of the results database.

  18. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

    PubMed

    Østergaard, Leif; Jespersen, Sune Nørhøj; Mouridsen, Kim; Mikkelsen, Irene Klærke; Jonsdottír, Kristjana Ýr; Tietze, Anna; Blicher, Jakob Udby; Aamand, Rasmus; Hjort, Niels; Iversen, Nina Kerting; Cai, Changsi; Hougaard, Kristina Dupont; Simonsen, Claus Z; Von Weitzel-Mudersbach, Paul; Modrau, Boris; Nagenthiraja, Kartheeban; Riisgaard Ribe, Lars; Hansen, Mikkel Bo; Bekke, Susanne Lise; Dahlman, Martin Gervais; Puig, Josep; Pedraza, Salvador; Serena, Joaquín; Cho, Tae-Hee; Siemonsen, Susanne; Thomalla, Götz; Fiehler, Jens; Nighoghossian, Norbert; Andersen, Grethe

    2013-05-01

    The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

  19. Evaluation of interactions between RAW264.7 macrophages and small molecules by capillary electrophoresis.

    PubMed

    Wang, Feng-Qin; Li, Qiao-Qiao; Zhang, Qian; Wang, Yin-Zhen; Hu, Yuan-Jia; Li, Peng; Wan, Jian-Bo; Yang, Feng-Qing; Xia, Zhi-Ning

    2017-03-01

    In this study, the affinity interactions between RAW 264.7 macrophages and three small molecules including naringin, oleuropein and paeoniflorin were evaluated by affinity capillary electrophoresis (ACE), partial filling affinity capillary electrophoresis (PFACE) and frontal analysis capillary electrophoresis (FACE), respectively. The result indicated that ACE (varying concentrations of cell suspension were filled in the capillary as receptor) may not be suitable for the evaluation of interactions between cell and small molecules due to the high viscosity of cell suspension; PFACE can qualitatively evaluate the interaction, but the difference in viscosity between RAW264.7 suspension and buffer effects on the liner relationship between filling length and injection time, which makes the calculation of binding constant difficult. Furthermore, based on the PFACE results, naringin showed stronger interaction with macrophages than the other two molecules; taking advantage of the aggregation phenomenon of cell induced by electric field, FACE was successfully used to determine the stoichiometry (n = 5×10 9 ) and binding constant (K b = 1×10 4 L/mol) of the interaction between RAW264.7 and naringin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The Dynamics of Miscible Interfaces: Simulations

    NASA Technical Reports Server (NTRS)

    Meiburg, Eckart

    2002-01-01

    The goal of this experimental/computational investigation (joint with Prof Maxworthy at USC) has been to study the dynamics of miscible interfaces, both from a scientific and a practical point of view, and to prepare a related experiment to be flown on the International Space Station. In order to address these effects, we have focused experimental and computational investigations on miscible displacements in cylindrical capillary tubes, as well as in Hele-Shaw cells. Regarding the flow in a capillary tube, the question was addressed as to whether Korteweg stresses and/or divergence effects can potentially account for discrepancies observed between conventional Stokes flow simulations and experiments for miscible flows in capillary tubes. An estimate of the vorticity and streamfunction fields induced by the Kortewegs stresses was derived, which shows these stresses to result in the formation of a vortex ring structure near the tip of the concentration front. Through this mechanism the propagation velocity of the concentration front is reduced, in agreement with the experimental observations. Divergence effects, on the other hand, were seen to be very small, and they have a negligible influence on the tip velocity. As a result, it can be concluded that they are not responsible for the discrepancies between experiments and conventional Stokes simulations. A further part of our investigation focussed on the development of high-accuracy three-dimensional spectral element simulation techniques for miscible flows in capillary tubes, including the effects of variable density and viscosity. Towards this end, the conservation equations are treated in cylindrical coordinates.

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