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Sample records for drain induced barrier

  1. Charge trapping induced drain-induced-barrier-lowering in HfO2/TiN p-channel metal-oxide-semiconductor-field-effect-transistors under hot carrier stress

    NASA Astrophysics Data System (ADS)

    Lo, Wen-Hung; Chang, Ting-Chang; Tsai, Jyun-Yu; Dai, Chih-Hao; Chen, Ching-En; Ho, Szu-Han; Chen, Hua-Mao; Cheng, Osbert; Huang, Cheng-Tung

    2012-04-01

    This letter studies the channel hot carrier stress (CHCS) behaviors on high dielectric constant insulator and metal gate HfO2/TiN p-channel metal-oxide-semiconductor field effect transistors. It can be found that the degradation is associated with electron trapping, resulting in Gm decrease and positive Vth shift. However, Vth under saturation region shows an insignificant degradation during stress. To compare that, the CHC-induced electron trapping induced DIBL is proposed to demonstrate the different behavior of Vth between linear and saturation region. The devices with different channel length are used to evidence the trapping-induced DIBL behavior.

  2. Steam bubble collapse induced water hammer in draining pipes

    SciTech Connect

    Griffith, P.; Silva, R.J.

    1991-08-01

    When hot steam replaces cold condensate in a horizontal or almost horizontal pipe, a steam bubble collapse induced water hammer often results. The effect of condensate drainage velocity and pipe declination on the incidence of steam bubble collapse induced water hammer is investigated experimentally. Declining the pipe more than 2.4{degrees} allows drainage velocities up to 3 ft/sec (1m/s) in a two inch (5 cm) pipe without water hammer. A semi-empirical theory allows extrapolation to other pressures, pipe sizes and inclinations. 4 refs.

  3. Characteristics of n-Type Asymmetric Schottky-Barrier Transistors with Silicided Schottky-Barrier Source and Heavily n-Type Doped Channel and Drain

    NASA Astrophysics Data System (ADS)

    Lin, Zer-Ming; Lin, Horng-Chih; Huang, Tiao-Yuan

    2012-06-01

    In this study, we explore the operation of operation a novel asymmetric Schottky-barrier transistor (ASSBT) through using technology computer aided design (TCAD). The new ASSBT features a silicided Schottky-barrier (SB) source, with the channel and drain made of heavily n-doped silicon. By eliminating the SB drain junction contained in conventional symmetrical-type SB metal-oxide-semiconductor field-effect transistors (MOSFETs), a larger on-state current is achievable. Moreover, combined with the adoption of fully depleted thin-film channel, the off-state leakage current can be efficiently suppressed as well. In addition, we also comprehensively analyze the transport mechanisms dominating in different operational regions of this new ASSBT. A pseudo-subthreshold region that shows worse subthreshold swing (SS) than the subthreshold region is identified. A decrease in channel and/or gate oxide thicknesses can contribute to the improvement of the SS of this region. A modified form of scaling length (λ) is also introduced to describe the impacts of structural parameters and gate configurations on the SS characteristics of this new ASSBT.

  4. Liquid draining shut-off induced geyser and slosh wave excitation at suction dip during draining in microgravity

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Shyu, K. L.

    1992-01-01

    The dynamical behavior of vapor ingestion, liquid residual at the incipience of suction dip, liquid hydrogen shut-off at the incipience of suction dip, and slosh wave excitation under normal and various reduced gravity environments and different flow rates of liquid during draining have been investigated. It shows that the liquid residual at the incipience of suction dip increases as the values of gravity environment decrease from normal gravity to lower reduced gravity, and also that the liquid residual increases as the flow rates of liquid increase during the courses of liquid hydrogen draining. It also shows that slosh waves accompanied by strong geyser are developed for surge-related flowfields at the moment of liquid hydrogen shut-off. Slosh wave excitation, during the liquid hydrogen shut-off, shift the fluid mass distribution in the container which imposes time-dependent variation in spacecraft moment of inertia.

  5. Liquid draining shut-off induced geyser and slosh wave excitation at suction dip during draining in microgravity

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Shyu, K. L.

    1992-01-01

    The dynamical behavior of vapor ingestion, liquid residual at the incipience of suction dip, liquid hydrogen shut-off at the incipience of suction dip, and slosh wave excitation under normal and various reduced gravity environments and different flow rates of liquid during draining have been investigated. It shows that the liquid residual at the incipience of suction dip increases as the values of gravity environment decrease from normal gravity to lower reduced gravity, and also that the liquid residual increases as the flow rates of liquid increase during the courses of liquid hydrogen draining. It also shows that slosh waves accompanied by strong geyser are developed for surge-related flowfields at the moment of liquid hydrogen shut-off. Slosh wave excitation, during the liquid hydrogen shut-off, shift the fluid mass distribution in the container which imposes time-dependent variation in spacecraft moment of inertia.

  6. Analysis of the effect of sidewall on the performance of 6H-SiC Schottky barrier source/drain NMOSFETs

    NASA Astrophysics Data System (ADS)

    Tang, Xiao-Yan; Zhang, Yi-Men; Zhang, Yu-Ming; Gao, Jin-Xia

    2004-07-01

    Between source/drain and gate of SiC Schottky barrier source/drain MOSFET (SiC SBSD-MOSFET), there must be a sidewall as isolation. The width of sidewall strongly affects on the device performance. In this paper the effect of sidewall on the performance of 6H-SiC SBSD-NMOSFET is simulated with the 2D simulator MEDICI. The simulated results show that a sidewall with width less than 0.1mum slightly affects the device performance. However, when the width of sidewall exceeds 0.1mum, the conduction does not occur until the drain voltage is high enough and saturation current sharply decreases. The effect of the sidewall on device performance can be reduced by decreasing the doping concentration in the epitaxial layer.

  7. Enhancement of programming speed on gate-all-around poly-silicon nanowire nonvolatile memory using self-aligned NiSi Schottky barrier source/drain

    NASA Astrophysics Data System (ADS)

    Ho, Ching-Yuan; Chang, Yaw-Jen; Chiou, Y. L.

    2013-08-01

    The programming characteristics of gate-all-around silicon-oxide-nitride-oxide silicon (SONOS) nonvolatile memories are presented using NiSi/poly-Si nanowires (SiNW) Schottky barrier (SB) heterojunctions. The non-uniform thermal stress distribution on SiNW channels due to joule heating affected the carrier transport behavior. Under a high drain voltage, impact ionization was found as a large lateral field enhances carrier velocity. As gate voltage (Vg) increased, the difference in the drain current within a range of various temperature conditions can be mitigated because a high gate field lowers the SB height of a NiSi source/SiNW/NiSi drain junction to ensure efficient hot-carrier generation. By applying the Fowler-Nordheim programming voltage to the SONOS nanowire memory, the SB height (Φn = 0.34 eV) could be reduced by image force; thus, hot electrons could be injected from SB source/drain electrodes into the SiN storage node. To compare both SiNW and Si nanocrystal SONOS devices, the SB SiNW SONOS device was characterized experimentally to propose a wider threshold-voltage window, exhibiting efficient programming characteristics.

  8. Hsp70 vaccination-induced primary immune responses in efferent lymph of the draining lymph node.

    PubMed

    Vrieling, Manouk; Santema, Wiebren; Vordermeier, Martin; Rutten, Victor; Koets, Ad

    2013-10-01

    Bovine paratuberculosis is a highly prevalent chronic infection of the small intestine in cattle, caused by Mycobacterium avium subspecies paratuberculosis (MAP). In earlier studies we showed the protective effect of Hsp70/DDA subunit vaccination against paratuberculosis. In the current study we set out to measure primary immune responses generated at the site of Hsp70 vaccination. Lymph vessel cannulation was performed to obtain efferent lymph from the prescapular lymph node draining the neck area where the vaccine was applied. Hsp70 vaccination induced a significant increase of CD21(+) B cells in efferent lymph, accounting for up to 40% of efferent cells post-vaccination. Proliferation (Ki67(+)) within the CD21(+) B cell and CD4(+) T cell populations peaked between day 3 and day 5 post-vaccination. From day 7, Hsp70-specific antibody secreting cells (ASCs) could be detected in efferent lymph. Hsp70-specific antibodies, mainly of the IgG1 isotype, were also detected from this time point onwards. However, post-vaccination IFN-γ production in efferent lymph was non-sustained. In conclusion, Hsp70-vaccination induces only limited Th1 type immune responsiveness as reflected in efferent lymph draining the vaccination site. This is in line with our previous observations in peripheral blood. The main primary immunological outcome of the Hsp70/DDA subunit vaccination is B cell activation and abundant Hsp70-specific IgG1 production. This warrants the question whether Hsp70-specific antibodies contribute to the observed protective effect of Hsp70 vaccination in calves.

  9. Barrier reduction via implementation of InGaN interlayer in wafer-bonded current aperture vertical electron transistors consisting of InGaAs channel and N-polar GaN drain

    SciTech Connect

    Kim, Jeonghee Laurent, Matthew A.; Li, Haoran; Lal, Shalini; Mishra, Umesh K.

    2015-01-12

    This letter reports the influence of the added InGaN interlayer on reducing the inherent interfacial barrier and hence improving the electrical characteristics of wafer-bonded current aperture vertical electron transistors consisting of an InGaAs channel and N-polar GaN drain. The current-voltage characteristics of the transistors show that the implementation of N-polar InGaN interlayer effectively reduces the barrier to electron transport across the wafer-bonded interface most likely due to its polarization induced downward band bending, which increases the electron tunneling probability. Fully functional wafer-bonded transistors with nearly 600 mA/mm of drain current at V{sub GS} = 0 V and L{sub go} = 2 μm have been achieved, and thus demonstrate the feasibility of using wafer-bonded heterostructures for applications that require active carrier transport through both materials.

  10. Barrier island bistability induced by biophysical interactions

    NASA Astrophysics Data System (ADS)

    Durán Vinent, Orencio; Moore, Laura J.

    2015-02-01

    Barrier islands represent about 10% of the world’s coastline, sustain rich ecosystems, host valuable infrastructure and protect mainland coasts from storms. Future climate-change-induced increases in the intensity and frequency of major hurricanes and accelerations in sea-level rise will have a significant impact on barrier islands--leading to increased coastal hazards and flooding--yet our understanding of island response to external drivers remains limited. Here, we find that island response is intrinsically bistable and controlled by previously unrecognized dynamics: the competing, and quantifiable, effects of storm erosion, sea-level rise, and the aeolian and biological processes that enable and drive dune recovery. When the biophysical processes driving dune recovery dominate, islands tend to be high in elevation and vulnerability to storms is minimized. Alternatively, when the effects of storm erosion dominate, islands may become trapped in a perpetual state of low elevation and maximum vulnerability to storms, even under mild storm conditions. When sea-level rise dominates, islands become unstable and face possible disintegration. This quantification of barrier island dynamics is supported by data from the Virginia Barrier Islands, USA and provides a broader context for considering island response to climate change and the likelihood of potentially abrupt transitions in island state.

  11. Cystic Fibrosis patients have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes

    PubMed Central

    Chan, Yvonne R.; Chen, Kong; Duncan, Steven R.; Lathrop, Kira; Latoche, Joseph; Logar, Alison; Pociask, Derek A.; Wahlberg, Brendon; Ray, Prabir; Ray, Anuradha; Pilewski, Joseph M.; Kolls, Jay K.

    2012-01-01

    Background Interleukin (IL)-17 is an important cytokine signature of a T helper differentiation pathway, Th17. This T cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remains to be completely characterized. Objective We set out to determine the frequency of Th17 cells in cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens. Methods Explanted lungs from patients undergoing transplant or organ donors (CF = 18, non-CF, non-bronchiectatic = 10) were collected. Hilar nodes and parenchymal lung tissue were processed. We examined them for Th17 signature by immunofluorescence and quantitative real time PCR. T cells were isolated and stimulated with antigens from Pseudomonas aeruginosa and Aspergillus. Cytokine profiles and staining by flow cytometry were used to assess the reactivity of these cells to antigen stimulation. Results We found a strong IL-17 phenotype in CF compared to non-CF controls. Within this tissue, we found pathogen-antigen-responsive CD4+IL17+ cells. There were double positive IL-17+IL-22+ cells and the IL-22+ population had higher proportions of memory characteristics. Antigen-specific Th17 responses were stronger in the draining lymph nodes compared to matched parenchymal lung. Conclusion Inducible proliferation of Th17(22) with memory cell characteristics is seen in CF lung. The function of these individual subpopulations will require further study regarding their development. T-cells are likely not the exclusive producers of IL-17 and IL-22 and this will require further characterization. PMID:22795370

  12. An analysis of molten-corium-induced failure of drain pipes in BWR Mark 2 containments

    SciTech Connect

    Taleyarkhan, R.P. ); Podowski, M.Z. )

    1991-01-01

    This study has focused on mechanistic simulation and analysis of potential failure modes for inpedestal drywell drain pipes in the Limerick boiling water reactor (BWR) Mark 2 containment. Physical phenomena related to surface tension breakdown, heatup, melting, ablation, crust formation and failure, and core material relocation into drain pipes with simultaneous melting of pipe walls were modeled and analyzed. The results of analysis have been used to assess the possibility of drain pipe failure and the resultant loss of pressure-suppression capability. Estimates have been made for the timing and amount of molten corium released to the wetwell. The study has revealed that significantly different melt progression sequences can result depending upon the failure characteristics of the frozen metallic crust which forms over the drain cover during the initial stages of debris pour. Another important result is that it can take several days for the molten fuel to ablate the frozen metallic debris layer -- if the frozen layer has cooled below 1100 K before fuel attack. 10 refs., 3 figs., 4 tabs.

  13. Effects of substrate leakage and drain-side thermal barriers in In0.53Ga0.47As/GaAs0.5Sb0.5 quantum-well tunneling field-effect transistors

    NASA Astrophysics Data System (ADS)

    Yu, Tao; Teherani, James T.; Antoniadis, Dimitri A.; Hoyt, Judy L.

    2014-09-01

    The device leakage current and the ON-state characteristics of In0.53Ga0.47As/GaAs0.5Sb0.5 quantum-well tunneling field-effect transistors (QWTFETs) are examined on the basis of temperature-dependent measurements. Different from commonly observed Shockley-Reed-Hall (SRH) recombination in the OFF-state, substrate leakage is identified as the source of OFF-current, which limits the steepness of the device transfer characteristics. In addition, analysis of the TFET operation in the linear regime reveals a current barrier due to an ungated region near the drain, which accounts for the unexpected parasitic resistance and current saturation at low temperatures. This barrier can be eliminated by reducing the gate-to-drain distance, as illustrated by device simulations. The applied methodology provides a design guideline for the gate-to-drain alignment tolerance in TFETs.

  14. Influence of source and drain contacts on the properties of indium-gallium-zinc-oxide thin-film transistors based on amorphous carbon nanofilm as barrier layer.

    PubMed

    Luo, Dongxiang; Xu, Hua; Zhao, Mingjie; Li, Min; Xu, Miao; Zou, Jianhua; Tao, Hong; Wang, Lei; Peng, Junbiao

    2015-02-18

    Amorphous indium-gallium-zinc-oxide thin film transistors (α-IGZO TFTs) with damage-free back channel wet-etch (BCE) process were achieved by introducing a carbon nanofilm as a barrier layer. We investigate the effects of different source-and-drain (S/D) materials on TFT performance. We find the TFT with Ti/C S/D electrodes exhibits a superior performance with higher output current, lower threshold voltage, and higher effective electron mobility compared to that of Mo/C S/D electrodes. Transmittance electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) are employed to analysis the interfacial interaction between S/D metal/C/α-IGZO layers. The results indicate that the better performance of TFTs with Ti/C electrodes should be attributed to the formations of Ti-C and Ti-O at the Ti/C-contact regions, which lead to a lower contact resistance, whereas Mo film is relatively stable and does not react easily with C nanofilm, resulting in a nonohmic contact behavior between Mo/C and α-IGZO layer. However, both kinds of α-IGZO TFTs show good stability under thermal bias stress, indicating that the inserted C nanofilms could avoid the impact on the α-IGZO channel regions during S/D electrodes formation. Finally, we successfully fabricated a high-definition active-matrix organic lighting emitting diode prototype driven by α-IGZO TFTs with Ti/C electrodes in a pilot line.

  15. Effect of asymmetrical double-pockets and gate-drain underlap on Schottky barrier tunneling FET: Ambipolar conduction vs. high frequency performance

    NASA Astrophysics Data System (ADS)

    Shaker, Ahmed; Ossaimee, Mahmoud; Zekry, A.

    2016-08-01

    In this paper, a proposed structure based on asymmetrical double pockets SB-TFET with gate-drain underlap is presented. 2D extensive modeling and simulation, using Silvaco TCAD, were carried out to study the effect of both underlap length and pockets' doping on the transistor performance. It was found that the underlap from the drain side suppresses the ambipolar conduction and doesn't enhance the high-frequency characteristics. The enhancement of the high-frequency characteristics could be realized by increasing the doping of the drain pocket over the doping of the source pocket. An optimum choice was found which gives the conditions of minimum ambipolar conduction, maximum ON current and maximum cut-off frequency. These enhancements render the device more competitive as a nanometer transistor.

  16. Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells.

    PubMed

    González, Fermín E; Ortiz, Carolina; Reyes, Montserrat; Dutzan, Nicolás; Patel, Vyomesh; Pereda, Cristián; Gleisner, Maria A; López, Mercedes N; Gutkind, J Silvio; Salazar-Onfray, Flavio

    2014-07-01

    We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.

  17. Influence of the Thickness of the Barrier Layer in Nanoheterostructures and the Gate-Drain Capacitance on the Microwave and Noise Parameters of Field-Effect AlGaN/GaN HEMT

    NASA Astrophysics Data System (ADS)

    Mikhaylovich, S. V.; Fedorov, Yu. V.

    2016-07-01

    We perform a computational and analytical study of how the thickness of the barrier layer in nanoheterostructures and the gate-drain capacitance C gd influence the microwave parameters (limiting frequency of current amplification and maximum generation frequency) and noise parameters (noise factor) of a field-effect AlGaN/GaN high electron mobility transistor. The results of complex measurements of the parameters of such transistors based on nanoheterostructures with a barrier layer thickness of 3.5-15.7 nm, which were performed within the framework of four technological routes in the range 0.1-67 GHz, are presented. It is shown that in order to reduce the noise ratio and improve the microwave parameters, it is necessary to optimize both the parameters of nanoheterostructures and the manufacturing techniques. In particular, the thickness of the barrier layer should be reduced, and the gate length should be chosen such as to maximize the product of the squared maximum current amplification frequency in the interior of the transistor and the output impedance between the drain and the source. Additionally, attention should be given to the shape of the gate to reduce the capacitance C gd. Under certain conditions of manufacture of nitride field-effect HEMT, one can achieve a lower noise factor compared with the transistors based on arsenide nanoheterostructures.

  18. Scaling of lowered source/drain (LSD) and raised source/drain (RSD) ultra-thin body (UTB) SOI MOSFETs

    NASA Astrophysics Data System (ADS)

    An, Xia; Huang, Ru; Zhang, Xing; Wang, Yangyuan

    2005-03-01

    Ultra-thin body (UTB) SOI MOSFETs are considered as one of most promising candidates for deca-nano-scale regimes. The device characteristics of two different UTB MOSFETs with raised source/drain (RSD) and lowered source/drain (LSD), respectively, are investigated with DC and AC considerations. The results suggest that LSD-UTB SOI MOSFETs show better control of the off-state leakage current, about one order of magnitude lower than that of RSD-UTB MOSFETs. The short-channel effect (SCE) and drain-induced-barrier-lowering (DIBL) effect are more effectively suppressed in LSD-UTB MOSFETs. And the intrinsic delay of LSD-UTB device is smaller than that of RSD-UTB as a result of the greatly reduced parasitic capacitance. In addition, the LSD-UTB MOSFETs demonstrate better scaling capability than RSD-UTB MOSFETs. And LSD-UTB can greatly relax the requirement for silicon body thickness by ˜60%.

  19. Drain vs No Drain After Colorectal Surgery.

    PubMed

    Tsujinaka, Shingo; Konishi, Fumio

    2011-03-01

    In colorectal surgery, drains are expected to prevent hematoma, fluid collection, or abscess formation, to act as an indicator of postoperative complication, or to minimize the severity of complication-related symptoms. Routine drainage has not been advocated by meta-analyses as they failed to demonstrate any benefit in reducing anastomotic leak rate, minimizing symptoms, or serving as a warning function. Moreover, some reports even showed that drain itself is an independent risk factor of anastomosis. The introduction of total mesorectal excision (TME) for rectal cancer surgery has given further concern to this controversial issue, that the use of drain decreased anastomotic failure rate and the need for surgical re-intervention. While controversy still remains, the choice of using drain is left to the individual surgeon's preference in daily practice. Therefore, surgeons should be well acquainted with purpose of drainage (prophylaxis, information, or treatment), characteristics (materials), clinical application of drain (type of drainage system, timing of removal), surgical outcomes after using drain (incidence of postoperative complication), and drain-related complications. If drains are used, careful observation with proper use is crucial for the management. It is important that the duration of drainage should not be inadequately extended. Any complications directly associated with the use of drain should be avoided. New concepts of drain have been proposed as diagnostic tool using biomarkers, and as preventive device against anastomotic leak. This article overviews the available, published data on the use of drain in colorectal surgery.

  20. Impact of hot-carrier stress on gate-induced floating body effects and drain current transients of thin gate oxide partially depleted SOI nMOSFETs

    NASA Astrophysics Data System (ADS)

    Rafí, J. M.; Simoen, E.; Mercha, A.; Campabadal, F.; Claeys, C.

    2005-09-01

    The impact of hot-carrier (HC) stress on thin gate oxide PD SOI nMOSFETs is investigated by analyzing the front and back channel current-voltage characteristics and the switch-off drain current transients. A particular hot-carrier degradation mode, characterized by a turn-around behavior for front gate threshold voltage degradation, is analyzed for devices with different geometries, bias conditions and source/drain architecture. A significant positive back gate threshold voltage shift is also observed after long HC stress. The maximum hot-carrier degradation (HCD) is obtained for the highest front gate biases, corresponding to the conditions of maximum electron valence band injection of majority carriers into the floating body. The presence of the HCD is found to reduce both the generation and the recombination switch-off drain current transient times. Unbiased thermal annealing in the range of 200-250 °C significantly reduces the hot-carrier-induced damage affecting the back channel characteristics. Whereas front gate direct tunnel stress is not causing any significant degradation for stress biases up to about two times the power supply for this technology node and reasonably short stress times, for the highest stress conditions the drain current transients are found to be progressively faster till front gate dielectric breakdown occurs.

  1. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

    PubMed

    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  2. Anomalous increase in hot-carrier-induced threshold voltage shift in n-type drain extended metal-oxide-semiconductor transistors

    NASA Astrophysics Data System (ADS)

    Chen, Jone F.; Chen, Shiang-Yu; Lee, J. R.; Wu, Kuo-Ming; Huang, Tsung-Yi; Liu, C. M.

    2008-03-01

    Anomalous increase in positive threshold voltage shift (ΔVT) in n-type drain extended metal-oxide-semiconductor (DEMOS) transistors stressed under high drain voltage and gate voltage is observed. Charge pumping data and technology computer-aided-design simulations reveal that hot-electron injection and trapping in the gate oxide above channel region is responsible for ΔVT. Enhanced impact ionization rate resulted from the presence of large amount of negative oxide charge in channel region is identified to be the main mechanism for anomalous increase in ΔVT. From the results presented in this letter, hot-carrier-induced anomalous increase in ΔVT can become a serious reliability concern in DEMOS transistors.

  3. Oral or nasal antigen induces regulatory T cells that suppress arthritis and proliferation of arthritogenic T cells in joint draining lymph nodes.

    PubMed

    Broere, Femke; Wieten, Lotte; Klein Koerkamp, Elles I; van Roon, Joel A G; Guichelaar, Teun; Lafeber, Floris P J G; van Eden, Willem

    2008-07-15

    The propagation of mucosal tolerance as a therapeutic approach in autoimmune diseases remains a difficult goal to achieve, and therefore further mechanistic studies are necessary to develop potential clinical protocols to induce mucosal regulatory T cells (Tr cells). In this study we addressed whether oral or nasal proteoglycan induced functional Tr cells in the cartilage proteoglycan-induced chronic arthritis model. Both nasal and oral application of human proteoglycan before induction of disease suppressed arthritis severity and incidence. Tolerized mice showed enhanced numbers of IL-10 producing CD4(+) cells in the paw-draining lymph nodes. Furthermore, CD4(+) spleen cells displayed enhanced expression of molecules associated with Tr cells, such as IL-10, Foxp3, and TGF-beta. Transfer of CD4(+) spleen cells from mucosally tolerized donors into proteoglycan-immunized mice abolished arthritis and reduced humoral responses, indicative of Tr cells with the capacity to inhibit already induced immune responses. Tr cells were activated upon transfer, because enhanced proliferation was observed in the joint draining lymph nodes compared with activated T cells from nontolerized donors. Upon cotransfer with naive proteoglycan-specific T cells, mucosally induced Tr cells inhibited proliferation of these arthritogenic T cells in vivo. Herein we show that both oral and nasal Ag application induced Tr cells, which had a direct inhibitory effect on already established pathogenic B and T cell responses.

  4. Electrically Induced Redox Barriers for Treatment of Groundwater

    DTIC Science & Technology

    2005-03-01

    Chloride Calcium Nitrate Potassium Nitrite Magnesium Phosphate Sodium Fluoride Iron Sulfate Manganese Carbonate Chromium Bicarbonate Cadmium...mediated under field conditions. To assess changes in the microbial populations induced by the operation of the e-barrier, and to obtain a first-level...analysis and (b) total soil microbial DNA measurements. Produced Gases – At an electrical potential of 6.5 volts, gases were collected from the surface

  5. Zinc reduces epithelial barrier compromise induced by human seminal plasma

    PubMed Central

    Mullin, James M.; Diguilio, Katherine M.; Valenzano, Mary C.; Deis, Rachael; Thomas, Sunil; Zurbach, E. Peter; Abdulhaqq, Shaheed; Montaner, Luis J.

    2017-01-01

    Human semen has the potential to modulate the epithelial mucosal tissues it contacts, as seminal plasma (SP) is recognized to contain both pro- and anti-barrier components, yet its effects on epithelial barrier function are largely unknown. We addressed the role of human SP when exposed to the basal-lateral epithelial surface, a situation that would occur clinically with prior mechanical or disease-related injury of the human epithelial mucosal cell layers in contact with semen. The action of SP on claudins-2, -4, -5, and -7 expression, as well as on a target epithelium whose basolateral surface has been made accessible to SP, showed upregulation of claudins-4 and -5 in CACO-2 human epithelial cell layers, despite broad variance in SP-induced modulation of transepithelial electrical resistance and mannitol permeability. Upregulation of claudin-2 by SP also exhibited such variance by SP sample. We characterize individual effects on CACO-2 barrier function of nine factors known to be present abundantly in seminal plasma (zinc, EGF, citrate, spermine, fructose, urea, TGF, histone, inflammatory cytokines) to establish that zinc, spermine and fructose had significant potential to raise CACO-2 transepithelial resistance, whereas inflammatory cytokines and EGF decreased this measure of barrier function. The role of zinc as a dominant factor in determining higher levels of transepithelial resistance and lower levels of paracellular leak were confirmed by zinc chelation and exogenous zinc addition. As expected, SP presentation to the basolateral cell surface also caused a very dramatic yet transient elevation of pErk levels. Results suggest that increased zinc content in SP can compete against the barrier-compromising effect of negative modulators in SP when SP gains access to that epithelium’s basolateral surface. Prophylactic elevation of zinc in an epithelial cell layer prior to contact by SP may help to protect an epithelial barrier from invasion by SP-containing STD

  6. Barriers to Radiation-Induced In Situ Tumor Vaccination

    PubMed Central

    Wennerberg, Erik; Lhuillier, Claire; Vanpouille-Box, Claire; Pilones, Karsten A.; García-Martínez, Elena; Rudqvist, Nils-Petter; Formenti, Silvia C.; Demaria, Sandra

    2017-01-01

    The immunostimulatory properties of radiation therapy (RT) have recently generated widespread interest due to preclinical and clinical evidence that tumor-localized RT can sometimes induce antitumor immune responses mediating regression of non-irradiated metastases (abscopal effect). The ability of RT to activate antitumor T cells explains the synergy of RT with immune checkpoint inhibitors, which has been well documented in mouse tumor models and is supported by observations of more frequent abscopal responses in patients refractory to immunotherapy who receive RT during immunotherapy. However, abscopal responses following RT remain relatively rare in the clinic, and antitumor immune responses are not effectively induced by RT against poorly immunogenic mouse tumors. This suggests that in order to improve the pro-immunogenic effects of RT, it is necessary to identify and overcome the barriers that pre-exist and/or are induced by RT in the tumor microenvironment. On the one hand, RT induces an immunogenic death of cancer cells associated with release of powerful danger signals that are essential to recruit and activate dendritic cells (DCs) and initiate antitumor immune responses. On the other hand, RT can promote the generation of immunosuppressive mediators that hinder DCs activation and impair the function of effector T cells. In this review, we discuss current evidence that several inhibitory pathways are induced and modulated in irradiated tumors. In particular, we will focus on factors that regulate and limit radiation-induced immunogenicity and emphasize current research on actionable targets that could increase the effectiveness of radiation-induced in situ tumor vaccination. PMID:28348554

  7. Retinoic acid induces blood-brain barrier development.

    PubMed

    Mizee, Mark R; Wooldrik, Desiree; Lakeman, Kim A M; van het Hof, Bert; Drexhage, Joost A R; Geerts, Dirk; Bugiani, Marianna; Aronica, Eleonora; Mebius, Reina E; Prat, Alexandre; de Vries, Helga E; Reijerkerk, Arie

    2013-01-23

    The blood-brain barrier (BBB) is crucial in the maintenance of a controlled environment within the brain to safeguard optimal neuronal function. The endothelial cells (ECs) of the BBB possess specific properties that restrict the entry of cells and metabolites into the CNS. The specialized BBB endothelial phenotype is induced during neurovascular development by surrounding cells of the CNS. However, the molecular differentiation of the BBB endothelium remains poorly understood. Retinoic acid (RA) plays a crucial role in the brain during embryogenesis. Because radial glial cells supply the brain with RA during the developmental cascade and associate closely with the developing vasculature, we hypothesize that RA is important for the induction of BBB properties in brain ECs. Analysis of human postmortem fetal brain tissue shows that the enzyme mainly responsible for RA synthesis, retinaldehyde dehydrogenase, is expressed by radial glial cells. In addition, the most important receptor for RA-driven signaling in the CNS, RA-receptor β (RARβ), is markedly expressed by the developing brain vasculature. Our findings have been further corroborated by in vitro experiments showing RA- and RARβ-dependent induction of different aspects of the brain EC barrier. Finally, pharmacologic inhibition of RAR activation during the differentiation of the murine BBB resulted in the leakage of a fluorescent tracer as well as serum proteins into the developing brain and reduced the expression levels of important BBB determinants. Together, our results point to an important role for RA in the induction of the BBB during human and mouse development.

  8. Self-induced dust traps: overcoming planet formation barriers

    NASA Astrophysics Data System (ADS)

    Gonzalez, J.-F.; Laibe, G.; Maddison, S. T.

    2017-01-01

    Planet formation is thought to occur in discs around young stars by the aggregation of small dust grains into much larger objects. The growth from grains to pebbles and from planetesimals to planets is now fairly well understood. The intermediate stage has however been found to be hindered by the radial-drift and fragmentation barriers. We identify a powerful mechanism in which dust overcomes both barriers. Its key ingredients are i) backreaction from the dust onto the gas, ii) grain growth and fragmentation, and iii) large-scale gradients. The pile-up of growing and fragmenting grains modifies the gas structure on large scales and triggers the formation of pressure maxima, in which particles are trapped. We show that these self-induced dust traps are robust: they develop for a wide range of disc structures, fragmentation thresholds and initial dust-to-gas ratios. They are favored locations for pebbles to grow into planetesimals, thus opening new paths towards the formation of planets.

  9. The Draining Cylinder

    ERIC Educational Resources Information Center

    James Graham-Eagle

    2009-01-01

    This article explores the time it takes for a liquid to drain from a cylindrical container through a hole in the bottom. Using dimensional analysis and some thought experiments this time is determined and Torricelli's law derived as a consequence. Finally, the effect of pouring liquid into the container as it drains is considered.

  10. The Draining Cylinder

    ERIC Educational Resources Information Center

    James Graham-Eagle

    2009-01-01

    This article explores the time it takes for a liquid to drain from a cylindrical container through a hole in the bottom. Using dimensional analysis and some thought experiments this time is determined and Torricelli's law derived as a consequence. Finally, the effect of pouring liquid into the container as it drains is considered.

  11. Effects of drain bias on the statistical variation of double-gate tunnel field-effect transistors

    NASA Astrophysics Data System (ADS)

    Choi, Woo Young

    2017-04-01

    The effects of drain bias on the statistical variation of double-gate (DG) tunnel field-effect transistors (TFETs) are discussed in comparison with DG metal–oxide–semiconductor FETs (MOSFETs). Statistical variation corresponds to the variation of threshold voltage (V th), subthreshold swing (SS), and drain-induced barrier thinning (DIBT). The unique statistical variation characteristics of DG TFETs and DG MOSFETs with the variation of drain bias are analyzed by using full three-dimensional technology computer-aided design (TCAD) simulation in terms of the three dominant variation sources: line-edge roughness (LER), random dopant fluctuation (RDF) and workfunction variation (WFV). It is observed than DG TFETs suffer from less severe statistical variation as drain voltage increases unlike DG MOSFETs.

  12. Ionic liquid gating on atomic layer deposition passivated GaN: Ultra-high electron density induced high drain current and low contact resistance

    SciTech Connect

    Zhou, Hong; Du, Yuchen; Ye, Peide D.

    2016-05-16

    Herein, we report on achieving ultra-high electron density (exceeding 10{sup 14 }cm{sup −2}) in a GaN bulk material device by ionic liquid gating, through the application of atomic layer deposition (ALD) of Al{sub 2}O{sub 3} to passivate the GaN surface. Output characteristics demonstrate a maximum drain current of 1.47 A/mm, the highest reported among all bulk GaN field-effect transistors, with an on/off ratio of 10{sup 5} at room temperature. An ultra-high electron density exceeding 10{sup 14 }cm{sup −2} accumulated at the surface is confirmed via Hall-effect measurement and transfer length measurement. In addition to the ultra-high electron density, we also observe a reduction of the contact resistance due to the narrowing of the Schottky barrier width on the contacts. Taking advantage of the ALD surface passivation and ionic liquid gating technique, this work provides a route to study the field-effect and carrier transport properties of conventional semiconductors in unprecedented ultra-high charge density regions.

  13. Ionic liquid gating on atomic layer deposition passivated GaN: Ultra-high electron density induced high drain current and low contact resistance

    NASA Astrophysics Data System (ADS)

    Zhou, Hong; Du, Yuchen; Ye, Peide D.

    2016-05-01

    Herein, we report on achieving ultra-high electron density (exceeding 1014 cm-2) in a GaN bulk material device by ionic liquid gating, through the application of atomic layer deposition (ALD) of Al2O3 to passivate the GaN surface. Output characteristics demonstrate a maximum drain current of 1.47 A/mm, the highest reported among all bulk GaN field-effect transistors, with an on/off ratio of 105 at room temperature. An ultra-high electron density exceeding 1014 cm-2 accumulated at the surface is confirmed via Hall-effect measurement and transfer length measurement. In addition to the ultra-high electron density, we also observe a reduction of the contact resistance due to the narrowing of the Schottky barrier width on the contacts. Taking advantage of the ALD surface passivation and ionic liquid gating technique, this work provides a route to study the field-effect and carrier transport properties of conventional semiconductors in unprecedented ultra-high charge density regions.

  14. Osteopontin deficiency affects imiquimod-induced psoriasis-like murine skin inflammation and lymphocyte distribution in skin, draining lymph nodes and spleen.

    PubMed

    Frenzel, Denis F; Borkner, Lisa; Scheurmann, Jan; Singh, Kamayani; Scharffetter-Kochanek, Karin; Weiss, Johannes M

    2015-04-01

    Osteopontin (OPN) that enhances autoimmunity is expressed in psoriasis lesions; however, its functions in psoriatic inflammation are unknown. We investigated the role of OPN in OPN deficient mice (OPN-/-) by inducing psoriasis-like inflammation through skin application of imiquimod (IMQ). OPN-/- mice treated with IMQ showed delayed onset ear swelling and attracted less inflammatory cells to the skin. IMQ-induced lymph node swelling was reduced in the absence of OPN, and IMQ-mediated expansion of B cells was inhibited. Further, reduction of CD4(+) T-cell numbers by IMQ in lymph nodes was suppressed in OPN-/- mice, with an increase in the CD4/CD8 ratio. A comparable pattern was found in spleen. Importantly, IMQ-induced IL-17 and IL-4 expression by CD4(+) lymph node T cells was reduced in OPN-/- mice. In conclusion, OPN may modulate psoriasis-like inflammation through altering lymphocyte distribution in skin and draining lymph nodes and by inducing IL-17 expression of inflammatory T cells.

  15. Short-channel drain current model for asymmetric heavily / lightly doped DG MOSFETs

    NASA Astrophysics Data System (ADS)

    Dutta, Pradipta; Syamal, Binit; Koley, Kalyan; Dutta, Arka; Sarkar, C. K.

    2017-08-01

    The paper presents a drain current model for double gate metal oxide semiconductor field effect transistors (DG MOSFETs) based on a new velocity saturation model that accounts for short-channel velocity saturation effect independently in the front and the back gate controlled channels under asymmetric front and back gate bias and oxide thickness. To determine the front and the back-channel velocity saturation, drain-induced barrier lowering is evaluated by effective gate voltages at the front and back gates obtained from surface potential at the threshold condition after considering symmetric and asymmetric front and back oxide thickness. The model also incorporates surface roughness scattering and ionized impurity scattering to estimate drain current for heavily / lightly doped channel for short-channel asymmetric DG MOSFET and a good agreement has been achieved with TCAD simulations, with a relative error of around 3-7%.

  16. A threshold voltage model of short-channel fully-depleted recessed-source/drain (Re-S/D) UTB SOI MOSFETs including substrate induced surface potential effects

    NASA Astrophysics Data System (ADS)

    Kumar, Ajit; Tiwari, Pramod Kumar

    2014-05-01

    In this paper, a threshold voltage model of short-channel recessed-source/drain (Re-S/D) ultra-thin body (UTB) SOI MOSFETs has been presented considering the substrate induced surface potential (SISP) to improve the model accuracy over wide ranges of device parameters and substrate bias. The potential distribution of the front and the back surfaces of the Si-body have been derived using the evanescent mode analysis method in which the channel potential is broken into one-dimensional long-channel potential and two-dimensional short-channel potential. A one-dimensional Poisson's equation has also been solved in the substrate region to account the effect of substrate induced surface potential (SISP) at substrate/buried-oxide interface. The minimum front- and back-surface potentials of silicon body have been used to obtain front and back channel threshold voltages, respectively. However, the smaller one between front and back channel threshold voltages is considered to be the threshold voltage of the device. The accuracy of the present model has been extended up to 10 nm channel length by incorporating the quantum effects induced correction term. The model results are verified with simulation results obtained using ATLAS™ from Silvaco.

  17. Ultrasound-Induced Blood-Brain Barrier Opening

    PubMed Central

    Konofagou, Elisa E.; Tung, Yao-Sheng; Choi, James; Deffieux, Thomas; Baseri, Babak; Vlachos, Fotios

    2014-01-01

    Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe and localized opening of the BBB has been proven to present a significant challenge. Of the methods used for BBB disruption shown to be effective, Focused Ultrasound (FUS), in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. FUS may thus have a huge impact in trans-BBB brain drug delivery. The primary objective in this paper is to elucidate the interactions between ultrasound, microbubbles and the local microenvironment during BBB opening with FUS, which are responsible for inducing the BBB disruption. The mechanism of the BBB opening in vivo is monitored through the MRI and passive cavitation detection (PCD), and the safety of BBB disruption is assessed using H&E histology at distinct pressures, pulse lengths and microbubble diameters. It is hereby shown that the BBB can be disrupted safely and transiently under specific acoustic pressures (under 0.45 MPa) and microbubble (diameter under 8 μm) conditions. PMID:22201586

  18. Ultrasound-induced blood-brain barrier opening.

    PubMed

    Konofagou, Elisa E; Tung, Yao-Sheng; Choi, James; Deffieux, Thomas; Baseri, Babak; Vlachos, Fotios

    2012-06-01

    Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe and localized opening of the BBB has been proven to present a significant challenge. Of the methods used for BBB disruption shown to be effective, Focused Ultrasound (FUS), in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. FUS may thus have a huge impact in trans-BBB brain drug delivery. The primary objective in this paper is to elucidate the interactions between ultrasound, microbubbles and the local microenvironment during BBB opening with FUS, which are responsible for inducing the BBB disruption. The mechanism of the BBB opening in vivo is monitored through the MRI and passive cavitation detection (PCD), and the safety of BBB disruption is assessed using H&E histology at distinct pressures, pulse lengths and microbubble diameters. It is hereby shown that the BBB can be disrupted safely and transiently under specific acoustic pressures (under 0.45 MPa) and microbubble (diameter under 8 μm) conditions.

  19. Observation of Tropical Cyclone Self-Induced Barrier Layer

    NASA Astrophysics Data System (ADS)

    Steffen, J.; Chen, S.; Shay, L. K.; Jaimes de la Cruz, B.

    2016-02-01

    Analysis of 153 in-situ ocean profiles influenced by three hurricanes, Isaac (category 1), Iselle (category 4), and Julio (category 3) reveal these hurricanes can create their own salinity-driven ocean barrier layer from heavy precipitation. The freshening of salinity that results from 150-300 mm of rainfall in these hurricanes is about 0.1-0.2 PSU. Eastern Pacific Argo floats near the tracks of Iselle and Julio indicate the barrier layer potential energy values (BLPE) are between 750- 2000 J/m² just after TC passage. AXCTD profiles deployed before, during, and after Isaac in the Gulf of Mexico show how the barrier layer develops throughout a TC passage. In these TCs, the corresponding maximum barrier depths are only 10-20 m deep and are independent of density stratification within the isothermal layer. This suggests BLPE is a better measure of barrier layers' capacity to suppress mixing and minimize SST cooling from hurricanes.

  20. Performance Evaluation and Design Considerations of Electrically Activated Drain Extension Tunneling GNRFET: A Quantum Simulation Study

    NASA Astrophysics Data System (ADS)

    Ghoreishi, Seyed Saleh; Yousefi, Reza; Taghavi, Neda

    2017-07-01

    In this paper, a tunneling graphene nanoribbon field effect transistor with electrically activated drain extension, namely, EA-T-GNRFET, is proposed. The proposed structure includes a side gate at the drain side with a constant voltage and length of 0.4 V and 15 nm, respectively. Simulations are performed based on the non-equilibrium Green's function method coupled with the Poisson equation in the mode space representation. This side gate creates an additional step in potential profile at the drain side, which increases and decreases the width of tunneling barrier and leakage current, respectively. Furthermore, the proposed structure has lower drain induced barrier thinning, lower sub-threshold swing (SS) and higher I ON/I OFF ratio than the conventional structure. Also, other characteristics of the device such as switching delay ( τ ), power delay product (PDP) and unity-gain frequency (f t) are improved in the proposed device. These advantages make EA-T-GNRFET more suitable for digital and analog applications.

  1. Short-Channel Tunneling Field-Effect Transistor with Drain-Overlap and Dual-Metal Gate Structure for Low-Power and High-Speed Operations.

    PubMed

    Yoon, Young Jun; Eun, Hye Rim; Seo, Jae Hwa; Kang, Hee-Sung; Lee, Seong Min; Lee, Jeongmin; Cho, Seongjae; Tae, Heung-Sik; Lee, Jung-Hee; Kang, In Man

    2015-10-01

    We have investigated and proposed a highly scaled tunneling field-effect transistor (TFET) based on Ge/GaAs heterojunction with a drain overlap to suppress drain-induced barrier thinning (DIBT) and improve low-power (LP) performance. The highly scaled TFET with a drain overlap achieves lower leakage tunneling current because of the decrease in tunneling events between the source and drain, whereas a typical short-channel TFET suffers from a great deal of tunneling leakage current due to the DIBT at the off-state. However, the drain overlap inevitably increases the gate-to-drain capacitance (Cgd) because of the increase in the overlap capacitance (Cov) and inversion capacitance (Cinv). Thus, in this work, a dual-metal gate structure is additionally applied along with the drain overlap. The current performance and the total gate capacitance (Cgg) of the device with a dual-metal gate can be possibly controlled by adjusting the metal gate workfunction (φgate) and φoverlap-gate in the overlapping regions. As a result, the intrinsic delay time (τ) is greatly reduced by obtaining lower Cgg divided by the on-state current (Ion), i.e., Cgg/Ion. We have successfully demonstrated excellent LP and high-speed performance of a highly scaled TFET by adopting both drain overlap and dual-metal gate with DIBT minimization.

  2. Influence of Field-Induced Drain on the Characteristics of Poly-Si Thin-Film Transistor using a Self-Aligned Double Spacer Process

    NASA Astrophysics Data System (ADS)

    Ahn, Jeong-Ah; Kim, Ohyun

    2004-03-01

    The electric characteristics of field-induced drain (FID) poly-Si thin-film transistors (poly-Si TFT) with an independently biased self-aligned sub-gate using a double space process are investigated. The on/off current ratio of this FID TFT is approximately 9.3× 107 and the off-state leakage current is 200 times lower than that of the conventional TFT and 60 times lower than that of the LDD TFT at VSG=VDS=5 V. The self-aligned double spacer process can remove the sub-gate misalignment error and the length of the sub-gate can be easily controlled by the poly-Si thickness and a hard mask. In particular, the use of the dual hard mask can realize a long sub-gate without thick sub-gate poly-Si (>500 nm). The optimum sub-gate voltage is about 5 V and the optimum effective sub-gate length is between 200 nm and 300 nm in these FID TFTs.

  3. Photon induced tunneling of electron through a graphene electrostatic barrier

    SciTech Connect

    Biswas, R.; Sinha, C.

    2013-11-14

    The influence of an external intense laser field on the tunneling transport (ballistic) of the Dirac fermions through a monolayer graphene electrostatic barrier is studied in the framework of the Floquet approach for a continuous wave, linearly polarized, monochromatic laser. The Klein tunneling is shown to be suppressed by the irradiation of a strong laser field, arising due to breaking of chiral symmetry. The symmetric nature of the field free angular transmission spectrum around the normal to the well-barrier interface is destroyed due to the additional coupling between the pseudo-spin and the time dependent vector potential. The energy distribution of the tunneling spectrum displays Fano resonance which is absent for a laser assisted conventional electrostatic barrier but similar to the case of quantum well structures, providing an optical tool to identify field free quasi bound states inside the graphene nanostructures.

  4. Murine filaggrin-2 is involved in epithelial barrier function and down-regulated in metabolically induced skin barrier dysfunction.

    PubMed

    Hansmann, Britta; Ahrens, Kerstin; Wu, Zhihong; Proksch, Ehrhardt; Meyer-Hoffert, Ulf; Schröder, Jens-Michael

    2012-04-01

    The S100 fused-type proteins (SFTPs) are thought to be involved in the barrier formation and function of the skin. Mutations in the profilaggrin gene, one of the best investigated members of this family, are known to be the major risk factors for ichthyosis vulgaris and atopic dermatitis. Recently, we identified human filaggrin-2 as a new member of the SFTP family. To achieve further insight into its function, here the murine filaggrin-2 was analysed as a possible orthologue. The 5' and 3' ends of the mouse filaggrin-2 cDNA of the BALB/c strain were sequenced and confirmed an organization typical for SFTPs. Murine filaggrin-2 showed an expression pattern mainly in keratinizing epithelia in the upper cell layers on both mRNA and protein levels. The expression in cultured mouse keratinocytes was increased upon elevated Ca(2+) levels. Immunoblotting experiments indicated an intraepidermal processing of the 250-kDa full-length protein. In metabolically (essential fatty acid-deficient diet) induced skin barrier dysfunction, filaggrin-2 expression was significantly reduced, whereas filaggrin expression was up-regulated. In contrast, mechanical barrier disruption with acetone treatment did not affect filaggrin-2 mRNA expression. These results suggest that filaggrin-2 may contribute to epidermal barrier function and its regulation differs, at least in parts, from that of filaggrin.

  5. TNF-induced endothelial barrier disruption: beyond actin and Rho.

    PubMed

    Marcos-Ramiro, B; García-Weber, D; Millán, J

    2014-12-01

    The decrease of endothelial barrier function is central to the long-term inflammatory response. A pathological alteration of the ability of endothelial cells to modulate the passage of cells and solutes across the vessel underlies the development of inflammatory diseases such as atherosclerosis and multiple sclerosis. The inflammatory cytokine tumour necrosis factor (TNF) mediates changes in the barrier properties of the endothelium. TNF activates different Rho GTPases, increases filamentous actin and remodels endothelial cell morphology. However, inhibition of actin-mediated remodelling is insufficient to prevent endothelial barrier disruption in response to TNF, suggesting that additional molecular mechanisms are involved. Here we discuss, first, the pivotal role of Rac-mediated generation of reactive oxygen species (ROS) to regulate the integrity of endothelial cell-cell junctions and, second, the ability of endothelial adhesion receptors such as ICAM-1, VCAM-1 and PECAM-1, involved in leukocyte transendothelial migration, to control endothelial permeability to small molecules, often through ROS generation. These adhesion receptors regulate endothelial barrier function in ways both dependent on and independent of their engagement by immune cells, and orchestrate the crosstalk between leukocyte transendothelial migration and endothelial permeability during inflammation.

  6. Pavement base drain evaluation

    NASA Astrophysics Data System (ADS)

    Hoffman, G. L.

    1981-06-01

    Portions of a highway drainage system design was revised. Essentially, the longitudinal drainage trench was moved closer to the pavement/shoulder joint, and the fine concrete sand layer was eliminated as a trench backfill material. The specified backfill material is a coarser crushed aggregate (pea gravel). An evaluation of the effects of these changes on pavement performance is given and the new pavement base drain system is compared to the older pipe foundation underdrain system at the same site.

  7. Diet-induced obesity causes metabolic impairment independent of alterations in gut barrier integrity.

    PubMed

    Kless, Caroline; Müller, Veronika Maria; Schüppel, Valentina Luise; Lichtenegger, Martina; Rychlik, Michael; Daniel, Hannelore; Klingenspor, Martin; Haller, Dirk

    2015-05-01

    The causal relationship between diet-induced obesity and metabolic disorders is not clear yet. One hypothesis is whether the obese state or high-fat diet per se affects intestinal barrier function provoking metabolic comorbidities. In three independent experiments with AKR/J, SWR/J, or BL/6J mice, we addressed the impact of genetic background, excess body fat storage, duration of high-fat feeding, and quality/quantity of dietary fat on glucose tolerance and gut barrier integrity in vivo and ex vivo. Impaired glucose tolerance in diet-induced obese BL/6J and AKR/J mice was not accompanied by an altered intestinal barrier function. Enforced dietary challenge by prolonged feeding and increasing fat quantity in BL/6J mice still failed to aggravate metabolic and intestinal deterioration. Despite a low-grade inflammatory status in adipose tissue, barrier function of BL/6J mice fed lard high-fat diet revealed no evidence for a diet-induced loss in barrier integrity. None of our results provided any evidence that gut barrier function is a subject to dietary regulation and obesity per se seems not to cause gut barrier impairment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. NMDA- and endothelin-1-induced increases in blood-brain barrier permeability quantitated with Lucifer yellow.

    PubMed

    Miller, R D; Monsul, N T; Vender, J R; Lehmann, J C

    1996-03-01

    At 48 h following intrastriatal injection of N-methyl-D-aspartate (NMDA; 100 nmol/microliter) or endothelin-1 (ET-1; 143 pmol/microliter), significant increases in brain penetration of the highly polar, fluorescent tracer Lucifer yellow were observed. The competitive NMDA receptor antagonist selfotel (CGS-19755; 30 nmol/microliter, i.c.) significantly reduced the NMDA-induced increases in blood-brain barrier permeability, but not those induced by ET-1. These results suggest that NMDA receptors can mediate increases in blood-brain barrier permeability but do not primarily mediate increases in blood-brain barrier permeability caused by ET-1. This is the first study to our knowledge investigating the relationship between excitotoxicity and disruption of the blood-brain barrier, a major pathophysiological event in stroke and traumatic brain injury.

  9. Impaired skin barrier function in mice with colon carcinoma induced by azoxymethane and dextran sodium sulfate.

    PubMed

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2015-01-01

    We have previously reported that impaired skin barrier function was induced by small intestinal injury in mice. Therefore, we postulated that other intestinal diseases might also influence skin barrier function. In this study, we evaluated the skin barrier function of hairless mice with colon carcinoma that was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). In mice treated with these drugs, we observed elevated transepidermal water loss and reduced skin hydration levels, compared to those in the control mice. In addition, plasma nitrogen di/trioxide (NO2(-)/NO3(-)) levels were significantly elevated, and expression of type I collagen was significantly reduced in the treated mice, compared to those in control. These results suggest that impaired skin barrier function occurs in mice when colon carcinoma is present.

  10. Stacking fault induced tunnel barrier in platelet graphite nanofiber

    SciTech Connect

    Lan, Yann-Wen E-mail: ywlan@phys.sinica.edu.tw; Chang, Yuan-Chih; Chang, Chia-Seng; Chen, Chii-Dong E-mail: ywlan@phys.sinica.edu.tw; Chang, Wen-Hao; Li, Yuan-Yao

    2014-09-08

    A correlation study using image inspection and electrical characterization of platelet graphite nanofiber devices is conducted. Close transmission electron microscopy and diffraction pattern inspection reveal layers with inflection angles appearing in otherwise perfectly stacked graphene platelets, separating nanofibers into two domains. Electrical measurement gives a stability diagram consisting of alternating small-large Coulomb blockade diamonds, suggesting that there are two charging islands coupled together through a tunnel junction. Based on these two findings, we propose that a stacking fault can behave as a tunnel barrier for conducting electrons and is responsible for the observed double-island single electron transistor characteristics.

  11. Tidally induced ''upwelling'' by the Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Thompson, Rory O. R. Y.; Golding, T. J.

    1981-07-01

    The Great Barrier Reef is similar to some other coral reefs in growing right up to the edge of the shelf in a region of nutrient-poor surface water but large tides. It is suggested that the resultant strong tidal currents suck in nutrient-rich water from the depth where the tidal flow speed drops to the fastest internal wave speed. The nutrients could encourage the reef to grow vigorously at the edge of the shelf. Some observations in Cook's Passage (14°32'S, 145°34'E) were made to test the concept and are encouraging.

  12. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.

    PubMed

    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.

  13. Inflammation-induced alterations in the skin barrier function: implications in atopic dermatitis.

    PubMed

    Vestergaard, Christian; Hvid, Malene; Johansen, Claus; Kemp, Kaare; Deleuran, Bent; Deleuran, Mette

    2012-01-01

    The pathogenesis of atopic dermatitis (AD) is very complex, but best characterized by an inflammatory reaction in the skin and a disrupted skin barrier. Until recently, these two factors have been studied as separate entities; however, it has been shown that inflammatory cytokines can regulate filaggrin, a very important component of the skin barrier, as well as proteins involved in the processing and maturation of filaggrin. Therefore, inflammation itself may be able to induce a functional skin barrier dysfunction and thereby aggravate the eczematous reaction in AD.

  14. Induced phytoextraction/soil washing of lead using biodegradable chelate and permeable barriers.

    PubMed

    Kos, Bostjan; Lestan, Domen

    2003-02-01

    Chelate-induced remediation has been proposed as an effective tool for the extraction of lead (Pb) from contaminated soils by plants. However, side-effects, mainly mobilization and leaching of Pb, raise environmental concerns. Biodegradable, synthetic organic chelate ethylenediaminedisuccinic acid (EDDS), and commonly used ethylenedimanetetraacetic acid (EDTA) were used for induced phytoextraction with a test plant Brassica rapa and in situ washing of soil contaminated with 1350 mg/kg of Pb. Horizontal permeable barriers were placed 20 cm deep in soil columns and tested for their ability to prevent leaching of Pb. The reactive materials in the barriers were nutrient enriched vermiculite, peat or agricultural hydrogel, and apatite. EDTA and EDDS addition increased Pb concentrations in the test plant by 158 and 89 times compared to the control, to 817 and 464 mg/kg, respectively. In EDTA treatments, approximately 25% or more of total initial soil Pb was leached in single cycle of chelate addition. In EDDS treatments, 20% of the initial Pb was leached from columns with no barrier, while barriers with vermiculite or hydrogel and apatite decreased leaching by more than 60 times, to 0.35%. 11.6% of total initial Pb was washed from the soil above the barrier with vermiculite and apatite, where almost all leached Pb was accumulated. Results indicate that use of biodegradable chelate EDDS and permeable barriers may lead to environmentally safe induced Pb phytoextraction and in situ washing of Pb.

  15. Modeling Oxidation Induced Stresses in Thermal Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Ferguson, B. L.; Freborg, A. M.; Petrus, G. J.; Brindley, William J.

    1998-01-01

    The use of thermal barrier coatings (TBC's) in gas turbines has increased dramatically in recent years, due mainly to the need for component protection from ever increasing service temperatures. Oxidation of the bond coat has been identified as an important contributing factor to spallation of the ceramic top coat during service. Additional variables found to influence TBC thermal cycle life include bond coat coefficient of thermal expansion, creep behavior of both the ceramic and bond coat layers, and modulus of elasticity. The purpose of this work was to characterize the effects of oxidation on the stress states within the TBC system, as well as to examine the interaction of oxidation with other factors affecting TBC life.

  16. Nifedipine prevents sodium caprate-induced barrier dysfunction in human epidermal keratinocyte cultures.

    PubMed

    Uchino, Yoshihiro; Matsumoto, Junichi; Watanabe, Takuya; Hamabashiri, Masato; Tsuchiya, Takashi; Kimura, Ikuya; Yamauchi, Atsushi; Kataoka, Yasufumi

    2015-01-01

    Tight junctions (TJs) of the epidermis play an important role in maintaining the epidermal barrier. TJ breakdown is associated with skin problems, such as wrinkles and transepidermal water loss (TEWL). Clinical studies have reported that topical nifedipine is effective in reducing the depth of wrinkles and improving TEWL. However, it remains unknown whether nifedipine influences the TJ function in the epidermis. In the present study, we investigated the effect of nifedipine on epidermal barrier dysfunction in normal human epidermal keratinocytes (NHEKs) treated with sodium caprate (C10), a TJ inhibitor. Nifedipine reversed the C10-decreased transepithelial electrical resistance values as a measure of disruption of the epidermal barrier. Immunocytochemical observations revealed that nifedipine improved the C10-induced irregular arrangement of claudin-1, a key protein in TJs. Taken together, these findings suggest that nifedipine prevents epidermal barrier dysfunction, at least in part, by reconstituting the irregular claudin-1 localization at TJs in C10-treated NHEKs.

  17. On the drain bias dependence of long-channel silicon-on-insulator-based tunnel field-effect transistors

    NASA Astrophysics Data System (ADS)

    Fukuda, Koichi; Mori, Takahiro; Asai, Hidehiro; Hattori, Junichi; Mizubayashi, Wataru; Morita, Yukinori; Fuketa, Hiroshi; Migita, Shinji; Ota, Hiroyuki; Masahara, Meishoku; Endo, Kazuhiko; Matsukawa, Takashi

    2017-04-01

    The drain bias dependence of tunnel field-effect transistors (TFETs) is examined on the basis of the measured characteristics and device simulation to understand the electrical behavior of TFETs. Our analyses focus on the long-channel silicon-on-insulator (SOI)-based TFETs as a good basis for further studies of short-channel effects, scaling issues, and more complicated device structures, such as multigate or nanowire TFETs. By device simulation, it is revealed that the drain bias dependence of the transfer characteristics of the measured TFETs is governed by two physical mechanisms: the density of states (DOS) occupancy factor, which depends on drain-to-source bias voltage, and channel electrostatic potential, which is limited by the drain bias through strong carrier accumulation. These mechanisms differ from the drain-induced barrier lowering (DIBL) of metal-oxide-semiconductor field-effect-transistors (MOSFETs), and cause a significant impact even in long-channel SOIs. Finally, the obtained insights are successfully implemented in a TFET compact model.

  18. Two-barrier stability that allows low-power operation in current-induced domain-wall motion

    NASA Astrophysics Data System (ADS)

    Kim, Kab-Jin; Hiramatsu, Ryo; Koyama, Tomohiro; Ueda, Kohei; Yoshimura, Yoko; Chiba, Daichi; Kobayashi, Kensuke; Nakatani, Yoshinobu; Fukami, Shunsuke; Yamanouchi, Michihiko; Ohno, Hideo; Kohno, Hiroshi; Tatara, Gen; Ono, Teruo

    2013-06-01

    Energy barriers in magnetization reversal dynamics have long been of interest because the barrier height determines the thermal stability of devices as well as the threshold force triggering their dynamics. Especially in memory and logic applications, there is a dilemma between the thermal stability of bit data and the operation power of devices, because larger energy barriers for higher thermal stability inevitably lead to larger magnetic fields (or currents) for operation. Here we show that this is not the case for current-induced magnetic domain-wall motion induced by adiabatic spin-transfer torque. By quantifying domain-wall depinning energy barriers by magnetic field and current, we find that there exist two different pinning barriers, extrinsic and intrinsic energy barriers, which govern the thermal stability and threshold current, respectively. This unique two-barrier system allows low-power operation with high thermal stability, which is impossible in conventional single-barrier systems.

  19. Two-barrier stability that allows low-power operation in current-induced domain-wall motion.

    PubMed

    Kim, Kab-Jin; Hiramatsu, Ryo; Koyama, Tomohiro; Ueda, Kohei; Yoshimura, Yoko; Chiba, Daichi; Kobayashi, Kensuke; Nakatani, Yoshinobu; Fukami, Shunsuke; Yamanouchi, Michihiko; Ohno, Hideo; Kohno, Hiroshi; Tatara, Gen; Ono, Teruo

    2013-01-01

    Energy barriers in magnetization reversal dynamics have long been of interest because the barrier height determines the thermal stability of devices as well as the threshold force triggering their dynamics. Especially in memory and logic applications, there is a dilemma between the thermal stability of bit data and the operation power of devices, because larger energy barriers for higher thermal stability inevitably lead to larger magnetic fields (or currents) for operation. Here we show that this is not the case for current-induced magnetic domain-wall motion induced by adiabatic spin-transfer torque. By quantifying domain-wall depinning energy barriers by magnetic field and current, we find that there exist two different pinning barriers, extrinsic and intrinsic energy barriers, which govern the thermal stability and threshold current, respectively. This unique two-barrier system allows low-power operation with high thermal stability, which is impossible in conventional single-barrier systems.

  20. Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

    PubMed

    Yu, Jinyan; Ma, Zhongsen; Shetty, Sreerama; Ma, Mengshi; Fu, Jian

    2016-07-01

    Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction.

  1. Low Barrier Carbon Induced CO Dissociation on Stepped Cu

    NASA Astrophysics Data System (ADS)

    Ng, M. L.; Abild-Pedersen, F.; Kaya, S.; Mbuga, F.; Ogasawara, H.; Nilsson, A.

    2015-06-01

    Using x-ray photoelectron spectroscopy we observe the breaking of the strong interatomic bond in molecular CO at low temperature on a stepped Cu surface. Since the electronic structure of Cu does not allow for the splitting of CO at such low temperatures it suggests that there may be a less obvious pathway for the process. Through x-ray photoelectron spectroscopy we can clearly identify products associated with the dissociation of CO and the subsequent formation of stable graphitic carbon on the surface. However, the dissociation of CO can be inhibited when the stepped Cu surface is kept clean from surface carbon. These observations imply that the reaction is driven by the presence of small amounts of weakly bound carbon at the surface. Density-functional theory calculations confirm that carbon atoms on a stepped Cu surface indeed are the preferred adsorption sites for CO, which increases the stabilization of CO on the surface and weakens the C-O bond. This results in the breaking of the C-O bond at the step edge via the Boudouard reaction (2 COads→Cads+CO2 ) with a barrier of 0.71 eV.

  2. NITROTYROSINATION OF A TUBULIN INDUCES EPITHELIAL BARRIER DYSFUNCTION

    EPA Science Inventory

    Nitrotyrosination of a-Tubulin Induces Epithelial Transport Dysfunction. Yuh-Chin Huang, Lisa Dailey, Wen-Li Zhang and Ilona Jaspers. ORD, Environmental Protection Agency and CEMLB, University of North Carolina

    a-Tubulin undergoes a cyclic removal and readdition of tyrosin...

  3. NITROTYROSINATION OF A TUBULIN INDUCES EPITHELIAL BARRIER DYSFUNCTION

    EPA Science Inventory

    Nitrotyrosination of a-Tubulin Induces Epithelial Transport Dysfunction. Yuh-Chin Huang, Lisa Dailey, Wen-Li Zhang and Ilona Jaspers. ORD, Environmental Protection Agency and CEMLB, University of North Carolina

    a-Tubulin undergoes a cyclic removal and readdition of tyrosin...

  4. Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis

    PubMed Central

    Viswanathan, V. K.; Weflen, Andrew; Koutsouris, Athanasia; Roxas, Jennifer L.; Hecht, Gail

    2012-01-01

    Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen that perturbs intestinal epithelial function. Many of the alterations in the host cells are mediated by effector molecules that are secreted directly into epithelial cells by the EPEC type III secretion system. The secreted effector molecule EspF plays a key role in redistributing tight junction proteins and altering epithelial barrier function. EspF has also been shown to localize to mitochondria and trigger membrane depolarization and eventual host cell death. The relationship, if any, between EspF-induced host cell death and epithelial barrier disruption is presently not known. Site-directed mutation of leucine 16 (L16E) of EspF impairs both mitochondrial localization and consequent host cell death. Although the mutation lies within a region critical for type III secretion, EspF(L16E) is secreted efficiently from EPEC. Despite its inability to promote cell death, EspF(L16E) was not impaired for tight junction alteration or barrier disruption. Consistent with this, the pan-caspase inhibitor Q-VD-OPH, despite reducing EPEC-induced host cell death, had no effect on infection-mediated barrier function alteration. Thus EPEC alters the epithelial barrier independent of its ability to induce host cell death. PMID:18356531

  5. Dielectric barrier discharge plasma induced degradation of aqueous atrazine.

    PubMed

    Feng, Jingwei; Jiang, Lin; Zhu, Dan; Su, Kuizu; Zhao, Dayong; Zhang, Jibiao; Zheng, Zheng

    2016-05-01

    Degradation of herbicide atrazine in aqueous solution was investigated using a plate type dielectric barrier discharge (DBD) plasma reactor. DBD plasma was generated at the gas-liquid interface of the formed water film. At discharge time of 14 min, atrazine was degradated effectively with a degradation rate of 99 % at the discharge power of 200 W. The experimental data fitted well with first-order kinetics and the energy efficiency for 90 % degradation of atrazine (G value) was calculated, obtaining a rate constant of 0.35 min(-1) and a G value of 1.27 × 10(-10) mol J(-1) (98.76 mg kW(-1) h(-1)) at a discharge power of 200 W, respectively. The addition of Fe(2+) increased the rate constant and G value dramatically, and a significant decrease of the rate constant and G value was observed with the addition of radical scavengers (tert-butyl alcohol, isopropyl alcohol, or Na2CO3). The generated aqueous O3 and H2O2 were determined, which promoted the degradation of herbicide atrazine. Dechlorination was observed and the experimentally detected Cl(-) was 1.52 mg L(-1) at a discharge time of 14 min. The degradation intermediates of atrazine were detected by means of liquid chromatography-mass spectrometry; dechlorination, hydroxylation, dealkylation, and alkyl oxidation processes were involved in the degradation pathways of atrazine.

  6. Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

    PubMed Central

    Xing, Junjie; Moldobaeva, Nurgul

    2011-01-01

    Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial

  7. Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta

    PubMed Central

    Xie, Lishi; Chiang, Eddie T.; Kelly, Gabriel T.; Kanteti, Prasad; Singleton, Patrick A.; Camp, Sara M.; Zhou, Tingting; Dudek, Steven M.; Natarajan, Viswanathan; Wang, Ting; Black, Steven M.; Garcia, Joe G. N.; Jacobson, Jeffrey R.

    2016-01-01

    Protein Kinase C (PKC) plays a significant role in thrombin-induced loss of endothelial cell (EC) barrier integrity; however, the existence of more than 10 isozymes of PKC and tissue–specific isoform expression has limited our understanding of this important second messenger in vascular homeostasis. In this study, we show that PKCδ isoform promotes thrombin-induced loss of human pulmonary artery EC barrier integrity, findings substantiated by PKCδ inhibitory studies (rottlerin), dominant negative PKCδ construct and PKCδ silencing (siRNA). In addition, we identified PKCδ as a signaling mediator upstream of both thrombin-induced MLC phosphorylation and Rho GTPase activation affecting stress fiber formation, cell contraction and loss of EC barrier integrity. Our inhibitor-based studies indicate that thrombin-induced PKCδ activation exerts a positive feedback on Rho GTPase activation and contributes to Rac1 GTPase inhibition. Moreover, PKD (or PKCμ) and CPI-17, two known PKCδ targets, were found to be activated by PKCδ in EC and served as modulators of cytoskeleton rearrangement. These studies clarify the role of PKCδ in EC cytoskeleton regulation, and highlight PKCδ as a therapeutic target in inflammatory lung disorders, characterized by the loss of barrier integrity, such as acute lung injury and sepsis. PMID:27442243

  8. Activation barrier scaling and crossover for noise-induced switching in micromechanical parametric oscillators.

    PubMed

    Chan, H B; Stambaugh, C

    2007-08-10

    We explore fluctuation-induced switching in parametrically driven micromechanical torsional oscillators. The oscillators possess one, two, or three stable attractors depending on the modulation frequency. Noise induces transitions between the coexisting attractors. Near the bifurcation points, the activation barriers are found to have a power law dependence on frequency detuning with critical exponents that are in agreement with predicted universal scaling relationships. At large detuning, we observe a crossover to a different power law dependence with an exponent that is device specific.

  9. Streptozotocin-induced diabetes, and the optic nerve blood barrier.

    PubMed

    Alemán, R; Mompeó, B; Castaño, I

    2016-04-01

    To study the features of the endoneurial micro-vessels of the optic nerve in streptozotocin-induced diabetic animals. Optic nerves from control and streptozotocin-induced diabetic animals were studied by light and transmission electron microscopy. Patency was determined by indirect immunofluorescence albumin detection. The expression of major histocompatibility complex class II molecules was performed by direct immunofluorescence. The endoneurial vessels were counted, and the endothelial cell, the basement membrane, and the surface of the transverse section of the nerve were measured. Vessels of diabetic rats showed vessel wall thickening, preservation of pericytes, an increase in endothelial cell transcytosis, and an increased number of perivascular macrophage cells. It may be concluded that the effects of hyperglycaemia on the inner vessels of the optic nerve are more similar to the cerebral diabetic vessels than to the retinal vessels in diabetic animals. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Proxy records of Holocene storm events in coastal barrier systems: Storm-wave induced markers

    NASA Astrophysics Data System (ADS)

    Goslin, Jérôme; Clemmensen, Lars B.

    2017-10-01

    Extreme storm events in the coastal zone are one of the main forcing agents of short-term coastal system behavior. As such, storms represent a major threat to human activities concentrated along the coasts worldwide. In order to better understand the frequency of extreme events like storms, climate science must rely on longer-time records than the century-scale records of instrumental weather data. Proxy records of storm-wave or storm-wind induced activity in coastal barrier systems deposits have been widely used worldwide in recent years to document past storm events during the last millennia. This review provides a detailed state-of-the-art compilation of the proxies available from coastal barrier systems to reconstruct Holocene storm chronologies (paleotempestology). The present paper aims (I) to describe the erosional and depositional processes caused by storm-wave action in barrier and back-barrier systems (i.e. beach ridges, storm scarps and washover deposits), (ii) to understand how storm records can be extracted from barrier and back-barrier sedimentary bodies using stratigraphical, sedimentological, micro-paleontological and geochemical proxies and (iii) to show how to obtain chronological control on past storm events recorded in the sedimentary successions. The challenges that paleotempestology studies still face in the reconstruction of representative and reliable storm-chronologies using these various proxies are discussed, and future research prospects are outlined.

  11. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    PubMed

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases.

  12. Effects of Body Doping in a NAND Flash String without Source/Drain

    NASA Astrophysics Data System (ADS)

    Kim, Young Min; Cho, Il Hwan; Kwon, Hyuck-In; Lee, Jong-Ho

    2011-11-01

    Cell structure using fringing field from control gate (CG) is very promising for a scaled NAND flash memory beyond sub-40 nm node. We investigated a new NAND string structure not with n-type source/drain (S/D) regions but with p-type regions in the space between gates. Even though the NAND string has a p-type region instead of n-type S/D in the space between adjacent two cells, induced layer (virtual source/drain) can be easily formed in the space by the fringing field from the CGs. When comparing a conventional NAND string with n-type S/D, the proposed structure shows better drain induced barrier leakage (DIBL) and subthreshold swing (SS) characteristics, and also shows better immunity against the process variation than conventional structure with n-type S/D. The electrical characteristics of the proposed structure were investigated as parameters of the width and doping concentration at the p/n-type region. As a NAND cell string, the current drivability of the proposed structure was also studied.

  13. Barrier-induced chaos in a kicked rotor: Classical subdiffusion and quantum localization.

    PubMed

    Paul, Sanku; Pal, Harinder; Santhanam, M S

    2016-06-01

    The relation between classically chaotic dynamics and quantum localization is studied in a system that violates the assumptions of the Kolmogorov-Arnold-Moser (KAM) theorem, namely, the kicked rotor in a discontinuous potential barrier. We show that the discontinuous barrier induces chaos and more than two distinct subdiffusive energy growth regimes, the latter being an unusual feature for Hamiltonian chaos. We show that the dynamical localization in the quantized version of this system carries the imprint of non-KAM classical dynamics through the dependence of quantum break time on subdiffusion exponents. We briefly comment on the experimental feasibility of this system.

  14. Methamphetamine-induced nitric oxide promotes vesicular transport in blood–brain barrier endothelial cells

    PubMed Central

    Martins, Tânia; Burgoyne, Thomas; Kenny, Bridget-Ann; Hudson, Natalie; Futter, Clare E.; Ambrósio, António F.; Silva, Ana P.; Greenwood, John; Turowski, Patric

    2013-01-01

    Methamphetamine's (METH) neurotoxicity is thought to be in part due to its ability to induce blood–brain barrier (BBB) dysfunction. Here, we investigated the effect of METH on barrier properties of cultured rat primary brain microvascular endothelial cells (BMVECs). Transendothelial flux doubled in response to METH, irrespective of the size of tracer used. At the same time, transendothelial electrical resistance was unchanged as was the ultrastructural appearance of inter-endothelial junctions and the distribution of key junction proteins, suggesting that METH promoted vesicular but not junctional transport. Indeed, METH significantly increased uptake of horseradish peroxidase into vesicular structures. METH also enhanced transendothelial migration of lymphocytes indicating that the endothelial barrier against both molecules and cells was compromised. Barrier breakdown was only observed in response to METH at low micromolar concentrations, with enhanced vesicular uptake peaking at 1 μM METH. The BMVEC response to METH also involved rapid activation of endothelial nitric oxide synthase and its inhibition abrogated METH-induced permeability and lymphocyte migration, indicating that nitric oxide was a key mediator of BBB disruption in response to METH. This study underlines the key role of nitric oxide in BBB function and describes a novel mechanism of drug-induced fluid-phase transcytosis at the BBB. PMID:22960442

  15. Methamphetamine-induced nitric oxide promotes vesicular transport in blood-brain barrier endothelial cells.

    PubMed

    Martins, Tânia; Burgoyne, Thomas; Kenny, Bridget-Ann; Hudson, Natalie; Futter, Clare E; Ambrósio, António F; Silva, Ana P; Greenwood, John; Turowski, Patric

    2013-02-01

    Methamphetamine's (METH) neurotoxicity is thought to be in part due to its ability to induce blood-brain barrier (BBB) dysfunction. Here, we investigated the effect of METH on barrier properties of cultured rat primary brain microvascular endothelial cells (BMVECs). Transendothelial flux doubled in response to METH, irrespective of the size of tracer used. At the same time, transendothelial electrical resistance was unchanged as was the ultrastructural appearance of inter-endothelial junctions and the distribution of key junction proteins, suggesting that METH promoted vesicular but not junctional transport. Indeed, METH significantly increased uptake of horseradish peroxidase into vesicular structures. METH also enhanced transendothelial migration of lymphocytes indicating that the endothelial barrier against both molecules and cells was compromised. Barrier breakdown was only observed in response to METH at low micromolar concentrations, with enhanced vesicular uptake peaking at 1 μM METH. The BMVEC response to METH also involved rapid activation of endothelial nitric oxide synthase and its inhibition abrogated METH-induced permeability and lymphocyte migration, indicating that nitric oxide was a key mediator of BBB disruption in response to METH. This study underlines the key role of nitric oxide in BBB function and describes a novel mechanism of drug-induced fluid-phase transcytosis at the BBB.

  16. Plasmodium falciparum Histones Induce Endothelial Proinflammatory Response and Barrier Dysfunction

    PubMed Central

    Gillrie, Mark R.; Lee, Kristine; Gowda, D. Channe; Davis, Shevaun P.; Monestier, Marc; Cui, Liwang; Hien, Tran Tinh; Day, Nicholas P.J.; Ho, May

    2012-01-01

    Plasmodium falciparum is a protozoan parasite of human erythrocytes that causes the most severe form of malaria. Severe P. falciparum infection is associated with endothelial activation and permeability, which are important determinants of the outcome of the infection. How endothelial cells become activated is not fully understood, particularly with regard to the effects of parasite subcomponents. We demonstrated that P. falciparum histones extracted from merozoites (HeH) directly stimulated the production of IL-8 and other inflammatory mediators by primary human dermal microvascular endothelial cells through a signaling pathway that involves Src family kinases and p38 MAPK. The stimulatory effect of HeH and recombinant P. falciparum H3 (PfH3) was abrogated by histone-specific antibodies. The release of nuclear contents on rupture of infected erythrocytes was captured by live cell imaging and confirmed by detecting nucleosomes in the supernatants of parasite cultures. HeH and recombinant parasite histones also induced endothelial permeability through a charge-dependent mechanism that resulted in disruption of junctional protein expression and cell death. Recombinant human activated protein C cleaved HeH and PfH3 and abrogated their proinflammatory effects. Circulating nucleosomes of both human and parasite origin were detected in the plasma of patients with falciparum malaria and correlated positively with disease severity. These results support a pathogenic role for both host- and pathogen-derived histones in P. falciparum-caused malaria. PMID:22260922

  17. Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects

    PubMed Central

    MacRedmond, Ruth E.; Singhera, Gurpreet K.; Wadsworth, Samuel J.; Attridge, Susan; Bahzad, Mohammed; Williams, Kristy; Coxson, Harvey O.; White, Steven R.; Dorscheid, Delbert R.

    2014-01-01

    Objective The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this. Methods This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 μg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum. Results Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response. Conclusion Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling. PMID:25324978

  18. Effects of drain doping concentration on switching characteristics of tunnel field-effect transistor inverters

    NASA Astrophysics Data System (ADS)

    Kwon, Dae Woong; Kim, Jang Hyun; Park, Byung-Gook

    2016-11-01

    In order to investigate the effects of the modulation of drain doping concentration (N drain) on alternating current (AC) switching characteristics of a tunnel filed-effect transistor (TFET) inverter, the characteristics of TFETs with various N drains are analyzed rigorously through mixed-mode device and circuit TCAD simulations. As the N drain gets decreased, the drain current (I D) becomes reduced and the gate-to-drain capacitance (C GD) reflects the entire gate capacitance (C GG) at a lower gate voltage (V G), which leads to the degradation of falling/rising delay in TFET inverters. These phenomena are explained successfully by the change of quasi-Fermi energy in the drain (E F_drain) as a function of V G. The E F_drain rises dramatically from when tunneling current starts to flow from the source in the n-type TFET with low N drain. As a result, drain-side channel inversion occurs at a lower V G due to the reduction of the energy barrier between the E F_drain and the conduction band edge of the channel.

  19. Lovastatin Inhibits the Thrombin-Induced Loss of Barrier Integrity in Bovine Corneal Endothelium

    PubMed Central

    2010-01-01

    Purpose: Increased actomyosin contraction of the dense band of actin cytoskeleton at the apical junctional complex (perijunctional actomyosin ring, PAMR) breaks down the barrier integrity of corneal endothelium. This study has investigated the efficacy of statins, which inhibit activation of RhoA, in opposing the thrombin-induced loss of barrier integrity of monolayers of cultured bovine corneal endothelium. Methods: Myosin light chain (MLC) phosphorylation, a biochemical measure of actomyosin contraction, was assayed by urea–glycerol gel electrophoresis, followed by western blot analysis. The locus of MLC phosphorylation and changes in the organization of the PAMR were visualized by immunostaining. Phosphorylation of MYPT1, a regulatory subunit of myosin light-chain phosphatase (MLCP), was assessed by Western blot analysis to determine down-regulation of RhoA. The barrier integrity was assessed in terms of trans-endothelial electrical resistance (TER), and further confirmed by determining permeability to FITC dextran (10 kDa) and distribution of ZO-1, a marker of tight junctional assembly. Results: Lovastatin, a prototype of lipophilic statins, induced MLC dephosphorylation under basal conditions. It opposed increase in phosphorylation of MLC and MYPT1 in response to thrombin and nocodazole, agents known to activate RhoA in the endothelium. Pretreatment with the statin opposed the thrombin- and nocodazole-induced disruption of the PAMR and the thrombin-induced decline in TER. Lovastatin also opposed the thrombin- and nocodazole-induced increase in permeability to FITC dextran and redistribution of ZO-1. However, upon supplementation with GGPP (geranylgeranyl pyrophosphate), lovastatin failed to oppose the effects of thrombin and nocodazole on the PAMR, ppMLC, and ZO-1 distribution. Conclusions: Lovastatin attenuates RhoA activation in the corneal endothelium presumably by reducing its isoprenylation. This underlies the suppression of the thrombin-induced loss in

  20. Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction.

    PubMed

    Meng, Fanyong; Meliton, Angelo; Moldobaeva, Nurgul; Mutlu, Gokhan; Kawasaki, Yoshihiro; Akiyama, Tetsu; Birukova, Anna A

    2015-03-01

    Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac pathway as a key mechanism of HGF-mediated endothelial barrier protection. However, anti-inflammatory effects of HGF are less understood. This study examined effects of HGF on the pulmonary endothelial cell (EC) inflammatory activation and barrier dysfunction caused by the gram-negative bacterial pathogen lipopolysaccharide (LPS). We tested involvement of the novel Rac-specific guanine nucleotide exchange factor Asef in the HGF anti-inflammatory effects. HGF protected the pulmonary EC monolayer against LPS-induced hyperpermeability, disruption of monolayer integrity, activation of NF-kB signaling, expression of adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and production of IL-8. These effects were critically dependent on Asef. Small-interfering RNA-induced downregulation of Asef attenuated HGF protective effects against LPS-induced EC barrier failure. Protective effects of HGF against LPS-induced lung inflammation and vascular leak were also diminished in Asef knockout mice. Taken together, these results demonstrate potent anti-inflammatory effects by HGF and delineate a key role of Asef in the mediation of the HGF barrier protective and anti-inflammatory effects. Modulation of Asef activity may have important implications in therapeutic strategies aimed at the treatment of sepsis and acute lung injury/ARDS-induced gram-negative bacterial pathogens.

  1. Plumbing the brain drain.

    PubMed Central

    Saravia, Nancy Gore; Miranda, Juan Francisco

    2004-01-01

    Opportunity is the driving force of migration. Unsatisfied demands for higher education and skills, which have been created by the knowledge-based global economy, have generated unprecedented opportunities in knowledge-intensive service industries. These multi-trillion dollar industries include information, communication, finance, business, education and health. The leading industrialized nations are also the focal points of knowledge-intensive service industries and as such constitute centres of research and development activity that proactively draw in talented individuals worldwide through selective immigration policies, employment opportunities and targeted recruitment. Higher education is another major conduit of talent from less-developed countries to the centres of the knowledge-based global economy. Together career and educational opportunities drive "brain drain and recirculation". The departure of a large proportion of the most competent and innovative individuals from developing nations slows the achievement of the critical mass needed to generate the enabling context in which knowledge creation occurs. To favourably modify the asymmetric movement and distribution of global talent, developing countries must implement bold and creative strategies that are backed by national policies to: provide world-class educational opportunities, construct knowledge-based research and development industries, and sustainably finance the required investment for these strategies. Brazil, China and India have moved in this direction, offering world-class education in areas crucial to national development, such as biotechnology and information technology, paralleled by investments in research and development. As a result, only a small proportion of the most highly educated individuals migrate from these countries, and research and development opportunities employ national talent and even attract immigrants. PMID:15375451

  2. Plumbing the brain drain.

    PubMed

    Saravia, Nancy Gore; Miranda, Juan Francisco

    2004-08-01

    Opportunity is the driving force of migration. Unsatisfied demands for higher education and skills, which have been created by the knowledge-based global economy, have generated unprecedented opportunities in knowledge-intensive service industries. These multi-trillion dollar industries include information, communication, finance, business, education and health. The leading industrialized nations are also the focal points of knowledge-intensive service industries and as such constitute centres of research and development activity that proactively draw in talented individuals worldwide through selective immigration policies, employment opportunities and targeted recruitment. Higher education is another major conduit of talent from less-developed countries to the centres of the knowledge-based global economy. Together career and educational opportunities drive "brain drain and recirculation". The departure of a large proportion of the most competent and innovative individuals from developing nations slows the achievement of the critical mass needed to generate the enabling context in which knowledge creation occurs. To favourably modify the asymmetric movement and distribution of global talent, developing countries must implement bold and creative strategies that are backed by national policies to: provide world-class educational opportunities, construct knowledge-based research and development industries, and sustainably finance the required investment for these strategies. Brazil, China and India have moved in this direction, offering world-class education in areas crucial to national development, such as biotechnology and information technology, paralleled by investments in research and development. As a result, only a small proportion of the most highly educated individuals migrate from these countries, and research and development opportunities employ national talent and even attract immigrants.

  3. Bacillus cereus induces permeability of an in vitro blood-retina barrier.

    PubMed

    Moyer, A L; Ramadan, R T; Thurman, J; Burroughs, A; Callegan, M C

    2008-04-01

    Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcR-regulated toxins may not contribute significantly to RPE barrier permeability during infection.

  4. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    PubMed

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism.

  5. Influence of antioxidants on blood-brain barrier permeability during adrenaline-induced hypertension.

    PubMed

    Oztaş, B; Erkin, E; Dural, E; Isbir, T

    2000-11-01

    We have examined the effect of antioxidants (vitamin E, and selenium) on the blood-brain barrier permeability during adreneline-induced acute hypertension in the female rats. The rats supplemented with nontoxic doses of sodium selenite in drinking water for three months or vitamin E was given intraperitoneally before adrenaline-induced acute hypertension. Evans-blue was used as a blood-brain barrier tracer. Mean values for Evans-blue dye were found to be 0.28 +/- 0.04 microg/g tissue in control animals and 1.0 +/- 0.2 microg tissue after adrenaline-induced acute hypertension (p < .01). Rats pretreated with selenium or vitamin E also showed macroscopic leakage of Evans-blue albumin after adrenaline injection i.e., there was no significant difference in protein extravasation between untreated and treated animals (p > .5). The mean value for Evans-blue dye was found to be 1.0 +/- 0.2 microg/g tissue in acute hypertension group, 0.9 +/- 0.2 microg/g tissue in selenium pretreated animals and 1.0 +/- 0.2 micrg/g tissue vitamin E injected animals after acute hypertension. The results show that antioxidants did not influence the blood-brain barrier breakdown during adrenaline-induced acute hypertension.

  6. Iloprost improves endothelial barrier function in LPS-induced lung injury

    PubMed Central

    Birukova, Anna A.; Wu, Tinghuai; Tian, Yufeng; Meliton, Angelo; Sarich, Nicolene; Tian, Xinyong; Leff, Alan; Birukov, Konstantin G.

    2013-01-01

    RATIONALE Protective effects of prostacyclin and its stable analog Iloprost are mediated by elevation of intracellular cAMP leading to enhancement of peripheral actin cytoskeleton and cell-cell adhesive structures. This study tested hypothesis that iloprost may exhibit protective effects against lung injury and endothelial barrier dysfunction induced by bacterial wall lypopolysacharide (LPS). METHODS Endothelial barrier dysfunction was assessed by measurements of transendothelial permeability, morphologically, and analysis of LPS-activated inflammatory signaling. In vivo, C57BL/6J mice were challenged with LPS with or without iloprost or 8-bromoadenosine-3′,5′-cyclic monophosphate (Br-cAMP) treatment. Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, and Evans blue extravasation. RESULTS Iloprost and Br-cAMP attenuated disruption of endothelial monolayer and suppressed activation of p38 mitogen activated protein (MAP) kinase, NFκB pathway, Rho signaling, ICAM1 expression, and neutrophil migration after LPS challenge. In vivo, iloprost was effective against LPS-induced protein and neutrophil accumulation in bronchoalveolar lavage fluid and reduced myeloperoxidase activation, ICAM-1 expression, and Evans blue extravasation in the lungs. Inhibition of Rac activity abolished barrier protective and anti-inflammatory effects of iloprost and Br-cAMP. CONCLUSION Iloprost-induced elevation of intracellular cAMP triggers Rac signaling, which attenuates LPS-induced NFκB and p38 MAPK inflammatory pathways and Rho-dependent mechanism of endothelial permeability. PMID:22790920

  7. Compact drain-current model for undoped cylindrical surrounding-gate metal-oxide-semiconductor field effect transistors including short channel effects

    NASA Astrophysics Data System (ADS)

    Smaani, Billel; Latreche, Saida; Iñiguez, Benjamín

    2013-12-01

    In this paper, we present a compact model for undoped short-channel cylindrical surrounding-gate MOSFETs. The drain-current model is expressed as a function of the mobile charge density, which is calculated using the analytical expressions of the surface potential and the difference between surface and center potentials model. The short-channel effects are well incorporated in the drain-current model, such as the drain-induced barrier lowering, the charge sharing effect (VT Roll-off), the subthreshold slope degradation, and the channel length modulation. A comparison of the model results with 3D numerical simulations using Silvaco Atlas-TCAD presents a good agreement from subthreshold to strong inversion regime and for different bias voltages.

  8. Rebeccamycin Attenuates TNF-α-Induced Intestinal Epithelial Barrier Dysfunction by Inhibiting Myosin Light Chain Kinase Production.

    PubMed

    Watari, Akihiro; Sakamoto, Yuta; Hisaie, Kota; Iwamoto, Kazuki; Fueta, Miho; Yagi, Kiyohito; Kondoh, Masuo

    2017-01-01

    Although proinflammatory cytokine-induced disruption of intestinal epithelial barrier integrity is associated with intestinal inflammatory disease, effective treatment for barrier dysfunction is lacking. Previously, we demonstrated that rebeccamycin alleviates epithelial barrier dysfunction induced by inflammatory cytokines in Caco-2 cell monolayers; however, the underlying mechanism remained unclear. Here, we investigated the mechanism by which rebeccamycin protects the epithelial barrier function of Caco-2 cells exposed to TNF-α. To confirm the epithelial barrier function of Caco-2 cell monolayers, transepithelial electrical resistance (TER) and paracellular permeability were measured. Production levels and localization of tight junction (TJ) proteins were analyzed by immunoblot and immunofluorescence, respectively. Phosphorylated myosin light chain (pMLC) and MLC kinase (MLCK) mRNA expression levels were determined by immunoblot and quantitative RT-PCR, respectively. Rebeccamycin attenuated the TNF-α-induced reduction in TER and increase in paracellular permeability. Rebeccamycin increased claudin-5 expression, but not claudin-1, -2, -4, occludin or ZO-1 expression, and prevented the TNF-α-induced changes in ZO-1 and occludin localization. Rebeccamycin suppressed the TNF-α-induced increase in MLCK mRNA expression, thus suppressing MLC phosphorylation. The rebeccamycin-mediated reduction in MLCK production and protection of epithelial barrier function were alleviated by Chk1 inhibition. Rebeccamycin attenuates TNF-α-induced disruption of intestinal epithelial barrier integrity by inducing claudin-5 expression and suppressing MLCK production via Chk1 activation. © 2017 The Author(s)Published by S. Karger AG, Basel.

  9. The role of intrinsic apoptotic signaling in hemorrhagic shock-induced microvascular endothelial cell barrier dysfunction.

    PubMed

    Sawant, Devendra A; Tharakan, Binu; Hunter, Felicia A; Childs, Ed W

    2014-11-01

    Hemorrhagic shock leads to endothelial cell barrier dysfunction resulting in microvascular hyperpermeability. Hemorrhagic shock-induced microvascular hyperpermeability is associated with worse clinical outcomes in patients with traumatic injuries. The results from our laboratory have illustrated a possible pathophysiological mechanism showing involvement of mitochondria-mediated "intrinsic" apoptotic signaling in regulating hemorrhagic shock-induced microvascular hyperpermeability. Hemorrhagic shock results in overexpression of Bcl-2 family of pro-apoptotic protein, BAK, in the microvascular endothelial cells. The increase in BAK initiates "intrinsic" apoptotic signaling cascade with the release of mitochondrial cytochrome c in the cytoplasm and activation of downstream effector caspase-3, leading to loss of endothelial cell barrier integrity. Thus, this review article offers a brief overview of important findings from our past and present research work along with new leads for future research. The summary of our research work will provide information leading to different avenues in developing novel strategies against microvascular hyperpermeability following hemorrhagic shock.

  10. Cluster Model for Near-barrier Fusion Induced by Weakly Bound and Halo Nuclei

    SciTech Connect

    Beck, C.; Keeley, N.

    2008-05-12

    The influence on the fusion process of coupling transfer/breakup channels is investigated for the medium weight {sup 6,7}Li+{sup 59}Co systems in the vicinity of the Coulomb barrier. Coupling effects are discussed within a comparison of predictions of the Continuum Discretized Coupled-Channels model. Applications to {sup 6}He+{sup 59}Co induced by the borromean halo nucleus {sup 6}He are also proposed.

  11. Near-barrier Fusion Induced by Stable Weakly Bound and Exotic Halo Light Nuclei

    SciTech Connect

    Beck, C.; Zafra, A. Sanchez I.; Diaz-Torres, A.; Thompson, I. J.; Keeley, N.

    2006-08-14

    The effect of breakup is investigated for the medium weight 6Li+59Co system in the vicinity of the Coulomb barrier. The strong coupling of breakup/transfer channels to fusion is discussed within a comparison of predictions of the Continuum Discretized Coupled-Channels model which is also applied to 6He+59Co a reaction induced by the borromean halo nucleus 6He.

  12. Edge-induced Schottky barrier modulation at metal contacts to exfoliated molybdenum disulfide flakes

    SciTech Connect

    Nouchi, Ryo

    2016-08-14

    Ultrathin two-dimensional semiconductors obtained from layered transition-metal dichalcogenides such as molybdenum disulfide (MoS{sub 2}) are promising for ultimately scaled transistors beyond Si. Although the shortening of the semiconductor channel is widely studied, the narrowing of the channel, which should also be important for scaling down the transistor, has been examined to a lesser degree thus far. In this study, the impact of narrowing on mechanically exfoliated MoS{sub 2} flakes was investigated according to the channel-width-dependent Schottky barrier heights at Cr/Au contacts. Narrower channels were found to possess a higher Schottky barrier height, which is ascribed to the edge-induced band bending in MoS{sub 2}. The higher barrier heights degrade the transistor performance as a higher electrode-contact resistance. Theoretical analyses based on Poisson's equation showed that the edge-induced effect can be alleviated by a high dopant impurity concentration, but this strategy should be limited to channel widths of roughly 0.7 μm because of the impurity-induced charge-carrier mobility degradation. Therefore, proper termination of the dangling bonds at the edges should be necessary for aggressive scaling with layered semiconductors.

  13. Edge-induced Schottky barrier modulation at metal contacts to exfoliated molybdenum disulfide flakes

    NASA Astrophysics Data System (ADS)

    Nouchi, Ryo

    2016-08-01

    Ultrathin two-dimensional semiconductors obtained from layered transition-metal dichalcogenides such as molybdenum disulfide (MoS2) are promising for ultimately scaled transistors beyond Si. Although the shortening of the semiconductor channel is widely studied, the narrowing of the channel, which should also be important for scaling down the transistor, has been examined to a lesser degree thus far. In this study, the impact of narrowing on mechanically exfoliated MoS2 flakes was investigated according to the channel-width-dependent Schottky barrier heights at Cr/Au contacts. Narrower channels were found to possess a higher Schottky barrier height, which is ascribed to the edge-induced band bending in MoS2. The higher barrier heights degrade the transistor performance as a higher electrode-contact resistance. Theoretical analyses based on Poisson's equation showed that the edge-induced effect can be alleviated by a high dopant impurity concentration, but this strategy should be limited to channel widths of roughly 0.7 μm because of the impurity-induced charge-carrier mobility degradation. Therefore, proper termination of the dangling bonds at the edges should be necessary for aggressive scaling with layered semiconductors.

  14. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.

    PubMed

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J; Dekker, Jan; van Mil, Saskia W C; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-08-11

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.

  15. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon

    PubMed Central

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J.; Dekker, Jan; van Mil, Saskia W. C.; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-01-01

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. PMID:26216954

  16. Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions.

    PubMed

    Miclescu, Adriana; Sharma, Hari Shanker; Martijn, Cécile; Wiklund, Lars

    2010-11-01

    To investigate the effects of cardiac arrest and the reperfusion syndrome on blood-brain barrier permeability and evaluate whether methylene blue counteracts blood-brain barrier disruption in a pig model of controlled cardiopulmonary resuscitation. Randomized, prospective, laboratory animal study. University-affiliated research laboratory. Forty-five piglets. Forty-five anesthetized piglets were subjected to cardiac arrest alone or 12-min cardiac arrest followed by 8 mins cardiopulmonary resuscitation. The first group (n = 16) was used to evaluate blood-brain barrier disruptions after untreated cerebral ischemia after 0, 15, or 30 mins after untreated cardiac arrest. The other two groups received either an infusion of saline (n = 10) or infusion of saline with methylene blue (n = 12) 1 min after the start of cardiopulmonary resuscitation and continued 50 mins after return of spontaneous circulation. In these groups, brains were removed for immunohistological analyses at 30, 60, and 180 mins after return of spontaneous circulation. An increase of injured neurons and albumin immunoreactivity was demonstrated with increasing duration of ischemia/reperfusion. Less blood-brain barrier disruption was observed in subjects receiving methylene blue as demonstrated by decreased albumin leakage (p < .01), water content (p < .05), and neuronal injury (p < .01). Methylene blue treatment reduced cerebral tissue nitrite/nitrate content (p < .05) and the number of inducible and neuronal nitric oxide synthase-activated cortical cells during administration (p < .01). Meanwhile, the number of cortical endothelial nitric oxide synthase-activated cells increased over time (p < .001). Cerebral tissue water content, blood-brain barrier permeability and neurologic injury were increased early in reperfusion after cardiac arrest. Methylene blue exerted neuroprotective effects against the brain damage associated with the ischemia/reperfusion injury and ameliorated the blood-brain barrier

  17. Signaling pathways induced by serine proteases to increase intestinal epithelial barrier function

    PubMed Central

    Shang, Judie; Dion, Sébastien P.; Désilets, Antoine; Leduc, Richard

    2017-01-01

    Changes in barrier function of the gastrointestinal tract are thought to contribute to the inflammatory bowel diseases Crohn’s disease and ulcerative colitis. Previous work in our lab demonstrated that apical exposure of intestinal epithelial cell lines to serine proteases results in an increase in transepithelial electrical resistance (TER). However, the underlying mechanisms governing this response are unclear. We aimed to determine the requirement for proteolytic activity, epidermal growth factor receptor (EGFR) activation, and downstream intracellular signaling in initiating and maintaining enhanced barrier function following protease treatment using a canine intestinal epithelial cell line (SCBN). We also examined the role of phosphorylation of myosin regulatory light chain on the serine protease-induced increase in TER through. It was found that proteolytic activity of the serine proteases trypsin and matriptase is required to initiate and maintain the protease-mediated increase in TER. We also show that MMP-independent EGFR activation is essential to the sustained phase of the protease response, and that Src kinases may mediate EGFR transactivation. PI3-K and ERK1/2 signaling were important in reaching a maximal increase in TER following protease stimulation; however, their upstream activators are yet to be determined. CK2 inhibition prevented the increase in TER induced by serine proteases. The bradykinin B(2) receptor was not involved in the change in TER in response to serine proteases, and no change in phosphorylation of MLC was observed after trypsin or matriptase treatment. Taken together, our data show a requirement for ongoing proteolytic activity, EGFR transactivation, as well as downstream PI3-K, ERK1/2, and CK2 signaling in protease-mediated barrier enhancement of intestinal epithelial cells. The pathways mediating enhanced barrier function by proteases may be novel therapeutic targets for intestinal disorders characterized by disrupted

  18. Signaling pathways induced by serine proteases to increase intestinal epithelial barrier function.

    PubMed

    Lahey, Kelcie A; Ronaghan, Natalie J; Shang, Judie; Dion, Sébastien P; Désilets, Antoine; Leduc, Richard; MacNaughton, Wallace K

    2017-01-01

    Changes in barrier function of the gastrointestinal tract are thought to contribute to the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Previous work in our lab demonstrated that apical exposure of intestinal epithelial cell lines to serine proteases results in an increase in transepithelial electrical resistance (TER). However, the underlying mechanisms governing this response are unclear. We aimed to determine the requirement for proteolytic activity, epidermal growth factor receptor (EGFR) activation, and downstream intracellular signaling in initiating and maintaining enhanced barrier function following protease treatment using a canine intestinal epithelial cell line (SCBN). We also examined the role of phosphorylation of myosin regulatory light chain on the serine protease-induced increase in TER through. It was found that proteolytic activity of the serine proteases trypsin and matriptase is required to initiate and maintain the protease-mediated increase in TER. We also show that MMP-independent EGFR activation is essential to the sustained phase of the protease response, and that Src kinases may mediate EGFR transactivation. PI3-K and ERK1/2 signaling were important in reaching a maximal increase in TER following protease stimulation; however, their upstream activators are yet to be determined. CK2 inhibition prevented the increase in TER induced by serine proteases. The bradykinin B(2) receptor was not involved in the change in TER in response to serine proteases, and no change in phosphorylation of MLC was observed after trypsin or matriptase treatment. Taken together, our data show a requirement for ongoing proteolytic activity, EGFR transactivation, as well as downstream PI3-K, ERK1/2, and CK2 signaling in protease-mediated barrier enhancement of intestinal epithelial cells. The pathways mediating enhanced barrier function by proteases may be novel therapeutic targets for intestinal disorders characterized by disrupted epithelial

  19. Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood-Brain Barrier Damage.

    PubMed

    Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

    2017-01-01

    Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood-brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption.

  20. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10.

    PubMed

    Nickols, Jordan; Obiako, Boniface; Ramila, K C; Putinta, Kevin; Schilling, Sarah; Sayner, Sarah L

    2015-12-15

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. Copyright © 2015 the American Physiological Society.

  1. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10

    PubMed Central

    Nickols, Jordan; Obiako, Boniface; Ramila, K. C.; Putinta, Kevin; Schilling, Sarah

    2015-01-01

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. PMID:26475732

  2. Human sebum extract induces barrier disruption and cytokine expression in murine epidermis.

    PubMed

    Guo, Jiun-Wen; Lin, Tzu-Kai; Wu, Chin-Han; Wei, Kai-Che; Lan, Cheng-Che E; Peng, Amy Chia-Ying; Tsai, Jui-Chen; Sheu, Hamm-Ming

    2015-04-01

    Previous studies have shown that human sebum may play a role in barrier function but with much debate. To elucidate the effects of human sebum on skin barrier function. We used hairless mouse skin to study the functional and morphological alternation of epidermis after the application of human sebum. The results showed a significant increase in transepidermal water loss and erythema value, and a decrease in skin hydration, accompanied by epidermal hyperplasia with parakeratosis following sebum application. Nile red staining together with electron microscopic examination confirmed the underlying mechanisms for sebum-induced barrier disruption are related directly to the interaction of sebum with the intracellular lipid lamellae of the SC, thereby leading to the increase in the fluidity of SC intracellular lipids as demonstrated by ATR-FTIR measurement. An inflammatory reaction characterized by an enhanced cytokine cascade, including up-regulation of TNF-α, IL-1α and IL-6, was also observed. On the other hand, there were insignificant expression of thymic stromal lymphopoietin and unchanged serum levels of IgE, suggesting non-immunogenic stimulation by sebum treatment. It may be concluded that inflammation induced by excess amount of sebum is more likely an irritant contact dermatitis rather than an allergic one. Moreover, these findings implicated possible relationships between sebum, irritant contact dermatitis, and seborrheic dermatitis. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption.

    PubMed

    Rajesh, Mohanraj; Mukhopadhyay, Partha; Bátkai, Sándor; Haskó, György; Liaudet, Lucas; Drel, Viktor R; Obrosova, Irina G; Pacher, Pál

    2007-07-01

    A nonpsychoactive cannabinoid cannabidiol (CBD) has been shown to exert potent anti-inflammatory and antioxidant effects and has recently been reported to lower the incidence of diabetes in nonobese diabetic mice and to preserve the blood-retinal barrier in experimental diabetes. In this study we have investigated the effects of CBD on high glucose (HG)-induced, mitochondrial superoxide generation, NF-kappaB activation, nitrotyrosine formation, inducible nitric oxide synthase (iNOS) and adhesion molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion, transendothelial migration of monocytes, and disruption of endothelial barrier function in human coronary artery endothelial cells (HCAECs). HG markedly increased mitochondrial superoxide generation (measured by flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine formation, upregulation of iNOS and adhesion molecules ICAM-1 and VCAM-1, transendothelial migration of monocytes, and monocyte-endothelial adhesion in HCAECs. HG also decreased endothelial barrier function measured by increased permeability and diminished expression of vascular endothelial cadherin in HCAECs. Remarkably, all the above mentioned effects of HG were attenuated by CBD pretreatment. Since a disruption of the endothelial function and integrity by HG is a crucial early event underlying the development of various diabetic complications, our results suggest that CBD, which has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in humans, may have significant therapeutic benefits against diabetic complications and atherosclerosis.

  4. Pathogen induced chemo-attractant hepoxilin A3 drives neutrophils, but not eosinophils across epithelial barriers.

    PubMed

    Kubala, S A; Patil, S U; Shreffler, W G; Hurley, B P

    2014-01-01

    Pathogen induced migration of neutrophils across mucosal epithelial barriers requires epithelial production of the chemotactic lipid mediator, hepoxilin A3 (HXA3). HXA3 is an eicosanoid derived from arachidonic acid. Although eosinophils are also capable of penetrating mucosal surfaces, eosinophilic infiltration occurs mainly during allergic processes whereas neutrophils dominate mucosal infection. Both neutrophils and eosinophils can respond to chemotactic gradients of certain eicosanoids, however, it is not known whether eosinophils respond to pathogen induced lipid mediators such as HXA3. In this study, neutrophils and eosinophils were isolated from human blood and placed on the basolateral side of polarized epithelial monolayers grown on permeable Transwell filters and challenged by various chemotactic gradients of distinct lipid mediators. We observed that both cell populations migrated across epithelial monolayers in response to a leukotriene B4 (LTB4) gradient, whereas only eosinophils migrated toward a prostaglandin D2 (PGD2) gradient. Interestingly, while pathogen induced neutrophil trans-epithelial migration was substantial, pathogen induced eosinophil trans-epithelial migration was not observed. Further, gradients of chemotactic lipids derived from pathogen infected epithelial cells known to be enriched for HXA3 as well as purified HXA3 drove significant numbers of neutrophils across epithelial barriers, whereas eosinophils failed to respond to these gradients. These data suggest that although the eicosanoid HXA3 serves as an important neutrophil chemo-attractant at mucosal surfaces during pathogenic infection, HXA3 does not appear to exhibit chemotactic activity toward eosinophils.

  5. IL-25 induces both inflammation and skin barrier dysfunction in atopic dermatitis.

    PubMed

    Deleuran, Mette; Hvid, Malene; Kemp, Kaare; Christensen, Gitte B; Deleuran, Bent; Vestergaard, Christian

    2012-01-01

    Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by having both an epidermal and a dermal component, shown as a barrier deficiency and inflammation. The mechanisms resulting in skewing the immune response in a Th2 direction in AD are still not fully elucidated. We suggest that IL-25 could be a major target in AD. IL-25 is produced by cells within the dermis of AD patients, and we suggest these to be dendritic cells (DCs). Furthermore, we show that IL-25 can inhibit filaggrin synthesis in keratinocytes. These results point towards a central role of IL-25 producing DCs that can induce both a Th2 response and inhibit filaggrin synthesis. We believe this strongly supports a role for IL-25 in AD, bridging the gap between inflammation and impaired skin barrier function.

  6. IL17A impairs blood-testis barrier integrity and induces testicular inflammation.

    PubMed

    Pérez, Cecilia Valeria; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Galardo, María Noel; Naito, Munekazu; Lustig, Livia; Jacobo, Patricia Verónica

    2014-12-01

    Experimental autoimmune orchitis is a useful model for studying testicular inflammation and germ/immune cell interactions. Th17 cells and their hallmark cytokine IL17A were reported to be involved in the development of autoimmune orchitis. The aim of the present work is to investigate the pathogenic role of IL17A in rat testis. In vitro experiments were performed in order to analyze effects of IL17A on Sertoli cell tight junctions. The addition of IL17A to normal rat Sertoli cell cultures induced a significant decline in transepithelial electrical resistance and a reduction of occludin expression and redistribution of occludin and claudin 11, altering the Sertoli cell tight junction barrier. Intratesticular injection of 1 μg of recombinant rat IL17A to Sprague-Dawley rats induced increased blood-testis barrier permeability, as shown by the presence of biotin tracer in the seminiferous tubule adluminal compartment, and delocalization of occludin and claudin 11. Results showed that IL17A induced focal inflammatory cell infiltration in the interstitium and germ cell sloughing in adjacent seminiferous tubules. Moreover, an increase in TUNEL+ apoptotic germ cells was also observed. Inflammatory ED1+ macrophages were the main population infiltrating the interstitium following IL17A injection. This correlated with an increase in mRNA expression of the monocyte chemoattractant protein Ccl2, its receptor Ccr2 and the vascular cell adhesion molecule Vcam1. Overall results suggest a relevant role of IL17A in the development of testicular inflammation, facilitating the recruitment of immune cells to the testicular interstitium and inducing impairment of blood-testis barrier function.

  7. Cholinergic receptor activation on epithelia protects against cytokine-induced barrier dysfunction.

    PubMed

    Dhawan, S; Hiemstra, I H; Verseijden, C; Hilbers, F W; Te Velde, A A; Willemsen, L E M; Stap, J; den Haan, J M; de Jonge, W J

    2015-04-01

    Various types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine-induced barrier dysfunction. The effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para-cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto- and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease. IL-1β induced production of chemokines (CXCL-1, CXCL-10, IL-8, CCL-7) and led to a rearrangement of TJ proteins (occludin and ZO-1). This response was inhibited by pre-treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL-1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre-incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL-1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine-induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL-8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context. Acetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions. © 2015

  8. Iloprost improves endothelial barrier function in lipopolysaccharide-induced lung injury.

    PubMed

    Birukova, Anna A; Wu, Tinghuai; Tian, Yufeng; Meliton, Angelo; Sarich, Nicolene; Tian, Xinyong; Leff, Alan; Birukov, Konstantin G

    2013-01-01

    The protective effects of prostacyclin and its stable analogue iloprost are mediated by elevation of intracellular cyclic AMP (cAMP) leading to enhancement of the peripheral actin cytoskeleton and cell-cell adhesive structures. This study tested the hypothesis that iloprost may exhibit protective effects against lung injury and endothelial barrier dysfunction induced by bacterial wall lipopolysaccharide (LPS). Endothelial barrier dysfunction was assessed by measurements of transendothelial permeability, morphologically and by analysis of LPS-activated inflammatory signalling. In vivo, C57BL/6J mice were challenged with LPS with or without iloprost or 8-bromoadenosine-3',5'-cyclic monophosphate (Br-cAMP) treatment. Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count and Evans blue extravasation. Iloprost and Br-cAMP attenuated the disruption of the endothelial monolayer, and suppressed the activation of p38 mitogen-activated protein kinase (MAPK), the nuclear factor (NF)-κB pathway, Rho signalling, intercellular adhesion molecular (ICAM)-1 expression and neutrophil migration after LPS challenge. In vivo, iloprost was effective against LPS-induced protein and neutrophil accumulation in bronchoalveolar lavage fluid, and reduced myeloperoxidase activation, ICAM-1 expression and Evans blue extravasation in the lungs. Inhibition of Rac activity abolished the barrier-protective and anti-inflammatory effects of iloprost and Br-cAMP. Iloprost-induced elevation of intracellular cAMP triggers Rac signalling, which attenuates LPS-induced NF-κB and p38 MAPK inflammatory pathways and the Rho-dependent mechanism of endothelial permeability.

  9. Effects of 2,4-dinitrophenol on ischemia-induced blood-brain barrier disruption.

    PubMed

    Ennis, S R; Keep, R F

    2006-01-01

    This study examines the effect of 2,4-dinitrophenol (DNP), a mitochondrial uncoupling agent, during focal brain ischemia induced by middle cerebral artery (MCA) occlusion. Blood-brain barrier (BBB) disruption was assessed after 2 hours of occlusion with 2 hours of reperfusion or 4 hours of permanent occlusion by measurement of the influx rate constant (K(i)) for 3H-inulin in the MCA territory ipsi- and contralateral to the occlusion. Three experimental groups were examined: vehicle and 1 and 5 mg/kg DNP treated animals (given 30 minutes prior to occlusion). Four hours of permanent MCA occlusion only induced a modest increase in the K(i) for inulin in vehicle-treated animals (0.09 +/- 0.01 vs. 0.07 +/- 0.01 microL/g/min in contralateral tissue). Although 5 mg/kg DNP significantly increased this disruption (p < 0.01), this effect was relatively minor (0.14 +/- 0.02 microL/g/min). In contrast, DNP treatment in transient ischemia markedly increased barrier disruption. The ipsilateral K(i) for 3H-inulin were 0.15 +/- 0.04, 0.37 +/- 0.06, and 0.79 +/- 0.17 microL/g/min in vehicle, 1 mg/kg DNP and 5 mg/kg DNP groups, respectively. DNP did not induce barrier disruption in the contralateral hemisphere. Thus, while there is evidence that DNP can be neuroprotective, it has adverse effects on the BBB during ischemia, particularly with reperfusion. Considering the importance of naturally- or therapeutically-induced reperfusion in limiting brain damage, this may limit the utility of DNP and mitochondrial uncouplers as therapeutic agents.

  10. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for draining...

  11. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for draining...

  12. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for draining...

  13. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for draining...

  14. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for draining...

  15. Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction.

    PubMed

    Kucharekova, M; Schalkwijk, J; Van De Kerkhof, P C M; Van De Valk, P G M

    2002-06-01

    In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in

  16. Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

    PubMed

    Smith, I M; Baker, A; Arneborg, N; Jespersen, L

    2015-11-01

    The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast

  17. Magnesium sulfate attenuates increased blood-brain barrier permeability during insulin-induced hypoglycemia in rats.

    PubMed

    Kaya, M; Küçük, M; Kalayci, R B; Cimen, V; Gürses, C; Elmas, I; Arican, N

    2001-09-01

    Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05+/-0.57 vs. 2.58+/-0.14 mg/dL in the Mg2+ group, and 7.14+/-0.42 vs. 2.78+/-0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4+/-0.66 vs. 118+/-2.23 mg/dL in the insulin group, and 7+/-1.59 vs. 118+/-4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.

  18. No drain, autologous transfusion drain or suction drain? A randomised prospective study in total hip replacement surgery of 168 patients.

    PubMed

    Cheung, Graham; Carmont, Michael R; Bing, Andrew J F; Kuiper, Jan-Herman; Alcock, Robert J; Graham, Niall M

    2010-10-01

    We performed a prospective, randomised controlled trial to assess the differences in the use of a conventional suction drain, an Autologous Blood Transfusion (ABT) drain and no drain, in 168 patients. There was no significant difference between the drainage from ABT drains ( mean : 345 ml) and the suction drain (314 ml). Forty percent of patients receiving a suction drain had a haemoglobin level less than 10 g/dL at 24 hours, compared to 35% with no drain and 28% with an ABT drain. Patients that had no drains had wounds that were dry significantly sooner, mean 3.0 days compared to a mean of 3.9 days with an ABT drain and a mean of 4 days with a suction drain. Patients that did not have a drain inserted stayed in hospital a significantly shorter period of time, compared with drains. We feel the benefits of quicker drying wounds, shorter hospital stays and the economic savings justify the conclusion that no drain is required after hip replacement.

  19. Interactions between surface discharges induced by volume discharges in a dielectric barrier discharge system

    SciTech Connect

    Gao, Yenan; Dong, Lifang Zhao, Longhu; Wang, Yongjie; Pan, Yuyang; Li, Ben

    2014-10-15

    The interaction between micro-discharges involved in surface discharges (SDs) is studied in dielectric barrier discharge system. Instantaneous images taken by high speed cameras show that the SDs are induced by volume discharges (VDs). They cannot cross the midperpendicular of two neighbouring volume charges at low voltage while they stretch along it at high voltage, indicating that there is interaction between SDs. The differences of plasma parameters between SD and VD are studied by optical emission spectroscopy. The simulation of the electric fields of the wall charges accumulated by VD further confirms the existence of the interaction.

  20. Quantum-state transfer via resonant tunneling through local-field-induced barriers

    NASA Astrophysics Data System (ADS)

    Lorenzo, S.; Apollaro, T. J. G.; Sindona, A.; Plastina, F.

    2013-04-01

    Efficient quantum-state transfer is achieved in a uniformly coupled spin-1/2 chain, with open boundaries, by application of local magnetic fields on the second and last-but-one spins, respectively. These effective barriers induce the appearance of two eigenstates, bilocalized at the edges of the chain, which allow a high-quality transfer also at relatively long distances. The same mechanism may be used to send an entire e-bit (e.g., an entangled qubit pair) from one to the other end of the chain.

  1. Akt1 promotes stimuli-induced endothelial-barrier protection through FoxO-mediated tight-junction protein turnover.

    PubMed

    Gao, Fei; Artham, Sandeep; Sabbineni, Harika; Al-Azayzih, Ahmad; Peng, Xiao-Ding; Hay, Nissim; Adams, Ralf H; Byzova, Tatiana V; Somanath, Payaningal R

    2016-10-01

    Vascular permeability regulated by the vascular endothelial growth factor (VEGF) through endothelial-barrier junctions is essential for inflammation. Mechanisms regulating vascular permeability remain elusive. Although 'Akt' and 'Src' have been implicated in the endothelial-barrier regulation, it is puzzling how both agents that protect and disrupt the endothelial-barrier activate these kinases to reciprocally regulate vascular permeability. To delineate the role of Akt1 in endothelial-barrier regulation, we created endothelial-specific, tamoxifen-inducible Akt1 knockout mice and stable ShRNA-mediated Akt1 knockdown in human microvascular endothelial cells. Akt1 loss leads to decreased basal and angiopoietin1-induced endothelial-barrier resistance, and enhanced VEGF-induced endothelial-barrier breakdown. Endothelial Akt1 deficiency resulted in enhanced VEGF-induced vascular leakage in mice ears, which was rescued upon re-expression with Adeno-myrAkt1. Furthermore, co-treatment with angiopoietin1 reversed VEGF-induced vascular leakage in an Akt1-dependent manner. Mechanistically, our study revealed that while VEGF-induced short-term vascular permeability is independent of Akt1, its recovery is reliant on Akt1 and FoxO-mediated claudin expression. Pharmacological inhibition of FoxO transcription factors rescued the defective endothelial barrier due to Akt1 deficiency. Here we provide novel insights on the endothelial-barrier protective role of VEGF in the long term and the importance of Akt1-FoxO signaling on tight-junction stabilization and prevention of vascular leakage through claudin expression.

  2. Pitch glide effect induced by a nonlinear string-barrier interaction

    NASA Astrophysics Data System (ADS)

    Kartofelev, Dmitri; Stulov, Anatoli; Välimäki, Vesa

    2015-10-01

    Interactions of a vibrating string with its supports and other spatially distributed barriers play a significant role in the physics of many stringed musical instruments. It is well known that the tone of the string vibrations is determined by the string supports, and that the boundary conditions of the string termination may cause a short-lasting initial fundamental frequency shifting. Generally, this phenomenon is associated with the nonlinear modulation of the stiff string tension. The aim of this paper is to study the initial frequency glide phenomenon that is induced only by the string-barrier interaction, apart from other possible physical causes, and without the interfering effects of dissipation and dispersion. From a numerical simulation perspective, this highly nonlinear problem may present various difficulties, not the least of which is the risk of numerical instability. We propose a numerically stable and a purely kinematic model of the string-barrier interaction, which is based on the travelling wave solution of the ideal string vibration. The model is capable of reproducing the motion of the vibrating string exhibiting the initial fundamental frequency glide, which is caused solely by the complex nonlinear interaction of the string with its termination. The results presented in this paper can expand our knowledge and understanding of the timbre evolution and the physical principles of sound generation of numerous stringed instruments, such as lutes called the tambura, sitar and biwa.

  3. Under-the-barrier dynamics in laser-induced relativistic tunneling.

    PubMed

    Klaiber, Michael; Yakaboylu, Enderalp; Bauke, Heiko; Hatsagortsyan, Karen Z; Keitel, Christoph H

    2013-04-12

    The tunneling dynamics in relativistic strong-field ionization is investigated with the aim to develop an intuitive picture for the relativistic tunneling regime. We demonstrate that the tunneling picture applies also in the relativistic regime by introducing position dependent energy levels. The quantum dynamics in the classically forbidden region features two time scales, the typical time that characterizes the probability density's decay of the ionizing electron under the barrier (Keldysh time) and the time interval which the electron spends inside the barrier (Eisenbud-Wigner-Smith tunneling time). In the relativistic regime, an electron momentum shift as well as a spatial shift along the laser propagation direction arise during the under-the-barrier motion which are caused by the laser magnetic field induced Lorentz force. The momentum shift is proportional to the Keldysh time, while the wave-packet's spatial drift is proportional to the Eisenbud-Wigner-Smith time. The signature of the momentum shift is shown to be present in the ionization spectrum at the detector and, therefore, observable experimentally. In contrast, the signature of the Eisenbud-Wigner-Smith time delay disappears at far distances for pure quasistatic tunneling dynamics.

  4. Sign preference in ion-induced nucleation: contributions to the free energy barrier.

    PubMed

    Keasler, Samuel J; Kim, Hyunmi; Chen, Bin

    2012-11-07

    We have performed a series of computer simulations using the AVUS-HR approach to better understand the origin of the sign preference in ion-induced nucleation. In particular, we emphasize the importance of distinguishing between the total formation free energy of a cluster, and the nucleation free energy, which involves only those steps contributing to the free energy barrier. We have separately considered how the ion-water potential energy, the water-water potential energy, and the entropy contribute to both the cluster formation free energy, and the nucleation free energy. These simulations have shown that while the ion-water potential energies make the largest contribution to the formation free energy difference between positive and negative ions, the entropy is the contribution leading to lower nucleation free energy barriers for negative ions. The primary reason for this is the larger stable (but precritical) clusters formed around negative ions. We have further shown that the distinction between formation and nucleation free energies is of particular importance when comparing small cations with larger anions where the formation free energies can be much lower for the cationic clusters, even though the nucleation barriers are lower for the anionic clusters.

  5. Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening

    PubMed Central

    Chu, Po-Chun; Liu, Hao-Li; Lai, Hsin-Yi; Lin, Chung-Yin; Tsai, Hong-Chieh; Pei, Yu-Cheng

    2015-01-01

    Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn’t affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications. PMID:26490653

  6. Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening.

    PubMed

    Chu, Po-Chun; Liu, Hao-Li; Lai, Hsin-Yi; Lin, Chung-Yin; Tsai, Hong-Chieh; Pei, Yu-Cheng

    2015-10-22

    Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn't affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications.

  7. Anthocyanins inhibit tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity.

    PubMed

    Cremonini, Eleonora; Mastaloudis, Angela; Hester, Shelly N; Verstraeten, Sandra V; Anderson, Maureen; Wood, Steven M; Waterhouse, Andrew L; Fraga, Cesar G; Oteiza, Patricia I

    2017-08-01

    An increased permeability of the intestinal barrier is proposed as a major event in the pathophysiology of conditions characterized by chronic gut inflammation. This study investigated the capacity of pure anthocyanins (AC), and berry and rice extracts containing different types and amounts of AC, to inhibit tumor necrosis alpha (TNFα)-induced permeabilization of Caco-2 cell monolayers. Caco-2 cells differentiated into intestinal epithelial cell monolayers were incubated in the absence/presence of TNFα, with or without the addition of AC or AC-rich plant extracts (ACRE). AC and ACRE inhibited TNFα-induced loss of monolayer permeability as assessed by changes in transepithelial electrical resistance (TEER) and paracellular transport of FITC-dextran. In the range of concentrations tested (0.25-1 μM), O-glucosides of cyanidin, and delphinidin, but not those of malvidin, peonidin and petunidin protected the monolayer from TNFα-induced decrease of TEER and increase of FITC-dextran permeability. Cyanidin and delphinidin acted by mitigating TNFα-triggered activation of transcription factor NF-κB, and downstream phosphorylation of myosin light chain (MLC). The protective actions of the ACRE on TNFα-induced TEER increase was positively correlated with the sum of cyanidins and delphinidins (r(2) = 0.83) content in the ACRE. However, no correlation was observed between TEER and ACRE total AC, malvidin, or peonidin content. Results support a particular capacity of cyanidins and delphinidins in the protection of the intestinal barrier against inflammation-induced permeabilization, in part through the inhibition of the NF-κB pathway.

  8. Alcohol-induced premature permeability in mouse placenta-yolk sac barriers in vivo.

    PubMed

    Haghighi Poodeh, S; Salonurmi, T; Nagy, I; Koivunen, P; Vuoristo, J; Räsänen, J; Sormunen, R; Vainio, S; Savolainen, M J

    2012-10-01

    Acute alcohol exposure induces malformation and malfunction of placenta-yolk sac tissues in rodents, reducing the labyrinth zone in the placenta and altering the permeability and fluidity of the cell membrane. During normal mouse placentation the cells line up in an optimal way to form a hemotrichorial placenta where layers II and III are connected through gap junctions. These act as molecular sieves that limit the passage of large molecules. PlGF is a developmentally regulated protein that controls the passage of molecules in the vasculosyncytial membranes and media of large blood vessels in the placental villi. In addition to the chorioallontoic placenta, rodents also have another type of placenta that consists of Reichert's membrane within the trophoblast cell layer on the maternal side and the parietal endodermal cells on the embryonic site. This forms a separate materno-fetal transport system. We study here whether alcohol affects these two placental barriers, leading to placental malfunction that in turn diminishes the nutrient supply to the embryo. CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals at 8.75 days post coitum (dpc). The placentas were collected on 9.5, 11.5 and 14.5 dpc and used for histopathological protein studies. Hemotrichorial cell layer structure interactions through connective tissue and gap junction were analyzed by electron microscopy. The permeability of the feto-maternal barrier was visualized with Evans Blue. VEGF, a permeability inducer, was found to be up-regulated in the mouse placenta after acute alcohol exposure, and permeability was also affected by altered structures in the barriers that separate the feto-maternal blood circulation which destroyed the gap junctions in the hemotrichorial cell layer, reduced the thickness of Reichert's membrane and interfered with with Reichert's trophoblast/Reichert's parietal interaction. These defects together could have caused the permeability malfunction

  9. Monocyte and M1 Macrophage-induced Barrier Defect Contributes to Chronic Intestinal Inflammation in IBD.

    PubMed

    Lissner, Donata; Schumann, Michael; Batra, Arvind; Kredel, Lea-Isabel; Kühl, Anja A; Erben, Ulrike; May, Claudia; Schulzke, Jörg-Dieter; Siegmund, Britta

    2015-06-01

    Macrophages are key players in inflammatory bowel diseases (IBD). This study aimed to determine site-specific effects of defined macrophage subtypes on the integrity of the intestinal epithelial barrier. Macrophage subtypes in situ in intestinal specimens of patients with IBD were visualized by immunohistochemistry. In vitro polarization of human peripheral CD14 cells yielded M1 or M2 macrophages. The influence of primary monocytes or macrophage subtypes on epithelial barrier integrity was analyzed by transepithelial resistance measurements, Western blot analysis, confocal laser scanning microscopy, and cytometric bead array in a coculture model of primary human macrophages and layers of intestinal epithelial cell lines. The lamina propria of the inflamed intestine in patients with IBD, predominantly in Crohn's disease, is massively infiltrated by CD68 cells also positive for inducible nitric oxide synthase and tumor necrosis factor (TNF) α. The presence of M1 macrophage shifted the balance in the local macrophage compartment towards a proinflammatory state. In the coculture model, monocytes and M1 macrophages reduced transepithelial resistance as a marker for epithelial barrier integrity. The mechanisms for paracellular leakage included intracellular relocalization of tight junction proteins like claudin-2 and epithelial cell apoptosis. Determined by specific cytokine blockade, M1 macrophages exerted their deleterious effect mainly through TNF-α, whereas monocyte-mediated damage was driven by the inflammasome effector cytokines, interleukin-1β and interleukin-18. Lamina propria monocytes and M1 macrophages invading intestinal tissues directly contribute to disrupting the epithelial barrier through deregulation of tight junction proteins and induction of epithelial cell apoptosis, thus driving intestinal inflammation in IBD.

  10. Monocyte and M1 Macrophage-induced Barrier Defect Contributes to Chronic Intestinal Inflammation in IBD

    PubMed Central

    Lissner, Donata; Schumann, Michael; Batra, Arvind; Kredel, Lea-Isabel; Kühl, Anja A.; Erben, Ulrike; May, Claudia; Schulzke, Jörg-Dieter

    2015-01-01

    Background: Macrophages are key players in inflammatory bowel diseases (IBD). This study aimed to determine site-specific effects of defined macrophage subtypes on the integrity of the intestinal epithelial barrier. Methods: Macrophage subtypes in situ in intestinal specimens of patients with IBD were visualized by immunohistochemistry. In vitro polarization of human peripheral CD14+ cells yielded M1 or M2 macrophages. The influence of primary monocytes or macrophage subtypes on epithelial barrier integrity was analyzed by transepithelial resistance measurements, Western blot analysis, confocal laser scanning microscopy, and cytometric bead array in a coculture model of primary human macrophages and layers of intestinal epithelial cell lines. Results: The lamina propria of the inflamed intestine in patients with IBD, predominantly in Crohn's disease, is massively infiltrated by CD68+ cells also positive for inducible nitric oxide synthase and tumor necrosis factor (TNF) α. The presence of M1 macrophage shifted the balance in the local macrophage compartment towards a proinflammatory state. In the coculture model, monocytes and M1 macrophages reduced transepithelial resistance as a marker for epithelial barrier integrity. The mechanisms for paracellular leakage included intracellular relocalization of tight junction proteins like claudin-2 and epithelial cell apoptosis. Determined by specific cytokine blockade, M1 macrophages exerted their deleterious effect mainly through TNF-α, whereas monocyte-mediated damage was driven by the inflammasome effector cytokines, interleukin-1β and interleukin-18. Conclusions: Lamina propria monocytes and M1 macrophages invading intestinal tissues directly contribute to disrupting the epithelial barrier through deregulation of tight junction proteins and induction of epithelial cell apoptosis, thus driving intestinal inflammation in IBD. PMID:25901973

  11. Hot-carrier-induced linear drain current and threshold voltage degradation for thin layer silicon-on-insulator field P-channel lateral double-diffused metal-oxide-semiconductor

    SciTech Connect

    Zhou, Xin; Qiao, Ming; He, Yitao; Li, Zhaoji; Zhang, Bo

    2015-11-16

    Hot-carrier-induced linear drain current (I{sub dlin}) and threshold voltage (V{sub th}) degradations for the thin layer SOI field p-channel lateral double-diffused MOS (pLDMOS) are investigated. Two competition degradation mechanisms are revealed and the hot-carrier conductance modulation model is proposed. In the channel, hot-hole injection induced positive oxide trapped charge and interface trap gives rise to the V{sub th} increasing and the channel conductance (G{sub ch}) decreasing, then reduces I{sub dlin}. In the p-drift region, hot-electron injection induced negative oxide trapped charge enhances the conductance of drift doping resistance (G{sub d}), and then increases I{sub dlin}. Consequently, the eventual I{sub dlin} degradation is controlled by the competition of the two mechanisms due to conductance modulation in the both regions. Based on the model, it is explained that the measured I{sub dlin} anomalously increases while the V{sub th} is increasing with power law. The thin layer field pLDMOS exhibits more severe V{sub th} instability compared with thick SOI layer structure; as a result, it should be seriously evaluated in actual application in switching circuit.

  12. Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: role of cold-sensitive TRP receptors in epidermal permeability barrier homoeostasis.

    PubMed

    Denda, Mitsuhiro; Tsutsumi, Moe; Denda, Sumiko

    2010-09-01

    TRPA1 and TRPM8 receptors are activated at low temperature (A1: below 17 degrees C and M8: below 22 degrees C). Recently, we observed that low temperature (below 22 degrees C) induced elevation of intracellular calcium in keratinocytes. Moreover, we demonstrated that topical application of TRPA1 agonists accelerated the recovery of epidermal permeability barrier function after disruption. In this study, we examined the effect of topical application of TRPM8 modulators on epidermal permeability barrier homoeostasis. Immunohistochemical study and RT-PCR confirmed the expression of TRPM8 or TRPM8-like protein in epidermal keratinocytes. Topical application of TRPM8 agonists, menthol and WS 12 accelerated barrier recovery after tape stripping. The effect of WS12 was blocked by a non-selective TRP antagonist, Ruthenium Red, and a TRPM8-specific antagonist, BTCT. Topical application of WS12 also reduced epidermal proliferation associated with barrier disruption under low humidity, and this effect was blocked by BTCT. Our results indicate that TRPM8 or a closely related protein in epidermal keratinocytes plays a role in epidermal permeability barrier homoeostasis and epidermal proliferation after barrier insult.

  13. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II

    PubMed Central

    Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement. PMID:28119542

  14. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.

    PubMed

    Wu, Zhiyong; Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.

  15. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  16. Targeting Palmitoyl acyltransferase ZDHHC21 Improves Gut Epithelial Barrier Dysfunction Resulting from Burn Induced Systemic Inflammation.

    PubMed

    Haines, Ricci J; Wang, Chunyan; Yang, Clement Gy; Eitnier, Rebecca A; Wang, Fang; Wu, Mack H

    2017-08-24

    Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular palmitoyl acyltransferase (PAT), ZDHHC21, in mediating signaling events required for gut hyperpermeability induced by inflammation. Using qPCR, we show that ZDHHC21 mRNA, production was enhanced by two-fold when intestinal epithelial cells were treated with TNFα/IFNγ in vitro. In addition, pharmacological targeting of PATs with 2-bromopalmitate (2-BP) showed significant improvement in TNFα/IFNγ mediated epithelial barrier dysfunction by using electric cell-substrate impedance sensing (ECIS) assays, as well as FITC-dextran permeability assays. Using the ABE assay and click chemistry, we show that TNFα/IFNγ treatment of intestinal epithelial cells results in enhanced detection of total palmitoylated proteins, and this response is inhibited by 2-BP. Using ZDHHC21 deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, H&E staining of small intestine, as well as transmission electron microscopy (TEM), showed mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. Copyright © 2017, American Journal of Physiology-Gastrointestinal and Liver Physiology.

  17. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking.

    PubMed

    Maggioli, E; McArthur, S; Mauro, C; Kieswich, J; Kusters, D H M; Reutelingsperger, C P M; Yaqoob, M; Solito, E

    2016-01-01

    Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood-brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  18. Bacillus cereus-induced permeability of the blood-ocular barrier during experimental endophthalmitis.

    PubMed

    Moyer, Andrea L; Ramadan, Raniyah T; Novosad, Billy D; Astley, Roger; Callegan, Michelle C

    2009-08-01

    The purpose of this study was to determine to what extent blood-retinal barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. Mice were intravitreally injected with 100 colony-forming units of B. cereus, and eyes were analyzed at specific times after infection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the retinal pigment epithelium. B. cereus induced the leakage of albumin and fibrin into the aqueous and vitreous humor by 8 hours after infection. BRB permeability occurred as early as 4 hours and increased 13.30-fold compared with uninfected controls by 8 hours. Production of proinflammatory cytokines IL-6, MIP-1alpha, IL-1beta, and KC increased over the course of infection. In the retina, ZO-1 disruption began by 4 hours and was followed by decreasing occludin and ZO-1 expression at 4 and 8 hours, respectively. Tubulin condensation and RPE65 degradation occurred by 12 hours. A quorum-sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Wild-type and mutant B. cereus sterile supernatants induced blood-ocular barrier permeability similarly to that of wild-type infection. These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 hours after infection. Disruption of tight junctions at the level of the retinal pigment epithelium may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability.

  19. Mast cell activation is involved in stress-induced epithelial barrier dysfunction in the esophagus.

    PubMed

    Zhong, Chan Juan; Wang, Kun; Zhang, Lu; Yang, Chang Qing; Zhang, Kuo; Zhou, Shu Pei; Duan, Li Ping

    2015-04-01

    We aimed to investigate the role of mast cell in stress-induced barrier dysfunction in the esophagus and its possible pathway involved using mast cell-deficient (Ws/Ws) rats. Ws/Ws rats and normal (+/+) rats were submitted to chronic restraint stress (CRS) 2 h/day for 7 days. Tissues were obtained from distal esophagus. Mast cells were counted under Alcian blue-safranin O stain. Activation of mast cells was assessed using transmission electron microscope. Esophageal epithelial barrier dysfunction was evaluated by measuring intercellular spaces (ICS) and by quantifying tight junction (TJ) proteins. The localization and expression of mast cell-derived tryptase and proteinase activated receptor 2 (PAR-2) were assessed. A higher number of mast cells and higher proportion of activated mast cells were observed in CRS +/+ rats compared with non-stress controls. Increased ICS and decreased expression of some TJ proteins were observed in the CRS +/+ rats but not in the CRS Ws/Ws rats. Tryptase and its receptor PAR-2 were found elevated concomitantly by nearly 100% in CRS +/+ rats, but not in CRS Ws/Ws rats. Mast cells play an important role in stress-induced epithelial barrier dysfunction in esophagus. The mechanism may involve the activation of PAR-2 by mast cell-derived tryptase, causing proinflammatory responses and the subsequent disruption of the epithelial TJ proteins and a disturbed cytoskeleton function, resulting in dilated intercellular spaces. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  20. Cross sections and barriers for nuclear fission induced by high-energy nucleons

    SciTech Connect

    Grudzevich, O. T.; Yavshits, S. G.

    2013-03-15

    The cross sections for the fission of {sup 232}Th, {sup 235,238}U, {sup 237}Np, and {sup 239}Pu target nuclei that was induced by 20- to 1000-MeV neutrons and protons were calculated. The respective calculations were based on the multiconfiguration-fission (MCFx) model, which was used to describe three basic stages of the interaction of high-energy nucleons with nuclei: direct processes (intranuclear cascade), equilibration of the emerging compound system, and the decay of the compound nucleus (statistical model). Fission barriers were calculated within the microscopic approach for isotopic chains formed by 15 to 20 nuclei of the required elements. The calculated fission cross sections were compared with available experimental data. It was shown that the input data set and the theoretical model used made it possible to predict satisfactorily cross section for nuclear fission induced by 20- to 1000-MeV nucleons.

  1. Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

    SciTech Connect

    Maeepea, O.; Karlsson, C.; Alm, A.

    1984-09-01

    Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers.

  2. Chemotherapy-induced mucosal barrier dysfunction: an updated review on the role of intestinal tight junctions.

    PubMed

    Wardill, Hannah R; Bowen, Joanne M

    2013-06-01

    Gut toxicity, or mucositis, is a major dose-limiting side effect of chemotherapy that until recently received very little attention. Despite significant research, the mechanisms that underpin chemotherapy-induced gut toxicity (CIGT) remain unclear. Recently however, there has been renewed interest in the role tight junctions play in the pathogenesis of CIGT and associated diarrhea. Thus, this review will cover the role of tight junctions in maintaining gastrointestinal homeostasis and touch on recently proposed mechanisms of how tight junctions may contribute to the development of chemotherapy-induced diarrhea. There is a wealth of anecdotal evidence regarding the role of tight junctions in the pathogenesis of gut toxicity. However, few studies have quantified or assessed the molecular changes in tight junctions in response to chemotherapy. This review will highlight the major findings of these studies and discuss the potential mechanisms by which tight junction disruption and mucosal barrier dysfunction may contribute to diarrhea. The significant clinical and economic impact associated with CIGT and diarrhea has only recently been appreciated. This has prompted significant research efforts in an attempt to reveal the pathophysiology of this debilitating complication. Renewed interest has been shown regarding the role of tight junctions in not only maintaining gastrointestinal health, but also contributing to mucosal barrier injury and diarrhea development. More detailed research into the effect chemotherapy has on the molecular characteristics of tight junctions will lead to a better understanding of the pathophysiology of CIGT and may uncover the therapeutic potential of tight junctions in treating diarrhea.

  3. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress

    PubMed Central

    KIM, KI CHEON; PIAO, MEI JING; HEWAGE, SUSARA RUWAN KUMARA MADDUMA; HAN, XIA; KANG, KYOUNG AH; JO, JIN OH; MOK, YOUNG SUN; SHIN, JENNIFER H.; PARK, YEUNSOO; YOO, SUK JAE; HYUN, JIN WON

    2016-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2′,7′-dichlorodihydro-fluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components. PMID:26573561

  4. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress.

    PubMed

    Kim, Ki Cheon; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Han, Xia; Kang, Kyoung Ah; Jo, Jin Oh; Mok, Young Sun; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Hyun, Jin Won

    2016-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components.

  5. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

    PubMed Central

    de Punder, Karin; Pruimboom, Leo

    2015-01-01

    Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases. PMID:26029209

  6. Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats.

    PubMed

    Yuan, Jing; Wang, Aihua; He, Yan; Si, Zhihua; Xu, Shan; Zhang, Shanchao; Wang, Kun; Wang, Dawei; Liu, Yiming

    2016-10-01

    Loss of blood-brain barrier (BBB) integrity is a downstream event caused by traumatic brain injury (TBI). BBB integrity is affected by certain physiological conditions, including inflammation and oxidative stress. Cordycepin is a susbtance with anti-inflammatory and anti-oxidative effects. Therefore, it is necessary to investigate whether cordycepin affects TBI-induced impairments of BBB integrity. Using TBI rats as the in vivo model and applying multiple techniques, including stroke severity evaluation, Evans blue assessment, quantitative real-time PCR, Western blotting and ELISA, we investigated the dose-dependent protective effects of cordycepin on the TBI-induced impairments of BBB integrity. Cordycepin treatment attenuated the TBI-induced impairments in a dose-dependent manner, and played a role in protecting BBB integrity. Cordycepin was able to alleviate TBI-induced loss of tight junction proteins zonula occludens protein-1 (ZO-1) and occludin, which are important for BBB integrity. Moreover, cordycepin suppressed pro-inflammatory factors, including IL-1β, iNOS, MPO and MMP-9, and promoted anti-inflammation-associated factors arginase 1 and IL-10. Furthermore, cordycepin inhibited NADPH oxidase (NOX) expression and activity following TBI, probably through NOX1, but not NOX2 and NOX4. Cordycepin has protective effects against brain damages induced by TBI. The protection of cordycepin on BBB integrity was probably achieved through recovery of tight junction proteins, inhibition of local inflammation, and prevention of NOX activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Listeriolysin O affects barrier function and induces chloride secretion in HT-29/B6 colon epithelial cells.

    PubMed

    Richter, Jan F; Gitter, Alfred H; Günzel, Dorothee; Weiss, Siegfried; Mohamed, Walid; Chakraborty, Trinad; Fromm, Michael; Schulzke, Jörg D

    2009-06-01

    Listeria monocytogenes is a food-borne pathogen, which is able to induce diarrhea when residing in the intestine. We studied the effect of listeriolysin O (LLO), an extracellular virulence factor of L. monocytogenes, on intestinal transport and barrier function in monolayers of HT-29/B6 human colon cells using the Ussing technique to understand the pathomechanisms involved. Mucosal addition of LLO, but not a LLO mutant, induced a dose- and pH-dependent increase in short-circuit current (I(SC)). Sodium and chloride tracer flux and DIDS sensitivity studies revealed that I(SC) was mainly due to electrogenic chloride secretion. Barrier function was impaired by LLO, as assessed by transepithelial resistance (R(t)) and mannitol flux measurements. Intracellular signal transduction occurred through Ca(2+) release from intracellular stores and PKC activation. In conclusion, listeriolysin induces chloride secretion and perturbs epithelial barrier function, thus potentially contributing to Listeria-induced diarrhea.

  8. Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement

    PubMed Central

    Higginbotham, Katherine; Tian, Yufeng; Gawlak, Grzegorz; Moldobaeva, Nurgul; Shah, Alok; Birukova, Anna A.

    2014-01-01

    Previous reports described important role of hepatocyte growth factor (HGF) in mitigation of pulmonary endothelial barrier dysfunction and cell injury induced by pathologic agonists and mechanical forces. HGF protective effects have been associated with Rac-GTPase signaling pathway activated by Rac-specific guanine nucleotide exchange factor Tiam1 and leading to enhancement of intercellular adherens junctions. This study tested involvement of a novel Rac-specific activator, Asef, in endothelial barrier enhancement by HGF and investigated a mechanism of HGF-induced Asef activation. Si-RNA-based knockdown of Tiam1 and Asef had an additive effect on attenuation of HGF-induced Rac activation and endothelial cell (EC) barrier enhancement. Tiam1 and Asef activation was abolished by pharmacologic inhibitors of HGF receptor and PI3-kinase. In contrast to Tiam1, Asef interacted with APC and associated with microtubule fraction upon HGF stimulation. EC treatment by low dose nocodazole to inhibit peripheral microtubule dynamics partially attenuated HGF-induced Asef peripheral translocation, but had negligible effect on Tiam1 translocation. These effects were associated with attenuation of HGF-induced barrier enhancement in EC pretreated with low ND dose and activation of Rac and its cytoskeletal effectors PAK1 and cortactin. These data demonstrate, that in addition to microtubule-independent Tiam1 activation, HGF engages additional microtubule- and APC-dependent pathway of Asef activation. These mechanisms may complement each other to provide the fine tuning of Rac signaling and endothelial barrier enhancement in response to various agonists. PMID:25101856

  9. ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function

    PubMed Central

    Cui, Dan; Arima, Mitsuru; Takubo, Keiyo; Kimura, Tokuhiro; Horiuchi, Keisuke; Minagawa, Takuya; Matsuda, Satoshi; Ikeda, Eiji

    2015-01-01

    Neural vascular barrier is essential for the life of multicellular organisms, and its impairment by tissue hypoxia is known to be a central of pathophysiology accelerating the progression of various intractable neural diseases. Therefore, the molecules involved in hypoxia-induced impairment of vascular barrier can be the targets to establish new therapies for intractable diseases. Here, we demonstrate that a disintegrin and metalloproteinases (ADAMs) 12 and 17 expressed in endothelial cells are the molecules responsible for the impairment of neural vascular barrier by hypoxia. Brain microvascular endothelial cells in vitro lost their barrier properties immediately after hypoxic stimulation through diminished localization of claudin-5, a tight junction molecule, on cell membranes. Hypoxic disappearance of claudin-5 from cell membranes and the consequent loss of barrier properties were completely suppressed by inhibition of the metalloproteinase activity which was found to be attributed to ADAM12 and ADAM17. Inhibition of either ADAM12 or ADAM17 was sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function. This is the first report to specify the molecules which are responsible for hypoxia-induced impairment of neural vascular barrier and furthermore can be the targets of new therapeutic strategies for intractable neural diseases. PMID:26242473

  10. ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function.

    PubMed

    Cui, Dan; Arima, Mitsuru; Takubo, Keiyo; Kimura, Tokuhiro; Horiuchi, Keisuke; Minagawa, Takuya; Matsuda, Satoshi; Ikeda, Eiji

    2015-08-05

    Neural vascular barrier is essential for the life of multicellular organisms, and its impairment by tissue hypoxia is known to be a central of pathophysiology accelerating the progression of various intractable neural diseases. Therefore, the molecules involved in hypoxia-induced impairment of vascular barrier can be the targets to establish new therapies for intractable diseases. Here, we demonstrate that a disintegrin and metalloproteinases (ADAMs) 12 and 17 expressed in endothelial cells are the molecules responsible for the impairment of neural vascular barrier by hypoxia. Brain microvascular endothelial cells in vitro lost their barrier properties immediately after hypoxic stimulation through diminished localization of claudin-5, a tight junction molecule, on cell membranes. Hypoxic disappearance of claudin-5 from cell membranes and the consequent loss of barrier properties were completely suppressed by inhibition of the metalloproteinase activity which was found to be attributed to ADAM12 and ADAM17. Inhibition of either ADAM12 or ADAM17 was sufficient to rescue the in vivo neural vasculature under hypoxia from the loss of barrier function. This is the first report to specify the molecules which are responsible for hypoxia-induced impairment of neural vascular barrier and furthermore can be the targets of new therapeutic strategies for intractable neural diseases.

  11. ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice.

    PubMed

    Chaudhry, Kamaljit K; Samak, Geetha; Shukla, Pradeep K; Mir, Hina; Gangwar, Ruchika; Manda, Bhargavi; Isse, Toyohi; Kawamoto, Toshihiro; Salaspuro, Mikko; Kaihovaara, Pertti; Dietrich, Paula; Dragatsis, Ioannis; Nagy, Laura E; Rao, Radha Krishna

    2015-08-01

    Acetaldehyde, the toxic ethanol (EtOH) metabolite, disrupts intestinal epithelial barrier function. Aldehyde dehydrogenase (ALDH) detoxifies acetaldehyde into acetate. Subpopulations of Asians and Native Americans show polymorphism with loss-of-function mutations in ALDH2. We evaluated the effect of ALDH2 deficiency on EtOH-induced disruption of intestinal epithelial tight junctions and adherens junctions, gut barrier dysfunction, and liver injury. Wild-type and ALDH2-deficient mice were fed EtOH (1 to 6%) in Lieber-DeCarli diet for 4 weeks. Gut permeability in vivo was measured by plasma-to-luminal flux of FITC-inulin, tight junction and adherens junction integrity was analyzed by confocal microscopy, and liver injury was assessed by the analysis of plasma transaminase activity, histopathology, and liver triglyceride. EtOH feeding elevated colonic mucosal acetaldehyde, which was significantly greater in ALDH2-deficient mice. ALDH2(-/-) mice showed a drastic reduction in the EtOH diet intake. Therefore, this study was continued only in wild-type and ALDH2(+/-) mice. EtOH feeding elevated mucosal inulin permeability in distal colon, but not in proximal colon, ileum, or jejunum of wild-type mice. In ALDH2(+/-) mice, EtOH-induced inulin permeability in distal colon was not only higher than that in wild-type mice, but inulin permeability was also elevated in the proximal colon, ileum, and jejunum. Greater inulin permeability in distal colon of ALDH2(+/-) mice was associated with a more severe redistribution of tight junction and adherens junction proteins from the intercellular junctions. In ALDH2(+/-) mice, but not in wild-type mice, EtOH feeding caused a loss of junctional distribution of tight junction and adherens junction proteins in the ileum. Histopathology, plasma transaminases, and liver triglyceride analyses showed that EtOH-induced liver damage was significantly greater in ALDH2(+/-) mice compared to wild-type mice. These data demonstrate that ALDH2

  12. Effects of solvent on TMP photophysics. Transition from no barrier to barrier case, induced by solvent properties

    NASA Astrophysics Data System (ADS)

    Sundström, Villy; Gillbro, Tomas

    1984-10-01

    The dynamics of the radiationless relaxation of triphenylmethane (TPM) molecules in the n-alcohols methanol to octadecanol have been studied with picosecond absorption recovery techniques as a function of viscosity, temperature, and wavelength of the exciting and analyzing light. It is shown that the solvent dependence of the relaxation rate in TPM molecules cannot, as is usually done, be described by a viscosity dependence only. In going through the n-alcohol series the excited state potential surface changes from a practically flat one (E0=0) in methanol to a surface having a definitive potential barrier (E0≊15 kJ mol-1) in the higher alcohols. This variation of the potential surface implies that the relaxation is largely controlled by rotational diffusion in methanol and ethanol whereas it is mainly controlled by the potential barrier in the higher alcohols. When the viscosity dependence of the relaxation rate is obtained, by compensating for the contribution from the potential barrier, a turnover behavior such as that predicted by activated barrier crossing theories, is observed. We have fitted the expression of Skinner and Wolynes [J. Chem. Phys. 69, 2143 (1978)] to our experimental results in the solvents where a barrier exists, and obtain a frequency of 550 cm-1 at both the well and the top of the potential. The fit is consistent with a friction that is lower than that corresponding to hydrodynamic slip boundary conditions. A decrease in solute-solvent friction relative the hydrodynamic value is also observed in going from small to large solvent molecules. This effect is attributed to a decreasing solute/solvent molecular volume ratio and to the structure of the TPM molecule which could prevent large solvent molecules from coming into close contact with the relaxing groups. In addition to these features we discuss the wavelength dependence and previously suggested change from single- to bi- and multiexponential decay of the relaxation kinetics. The

  13. Quantification of storm-induced bathymetric change in a back-barrier estuary

    USGS Publications Warehouse

    Ganju, Neil K.; Suttles, Steven E.; Beudin, Alexis; Nowacki, Daniel; Miselis, Jennifer L.; Andrews, Brian D.

    2017-01-01

    Geomorphology is a fundamental control on ecological and economic function of estuaries. However, relative to open coasts, there has been little quantification of storm-induced bathymetric change in back-barrier estuaries. Vessel-based and airborne bathymetric mapping can cover large areas quickly, but change detection is difficult because measurement errors can be larger than the actual changes over the storm timescale. We quantified storm-induced bathymetric changes at several locations in Chincoteague Bay, Maryland/Virginia, over the August 2014 to July 2015 period using fixed, downward-looking altimeters and numerical modeling. At sand-dominated shoal sites, measurements showed storm-induced changes on the order of 5 cm, with variability related to stress magnitude and wind direction. Numerical modeling indicates that the predominantly northeasterly wind direction in the fall and winter promotes southwest-directed sediment transport, causing erosion of the northern face of sandy shoals; southwesterly winds in the spring and summer lead to the opposite trend. Our results suggest that storm-induced estuarine bathymetric change magnitudes are often smaller than those detectable with methods such as LiDAR. More precise fixed-sensor methods have the ability to elucidate the geomorphic processes responsible for modulating estuarine bathymetry on the event and seasonal timescale, but are limited spatially. Numerical modeling enables interpretation of broad-scale geomorphic processes and can be used to infer the long-term trajectory of estuarine bathymetric change due to episodic events, when informed by fixed-sensor methods.

  14. Protective effects of isothiocyanates on blood-CSF barrier disruption induced by oxidative stress

    PubMed Central

    Alesi, Gina N.; Zhou, Ningna; Keep, Richard F

    2012-01-01

    The choroid plexuses (CPs) form the blood-cerebrospinal fluid (CSF) barrier (BCSFB) and play an important role in maintaining brain normal function and the brain response to injury. Many neurological disorders are associated with oxidative stress that can impact CP function. This study examined the effects of isothiocyanates, an abundant component in cruciferous vegetables, on H2O2-induced BCSFB disruption and CP cell death in vitro. It further examined the potential role of a transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), in isothiocyanate-induced protection. Sulforaphane (SF) significantly reduced H2O2-induced BCSFB disruption as assessed by transepithelial electrical resistance (29 ± 7% reduction vs. 92 ± 2% decrease in controls) and [3H]mannitol permeability. Allyl-isothiocyanate (AITC) had a similar protective effect. H2O2-induced epithelial cell death was also reduced by these isothiocyanates. In primary CP cells, SF and AITC reduced cell death by 42 ± 3% and 53 ± 10%, respectively. Similar protection was found in a CP cell line Z310. Protection was only found with pretreatment for 12–48 h and not with acute exposure (1 h). The protective effects of SF and AITC were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2, including heme oxygenase-1, NAD(P)H quinine oxidoreductase, and cysteine/glutamate exchange transporter. Thus isothiocyanates, as diet or medicine, may be a method for protecting BCSFB in neurological disorders. PMID:22573102

  15. Controlled Ultrasound-Induced Blood-Brain Barrier Disruption Using Passive Acoustic Emissions Monitoring

    PubMed Central

    Arvanitis, Costas D.; Livingstone, Margaret S.; Vykhodtseva, Natalia; McDannold, Nathan

    2012-01-01

    The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB) holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001) larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R2 = 0.78). Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology. PMID:23029240

  16. Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring.

    PubMed

    Arvanitis, Costas D; Livingstone, Margaret S; Vykhodtseva, Natalia; McDannold, Nathan

    2012-01-01

    The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB) holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001) larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R(2) = 0.78). Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology.

  17. Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

    PubMed

    Kuge, Tomoo; Greenwood-Van Meerveld, Beverley; Sokabe, Masahiro

    2006-07-24

    Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function.

  18. Generation of airborne listeria from floor drains

    USDA-ARS?s Scientific Manuscript database

    Listeria monocytogenes can colonize floor drains in poultry processing and further processing facilities remaining even after cleaning and disinfection. Therefore, during wash down, workers exercise caution to prevent escape and transfer of drain microflora to food contact surfaces. The objective ...

  19. Atmospheric pressure resistive barrier air plasma jet induced bacterial inactivation in aqueous environment

    NASA Astrophysics Data System (ADS)

    Thiyagarajan, Magesh; Sarani, Abdollah; Gonzales, Xavier

    2013-03-01

    An atmospheric pressure resistive barrier air plasma jet is designed to inactivate bacteria in aqueous media in direct and indirect exposure modes of treatment. The resistive barrier plasma jet is designed to operate at both dc and standard 50-60 Hz low frequency ac power input and the ambient air at 50% humidity level was used as the operating gas. The voltage-current characteristics of the plasma jet were analyzed and the operating frequency of the discharge was measured to be 20 kHz and the plasma power was measured to be 26 W. The plasma jet rotational temperatures (Trot) are obtained from the optical emission spectra, from the N2C-B(2+) transitions by matching the experimental spectrum results with the Spectra Air (SPECAIR) simulation spectra. The reactive oxygen and nitrogen species were measured using optical emission spectroscopy and gas analyzers, for direct and indirect treatment modes. The nitric oxides (NO) were observed to be the predominant long lived reactive nitrogen species produced by the plasma. Three different bacteria including Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), and Neisseria meningitidis (Gram-negative) were suspended in an aqueous media and treated by the resistive barrier air plasma jet in direct and indirect exposure modes. The results show that a near complete bacterial inactivation was achieved within 120 s for both direct and indirect plasma treatment of S. aureus and E. coli bacteria. Conversely, a partial inactivation of N. meningitidis was observed by 120 s direct plasma exposure and insignificant inactivation was observed for the indirect plasma exposure treatment. Plasma induced shifts in N. meningitidis gene expression was analyzed using pilC gene expression as a representative gene and the results showed a reduction in the expression of the pilC gene compared to untreated samples suggesting that the observed protection against NO may be regulated by other genes.

  20. Perifosine induced release of contents of trans cell-barrier transport efficient liposomes.

    PubMed

    Koklic, Tilen

    2014-10-01

    Perifosine (OPP) containing liposomal formulation was previously found to deliver almost half of liposome encapsulated content through a tight cellular barrier in vitro. In order to understand the role of different liposome components, especially perifosine, in transendothelial transport the physical characteristics of liposome membranes composed of phosphatidylcholine, and cholesterol, as a main lipid constituents, and variable amount of helper lipids: dioleoyl phosphatidylethanolamine (DOPE), and alkylphospholipid perifosine. For this purpose, electron paramagnetic resonance (EPR) with computer aided EPR spectra simulation and fluorescence polarization spectroscopy were used to investigate how different membrane components influence membrane characteristics and the release of liposome entrapped substances. Beside methylester of palmitic acid with nitroxide group at different position on acyl chain usually used for such studies, the spin labeled and fluorescent labeled analog of perifosine were introduced. OPP increases membrane fluidity of liposomes as well as the release of liposome encapsulated content. The release of neutral molecules increases with OPP concentration, while the release of charged molecules is about an order of magnitude slower. Optimal OPP concentration, for release of charged molecules, is about 15 mol%. These results are one step further toward the conclusion that the lysolipid-containing liposomes could be promising trans endothelial delivery system, since lysolipids, such as OPP, open tight cellular barriers, as was published before, and in the same time induce the release of liposome encapsulated content at physiological temperature, as shown here. Since many drug delivery systems are being developed, which mainly exploit the transcellular route of delivery through barrier-forming cells, we hope that the uniqueness of lysolipid-containing liposomes, exploiting the paracellular route, and thus avoiding efflux transporters, will foster

  1. Salmonella enterica induces joint inflammation and expression of interleukin-17 in draining lymph nodes early after onset of enterocolitis in mice.

    PubMed

    Noto Llana, Mariángeles; Sarnacki, Sebastián Hernán; Vázquez, María Victoria; Gartner, Alejandra Sonia; Giacomodonato, Mónica Nancy; Cerquetti, María Cristina

    2012-06-01

    In developing countries, one-third of reactive arthritis (ReA) cases are associated with Salmonella enterocolitis; nevertheless, there is no animal model for studying this pathology. Here we induced a self-limiting Salmonella enterica serovar Enteritidis enterocolitis in mice to analyze the onset of ReA. BALB/c mice received orally 20 μg of streptomycin 24 h before intragastric inoculation of a low dose (3 × 10(3) to 4 × 10(3) CFU) of S. Enteritidis. In response to Salmonella infection, a 30-fold increase in the expression of interleukin-17 (IL-17), measured by quantitative PCR, was observed in mesenteric lymph nodes 5 days postinfection. At this time synovitis was already evident, and concomitantly, a significant increase in joint tumor necrosis factor alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). The early development of joint lesions was accompanied by an increased expression of IL-17 in inguinal and popliteal lymph nodes. Infection with 10(7) CFU of an isogenic ΔinvG mutant bearing a defective type III secretion system of Salmonella encoded in the pathogenicity island 1 apparatus (TTSS-1) induced enterocolitis histologically similar to that triggered by the wild-type strain. Interestingly, despite the higher infective dose used, the mutant did not trigger intestinal IL-17. Moreover, no synovitis was observed in mice suffering ΔinvG enterocolitis. Neutralization of IL-17 in mice infected with S. Enteritidis prevented both synovitis and the increment of TNF-α in the joints, suggesting that IL-17 participates in the generation of Salmonella-induced ReA through the induction of TNF-α in the joints.

  2. Salmonella enterica Induces Joint Inflammation and Expression of Interleukin-17 in Draining Lymph Nodes Early after Onset of Enterocolitis in Mice

    PubMed Central

    Sarnacki, Sebastián Hernán; Vázquez, María Victoria; Gartner, Alejandra Sonia; Giacomodonato, Mónica Nancy

    2012-01-01

    In developing countries, one-third of reactive arthritis (ReA) cases are associated with Salmonella enterocolitis; nevertheless, there is no animal model for studying this pathology. Here we induced a self-limiting Salmonella enterica serovar Enteritidis enterocolitis in mice to analyze the onset of ReA. BALB/c mice received orally 20 μg of streptomycin 24 h before intragastric inoculation of a low dose (3 × 103 to 4 × 103 CFU) of S. Enteritidis. In response to Salmonella infection, a 30-fold increase in the expression of interleukin-17 (IL-17), measured by quantitative PCR, was observed in mesenteric lymph nodes 5 days postinfection. At this time synovitis was already evident, and concomitantly, a significant increase in joint tumor necrosis factor alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). The early development of joint lesions was accompanied by an increased expression of IL-17 in inguinal and popliteal lymph nodes. Infection with 107 CFU of an isogenic ΔinvG mutant bearing a defective type III secretion system of Salmonella encoded in the pathogenicity island 1 apparatus (TTSS-1) induced enterocolitis histologically similar to that triggered by the wild-type strain. Interestingly, despite the higher infective dose used, the mutant did not trigger intestinal IL-17. Moreover, no synovitis was observed in mice suffering ΔinvG enterocolitis. Neutralization of IL-17 in mice infected with S. Enteritidis prevented both synovitis and the increment of TNF-α in the joints, suggesting that IL-17 participates in the generation of Salmonella-induced ReA through the induction of TNF-α in the joints. PMID:22493084

  3. Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation

    PubMed Central

    Banerjee, Santanu; Sindberg, Gregory; Wang, Fuyuan; Meng, Jingjing; Sharma, Umakant; Zhang, Li; Dauer, Patricia; Chen, Chi; Dalluge, Joseph; Johnson, Timothy; Roy, Sabita

    2016-01-01

    Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of gram-positive pathogenic and reduction in bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. PMID:26906406

  4. Paracoccidioides brasilinsis-Induced Migration of Dendritic Cells and Subsequent T-Cell Activation in the Lung-Draining Lymph Nodes

    PubMed Central

    Silvana dos Santos, Suelen; Ferreira, Karen Spadari; Almeida, Sandro Rogerio

    2011-01-01

    Paracoccidioidomycosis is a mycotic disease caused by a dimorphic fungus, Paracoccidioides brasiliensis (Pb), that starts with inhalation of the fungus; thus, lung cells such as DC are part of the first line of defense against this microorganism. Migration of DC to the lymph nodes is the first step in initiating T cell responses. The mechanisms involved in resistance to Pb infection are poorly understood, but it is likely that DC play a pivotal role in the induction of effector T cells that control Pb infection. In this study, we showed that after Pb Infection, an important modification of lung DC receptor expression occurred. We observed an increased expression of CCR7 and CD103 on lung DC after infection, as well as MHC-II. After Pb infection, bone marrow-derived DC as well lung DC, migrate to lymph nodes. Migration of lung DC could represent an important mechanism of pathogenesis during PCM infection. In resume our data showed that Pb induced DC migration. Furthermore, we demonstrated that bone marrow-derived DC stimulated by Pb migrate to the lymph nodes and activate a T helper (Th) response. To the best of our knowledge, this is the first reported data showing that Pb induces migration of DC and activate a T helper (Th) response. PMID:21611175

  5. Nutrient Drain Associated with Hardwood Plantation Culture

    Treesearch

    James B. Baker

    1978-01-01

    Past research and a tentative evaluation indicate that nutrient drain and possible site degradation could occur in southern hardwood plantations. The extent of nutrient drain on a given site would depend on the species, length of the rotation, and harvesting system used. The evaluation for cottonwood plantations in Mississippi indicates that nutrient drain is most...

  6. Parameterization of fusion barriers for light-projectiles-induced reactions using the proximity approach

    NASA Astrophysics Data System (ADS)

    Gharaei, R.; Sheibani, J.

    2016-05-01

    In this article we propose a pocket formula for fusion barriers calculated by three versions of the proximity formalism, namely AW 95, Bass 80 and Prox. 2010 potentials, for fusion reactions involving the collisions of the proton and helium projectiles with different targets in mass ranges 51≤ AT ≤ 130 and 40≤ AT ≤ 233 , respectively. For the first type of the colliding systems, it is shown that the proposed pocket formulas are able to predict the actual values of RB and VB within accuracies of ±0.4% and ±0.45% , respectively. Moreover, for the second type of the selected reactions, these accuracies are obtained ±0.24% and ±0.36% , respectively. In this study, the ability of the present pocket formulas is also demonstrated to predict the exact values of the fusion cross sections for our selected mass ranges. A comparison with the results of the previous pocket formulas reveals that our parameterized forms are more successful to reproduce the empirical data of the barrier height and position in the proton- and helium-induced reactions.

  7. Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown

    PubMed Central

    Ogura, Shuntaro; Kurata, Kaori; Hattori, Yuki; Takase, Hiroshi; Ishiguro-Oonuma, Toshina; Hwang, Yoonha; Ahn, Soyeon; Ikeda, Wataru; Kusuhara, Sentaro; Fukushima, Yoko; Nara, Hiromi; Sakai, Hideto; Fujiwara, Takashi; Matsushita, Jun; Ema, Masatsugu; Hirashima, Masanori; Shibuya, Masabumi; Takakura, Nobuyuki; Kim, Pilhan; Miyata, Takaki; Ogura, Yuichiro

    2017-01-01

    In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders. PMID:28194443

  8. Genetic and Anatomical Basis of the Barrier Separating Wakefulness and Anesthetic-Induced Unresponsiveness

    PubMed Central

    Hung, Hsiao-Tung; Koh, Kyunghee; Sowcik, Mallory; Sehgal, Amita; Kelz, Max B.

    2013-01-01

    A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states. PMID:24039590

  9. Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown.

    PubMed

    Ogura, Shuntaro; Kurata, Kaori; Hattori, Yuki; Takase, Hiroshi; Ishiguro-Oonuma, Toshina; Hwang, Yoonha; Ahn, Soyeon; Park, Inwon; Ikeda, Wataru; Kusuhara, Sentaro; Fukushima, Yoko; Nara, Hiromi; Sakai, Hideto; Fujiwara, Takashi; Matsushita, Jun; Ema, Masatsugu; Hirashima, Masanori; Minami, Takashi; Shibuya, Masabumi; Takakura, Nobuyuki; Kim, Pilhan; Miyata, Takaki; Ogura, Yuichiro; Uemura, Akiyoshi

    2017-02-09

    In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis. Notably, PC depletion directly induced inflammatory responses in ECs and perivascular infiltration of macrophages, whereby macrophage-derived VEGF and placental growth factor (PlGF) activated VEGFR1 in macrophages and VEGFR2 in ECs. Moreover, angiopoietin-2 (Angpt2) upregulation and Tie1 downregulation activated FOXO1 in PC-free ECs locally at the leaky aneurysms. This cycle of vessel damage was shut down by simultaneously blocking VEGF, PlGF, and Angpt2, thus restoring the BRB integrity. Together, our model provides new opportunities for identifying the sequential events triggered by PC deficiency, not only in DR, but also in various neurological disorders.

  10. Structure Effects in Collisions Induced by Halo and Weakly Bound Nuclei around the Coulomb Barrier

    NASA Astrophysics Data System (ADS)

    Scuderi, V.; di Pietro, A.; Acosta, L.; Amorini, F.; Borge, M. J. G.; Figuera, P.; Fisichella, M.; Fraile, L. M.; Gomez-Camacho, J.; Jeppesen, H.; Lattuada, M.; Martel, I.; Milin, M.; Musumarra, A.; Papa, M.; Pellegriti, M. G.; Raabe, R.; Randisi, G.; Rizzo, F.; Santonocito, D.; Sanchez, E. M. R.; Scalia, G.; Tengblad, O.; Torresi, D.; Vidal, A. M.; Zadro, M.

    In this contribution, results concerning different reaction channels for the collisions induced by the three Be isotopes, 9,10,11Be, on a 64Zn target at energies around the Coulomb barrier will be presented. The experiments with the radioactive 10,11Be beams were performed at REX-ISOLDE (CERN) whereas the experiment with the stable weakly bound 9Be beam was performed at LNS Catania. Elastic scattering angular distributions have been measured for the three systems 9,10,11Be + 64Zn at the same center of mass energy. The angular distributions were analyzed with optical potentials and reaction cross sections were obtained from optical model calculations, performed with the code PTOLEMY. For the 11Be + 64Zn reaction, the break-up angular distribution was also measured.

  11. Defect-induced performance degradation of 4H-SiC Schottky barrier diode particle detectors

    NASA Astrophysics Data System (ADS)

    Iwamoto, N.; Johnson, B. C.; Hoshino, N.; Ito, M.; Tsuchida, H.; Kojima, K.; Ohshima, T.

    2013-04-01

    The formation and evolution of defects in 4H-SiC Schottky barrier diode high-energy particle detectors have been investigated and correlated with the detectors' properties. Low temperature annealing at 300 °C is found to significantly recover the charge collection efficiency as degraded by 1 MeV electron irradiation. At higher temperatures, an anneal-induced degradation in the detector's performance is observed. Current-voltage, capacitance-voltage, and deep level transient spectroscopy (DLTS) measurements are used to ascertain the effect of defects on the detector performance. The latter reveals that the DLTS defect levels, EH1 and EH3, are related to the initial recovery of the charge collection efficiency.

  12. Photo-induced potential barrier in As-Se-Ge films

    NASA Astrophysics Data System (ADS)

    Katyal, S. C.; Okano, S.; Suzuki, M.; Bando, T.

    1988-05-01

    Photo-excited effects in AsSeGe and AsSeGeSn amorphous films have been studied under illumination of different light sources. AsSeGe system exhibited rectifying characteristics under illumination of the light with hν > E g, while AsSeGeSn film did not show such phenomena. The illumination of the IR light along with the light of hν > E g weakened the rectification behavior. The photovoltage and I-V characteristics results suggest the existence of "photo-induced" potential barrier in AsSeGe system, which is considered to concern the creation and destruction of neutral defect states D°.

  13. Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier.

    PubMed

    Lin, Yu-Chun; Niewiadomski, Pawel; Lin, Benjamin; Nakamura, Hideki; Phua, Siew Cheng; Jiao, John; Levchenko, Andre; Inoue, Takafumi; Rohatgi, Rajat; Inoue, Takanari

    2013-07-01

    Primary cilia function as specialized compartments for signal transduction. The stereotyped structure and signaling function of cilia inextricably depend on the selective segregation of molecules in cilia. However, the fundamental principles governing the access of soluble proteins to primary cilia remain unresolved. We developed a methodology termed 'chemically inducible diffusion trap at cilia' to visualize the diffusion process of a series of fluorescent proteins ranging in size from 3.2 nm to 7.9 nm into primary cilia. We found that the interior of the cilium was accessible to proteins as large as 7.9 nm. The kinetics of ciliary accumulation of this panel of proteins was exponentially limited by their Stokes radii. Quantitative modeling suggests that the diffusion barrier operates as a molecular sieve at the base of cilia. Our study presents a set of powerful, generally applicable tools for the quantitative monitoring of ciliary protein diffusion under both physiological and pathological conditions.

  14. 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.

  15. Optical Diagnostics of Air Flows Induced in Surface Dielectric Barrier Discharge Plasma Actuator

    NASA Astrophysics Data System (ADS)

    Kobatake, Takuya; Deguchi, Masanori; Suzuki, Junya; Eriguchi, Koji; Ono, Kouichi

    2014-10-01

    A surface dielectric barrier discharge (SDBD) plasma actuator has recently been intensively studied for the flow control over airfoils and turbine blades in the fields of aerospace and aeromechanics. It consists of two electrodes placed on both sides of the dielectric, where one is a top powered electrode exposed to the air, and the other is a bottom grounded electrode encapsulated with an insulator. The unidirectional gas flow along the dielectric surfaces is induced by the electrohydrodynamic (EHD) body force. It is known that the thinner the exposed electrode, the greater the momentum transfer to the air is, indicating that the thickness of the plasma is important. To analyze plasma profiles and air flows induced in the SDBD plasma actuator, we performed time-resolved and -integrated optical emission and schlieren imaging of the side view of the SDBD plasma actuator in atmospheric air. We applied a high voltage bipolar pulse (4-8 kV, 1-10 kHz) between electrodes. Experimental results indicated that the spatial extent of the plasma is much smaller than that of the induced flows. Experimental results further indicated that in the positive-going phase, a thin and long plasma is generated, where the optical emission is weak and uniform; on the other hand, in the negative-going phase, a thick and short plasma is generated, where a strong optical emission is observed near the top electrode.

  16. Observation of permeability of blood-labyrinth barrier during cytomegalovirus-induced hearing loss.

    PubMed

    Li, Xuanyi; Shi, Xi; Qiao, Yuehua; Xu, Kailin; Zeng, Lingyu; Wang, Caiji; Xu, Zhou; Niu, Haichen

    2014-07-01

    Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. This study aims to investigate the pathogenesis CMV-induced hearing loss from the view of integrity of blood-labyrinth-barrier (BLB). Newborn BALB/c mice were randomly divided into three groups (n=22, respectively): CMV group, control group and normal group. The CMV group and control group were intracerebrally injected with equal volume (15 μl) of murine CMV (MCMV; 10(4)IU/0.1 ml) and PBS, respectively, and normal group did not receive any treatment. After three weeks, auditory-evoked brainstem response was assessed, and permeability of BLB was evaluated by Evans blue method. Means between groups were compared using t-test. We observed that mice injected with MCMV had a hearing loss and it was connected with the permeability changes of BLB. Besides, using hematoxylin-eosin staining, we noticed hyperaemia in stria vascularis and spiral ligament and bleeding in scala vestibule and scala tympani in CMV group. All these data indicated the possible association between CMV-induced hearing loss and BLB dysfunction with the characteristics of inflammation. Our data provide a possible path to investigate the mechanism of CMV-induced hearing damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Role of defective methylation reactions in ethanol-induced dysregulation of intestinal barrier integrity.

    PubMed

    Thomes, Paul G; Osna, Natalia A; Bligh, Sarah M; Tuma, Dean J; Kharbanda, Kusum K

    2015-07-01

    Alcoholic liver disease (ALD) is a major healthcare challenge worldwide. Emerging evidence reveals that ethanol administration disrupts the intestinal epithelial tight junction (TJ) complex; this defect allows for the paracellular translocation of gut-derived pathogenic molecules to reach the liver to cause inflammation and progressive liver injury. We have previously demonstrated a causative role of impairments in liver transmethylation reactions in the pathogenesis of ALD. We have further shown that treatment with betaine, a methylation agent that normalizes liver methylation potential, can attenuate ethanol-induced liver injury. Herein, we explored whether alterations in methylation reactions play a causative role in disrupting intestinal mucosal barrier function by employing an intestinal epithelial cell line. Monolayers of Caco-2 cells were exposed to ethanol or a-pan methylation reaction inhibitor, tubercidin, in the presence and absence of betaine. The structural and functional integrity of intestinal epithelial barrier was then examined. We observed that exposure to either ethanol or tubercidin disrupted TJ integrity and function by decreasing the localization of TJ protein occludin-1 to the intracellular junctions, reducing transepithelial electrical resistance and increasing dextran influx. All these detrimental effects of ethanol and tubercidin were attenuated by co-treatment with betaine. We further show that the mechanism of betaine protection was through BHMT-mediated catalysis. Collectively, our data suggest a novel mechanism for alcohol-induced gut leakiness and identifies the importance of normal methylation reactions in maintaining TJ integrity. We also propose betaine as a potential therapeutic option for leaky gut in alcohol-consuming patients who are at the risk of developing ALD. Published by Elsevier Inc.

  18. Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function

    PubMed Central

    Wu, Richard Y.; Abdullah, Majd; Määttänen, Pekka; Pilar, Ana Victoria C.; Scruten, Erin; Johnson-Henry, Kathene C.; Napper, Scott; O’Brien, Catherine; Jones, Nicola L.; Sherman, Philip M.

    2017-01-01

    Prebiotics are non-digestible oligosaccharides that promote the growth of beneficial gut microbes, but it is unclear whether they also have direct effects on the intestinal mucosal barrier. Here we demonstrate two commercial prebiotics, inulin and short-chain fructo-oligosaccharide (scFOS), when applied onto intestinal epithelia in the absence of microbes, directly promote barrier integrity to prevent pathogen-induced barrier disruptions. We further show that these effects involve the induction of select tight junction (TJ) proteins through a protein kinase C (PKC) δ-dependent mechanism. These results suggest that in the absence of microbiota, prebiotics can directly exert barrier protective effects by activating host cell signaling in the intestinal epithelium, which represents a novel alternative mechanism of action of prebiotics. PMID:28098206

  19. Use of drains in surgery: a review.

    PubMed

    Durai, Rajaraman; Mownah, Abdoolla; Ng, Philip C H

    2009-06-01

    Drains have been used in surgery for several years to remove body fluids thereby preventing the accumulation of serous fluid and improving wound healing. Drains may be classified as closed or open systems, and active or passive depending on their intended function. Closed vacuum drains apply negative suction in a sealed environment, producing apposition of tissues and thus promoting healing. Correct assessment of clinical indications might reduce unnecessary usage. This article will introduce the principles and practice of various types of drains and highlight the importance of understanding how surgical drains promote quality patient care.

  20. Safety drain system for fluid reservoir

    NASA Technical Reports Server (NTRS)

    England, John Dwight (Inventor); Kelley, Anthony R. (Inventor); Cronise, Raymond J. (Inventor)

    2012-01-01

    A safety drain system includes a plurality of drain sections, each of which defines distinct fluid flow paths. At least a portion of the fluid flow paths commence at a side of the drain section that is in fluid communication with a reservoir's fluid. Each fluid flow path at the side communicating with the reservoir's fluid defines an opening having a smallest dimension not to exceed approximately one centimeter. The drain sections are distributed over at least one surface of the reservoir. A manifold is coupled to the drain sections.

  1. Size and shape effect of SiC source/drain on strained Si.

    PubMed

    Byeon, D S; Kim, S W; Ko, D H

    2014-10-01

    Strained Si is used to enhance carrier mobility in MOSFET devices. Epi-grown Si(1-x)C(x) as a source/drain induces strain on a channel because its lattice constant is smaller than Si. The distribution of stress varies with the layout of the device and can involve gate length, source/drain width, elevation height, etc. In this work, we report on how these parameters effect channel strain by employing the Finite Element Method. A 3-dimensional model and anisotropic properties such as the elastic constant and Poisson's ratio were adopted for high accuracy. Si0.983C0.017 was used as the source/drain on a Si substrate. The lateral channel strain was calculated based on a 30-90 nm gate length, a 30-90 nm source/drain width and 0-30 nm elevated source/drain shapes. The results showed that, when the gate length is longer, the channel strain is lower. On the other hand, source/drain width affects channel strain in a reverse manner. For models with the same gate length and source/drain width: 30, 60, 90 nm, the average channel strain is lower when the gate length and source/drain width are shorter. An additional parameter, namely, source/drain elevation height, was also studied. Interestingly, the effect of elevated shape is dependent on gate length and source/drain width.

  2. A2A Adenosine Receptor Antagonism Reverts the Blood-Brain Barrier Dysfunction Induced by Sleep Restriction

    PubMed Central

    Hurtado-Alvarado, Gabriela; Domínguez-Salazar, Emilio; Velázquez-Moctezuma, Javier

    2016-01-01

    Chronic sleep restriction induces blood-brain barrier disruption and increases pro-inflammatory mediators in rodents. Those inflammatory mediators may modulate the blood-brain barrier and constitute a link between sleep loss and blood-brain barrier physiology. We propose that adenosine action on its A2A receptor may be modulating the blood-brain barrier dynamics in sleep-restricted rats. We administrated a selective A2A adenosine receptor antagonist (SCH58261) in sleep-restricted rats at the 10th day of sleep restriction and evaluated the blood-brain barrier permeability to dextrans coupled to fluorescein (FITC-dextrans) and Evans blue. In addition, we evaluated by western blot the expression of tight junction proteins (claudin-5, occludin, ZO-1), adherens junction protein (E-cadherin), A2A adenosine receptor, adenosine-synthesizing enzyme (CD73), and neuroinflammatory markers (Iba-1 and GFAP) in the cerebral cortex, hippocampus, basal nuclei and cerebellar vermis. Sleep restriction increased blood-brain barrier permeability to FITC-dextrans and Evans blue, and the effect was reverted by the administration of SCH58261 in almost all brain regions, excluding the cerebellum. Sleep restriction increased the expression of A2A adenosine receptor only in the hippocampus and basal nuclei without changing the expression of CD73 in all brain regions. Sleep restriction reduced the expression of tight junction proteins in all brain regions, except in the cerebellum; and SCH58261 restored the levels of tight junction proteins in the cortex, hippocampus and basal nuclei. Finally, sleep restriction induced GFAP and Iba-1 overexpression that was attenuated with the administration of SCH58261. These data suggest that the action of adenosine on its A2A receptor may have a crucial role in blood-brain barrier dysfunction during sleep loss probably by direct modulation of brain endothelial cell permeability or through a mechanism that involves gliosis with subsequent inflammation and

  3. The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis.

    PubMed

    Yan-yu, Wu; Xue-min, Wang; Yi-Mei, Tan; Ying, Cheng; Na, Liu

    2011-12-01

    Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the

  4. Analysis of the impedance field of saturated MOSFETs and drain thermal noise

    NASA Astrophysics Data System (ADS)

    Lee, Kie-Young

    2017-04-01

    The effect of the velocity saturation region (VSR) on the impedance field of proto-type MOSFET devices, which operate in the saturation region, was investigated to analyze the drain thermal noise. An enhanced impedance field for the drain thermal noise was derived based on the well-known physical analyses of MOSFET noise. The mechanism of the VSR in inducing the drain thermal noise has been explicated by using a self-consistent equivalent circuit model of the saturated MOSFETs. This alternative description was found to be consistent with the analytical derivation. The present analysis has been demonstrated to be consistent with the behavior of empirical drain thermal noise.

  5. Antioxidant protects blood-testis barrier against synchrotron radiation X-ray-induced disruption

    PubMed Central

    Zhang, Tingting; Liu, Tengyuan; Shao, Jiaxiang; Sheng, Caibin; Hong, Yunyi; Ying, Weihai; Xia, Weiliang

    2015-01-01

    Synchrotron radiation (SR) X-ray has wide biomedical applications including high resolution imaging and brain tumor therapy due to its special properties of high coherence, monochromaticity and high intensity. However, its interaction with biological tissues remains poorly understood. In this study, we used the rat testis as a model to investigate how SR X-ray would induce tissue responses, especially the blood-testis barrier (BTB) because BTB dynamics are critical for spermatogenesis. We irradiated the male gonad with increasing doses of SR X-ray and obtained the testicles 1, 10 and 20 d after the exposures. The testicle weight and seminiferous tubule diameter reduced in a dose- and time-dependent manner. Cryosections of testes were stained with tight junction (TJ) component proteins such as occludin, claudin-11, JAM-A and ZO-1. Morphologically, increasing doses of SR X-ray consistently induced developing germ cell sloughing from the seminiferous tubules, accompanied by shrinkage of the tubules. Interestingly, TJ constituent proteins appeared to be induced by the increasing doses of SR X-ray. Up to 20 d after SR X-ray irradiation, there also appeared to be time-dependent changes on the steady-state level of these protein exhibiting differential patterns at 20-day after exposure, with JAM-A/claudin-11 still being up-regulated whereas occludin/ZO-1 being down-regulated. More importantly, the BTB damage induced by 40 Gy of SR X-ray could be significantly attenuated by antioxidant N-Acetyl-L-Cysteine (NAC) at a dose of 125 mg/kg. Taken together, our studies characterized the changes of TJ component proteins after SR X-ray irradiation, illustrating the possible protective effects of antioxidant NAC to BTB integrity. PMID:26413412

  6. An improved performance of copper phthalocyanine OFETs with channel and source/drain contact modifications

    NASA Astrophysics Data System (ADS)

    Huanqin, Dang; Xiaoming, Wu; Xiaowei, Sun; Runqiu, Zou; Ruochuan, Zhang; Shougen, Yin

    2015-10-01

    We report an effective method to improve the performance of p-type copper phthalocyanine (CuPc) based organic field-effect transistors (OFETs) by employing a thin para-quaterphenyl (p-4p) film and simultaneously applying V2O5 to the source/drain regions. The p-4p layer was inserted between the insulating layer and the active layer, and V2O5 layer was added between CuPc and Al in the source-drain (S/D) area. As a result, the field-effect saturation mobility and on/off current ratio of the optimized device were improved to 5 × 10-2 cm2/(V·s) and 104, respectively. We believe that because p-4p could induce CuPc to form a highly oriented and continuous film, this resulted in the better injection and transport of the carriers. Moreover, by introducing the V2O5 electrode's modified layers, the height of the carrier injection barrier could be effectively tuned and the contact resistance could be reduced. Project supported by the National Natural Science Foundation of China (No. 60676051), the National High Technology Research and Development Program of China (No. 2013A A014201), the Scientific Developing Foundation of Tianjin Education Commission (No. 2011ZD02), the Key Science and Technology Support Program of Tianjin (No. 14ZCZDGX00006), and the Foundation of Key Discipline of Material Physics and Chemistry of Tianjin.

  7. Aquaporin 5 regulates cigarette smoke induced emphysema by modulating barrier and immune properties of the epithelium.

    PubMed

    Aggarwal, Neil R; Chau, Eric; Garibaldi, Brian T; Mock, Jason R; Sussan, Thomas; Rao, Keshav; Rao, Kaavya; Menon, Anil G; D'Alessio, Franco R; Damarla, Mahendra; Biswal, Shyam; King, Landon S; Sidhaye, Venkataramana K

    2013-10-01

    Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality. Cigarette smoke, the most common risk factor for COPD, induces airway and alveolar epithelial barrier permeability and initiates an innate immune response. Changes in abundance of aquaporin 5 (AQP5), a water channel, can affect epithelial permeability and immune response after cigarette smoke exposure. To determine how AQP5-derived epithelial barrier modulation affects epithelial immune response to cigarette smoke and development of emphysema, WT and AQP5(-/-) mice were exposed to cigarette smoke (CS). We measured alveolar cell counts and differentials, and assessed histology, mean-linear intercept (MLI), and surface-to-volume ratio (S/V) to determine severity of emphysema. We quantified epithelial-derived signaling proteins for neutrophil trafficking, and manipulated AQP5 levels in an alveolar epithelial cell line to determine specific effects on neutrophil transmigration after CS exposure. We assessed paracellular permeability and epithelial turnover in response to CS. In contrast to WT mice, AQP5(-/-) mice exposed to 6 months of CS did not demonstrate a significant increase in MLI or a significant decrease in S/V compared with air-exposed mice, conferring protection against emphysema. After sub-acute (4 weeks) and chronic (6 mo) CS exposure, AQP5(-/-) mice had fewer alveolar neutrophil but similar lung neutrophil numbers as WT mice. The presence of AQP5 in A549 cells, an alveolar epithelial cell line, was associated with increase neutrophil migration after CS exposure. Compared with CS-exposed WT mice, neutrophil ligand (CD11b) and epithelial receptor (ICAM-1) expression were reduced in CS-exposed AQP5(-/-) mice, as was secreted LPS-induced chemokine (LIX), an epithelial-derived neutrophil chemoattractant. CS-exposed AQP5(-/-) mice demonstrated decreased type I pneumocytes and increased type II pneumocytes compared with CS-exposed WT mice suggestive of enhanced epithelial

  8. Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum

    PubMed Central

    Chen, Xuesong; Lan, Xun; Roche, Ian; Liu, Rugao; Geiger, Jonathan D.

    2013-01-01

    The blood-brain barrier (BBB) is important physiologically. Pathologically, BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson's disease (PD). Recent studies indicate that caffeine is protective against PD, but by poorly understood mechanisms. Using a MPTP neurotoxin model of PD we tested the hypothesis that the protective actions of caffeine were due to, at least in part, preventing MPTP-induced BBB dysfunction. FVB mice were pretreated with caffeine (10 mg/kg, i.p.) or saline for 7 days prior to initiation of neurotoxin treatments; during the 7 days of neurotoxin treatment, caffeine or saline continued to be administered 10 min before each dose of MPTP (20 mg/kg, i.p.). Striatum (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight junction protein expression levels, integrity of dopaminergic neurons, and activation of astrocytes and microglia using immunostaining, immunoblotting and real-time PCR techniques. We found that caffeine blocked MPTP-induced decreases in numbers of TH-positive dopaminergic neurons, increases in leakage of Evan's blue dye and FITC-albumin in striatum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin and ZO-1, and increases in reactive gliosis. Our results suggest that caffeine might protect against PD and PD-like features in animal models, in part, by stabilizing the BBB. PMID:18808450

  9. Effect of "rose essential oil" inhalation on stress-induced skin-barrier disruption in rats and humans.

    PubMed

    Fukada, Mika; Kano, Eri; Miyoshi, Michio; Komaki, Ryoichi; Watanabe, Tatsuo

    2012-05-01

    In stressed animals, several brain regions (e.g., hypothalamic paraventricular nucleus [PVN]) exhibit neuronal activation, which increases plasma adrenocorticotropic hormone (ACTH) and glucocorticoids. We previously reported that so-called "green odor" inhibits stress-induced activation of the hypothalamo-pituitary-adrenocortical axis (HPA axis) and thereby prevents the chronic stress-induced disruption of the skin barrier. Here, we investigated whether rose essential oil, another sedative odorant, inhibits the stress-induced 1) increases in PVN neuronal activity in rats and plasma glucocorticoids (corticosterone [CORT] in rats and cortisol in humans) and 2) skin-barrier disruption in rats and humans. The results showed that in rats subjected to acute restraint stress, rose essential oil inhalation significantly inhibited the increase in plasma CORT and reduced the increases in the number of c-Fos-positive cells in PVN. Inhalation of rose essential oil significantly inhibited the following effects of chronic stress: 1) the elevation of transepidermal water loss (TEWL), an index of the disruption of skin-barrier function, in both rats and humans and 2) the increase in the salivary concentration of cortisol in humans. These results suggest that in rats and humans, chronic stress-induced disruption of the skin barrier can be limited or prevented by rose essential oil inhalation, possibly through its inhibitory effect on the HPA axis.

  10. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function

    PubMed Central

    Zheng, Wei; Sivasankar, M. Preeti

    2016-01-01

    Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05) and a reduction in transepithelial electrical resistance (TEER) by 180.0% (p<0.001). While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05). Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium. PMID:27643990

  11. Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles.

    PubMed

    Sheikov, Nickolai; McDannold, Nathan; Vykhodtseva, Natalia; Jolesz, Ferenc; Hynynen, Kullervo

    2004-07-01

    Local blood-brain barrier (BBB) opening is an advantageous approach for targeted drug delivery to the brain. Recently, it has been shown that focused ultrasound (US) exposures (sonications), when applied in the presence of preformed gas bubbles, caused magnetic-resonance (MR) proven reversible opening of the BBB in targeted locations. The cellular mechanisms of such transient barrier disruption are largely unknown. We investigated US-induced changes in endothelial cell fine morphology that resulted in the BBB opening in rabbits. To obtain evidence for the passage of blood-borne macromolecules through the opened transvascular routes, an immunocytochemical procedure for endogenous immunoglobulinG (IgG) was performed, in addition to the routine electron microscopy. An increased number of vesicles and vacuoles, fenestration and channel formation, as well as opening of some tight junctions, were seen in capillaries after low-power (0.55 W) sonication. Immunosignals presented in some of the vesicles and vacuoles, in the cytoplasmic channels and, so rarely, in intercellular clefts; immunosignals could also be seen in neuropil around the blood vessels. Damage to the cellular ultrastructure was not seen in these areas. However, cell destruction and leakage of IgG through defects of the endothelial lining took place at 3 W sonications. The data reveals that several mechanisms of transcapillary passage are possible after such sonications: 1. transcytosis; 2. endothelial cell cytoplasmic openings--fenestration and channel formation; 3. opening of a part of tight junctions; and 4. free passage through the injured endothelium (with the higher power sonications). These findings could be considered in further development of the strategy for drug delivery to brain parenchyma.

  12. Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines

    PubMed Central

    2014-01-01

    Background Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. Polyamines are pivotal in the control of intestinal barrier function and are also involved in the regulation of intercellular junction proteins. Different probiotic strains may inhibit gliadin-induced toxic effects and the Lactobacillus rhamnosus GG (L.GG) is effective in the prevention and treatment of gastrointestinal diseases. Aims of the study were to establish in epithelial Caco-2 cells whether i) gliadin affects paracellular permeability and polyamine profile; ii) co-administration of viable L.GG, heat-killed L.GG (L.GG-HK) or its conditioned medium (L.GG-CM) preserves the intestinal epithelial barrier integrity. Additionally, the effects of L.GG on TJ protein expression were tested in presence or absence of polyamines. Results Administration of gliadin (1 mg/ml) to Caco-2 cells for 6 h caused a significant alteration of paracellular permeability as demonstrated by the rapid decrease in transepithelial resistance with a concomitant zonulin release. These events were followed by a significant increase in lactulose paracellular transport and a slight lowering in ZO-1 and Occludin expression without affecting Claudin-1. Besides, the single and total polyamine content increased significantly. The co-administration of viable L.GG (108 CFU/ml), L.GG-HK and L.GG-CM with gliadin significantly restored barrier function as demonstrated by transepithelial resistance, lactulose flux and zonulin release. Viable L.GG and L.GG-HK, but not L.GG-CM, led to a significant reduction in the single and total polyamine levels. Additionally, only the co-administration of viable L.GG with gliadin significantly increased ZO-1, Claudin-1 and Occludin gene expression compared to control cells. When Caco-2 cells treated with viable L.GG and gliadin were deprived in the polyamine

  13. Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein tyrosine phosphorylation in monolayers of intestinal epithelial cell.

    PubMed

    Katsube, Takanori; Tsuji, Hideo; Onoda, Makoto

    2007-06-01

    The intestinal epithelium provides a barrier to the transport of harmful luminal molecules into the systemic circulation. A dysfunctional epithelial barrier is closely associated with the pathogenesis of a variety of intestinal and systemic disorders. We investigated here the effects of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) on the barrier function of a human intestinal epithelial cell line, Caco-2. When treated with H(2)O(2), Caco-2 cell monolayers grown on permeable supports exhibited several remarkable features of barrier dysfunction as follows: a decrease in transepithelial electrical resistance, an increase in paracellular permeability to dextran, and a disruption of the intercellular junctional localization of the scaffolding protein ZO-1. In addition, an induction of tyrosine phosphorylation of numerous cellular proteins including ZO-1, E-cadherin, and beta-catenin, components of tight and adherens junctions, was observed. On the other hand, combined treatment of Caco-2 monolayers with H(2)O(2) and an NO donor (NOC5 or NOC12) relieved the damage to the barrier function and suppressed the protein tyrosine phosphorylation induced by H(2)O(2) alone. These results suggest that NO protects the barrier function of intestinal epithelia from oxidative stress by modulating some intracellular signaling pathways of protein tyrosine phosphorylation in epithelial cells.

  14. Cyclosporin A induces hyperpermeability of the blood-brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function.

    PubMed

    Dohgu, Shinya; Sumi, Noriko; Nishioku, Tsuyoshi; Takata, Fuyuko; Watanabe, Takuya; Naito, Mikihiko; Shuto, Hideki; Yamauchi, Atsushi; Kataoka, Yasufumi

    2010-10-10

    Cyclosporin A, a potent immunosuppressant, can often produce neurotoxicity in patients, although its penetration into the brain is restricted by the blood-brain barrier (BBB). Brain pericytes and astrocytes, which are periendothelial accessory structures of the BBB, can be involved in cyclosporin A-induced BBB disruption. However, the mechanism by which cyclosporin A causes BBB dysfunction remains unknown. Here, we show that in rodent brain endothelial cells, cyclosporin A decreased transendothelial electrical resistance (TEER) by inhibiting intracellular signal transduction downstream of adrenomedullin, an autocrine regulator of BBB function. Cyclosporin A stimulated adrenomedullin release from brain endothelial cells, but did not affect binding of adrenomedullin to its receptors. This cyclosporin A-induced decrease in TEER was attenuated by exogenous addition of adrenomedullin. Cyclosporin A dose-dependently decreased the total cAMP concentration in brain endothelial cells. A combination of cyclosporin A (1microM) with an adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536; 10microM), or a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89; 1microM), markedly increased sodium fluorescein permeability in brain endothelial cells, whereas each drug alone had no effect. Thus, these data suggest that cyclosporin A inhibits the adenylyl cyclase/cyclic AMP/PKA signaling pathway activated by adrenomedullin, leading to impairment of brain endothelial barrier function. Copyright 2010. Published by Elsevier B.V.

  15. Bifidobacteria Prevent Tunicamycin-Induced Endoplasmic Reticulum Stress and Subsequent Barrier Disruption in Human Intestinal Epithelial Caco-2 Monolayers

    PubMed Central

    Akiyama, Takuya; Oishi, Kenji

    2016-01-01

    Endoplasmic reticulum (ER) stress is caused by accumulation of unfolded and misfolded proteins in the ER, thereby compromising its vital cellular functions in protein production and secretion. Genome wide association studies in humans as well as experimental animal models linked ER stress in intestinal epithelial cells (IECs) with intestinal disorders including inflammatory bowel diseases. However, the mechanisms linking the outcomes of ER stress in IECs to intestinal disease have not been clarified. In this study, we investigated the impact of ER stress on intestinal epithelial barrier function using human colon carcinoma-derived Caco-2 monolayers. Tunicamycin-induced ER stress decreased the trans-epithelial electrical resistance of Caco-2 monolayers, concomitant with loss of cellular plasma membrane integrity. Epithelial barrier disruption in Caco-2 cells after ER stress was not caused by caspase- or RIPK1-dependent cell death but was accompanied by lysosomal rupture and up-regulation of the ER stress markers Grp78, sXBP1 and Chop. Interestingly, several bifidobacteria species inhibited tunicamycin-induced ER stress and thereby diminished barrier disruption in Caco-2 monolayers. Together, these results showed that ER stress compromises the epithelial barrier function of Caco-2 monolayers and demonstrate beneficial impacts of bifidobacteria on ER stress in IECs. Our results identify epithelial barrier loss as a potential link between ER stress and intestinal disease development, and suggest that bifidobacteria could exert beneficial effects on this phenomenon. PMID:27611782

  16. Hepatocyte growth factor triggers distinct mechanisms of Asef and Tiam1 activation to induce endothelial barrier enhancement.

    PubMed

    Higginbotham, Katherine; Tian, Yufeng; Gawlak, Grzegorz; Moldobaeva, Nurgul; Shah, Alok; Birukova, Anna A

    2014-11-01

    Previous reports described an important role of hepatocyte growth factor (HGF) in mitigation of pulmonary endothelial barrier dysfunction and cell injury induced by pathologic agonists and mechanical forces. HGF protective effects have been associated with Rac-GTPase signaling pathway activated by Rac-specific guanine nucleotide exchange factor Tiam1 and leading to enhancement of intercellular adherens junctions. This study tested involvement of a novel Rac-specific activator, Asef, in endothelial barrier enhancement by HGF and investigated a mechanism of HGF-induced Asef activation. Si-RNA-based knockdown of Tiam1 and Asef had an additive effect on attenuation of HGF-induced Rac activation and endothelial cell (EC) barrier enhancement. Tiam1 and Asef activation was abolished by pharmacologic inhibitors of HGF receptor and PI3-kinase. In contrast to Tiam1, Asef interacted with APC and associated with microtubule fraction upon HGF stimulation. EC treatment by low dose nocodazole to inhibit peripheral microtubule dynamics partially attenuated HGF-induced Asef peripheral translocation, but had negligible effect on Tiam1 translocation. These effects were associated with attenuation of HGF-induced barrier enhancement in EC pretreated with low ND dose and activation of Rac and its cytoskeletal effectors PAK1 and cortactin. These data demonstrate, that in addition to microtubule-independent Tiam1 activation, HGF engages additional microtubule- and APC-dependent pathway of Asef activation. These mechanisms may complement each other to provide the fine tuning of Rac signaling and endothelial barrier enhancement in response to various agonists. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function.

    PubMed

    Xu, Bin; Li, Yan-Li; Xu, Ming; Yu, Chang-Chun; Lian, Meng-Qiao; Tang, Ze-Yao; Li, Chuan-Xun; Lin, Yuan

    2017-03-06

    Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, anti-oxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg(-1)·d(-1), ig) or with sulfasalazine (SASP, 100 mg·kg(-1)·d(-1), ig) as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon. In Caco-2 cells, geniposide (25-100 μmol/L) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER). The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-κB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins (occludin and ZO-1), and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPK-mediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway..

  18. Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents.

    PubMed

    Nitsch, C; Klatzo, I

    1983-06-01

    In unrestrained rabbits with generalized epileptic seizures induced by systemic application of convulsant drugs, regional changes in blood-brain barrier (BBB) permeability to macromolecules were investigated using Evans Blue (EB) as indicator. BBB leakage due to seizures was present only in animals in which the mean arterial blood pressure rose about 50 mm Hg with the onset of convulsive motor activity. However, a blood pressure increase was not necessarily associated with the occurrence of BBB opening. Pentylenetetrazole-induced seizures resulted in bilateral EB leakage mainly in the hypothalamus, with exception of the mammillary bodies, and the preoptic area, and they were associated, in most cases, with an intensive staining of the cerebellum and also of the midbrain tegmentum. In contrast, seizures due to the GABA receptor blocker bicuculline brought about a penetration of the dye in the region of the pallidum, whereas the GABA synthesis inhibitor methoxypyridoxine produced BBB breakdown in the hippocampus. Methionine-sulfoximine convulsions resulted in a selective stain of the corpora mammillaria, and kainic acid induced a diffuse leakage in neocortical brain areas. As a rule, BBB breakdown was bilateral and confined to anatomically limited brain areas, suggesting that BBB integrity was not only disturbed by abrupt increases in the intraluminal pressure, but was also influenced from the brain tissue. The fluorescence microscopic observations revealed that the tracer penetrated into the neuropil through larger vessels. It had the tendency to accumulate in neurons. In case of the hippocampus, CA2 pyramidal cells revealed more intense uptake of EB than those of the adjacent fields.

  19. Study of flow fields induced by surface dielectric barrier discharge actuator in low-pressure air

    SciTech Connect

    Che, Xueke E-mail: st@mail.iee.ac.cn; Nie, Wansheng; Tian, Xihui; Hou, Zhiyong; He, Haobo; Zhou, Penghui; Zhou, Siyin; Yang, Chao; Shao, Tao E-mail: st@mail.iee.ac.cn

    2014-04-15

    Surface dielectric barrier discharge (SDBD) is a promising method for a flow control. Flow fields induced by a SDBD actuator driven by the ac voltage in static air at low pressures varying from 1.0 to 27.7 kPa are measured by the particle image velocimetry method. The influence of the applied ac voltage frequency and magnitude on the induced flow fields is studied. The results show that three different classes of flow fields (wall jet flow field, complex flow field, and vortex-shape flow field) can be induced by the SDBD actuator in the low-pressure air. Among them, the wall jet flow field is the same as the tangential jet at atmospheric pressure, which is, together with the vertical jet, the complex flow field. The vortex-shape flow field is composed of one vertical jet which points towards the wall and two opposite tangential jets. The complex and the vortex-shape flow fields can be transformed to the wall jet flow field when the applied ac voltage frequency and magnitude are changed. It is found that the discharge power consumption increases initially, decreases, and then increases again at the same applied ac voltage magnitude when the air pressure decreases. The tangential velocity of the wall jet flow field increases when the air pressure decreases. It is however opposite for the complex flow field. The variation of the applied ac voltage frequency influences differently three different flow fields. When the applied ac voltage magnitude increases at the same applied ac voltage frequency, the maximal jet velocity increases, while the power efficiency increases only initially and then decreases again. The discharge power shows either linear or exponential dependences on the applied ac voltage magnitude.

  20. Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract.

    PubMed

    Sasu, Alciona; Herman, Hildegard; Mariasiu, Teodora; Rosu, Marcel; Balta, Cornel; Anghel, Nicoleta; Miutescu, Eftimie; Cotoraci, Coralia; Hermenean, Anca

    2015-10-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100 mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.

  1. Serine protease inhibitor A3K protects rabbit corneal endothelium from barrier function disruption induced by TNF-α.

    PubMed

    Hu, Jiaoyue; Zhang, Zhenhao; Xie, Hui; Chen, Lelei; Zhou, Yueping; Chen, Wensheng; Liu, Zuguo

    2013-08-09

    To determine if a serine protease inhibitor A3K (SA3K) reduces TNF-α-induced declines in rabbit corneal endothelial junctional barrier integrity. New Zealand rabbit corneas were incubated ex vivo for 24 hours in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS with or without TNF-α, in the presence or absence of SA3K at different concentrations. Corneal endothelial barrier function permeability was determined based on measurements of FITC-dextran tissue accumulation. Apical junctional complex (AJC) integrity was evaluated of zonula occludens-1 (ZO-1), vascular endothelial (VE)-cadherin, and filamentous actin (F-actin) and associated microtubules, as well as myosin light chain (MLC) by immunofluorescent staining, Western blot analysis, and/or RT-PCR. TNF-α (20 ng/mL) increased corneal endothelial FITC-dextran permeability by 1.8-fold compared with the untreated control. SA3K (100-200 nM) dose dependently suppressed TNF-α-induced increases in permeability. SA3K nearly completely reversed TNF-α-induced disruptions of tight junctional ZO-1 and subjacent adherens junctions VE-cadherin integrity. Interestingly, SA3K reversed TNF-α-induced disruption of AJC linkage to the cytoskeletal F-actin array by restoring F-actin double-band structures. SA3K also attenuated TNF-α-induced microtubule disassembly. Furthermore, SA3K blocked increases in MLC phosphorylation status elicited by TNF-α. SA3K exposure markedly reduced TNF-α-induced disruption of barrier structure and function in the rabbit corneal endothelium by maintaining AJC integrity. These protective effects are due to suppression of MLC activation. SA3K may have, in vivo, a therapeutic potential to offset TNF-α-induced declines in endothelial barrier structural integrity and function.

  2. Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide.

    PubMed

    Kimura, Kazuhiro; Morita, Yukiko; Orita, Tomoko; Haruta, Junpei; Takeji, Yasuhiro; Sonoda, Koh-Hei

    2013-04-17

    TNF-α disrupts the barrier function of cultured human corneal epithelial (HCE) cells. We investigated the effects of the cytoprotective drug rebamipide on this barrier disruption by TNF-α as well as on corneal epithelial damage in a rat model of dry eye. The barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance. The distribution of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, and the p65 subunit of nuclear factor-κB (NF-κB) was determined by immunofluorescence microscopy. Expression of junctional proteins as well as phosphorylation of the NF-κB inhibitor IκB-α and myosin light chain (MLC) were examined by immunoblot analysis. A rat model of dry eye was developed by surgical removal of exorbital lacrimal glands. Rebamipide inhibited the disruption of barrier function as well as the downregulation of ZO-1 expression, and the disappearance of ZO-1 from the interfaces of neighboring HCE cells induced by TNF-α. It also inhibited the phosphorylation and downregulation of IκB-α, the translocation of p65 to the nucleus, the formation of actin stress fibers, and the phosphorylation of MLC induced by TNF-α in HCE cells. Treatment with rebamipide eyedrops promoted the healing of corneal epithelial defects as well as attenuated the loss of ZO-1 from the surface of corneal epithelial cells in rats. Rebamipide protects corneal epithelial cells from the TNF-α-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton. Rebamipide is, thus, a potential drug for preventing or ameliorating the loss of corneal epithelial barrier function associated with ocular inflammation.

  3. Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction.

    PubMed

    Li, Yu-Meng; Wang, Hai-Bin; Zheng, Jin-Guang; Bai, Xiao-Dong; Zhao, Zeng-Kai; Li, Jing-Yuan; Hu, Sen

    2015-10-14

    To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS group (65.1 ± 4.7 U/L vs

  4. Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction

    PubMed Central

    Li, Yu-Meng; Wang, Hai-Bin; Zheng, Jin-Guang; Bai, Xiao-Dong; Zhao, Zeng-Kai; Li, Jing-Yuan; Hu, Sen

    2015-01-01

    AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS

  5. HYDROGEN-RICH MEDIUM AMELIORATES LIPOPOLYSACCHARIDE-INDUCED BARRIER DYSFUNCTION VIA RHOA-MDIA1 SIGNALING IN CACO-2 CELLS.

    PubMed

    Yang, Tao; Wang, Lu; Sun, Ruiqiang; Chen, Hongguang; Zhang, Hongtao; Yu, Yang; Wang, Yanyan; Wang, Guolin; Yu, Yonghao; Xie, Keliang

    2016-02-01

    Gastrointestinal barrier dysfunction is associated with the severity and prognosis of sepsis. Hydrogen gas (H2) can ameliorate multiple organ damage in septic animals. Ras homolog gene family member A (RhoA) and mammalian diaphanous-related formin 1 (mDia1) are important to regulate tight junction (TJ) and adherens junction (AJ), both of which determine the integrity of the intestinal barrier. This study was aimed to investigate whether H2 could modulate lipopolysaccharide (LPS)-stimulated dysfunction of the intestinal barrier and whether RhoA-mDia1 signaling is involved. Caco-2 cells were exposed to different concentrations of LPS (1 μg/mL-1 mg/mL). The permeability of the intestinal barrier was evaluated by transepithelial resistance (TER) and fluorescein-isothiocyanate-dextran flux. Expression and distribution of occludin and E-cadherin were analyzed by Western blot and immunofluorescence. RhoA activity was measured by G-Lisa assay, and mDia1 expression was assessed by Western blot. LPS (100 μg/mL) decreased TER and increased fluorescein-isothiocyanate-dextran flux, which were alleviated by H2-rich medium. Also, H2 down-regulated LPS-induced oxidative stress. Moreover, H2 improved the down-regulated expression and redistribution of occludin and E-cadherin caused by LPS. Additionally, H2 alleviated LPS-caused RhoA activation, and the beneficial effects of H2 on barrier were counteracted by RhoA agonist CN03. Rho inhibitor C3 exoenzyme mitigated LPS-induced barrier breakdown. Furthermore, H2-rich medium increased mDia1 expression, and mDia1 knockdown abolished protections of H2 on barrier permeability. mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling.

  6. Quantum tunneling time of a Bose-Einstein condensate traversing through a laser-induced potential barrier

    SciTech Connect

    Duan Zhenglu; Fan Bixuan; Yuan Chunhua; Zhang Weiping; Cheng Jing; Zhu Shiyao

    2010-05-15

    We theoretically study the effect of atomic nonlinearity on the tunneling time in the case of an atomic Bose-Einstein condensate (BEC) traversing the laser-induced potential barrier. The atomic nonlinearity is controlled to appear only in the region of the barrier by employing the Feshbach resonance technique to tune interatomic interaction in the tunneling process. Numerical simulation shows that the atomic nonlinear effect dramatically changes the tunneling behavior of the BEC matter wave packet and results in the violation of the Hartman effect and the occurrence of negative tunneling time.

  7. Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link

    PubMed Central

    Velázquez-Moctezuma, J.

    2016-01-01

    Sleep is a vital phenomenon related to immunomodulation at the central and peripheral level. Sleep deficient in duration and/or quality is a common problem in the modern society and is considered a risk factor to develop neurodegenerative diseases. Sleep loss in rodents induces blood-brain barrier disruption and the underlying mechanism is still unknown. Several reports indicate that sleep loss induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them may promote changes in cellular components of the blood-brain barrier, particularly on brain endothelial cells. In the present review we discuss the role of inflammatory mediators that increase during sleep loss and their association with general disturbances in peripheral endothelium and epithelium and how those inflammatory mediators may alter the blood-brain barrier. Finally, this manuscript proposes a hypothetical mechanism by which sleep loss may induce blood-brain barrier disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins. PMID:27738642

  8. Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link.

    PubMed

    Hurtado-Alvarado, G; Domínguez-Salazar, E; Pavon, L; Velázquez-Moctezuma, J; Gómez-González, B

    2016-01-01

    Sleep is a vital phenomenon related to immunomodulation at the central and peripheral level. Sleep deficient in duration and/or quality is a common problem in the modern society and is considered a risk factor to develop neurodegenerative diseases. Sleep loss in rodents induces blood-brain barrier disruption and the underlying mechanism is still unknown. Several reports indicate that sleep loss induces a systemic low-grade inflammation characterized by the release of several molecules, such as cytokines, chemokines, and acute-phase proteins; all of them may promote changes in cellular components of the blood-brain barrier, particularly on brain endothelial cells. In the present review we discuss the role of inflammatory mediators that increase during sleep loss and their association with general disturbances in peripheral endothelium and epithelium and how those inflammatory mediators may alter the blood-brain barrier. Finally, this manuscript proposes a hypothetical mechanism by which sleep loss may induce blood-brain barrier disruption, emphasizing the regulatory effect of inflammatory molecules on tight junction proteins.

  9. Self-screening of the quantum confined Stark effect by the polarization induced bulk charges in the quantum barriers

    SciTech Connect

    Zhang, Zi-Hui; Liu, Wei; Ju, Zhengang; Tiam Tan, Swee; Ji, Yun; Kyaw, Zabu; Zhang, Xueliang; Wang, Liancheng; Wei Sun, Xiao E-mail: volkan@stanfordalumni.org; Volkan Demir, Hilmi E-mail: volkan@stanfordalumni.org

    2014-06-16

    InGaN/GaN light-emitting diodes (LEDs) grown along the polar orientations significantly suffer from the quantum confined Stark effect (QCSE) caused by the strong polarization induced electric field in the quantum wells, which is a fundamental problem intrinsic to the III-nitrides. Here, we show that the QCSE is self-screened by the polarization induced bulk charges enabled by designing quantum barriers. The InN composition of the InGaN quantum barrier graded along the growth orientation opportunely generates the polarization induced bulk charges in the quantum barrier, which well compensate the polarization induced interface charges, thus avoiding the electric field in the quantum wells. Consequently, the optical output power and the external quantum efficiency are substantially improved for the LEDs. The ability to self-screen the QCSE using polarization induced bulk charges opens up new possibilities for device engineering of III-nitrides not only in LEDs but also in other optoelectronic devices.

  10. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    PubMed

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans.

  11. A short hairpin RNA-based adjuvant targeting NF-κB repressor IκBα promotes migration of dermal dendritic cells to draining lymph nodes and antitumor CTL responses induced by DNA vaccination.

    PubMed

    Gálvez-Cancino, Felipe; Roco, Jonathan; Rojas-Colonelli, Nicole; Flores, Camila; Murgas, Paola; Cruz-Gómez, Sebastián; Oyarce, César; Varas-Godoy, Manuel; Sauma, Daniela; Lladser, Alvaro

    2017-07-24

    DNA vaccination is an attractive approach to elicit tumor-specific cytotoxic CD8(+) T lymphocytes (CTL), which can mediate protective immunity against tumors. To initiate CTL responses, antigen-encoding plasmids employed for DNA vaccination need to activate dendritic cells (DC) through the stimulation of DNA-sensing innate immune receptors that converge in the activation of the master transcription factor NF-κB. To this end, NF-κB repressor IκBα needs to be degraded, allowing NF-κB to translocate to the nucleus and transcribe proinflammatory target genes, as well as its repressor IκBα. Therefore, NF-κB activation is self-limited by de novo synthesis of IκBa, which sequesters NF-κB in the cytosol. Hence, we tested whether co-delivering a shRNA-based adjuvant able to silence IκBα expression would further promote DNA-induced NFκB activation, DC activation and tumor-protective CTL responses induced by DNA vaccination in a preclinical model. First, an IκBα-targeting shRNA plasmid (shIκBα) was shown to reduce IκBα expression and promote NFκB-driven transcription in vitro, as well as up-regulate inflammatory target genes in vivo. Then, we showed that intradermal DNA electroporation induced the migration of skin migratory dendritic cells to draining lymph nodes and maturation of dermal dendritic cells (dDC). Interestingly, shIκBα further promoted the migration of mature skin migratory dendritic cells, in particular dDC, which are specialized in antigen cross-presentation and activation of CD8(+) T cells. Consistently, mice vaccinated with a plasmid encoding the melanoma-associated antigen tyrosinase-related protein 2 (TRP2) in combination with shIκBα enhanced TRP2-specific CTL responses and reduced the number of lung melanoma foci in mice challenged with intravenous injection of B16F10 cells. Moreover, therapeutic vaccination with pTRP2 and shIκBα delayed the growth of B16F10 melanoma subcutaneous tumors. Our data suggest that adjuvants promoting

  12. Astrocytes contribute to Aβ-induced blood-brain barrier damage through activation of endothelial MMP9.

    PubMed

    Spampinato, Simona Federica; Merlo, Sara; Sano, Yasuteru; Kanda, Takashi; Sortino, Maria Angela

    2017-08-01

    The blood-brain barrier (BBB) plays an important role in the maintenance of the brain homeostasis, and its proper functions are warranted by the interplay between different cellular components (endothelial cells, astrocytes and pericytes). BBB dysfunctions in pathological conditions, and particularly in Alzheimer's disease, have been documented. Here, using an in vitroBBB model, the interaction between endothelial cells and astrocytes exposed to Aβ1-42 was investigated. Human endothelial cells, cultured in monolayer or co-cultured with astrocytes, were exposed to Aβ1-42 (2 μM for 18 h). Aβ induced dysfunction of endothelial barrier, as assessed by enhanced permeability to FITC-conjugated dextran and reduced expression of claudin-5; these modifications were observed in the co-culture model, but not in endothelial cells cultured in monolayer. Similarly, Aβ-induced damage at the barrier was observed when endothelial cells were challenged in the presence of conditioned medium generated by astrocytes previously exposed to Aβ (ACM Aβ). Endothelial barrier damages were associated with enhanced matrix metalloprotease 9 (MMP9) activity, known to mediate claudin-5 disruption. These events were not related to the direct effects played by Aβ on endothelial cells, but they were rather the consequence of Aβ-induced vascular endothelial growth factor (VEGF) expression in astrocytes. Indeed, when vascular endothelial growth factor expression was down-regulated in astrocytes, neither barrier properties or MMP9 expression in endothelial cells were affected after Aβ exposure both in the co-culture model or in the presence of ACM Aβ. These data point out the importance of astrocytes' mediation in inducing endothelial sensitivity to Aβ1-42. © 2017 International Society for Neurochemistry.

  13. Americium/curium bushing melter drain tests

    SciTech Connect

    Smith, M.E.; Hardy, B.J.; Smith, M.E.

    1997-07-01

    Americium and curium were produced in the past at the Savannah River Site (SRS) for research, medical, and radiological applications. They have been stored in a nitric acid solution in an SRS reprocessing facility for a number of years. Vitrification of the americium/curium (Am/Cm) solution will allow the material to be safely stored or transported to the DOE Oak Ridge Reservation. Oak Ridge is responsible for marketing radionuclides for research and medical applications. The bushing melter technology being used in the Am/Cm vitrification research work is also under consideration for the stabilization of other actinides such as neptunium and plutonium. A series of melter drain tests were conducted at the Savannah River Technology Center to determine the relationship between the drain tube assembly operating variables and the resulting pour initiation times, glass flowrates, drain tube temperatures, and stop pour times. Performance criteria such as ability to start and stop pours in a controlled manner were also evaluated. The tests were also intended to provide support of oil modeling of drain tube performance predictions and thermal modeling of the drain tube and drain tube heater assembly. These drain tests were instrumental in the design of subsequent melter drain tube and drain tube heaters for the Am/Cm bushing melter, and therefore in the success of the Am/Cm vitrification and plutonium immobilization programs.

  14. Saffman-Taylor-like instability in a narrow gap induced by dielectric barrier discharge.

    PubMed

    Hou, Shang-Yan; Chu, Hong-Yu

    2015-07-01

    This work is inspired by the expansion of the plasma bubble in a narrow gap reported by Chu and Lee [Phys. Rev. Lett. 107, 225001 (2011)]. We report the unstable phenomena of the plasma-liquid interface with different curvature in a Hele-Shaw cell. Dielectric barrier discharge is produced in the cell at atmospheric pressure which is partially filled with silicone oil. We show that the Saffman-Taylor-like instability is observed on the bubble-type, channel-type, and drop-type interfaces. The Schlieren observation of the plasma-drop interaction reveals that there is a vapor layer around the drop and the particle image velocimetry shows the liquid flow inside the drop. We propose that the thermal Marangoni effect induced by the plasma heating is responsible for the unstable phenomena of the plasma-liquid interaction. The fluctuation of the interface is shown consistently with the Saffman-Taylor instability modified by the temperature-dependent velocity and surface tension.

  15. Mechanistic Study on the Degradation of Thermal Barrier Coatings Induced by Volcanic Ash Deposition

    NASA Astrophysics Data System (ADS)

    Arai, Masayuki

    2017-08-01

    Thermal stress generated on thermal barrier coatings (TBCs) by volcanic ash (VA) deposition was assessed measuring the tip deflection of a multilayered beam structure as a function of temperature. The TBC in this study was deposited onto the surface of a blade utilized in a land-based gas turbine which is composed of 8 wt.%Y2O3-ZrO2/CoNiCrAlY on a Ni-based superalloy. The VA-deposited TBC sample was heated at 1453 K, and the effect of VA deposition on TBC delamination was examined in comparison with a TBC sample without VA deposition as a reference. On the basis of the VA attack damage mechanism which was investigated via the tip deflection measurement and a comprehensive microstructure examination, a damage-coupled constitutive model was proposed. The proposed model was based on the infiltration of the molten VA inside pores and phase transformations of yttria -tabilized zirconia in the TBC system. The numerical analysis results, which were simulated utilizing the finite element code installing the developed constitutive model, showed us that VA attack on the TBC sample induced near-interfacial cracks because of a significant increasing in the coating stress.

  16. Evaluation of pathogen inactivation on sliced cheese induced by encapsulated atmospheric pressure dielectric barrier discharge plasma.

    PubMed

    Yong, Hae In; Kim, Hyun-Joo; Park, Sanghoo; Alahakoon, Amali U; Kim, Kijung; Choe, Wonho; Jo, Cheorun

    2015-04-01

    Pathogen inactivation induced by atmospheric pressure dielectric barrier discharge (DBD) (250 W, 15 kHz, air discharge) produced in a rectangular plastic container and the effect of post-treatment storage time on inactivation were evaluated using agar plates and cheese slices. When agar plates were treated with plasma, populations of Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes showed 3.57, 6.69, and 6.53 decimal reductions at 60 s, 45 s, and 7 min, respectively. When the pathogens tested were inoculated on cheese slices, 2.67, 3.10, and 1.65 decimal reductions were achieved at the same respective treatment times. The post-treatment storage duration following plasma treatment potently affected further reduction in pathogen populations. Therefore, the newly developed encapsulated DBD-plasma system for use in a container can be applied to improve the safety of sliced cheese, and increasing post-treatment storage time can greatly enhance the system's pathogen-inactivation efficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes.

    PubMed

    Wang, Yue; Jin, Shijie; Sonobe, Yoshifumi; Cheng, Yi; Horiuchi, Hiroshi; Parajuli, Bijay; Kawanokuchi, Jun; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2014-01-01

    The blood-brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis. Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity. BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Interleukin-1β (IL-1β), a major pro-inflammatory cytokine released from activated microglia, increases BBB permeability. Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production. Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects. Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation. Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.

  18. Radiation-induced blood-brain barrier changes: pathophysiological mechanisms and clinical implications.

    PubMed

    d'Avella, D; Cicciarello, R; Angileri, F F; Lucerna, S; La Torre, D; Tomasello, F

    1998-01-01

    The pathophysiology of whole-brain radiation (WBR) toxicity remains incompletely understood. The possibility of a primary change in blood-brain barrier (BBB) associated with microvascular damage was investigated. Rats were exposed to conventional fractionation in radiation (200 +/- cGy/d, 5d/wk; total dose, 4,000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid (AIB) technique coupled with standard electron microscopy (EM) and morphometric techniques as well as studies of the transcapillary passage of horseradish peroxidase (HRP). At 15 days after WBR, AIB transport across BBB increased significantly in cerebral cortex. EM disclosed vesicular transport of HRP across the intact endothelium without opening of the tight junctions. Ninety days after WBR, well-defined alterations of the microvasculature were observed. The main feature of cortical microvessels was their collapsed aspect, associated with perivascular edema containing cell debris. Data suggest a possible association between damage of the microvascular/glial unit of tissue injury and development of radiation-induced brain cerebral dysfunction. We hypothesize the following sequence of pathophysiological events: WBR causes an early increase in BBB permeability, which produces perivascular edema and microvascular collapse. The interference with microcirculation affects blood flow and energy supply to the tissue, resulting in structural damage on an ischemic/dysmetabolic basis.

  19. Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury

    PubMed Central

    Xie, Li-jie; Huang, Jin-xiu; Yang, Jian; Yuan, Fen; Zhang, Shuang-shuang; Yu, Qi-jing; Hu, Ji

    2017-01-01

    Propofol has been shown to exert neuroprotective effects on the injured spinal cord. However, the effect of propofol on the blood-spinal cord barrier (BSCB) after ischemia/reperfusion injury (IRI) is poorly understood. Therefore, we investigated whether propofol could maintain the integrity of the BSCB. Spinal cord IRI (SCIRI) was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Propofol, 30 mg/kg, was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion. Then, 48 hours later, we performed histological and mRNA/protein analyses of the spinal cord. Propofol decreased histological damage to the spinal cord, attenuated the reduction in BSCB permeability, downregulated the mRNA and protein expression levels of matrix metalloprotease-9 (MMP-9) and nuclear factor-κB (NF-κB), and upregulated the protein expression levels of occludin and claudin-5. Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression, by inhibiting the NF-κB signaling pathway, and by maintaining expression of tight junction proteins. PMID:28250758

  20. Response of upper ocean and impact of barrier layer on Sidr cyclone induced sea surface cooling

    NASA Astrophysics Data System (ADS)

    Vissa, Naresh Krishna; Satyanarayana, A. N. V.; Kumar, B. Prasad

    2013-09-01

    In the present study an attempt has been made to investigate the impact of salinity stratification on the SST during the tropical cyclone (TC) passage. In this context, a severe post monsoon cyclone, Sidr, (Category 4) that developed over the south-eastern Bay of Bengal (BoB) during 11-16 November, 2007 was chosen as a case study. Pre-existence of a thick barrier layer (BL), temperature inversions and a higher effective oceanic layer for cyclogenesis (EOLC) were noticed along the path of the Sidr cyclone. The analysis of available Argo floats along the Sidr cyclone track also revealed less cooling during as well as after its passage as was reported from satellite derived SST. The role of BL on Sidr induced sea surface cooling was investigated using a diagnostic mixed layer model. Model results also depict the reduced sea surface cooling during the passage of Sidr. This is attributed to the presence of BL which results in the inhibition of the entrainment of cool thermocline water into the shallow mixed layer. Climatological as well as in situ observations of tropical cyclone heat potential (TCHP) and EOLC shows that the Sidr cyclone propagated towards the regions of higher EOLC.

  1. Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells

    PubMed Central

    Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

    2013-01-01

    Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2. PMID:23637756

  2. Is aging a barrier to reprogramming? Lessons from induced pluripotent stem cells.

    PubMed

    Phanthong, Phetcharat; Raveh-Amit, Hadas; Li, Tong; Kitiyanant, Yindee; Dinnyes, Andras

    2013-12-01

    The discovery of induced pluripotent stem cells (iPSCs) has the potential to revolutionize the field of regenerative medicine. In the past few years, iPSCs have been the subject of intensive research towards their application in disease modeling and drug screening. In the future, these cells may be applied in cell therapy to replace or regenerate tissues by autologous transplantation. However, two major hurdles need to be resolved in order to reach the later goal: the low reprogramming efficiency and the safety risks, such as the integration of foreign DNA into the genome of the cells and the tumor formation potential arising from transplantation of residual undifferentiated cells. Recently, aging emerged as one of the barriers that accounts, at least in part, for the low reprogramming efficiency of bona fide iPSCs. Here, we review the molecular pathways linking aging and reprogramming along with the unanswered questions in the field. We discuss whether reprogramming rejuvenates the molecular and cellular features associated with age, and present the recent advances with iPSC-based models, contributing to our understanding of physiological and premature aging.

  3. Electroconvective Instability in Flow-shear-induced Transport Barrier: Threshold for Stable Vortices and Chaotic Eddies

    NASA Astrophysics Data System (ADS)

    Kwak, Rhokyun; Pham, Van Sang; Han, Jongyoon

    2014-11-01

    Suppression of turbulence and transport by shear flow is a common process in plasma fluid dynamics, while it has been rarely observed in nonionized fluids. Here, we visualize this effect in microfluidic nonionized system with electroconvective instability (EC) initiated by ion concentration polarization on ion selective membrane. The membranes act as the source of both instability and flow shear (wall shear of Hagen-Poiseuille (HP) flow) simultaneously, fitting the requisite for this shear suppression effect; turbulence in the domain of flow shear. To the best of our knowledge, this is the first characterization of flow-shear-induced transport barrier in microfluidics, captured by scaling analysis, experiment, and numerical modeling. Selected by balancing flow shear and velocity fluctuation, which generated by HP flow and vortical EC, the threshold for shear suppression scales by EC thickness dec/ w < 0.618. Stable unidirectional EC occurs under the threshold, while chaotic EC occurs over the threshold by overcoming flow shear. It also has significant implications on the energy saving of electrochemical systems (e . g . electrodialysis) to prevent chaotic turbulences and corresponding energy dissipations. This work was supported by the Advanced Research Projects Agency-Energy Grant (DE-AR0000294).

  4. Vaccinia virus-induced smallpox postvaccinal encephalitis in case of blood-brain barrier damage.

    PubMed

    Garcel, Aude; Fauquette, William; Dehouck, Marie-Pierre; Crance, Jean-Marc; Favier, Anne-Laure

    2012-02-08

    Smallpox vaccination is the only currently effective mean to combat the threat of variola virus used as a bioterrorism agent, although it is responsible for a rare but serious complication, the postvaccinal encephalitis (PVE). Development of safer vaccines therefore is a high priority as the PVE physiopathology is not well understood to date. If vaccinia virus (VACV) is responsible for PVE by central nervous system (CNS) dissemination, trans-migration of the VACV across the blood-brain barrier (BBB) would be supposed to be essential. Given the complexity of the pathogenesis of vaccinia neurovirulence, an in vitro BBB model was used to explore the mechanism of VACV to induce BBB permeability. Two VACV strains were studied, the neurovirulent Western Reserve strain (VACV-WR) and the vaccine reference Lister strain (VACV-List). A mouse model was also developed to study the ability of these two viral strains to propagate in the brain from the blood compartment, their neurovirulence and their neuropathogenesis. In vitro, the loss of permeability resulted from the tight-junctions disruption was induced by virus replication. The ability of VACV to release infectious particles at the abluminal side suggests the capacity of both VACV strains to migrate across the BBB from the blood to the CNS. In vivo, the virus replication in mice CNS was strain-dependent. The VACV-WR laboratory strain proved to be neuroinvasive and neurovirulent, whereas the VACV-List strain is safe in physiological conditions. Mice PVE was observed only with VACV-WR in the co-infection model, when BBB opening was obtained by lipopolysaccharide (LPS) treatment. This study suggests that VACV is able to cross the BBB but encephalitis occurs only in the presence of a co-infection by bacteria. So, a model of co-infection, mimicked by LPS treatment, could have important implication towards the assessment of neurovirulence of new vaccines.

  5. Dissipated power and induced velocity fields data of a micro single dielectric barrier discharge plasma actuator for active flow control.

    PubMed

    Pescini, E; Martínez, D S; De Giorgi, M G; Francioso, L; Ficarella, A

    2015-12-01

    In recent years, single dielectric barrier discharge (SDBD) plasma actuators have gained great interest among all the active flow control devices typically employed in aerospace and turbomachinery applications [1,2]. Compared with the macro SDBDs, the micro single dielectric barrier discharge (MSDBD) actuators showed a higher efficiency in conversion of input electrical power to delivered mechanical power [3,4]. This article provides data regarding the performances of a MSDBD plasma actuator [5,6]. The power dissipation values [5] and the experimental and numerical induced velocity fields [6] are provided. The present data support and enrich the research article entitled "Optimization of micro single dielectric barrier discharge plasma actuator models based on experimental velocity and body force fields" by Pescini et al. [6].

  6. Dissipated power and induced velocity fields data of a micro single dielectric barrier discharge plasma actuator for active flow control☆

    PubMed Central

    Pescini, E.; Martínez, D.S.; De Giorgi, M.G.; Francioso, L.; Ficarella, A.

    2015-01-01

    In recent years, single dielectric barrier discharge (SDBD) plasma actuators have gained great interest among all the active flow control devices typically employed in aerospace and turbomachinery applications [1,2]. Compared with the macro SDBDs, the micro single dielectric barrier discharge (MSDBD) actuators showed a higher efficiency in conversion of input electrical power to delivered mechanical power [3,4]. This article provides data regarding the performances of a MSDBD plasma actuator [5,6]. The power dissipation values [5] and the experimental and numerical induced velocity fields [6] are provided. The present data support and enrich the research article entitled “Optimization of micro single dielectric barrier discharge plasma actuator models based on experimental velocity and body force fields” by Pescini et al. [6]. PMID:26425667

  7. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism.

    PubMed

    Seth, A; Yan, Fang; Polk, D Brent; Rao, R K

    2008-04-01

    Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and beta-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCbetaI and PKCepsilon. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.

  8. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism

    PubMed Central

    Seth, A.; Yan, Fang; Polk, D.Brent; Rao, R. K.

    2009-01-01

    Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and β-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCβI and PKCε. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism. PMID:18292183

  9. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  10. Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models

    SciTech Connect

    Lee, Wonhwa; Kim, Tae Hoon; Ku, Sae-Kwang; Min, Kyoung-jin; Lee, Hyun-Shik; Kwon, Taeg Kyu; Bae, Jong-Sup

    2012-07-01

    Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. -- Highlights: ► Withaferin A inhibited LPS induced HMGB1 release. ► Withaferin A reduced HMGB1-mediated hyperpermeability. ► Withaferin A inhibited HMGB1-mediated adhesion and migration of leukocytes. ► Withaferin A inhibited HMGB1-mediated activation of NF-κB, IL-6 and TNF-α.

  11. Generation of airborne listeria from floor drain

    USDA-ARS?s Scientific Manuscript database

    Listeria monocytogenes can colonize in floor drains in poultry processing plants and further throughout processing facilities, remaining present even after cleaning and disinfection of the plant. Therefore, during wash down, workers exercise caution to prevent escape and transfer of drain microflor...

  12. Double frequency absorption induced by Al-Si Schottky barrier potential and mechanism of two-photon response

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoting; Gao, Yanjun; Chen, Zhanguo; Jia, Gang; Liu, Yunlong; Liu, Xiuhuan; Zh, Yuhong

    2006-01-01

    By observing two-photon response and anisotropy of the light-induced voltage in Si-Al Schottky barrier potential of the Si MSM (Metal-Semiconductor-Metal) planar structure two-photon response optical detector. It is certified from the experimental and theoretical analysis that the built-in electric field generated by the Schottky barrier potential will induce the phenomena of optical rectification in Si photodiode. Thus, it is deduced that there must be double-frequency absorption (DFA) caused by phase-mismatch in the mechanism of two-photon response of Si photodiode. If the intensity of the built-in electric field is strong enough, the DFA will be the main feature of the two-photon response.

  13. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF

    PubMed Central

    Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.

    2002-01-01

    Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189

  14. Alveolar macrophage inducible nitric oxide synthase-dependent pulmonary microvascular endothelial cell septic barrier dysfunction.

    PubMed

    Farley, K S; Wang, L F; Law, C; Mehta, S

    2008-11-01

    Inducible nitric oxide (NO) synthase (iNOS) from neutrophils and alveolar macrophages (AM) contributes to the pathophysiology of murine septic acute lung injury (ALI). It is not known if AM iNOS has a direct effect on septic pulmonary microvascular endothelial cell (PMVEC) permeability. We hypothesized that AM iNOS mediates PMVEC permeability in vitro under septic conditions through NO and peroxynitrite. 100,000 confluent PMVEC on cell-culture inserts were co-incubated with iNOS+/+ vs. iNOS-/- AM, in various ratios of AM to PMVEC. PMVEC injury was assessed by trans-PMVEC Evans Blue-labelled albumin flux in the presence or absence of cytomix (equimolar TNF-alpha, IL-1beta and IFN-gamma). Cytomix stimulation dose-dependently increased trans-PMVEC EB-albumin flux, which was exaggerated (1.4+/-0.1% vs. 0.4+/-0.1% in unstimulated PMVEC, p<0.05) in the presence of iNOS+/+, but not iNOS-/-, AM in the upper compartment. Similarly, iNOS+/+, but not iNOS-/-, AM in the lower compartment also enhanced septic trans-PMVEC albumin leak. The mechanism of iNOS-dependent septic PMVEC permeability was pursued through pharmacologic studies with inhibitors of NOS, and scavengers of NO, superoxide, and peroxynitrite, and treatment of PMVEC with the NO donor, DETA-NONOate. Septic iNOS+/+ AM-dependent trans-PMVEC albumin leak was significantly attenuated by pharmacologic iNOS inhibition (L-NAME and 1400W), and scavenging of either NO (oxyhemoglobin), superoxide (PEG-SOD), or peroxynitrite (FeTPPS). Exogenous NO (DETA-NONOate) had no effect on PMVEC permeability. These data are consistent with a direct role of AM iNOS in septic PMVEC barrier dysfunction, which is likely mediated, in part, through peroxynitrite.

  15. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

    PubMed Central

    Arjunan, Krishna Priya; Friedman, Gary; Fridman, Alexander; Clyne, Alisa Morss

    2012-01-01

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), has recently emerged as an efficient tool in medical applications including blood coagulation, sterilization and malignant cell apoptosis. Liquids and porcine aortic endothelial cells were treated with a non-thermal dielectric barrier discharge plasma in vitro. Plasma treatment of phosphate-buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration observed in serum-free medium compared with PBS. Species concentration inside cells peaked 1 h after treatment, followed by a decrease 3 h post treatment. Endothelial cells treated with a plasma dose of 4.2 J cm–2 had 1.7 times more cells than untreated samples 5 days after plasma treatment. The 4.2 J cm–2 plasma dose increased two-dimensional migration distance by 40 per cent compared with untreated control, while the number of cells that migrated through a three-dimensional collagen gel increased by 15 per cent. Tube formation was also enhanced by plasma treatment, with tube lengths in plasma-treated samples measuring 2.6 times longer than control samples. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers abrogated these angiogenic effects. These data indicate that plasma enhanced proliferation, migration and tube formation is due to FGF-2 release induced by plasma-produced ROS. Non-thermal plasma may be used as a potential tool for applying ROS in precise doses to enhance vascularization. PMID:21653568

  16. Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury.

    PubMed

    Cresci, Gail A; Glueck, Bryan; McMullen, Megan R; Xin, Wei; Allende, Daniella; Nagy, Laura E

    2017-09-01

    Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. C57BL/6J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 h before euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction (TJ) proteins, toll-like receptors, and tumor necrosis factor-alpha were assessed. Caco-2 monolayers with or without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic toll-like receptor mRNA expression and tumor necrosis factor-alpha protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: Leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-tributyrin mice. Prophylactic tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury. © 2017

  17. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development

    SciTech Connect

    Wang Qiang; Luo Wenjing; Zheng Wei; Liu Yiping; Xu Hui; Zheng Gang; Dai Zhongming; Zhang Wenbin; Chen Yaoming; Chen Jingyuan . E-mail: jy_chen@fmmu.edu.cn

    2007-02-15

    Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 {mu}g Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO{sub 4} solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p < 0.05) and brain tissues by 1.5-2.0-folds (p < 0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p < 0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.

  18. Simvastatin attenuates sepsis-induced blood-brain barrier integrity loss.

    PubMed

    Yang, Chen-Hsien; Kao, Ming-Chan; Shih, Ping-Cheng; Li, Kuang-Yao; Tsai, Pei-Shan; Huang, Chun-Jen

    2015-04-01

    Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Investigation of contribution of incomplete fusion in the total fusion process induced by 9Be on 181Ta target at near barrier energies

    NASA Astrophysics Data System (ADS)

    Kharab, Rajesh; Chahal, Rajiv; Kumar, Rajiv

    2016-02-01

    We have studied the relative contribution of incomplete fusion (ICF) and complete fusion (CF) in total fusion (TF) induced by 9Be on 181Ta target at energies in the vicinity of Coulomb barrier using classical dynamical model and Wong's formula in conjugation with energy dependent Woods-Saxon formula. It is found that at above barrier energies ICF contributes almost 30% in TF while at energies below the barrier qualitatively its contribution is much more than thirty percent.

  20. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  1. Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

    PubMed Central

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  2. Hypo-osmotic shock-induced subclinical inflammation of skin in a rat model of disrupted skin barrier function.

    PubMed

    Kishi, Chihiro; Minematsu, Takeo; Huang, Lijuan; Mugita, Yuko; Kitamura, Aya; Nakagami, Gojiro; Yamane, Takumi; Yoshida, Mikako; Noguchi, Hiroshi; Funakubo, Megumi; Mori, Taketoshi; Sanada, Hiromi

    2015-03-01

    Aging disrupts skin barrier function and induces xerosis accompanied by pruritus. In many cases, elderly patients complain of pruritus during skin hygiene care, a condition called aquagenic pruritus of the elderly (APE). To date, the pathophysiology and mechanism of action of APE have not been elucidated. We conducted the present study to test the hypothesis that hypo-osmotic shock of epidermal cells induces skin inflammation and elongation of C-fibers by nerve growth factor β (NGFβ) as a basic mechanism of APE. The dorsal skin of HWY rats, which are a model for disrupted skin barrier function, was treated with distilled water (hypotonic treatment [Hypo] group) or normal saline (isotonic treatment [Iso] group) by applying soaked gauze for 7 days. Untreated rats were used as a control (no-treatment [NT] group). Histochemical and immunohistochemical analyses revealed inflammatory responses in the epidermis and the dermal papillary layer in the Hypo group, while no alterations were observed in the Iso or NT groups. Induction of expression and secretion of NGFβ and elongation of C-fibers into the epidermis were found in the Hypo group. In contrast, secretion of NGFβ was significantly lower and elongation of C-fibers was not observed in the Iso group. These results suggest that hypo-osmotic shock-induced inflammatory reactions promote hypersensitivity to pruritus in skin with disrupted barrier function.

  3. Microbubble type and distribution dependence of focused ultrasound-induced blood-brain barrier opening.

    PubMed

    Wang, Shutao; Samiotaki, Gesthimani; Olumolade, Oluyemi; Feshitan, Jameel A; Konofagou, Elisa E

    2014-01-01

    Focused ultrasound, in the presence of microbubbles, has been used non-invasively to induce reversible blood-brain barrier (BBB) opening in both rodents and non-human primates. This study was aimed at identifying the dependence of BBB opening properties on polydisperse microbubble (all clinically approved microbubbles are polydisperse) type and distribution by using a clinically approved ultrasound contrast agent (Definity microbubbles) and in-house prepared polydisperse (IHP) microbubbles in mice. A total of 18 C57 BL/6 mice (n = 3) were used in this study, and each mouse was injected with either Definity or IHP microbubbles via the tail vein. The concentration and size distribution of activated Definity and IHP microbubbles were measured, and the microbubbles were diluted to 6 × 10(8)/mL before injection. Immediately after microbubble administration, mice were subjected to focused ultrasound with the following parameters: frequency = 1.5 MHz, pulse repetition frequency = 10 Hz, 1000 cycles, in situ peak rarefactional acoustic pressures = 0.3, 0.45 and 0.6 MPa for a sonication duration of 60 s. Contrast-enhanced magnetic resonance imaging was used to confirm BBB opening and allowed for image-based analysis. Permeability of the treated region and volume of BBB opening did not significantly differ between the two types of microbubbles (p > 0.05) at peak rarefractional acoustic pressures of 0.45 and 0.6 MPa, whereas IHP microbubbles had significantly higher permeability and opening volume (p < 0.05) at the relatively lower pressure of 0.3 MPa. The results from this study indicate that microbubble type and distribution could have significant effects on focused ultrasound-induced BBB opening at lower pressures, but less important effects at higher pressures, possibly because of the stable cavitation that governs the former. This difference may have become less significant at higher pressures, where inertial cavitation typically occurs.

  4. Early radiation-induced endothelial cell loss and blood-spinal cord barrier breakdown in the rat spinal cord.

    PubMed

    Li, Yu-Qing; Chen, Paul; Jain, Vipan; Reilly, Raymond M; Wong, C Shun

    2004-02-01

    Using a rat spinal cord model, this study was designed to characterize radiation-induced vascular endothelial cell loss and its relationship to early blood-brain barrier disruption in the central nervous system. Adult rats were given a single dose of 0, 2, 8, 19.5, 22, 30 or 50 Gy to the cervical spinal cord. At various times up to 2 weeks after irradiation, the spinal cord was processed for histological and immunohistochemical analysis. Radiation-induced apoptosis was assessed by morphology and TdT-mediated dUTP nick end labeling combined with immunohistochemical markers for endothelial and glial cells. Image analysis was performed to determine endothelial cell and microvessel density using immunohistochemistry with endothelial markers, namely endothelial barrier antigen, glucose transporter isoform 1, laminin and zonula occludens 1. Blood-spinal cord barrier permeability was assessed using immunohistochemistry for albumin and (99m)Tc-diethylenetriamine pentaacetic acid as a vascular tracer. Endothelial cell proliferation was assessed using in vivo BrdU labeling. During the first 24 h after irradiation, apoptotic endothelial cells were observed in the rat spinal cord. The decrease in endothelial cell density at 24 h after irradiation was associated with an increase in albumin immunostaining around microvessels. The decrease in the number of endothelial cells persisted for 7 days and recovery of endothelial density was apparent by day 14. A similar pattern of blood-spinal cord barrier disruption and recovery of permeability was observed over the 2 weeks, and an increase in BrdU-labeled endothelial cells was seen at day 3. These results are consistent with an association between endothelial cell death and acute blood-spinal cord barrier disruption in the rat spinal cord after irradiation.

  5. Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation*

    PubMed Central

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M.; Su, Yunchao

    2014-01-01

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326–333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor NG-nitro-l-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. PMID:25315770

  6. Effect of heat stress on endotoxin flux across mesenteric-drained and portal-drained viscera of dairy goat.

    PubMed

    Wang, L; Xue, B; Wang, K; Li, S; Li, Z

    2011-08-01

    This study was designed to evaluate the effect of heat stress on endotoxin flux across mesenteric-drained and portal-drained viscera of dairy goats. Three Saanen first lactation dairy goats were surgically fitted with indwelling catheters in the portal vein, the mesenteric vein and carotid, and were kept in thermal-neutral and then heat stress environment, for examining the effect of heat stress on endotoxin absorption and redox status. Average net absorption of endotoxin (EU/h) across mesenteric-drained viscera (MDV) and portal-drained viscera (PDV) during the whole period of heat stress increased by 279.05% and 227.92% in relation to thermo-neutral period. Plasma concentration of glutathione peroxidase (GSH-Px) and catalase (CAT) in mesenteric and portal vein, and that of superoxide dismutase (SOD) in mesenteric vein, increased significantly during heat stress. Main conclusions were: (i) net absorption of endotoxin in portal vein is mainly from non-mesenteric tissues both in heat stress and in thermo-neutral condition; (ii) heat stress may lead to the significant decrease in plasma SOD, GSH-Px, CAT flux across PDV and MDV, and the significant increase in endotoxin flux across PDV and MDV; and (iii) the increase in gastrointestinal permeability in dairy goats during heat stress may not be induced by the increase in oxidative stress.

  7. 14 CFR 23.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 23.1021 Section 23.1021... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Oil System § 23.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain...

  8. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible...

  9. 14 CFR 23.1021 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil system drains. 23.1021 Section 23.1021... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Oil System § 23.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain...

  10. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 29.1021 Section 29.1021... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible...

  11. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible...

  12. 14 CFR 23.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 23.1021 Section 23.1021... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Oil System § 23.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain...

  13. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and (b...

  14. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and (b...

  15. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and (b...

  16. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and...

  17. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 25.1021 Section 25.1021...

  18. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 29.1021 Section 29.1021...

  19. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 29.1021 Section 29.1021...

  20. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 25.1021 Section 25.1021...

  1. Rhinovirus-Induced Barrier Dysfunction in Polarized Airway Epithelial Cells Is Mediated by NADPH Oxidase 1▿

    PubMed Central

    Comstock, Adam T.; Ganesan, Shyamala; Chattoraj, Asamanja; Faris, Andrea N.; Margolis, Benjamin L.; Hershenson, Marc B.; Sajjan, Umadevi S.

    2011-01-01

    Previously, we showed that rhinovirus (RV), which is responsible for the majority of common colds, disrupts airway epithelial barrier function, as evidenced by reduced transepithelial resistance (RT), dissociation of zona occludins 1 (ZO-1) from the tight junction complex, and bacterial transmigration across polarized cells. We also showed that RV replication is required for barrier function disruption. However, the underlying biochemical mechanisms are not known. In the present study, we found that a double-stranded RNA (dsRNA) mimetic, poly(I:C), induced tight junction breakdown and facilitated bacterial transmigration across polarized airway epithelial cells, similar to the case with RV. We also found that RV and poly(I:C) each stimulated Rac1 activation, reactive oxygen species (ROS) generation, and Rac1-dependent NADPH oxidase 1 (NOX1) activity. Inhibitors of Rac1 (NSC23766), NOX (diphenylene iodonium), and NOX1 (small interfering RNA [siRNA]) each blocked the disruptive effects of RV and poly(I:C) on RT, as well as the dissociation of ZO-1 and occludin from the tight junction complex. Finally, we found that Toll-like receptor 3 (TLR3) is not required for either poly(I:C)- or RV-induced reductions in RT. Based on these results, we concluded that Rac1-dependent NOX1 activity is required for RV- or poly(I:C)-induced ROS generation, which in turn disrupts the barrier function of polarized airway epithelia. Furthermore, these data suggest that dsRNA generated during RV replication is sufficient to disrupt barrier function. PMID:21507984

  2. Propionate Protects against Lipopolysaccharide-Induced Mastitis in Mice by Restoring Blood-Milk Barrier Disruption and Suppressing Inflammatory Response.

    PubMed

    Wang, Jingjing; Wei, Zhengkai; Zhang, Xu; Wang, Yanan; Yang, Zhengtao; Fu, Yunhe

    2017-01-01

    Mastitis, an inflammation of the mammary glands, is a major disease affecting dairy animal worldwide. Propionate is one of the main short-chain fatty acid that can exert multiple effects on the inflammatory process. The purpose of this study is to investigate the mechanisms underlying the protective effects of sodium propionate against lipopolysaccharide (LPS)-induced mastitis model in mice. The data mainly confirm that inflammation and blood-milk barrier breakdown contribute to progression of the disease in this model. In mice with LPS, sodium propionate attenuates the LPS-induced histopathological changes, inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) production, myeloperoxidase activity in mammary tissues. Given their importance in the blood-milk barrier, tight junction proteins occludin and claudin-3 are further investigated. Our results show that sodium propionate strikingly increases the expressions of occludin and claudin-3 and reduces the blood-milk barrier permeability in this model. Furthermore, in LPS-stimulated mouse mammary epithelial cells (mMECs), LPS increased the expressions of phosphorylated (p)-p65, p-IκB proteins, which is attenuated by sodium propionate. Finally, we examine the possibility that propionate acts as a histone deacetylase (HDAC) inhibitor, the results show that both sodium propionate and trichostatin A increase the level of histone H3 acetylation and inhibit the increased production of TNF-α, IL-6, and IL-1β in LPS-stimulated mMECs. These data suggest that sodium propionate protects against LPS-induced mastitis mainly by restoring blood-milk barrier disruption and suppressing inflammation via NF-κB signaling pathway and HDAC inhibition.

  3. Unsteady draining flows from a rectangular tank

    NASA Astrophysics Data System (ADS)

    Forbes, Lawrence K.; Hocking, Graeme C.

    2007-08-01

    Two-dimensional, unsteady flow of a two-layer fluid in a tank is considered. Each fluid is inviscid and flows irrotationally. The lower, denser fluid flows with constant speed out through a drain hole of finite width in the bottom of the tank. The upper, lighter fluid is recharged at the top of the tank, with an input volume flux that matches the outward flux through the drain. As a result, the interface between the two fluids moves uniformly downwards, and is eventually withdrawn through the drain hole. However, waves are present at the interface, and they have a strong effect on the time at which the interface is first drawn into the drain. A linearized theory valid for small extraction rates is presented. Fully nonlinear, unsteady solutions are computed by means of a novel numerical technique based on Fourier series. For impulsive start of the drain, the nonlinear results are found to agree with the linearized theory initially, but the two theories differ markedly as the interface approaches the drain and nonlinear effects dominate. For wide drains, curvature singularities appear to form at the interface within finite time.

  4. Claudin-3 expression in radiation-exposed rat models: a potential marker for radiation-induced intestinal barrier failure.

    PubMed

    Shim, Sehwan; Lee, Jong-Geol; Bae, Chang-Hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation+neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  5. Sepsis induces albuminuria and alterations in the glomerular filtration barrier: a morphofunctional study in the rat

    PubMed Central

    2011-01-01

    Introduction Increased vascular permeability represents one of the hallmarks of sepsis. In the kidney, vascular permeability is strictly regulated by the 'glomerular filtration barrier' (GFB), which is comprised of glomerular endothelium, podocytes, their interposed basement membranes and the associated glycocalyx. Although it is likely that the GFB and its glycocalyx are altered during sepsis, no study has specifically addressed this issue. The aim of this study was to evaluate whether albuminuria -- the hallmark of GFB perm-selectivity -- occurs in the initial stage of sepsis and whether it is associated with morphological and biochemical changes of the GFB. Methods Cecal ligation and puncture (CLP) was used to induce sepsis in the rat. Tumor necrosis factor (TNF)-alpha levels in plasma and growth of microorganisms in the peritoneal fluid were evaluated at 0, 3 and 7 hours after CLP or sham-operation. At the same times, kidney specimens were collected and structural and ultrastructural alterations in the GFB were assessed. In addition, several components of GFB-associated glycocalyx, syndecan-1, hyluronan (HA) and sialic acids were evaluated by immunofluorescence, immunohistochemistry and lectin histochemistry techniques. Serum creatinine and creatinine clearance were measured to assess kidney function and albuminuria for changes in GFB permeability. Analysis of variance followed by Tukey's multiple comparison test was used. Results Septic rats showed increased TNF-alpha levels and growth of microorganisms in the peritoneal fluid. Only a few renal corpuscles had major ultrastructural and structural alterations and no change in serum creatinine or creatinine clearance was observed. Contrarily, urinary albumin significantly increased after CLP and was associated with diffuse alteration in the glycocalyx of the GFB, which consisted in a decrease in syndecan-1 expression and in HA and sialic acids contents. Sialic acids were also changed in their structure

  6. Might digital drains speed up the time to thoracic drain removal?

    PubMed

    Afoke, Jonathan; Tan, Carol; Hunt, Ian; Zakkar, Mustafa

    2014-07-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: might digital drains speed up the time to thoracic drain removal in terms of time till chest drain removal, hospital stay and overall cost? A total of 296 papers were identified as a result of the search as described below. Of these, five papers provided the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. A literature search revealed that several single-centre prospective randomized studies have shown significantly earlier removal of chest drains with digital drains ranging between 0.8 and 2.1 days sooner. However, there was heterogeneity in studies in the management protocol of chest drains in terms of the use of suction, number of drains and assessment for drain removal. Some protocols such as routinely keeping drains irrespective of the presence of air leak or drain output may have skewed results. Differences in exclusion criteria and protocols for discharging home with portable devices may have biased results. Due to heterogeneity in the management protocol of chest drains, there is conflicting evidence regarding hospital stay. The limited data on cost suggest that there may be significantly lower postoperative costs in the digital drain group. All the studies were single-centre series generally including patients with good preoperative lung function tests. Further larger studies with more robust chest drain management protocols are required especially to assess length of hospital stay, cost and whether the results are applicable to a larger patient population.

  7. Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

    PubMed

    Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

    2014-07-01

    Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

  8. Temperature dependent study of Fin-FET drain current through optimization of controlling gate parameters and dielectric material

    NASA Astrophysics Data System (ADS)

    Das, Rinku Rani; Maity, Santanu; Muchahary, Deboraj; Bhunia, Chandan Tilak

    2017-03-01

    Various limitations, such as gate leakage through hot carrier tunnelling, parasitic resistance and capacitance, Drain Induced Barrier Lowering (DIBL), subthreshold slope (SS), and threshold voltage roll-off are present due to size reduction. Improvements in transistor speed and performance while, reducing the device dimensions is possible using the concept of Multiple-gate Field Effect phenomenon. Temperature dependency in thin fin transistor has been systematically studied with respect to the dependence on the fin width, fin height, and gate length. In this paper the performance of miniaturized Fin-FET structure is optimized. Also, temperature (300K, 400K and 500K) dependent performances on DIBL, SS and threshold voltage are observed and optimized.

  9. Defect distribution and Schottky barrier at metal/Ge interfaces: Role of metal-induced gap states

    NASA Astrophysics Data System (ADS)

    Sasaki, Shogo; Nakayama, Takashi

    2016-11-01

    The defect distribution and Schottky barrier at metal/Ge interfaces were studied using first-principles calculation. It was shown that the defect density markedly increases around the interface owing to the stabilization caused by the hybridization of defect electronic states with metal-induced gap states (MIGS) and by the associated small elastic energy loss around the interface. By comparing the formation energies of various defects at a variety of metal/substrate interfaces, we showed that MIGS not only control the Schottky barrier but also promote a defect-density increase at most metal/semiconductor interfaces. Moreover, we showed that interface oxide layers block MIGS penetration into the Ge substrate and promote the observed breakdown of Fermi-level pinning.

  10. EFFECTS OF NUCLEAR INDUCED BREAKUP ON THE FUSION OF 6Li+12C AND 6He+12C SYSTEMS AROUND BARRIER ENERGIES

    NASA Astrophysics Data System (ADS)

    Duhan, Sukhvinder S.; Singh, Manjeet; Kharab, Rajesh

    2012-06-01

    We have studied the effects of nuclear induced breakup channel coupling on the fusion cross-section for 6Li+12C and 6He+12C systems in the near barrier energy regime using the dynamic polarization potential (DPP) approach. It has been found that there is enhancement in the fusion cross-section with respect to standard one-dimensional barrier penetration model in the below barrier energy regime while at energies above the barrier there is suppression of fusion cross-section with respect to simple barrier penetration model is observed. The agreement between data and predictions for 6Li+12C system improves significantly as a result of the inclusion of nuclear induced DPP.

  11. Draining characteristics of hemispherically bottomed cylinders in a low-gravity environment

    NASA Technical Reports Server (NTRS)

    Symons, E. P.

    1978-01-01

    An experimental investigation was conducted to study the phenomenon of vapor ingestion during the draining of a scale model, hemispherically bottomed cylindrical tank in a low-gravity environment. Where possible, experimental results are compared with previously obtained numerical predictions. It was observed that certain combinations of Weber and Bond number resulted in draining-induced axisymmetric slosh motion. The periods of the slosh waves were correlated with the square root of the draining parameter, the ratio (Weber number)/(Bond number plus one), as was the quantity of liquid remaining in the tank when vapor was ingested into the outlet line.

  12. Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier

    PubMed Central

    Griffin, Jarred M.; Kho, Dan; Graham, E. Scott; Nicholson, Louise F. B.; O’Carroll, Simon J.

    2016-01-01

    Background Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. Aims To determine if fAβ is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fAβ. Methods Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary β-amyloid1–42 (fAβ1–42) alone and in combination with statins. Results fAβ1–42 induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. Conclusions We conclude that fAβ1–42 has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects. PMID:27309956

  13. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

    2012-02-01

    Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

  14. Super natural killer cells that target metastases in the tumor draining lymph nodes.

    PubMed

    Chandrasekaran, Siddarth; Chan, Maxine F; Li, Jiahe; King, Michael R

    2016-01-01

    Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

  15. Non-sting barrier cream in radiotherapy-induced skin reactions.

    PubMed

    Scott, Audrey

    A pilot evaluation was undertaken in 13 patients with head and neck cancer exploring the use of a non-sting barrier film (Sorbaderm(®,) Aspen Medical Europe Ltd). The Society of Radiographers issued guidance in 2013 warning their members that the use of Aqueous cream for moisturising the skin during radiotherapy was potentially harmful. Patients were monitored over a period of 6 weeks and the aim was to explore whether applying non-sting barrier cream provided a protective barrier that did not impair treatment, slowed or prevented skin damage, was easy and simple to apply for patients and carers, improved quality of life for patients during radiotherapy or aided healing. There appeared to be a delay in skin breakdown in this evaluation from week 3 to week 4 and then only mild pain was recorded and with a maximum Radiation Therapy Oncology Group scale of 2.5 in the patient that had combined chemotherapy and radiotherapy. The patients' overall assessment demonstrated that the use of non-sting barrier cream provided symptom relief in both dry, tightening and itching of the skin associated with radiotherapy. All except one patient found the cream easy to apply. The head and neck nursing team rated the product as 'good' to 'very good'.

  16. A Modified Lightly Doped Drain Structure for VLSI MOSFET’s,

    DTIC Science & Technology

    1986-01-01

    channel current away from the SiO 2 interface in the high field drain region. Techniques proposed to accomplish this include either a buried channel device...measurements were done at the wafer level utilizing a floating gate induced drain current relaxation technique demonstrated in [70]. Resolution below 10-1 A...was possible with this technique . Gate current comparisons presented herein are for devices built side by side on the same chip, since small structural

  17. Hyperglycemia Induces Skin Barrier Dysfunctions with Impairment of Epidermal Integrity in Non-Wounded Skin of Type 1 Diabetic Mice

    PubMed Central

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakagawa, Takahiko; Nakae, Yuki; Terashima, Tomoya; Kurakane, Takeshi; Kubota, Mamoru; Maegawa, Hiroshi; Udagawa, Jun

    2016-01-01

    Diabetes causes skin complications, including xerosis and foot ulcers. Ulcers complicated by infections exacerbate skin conditions, and in severe cases, limb/toe amputations are required to prevent the development of sepsis. Here, we hypothesize that hyperglycemia induces skin barrier dysfunction with alterations of epidermal integrity. The effects of hyperglycemia on the epidermis were examined in streptozotocin-induced diabetic mice with/without insulin therapy. The results showed that dye leakages were prominent, and transepidermal water loss after tape stripping was exacerbated in diabetic mice. These data indicate that hyperglycemia impaired skin barrier functions. Additionally, the distribution of the protein associated with the tight junction structure, tight junction protein-1 (ZO-1), was characterized by diffuse and significantly wider expression in the diabetic mice compared to that in the control mice. In turn, epidermal cell number was significantly reduced and basal cells were irregularly aligned with ultrastructural alterations in diabetic mice. In contrast, the number of corneocytes, namely, denucleated and terminally differentiated keratinocytes significantly increased, while their sensitivity to mechanical stress was enhanced in the diabetic mice. We found that cell proliferation was significantly decreased, while apoptotic cells were comparable in the skin of diabetic mice, compared to those in the control mice. In the epidermis, Keratin 5 and keratin 14 expressions were reduced, while keratin 10 and loricrin were ectopically induced in diabetic mice. These data suggest that hyperglycemia altered keratinocyte proliferation/differentiation. Finally, these phenotypes observed in diabetic mice were mitigated by insulin treatment. Reduction in basal cell number and perturbation of the proliferation/differentiation process could be the underlying mechanisms for impaired skin barrier functions in diabetic mice. PMID:27846299

  18. Remediation of hemorrhagic shock-induced intestinal barrier dysfunction by treatment with diphenyldihaloketones EF24 and CLEFMA.

    PubMed

    Yadav, Vivek R; Hussain, Alamdar; Sahoo, Kaustuv; Awasthi, Vibhudutta

    2014-11-01

    Gut is very sensitive to hypoperfusion and hypoxia, and deranged gastrointestinal barrier is implicated in systemic failure of various organs. We recently demonstrated that diphenyldihaloketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one] improves survival in a rat model of hemorrhagic shock. In this study, we tested EF24 and its other analog CLEFMA (4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid) for their effect on intestinal barrier dysfunction in hypovolemic shock. Hypovolemia was induced in rats by withdrawing 50% of blood. EF24 or CLEFMA (0.4 mg/kg i.p.) treatment was provided, without volume resuscitation, after 1 hour of hemorrhage. Ileum was collected 5 hours after the treatment to investigate the expression of tight junction proteins (zonula occludens, claudin, and occludin) and epithelial injury markers [myeloperoxidase, ileal lipid-binding protein (ILBP), CD163, and plasma citrulline]. The ileal permeability for dextran-fluoroisothiocyanate and Evan's blue dye was determined. EF24 and CLEFMA reduced the hypovolemia-induced plasma citrulline levels and the ileal expression of myeloperoxidase, ILBP, and CD163. The drugs also restored the basal expression levels of zonula occludens, claudin, and occludin, which were substantially deranged by hypovolemia. In ischemic ileum, the expression of phospho(tyrosine)-zonula occludens-1 was reduced, which was reinstated by EF24 and CLEFMA. In contrast, the drug treatments maintained the hypovolemia-induced expression of phospho(threonine)-occludin, but reduced that of phospho(tyrosine)-occludin. Both EF24 and CLEFMA treatments reduced the intestinal permeability enhanced by hypovolemia. EF24 and CLEFMA attenuate hypovolemic gut pathology and protect barrier function by restoring the status of tight junction proteins. These effects were observed in unresuscitated shock, implying the benefit of EF24 and CLEFMA in prehospital care of shock.

  19. Hyperglycemia Induces Skin Barrier Dysfunctions with Impairment of Epidermal Integrity in Non-Wounded Skin of Type 1 Diabetic Mice.

    PubMed

    Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakagawa, Takahiko; Nakae, Yuki; Terashima, Tomoya; Kurakane, Takeshi; Kubota, Mamoru; Maegawa, Hiroshi; Udagawa, Jun

    2016-01-01

    Diabetes causes skin complications, including xerosis and foot ulcers. Ulcers complicated by infections exacerbate skin conditions, and in severe cases, limb/toe amputations are required to prevent the development of sepsis. Here, we hypothesize that hyperglycemia induces skin barrier dysfunction with alterations of epidermal integrity. The effects of hyperglycemia on the epidermis were examined in streptozotocin-induced diabetic mice with/without insulin therapy. The results showed that dye leakages were prominent, and transepidermal water loss after tape stripping was exacerbated in diabetic mice. These data indicate that hyperglycemia impaired skin barrier functions. Additionally, the distribution of the protein associated with the tight junction structure, tight junction protein-1 (ZO-1), was characterized by diffuse and significantly wider expression in the diabetic mice compared to that in the control mice. In turn, epidermal cell number was significantly reduced and basal cells were irregularly aligned with ultrastructural alterations in diabetic mice. In contrast, the number of corneocytes, namely, denucleated and terminally differentiated keratinocytes significantly increased, while their sensitivity to mechanical stress was enhanced in the diabetic mice. We found that cell proliferation was significantly decreased, while apoptotic cells were comparable in the skin of diabetic mice, compared to those in the control mice. In the epidermis, Keratin 5 and keratin 14 expressions were reduced, while keratin 10 and loricrin were ectopically induced in diabetic mice. These data suggest that hyperglycemia altered keratinocyte proliferation/differentiation. Finally, these phenotypes observed in diabetic mice were mitigated by insulin treatment. Reduction in basal cell number and perturbation of the proliferation/differentiation process could be the underlying mechanisms for impaired skin barrier functions in diabetic mice.

  20. Trapping in GaN-based metal-insulator-semiconductor transistors: Role of high drain bias and hot electrons

    SciTech Connect

    Meneghini, M. Bisi, D.; Meneghesso, G.; Zanoni, E.

    2014-04-07

    This paper describes an extensive analysis of the role of off-state and semi-on state bias in inducing the trapping in GaN-based power High Electron Mobility Transistors. The study is based on combined pulsed characterization and on-resistance transient measurements. We demonstrate that—by changing the quiescent bias point from the off-state to the semi-on state—it is possible to separately analyze two relevant trapping mechanisms: (i) the trapping of electrons in the gate-drain access region, activated by the exposure to high drain bias in the off-state; (ii) the trapping of hot-electrons within the AlGaN barrier or the gate insulator, which occurs when the devices are operated in the semi-on state. The dependence of these two mechanisms on the bias conditions and on temperature, and the properties (activation energy and cross section) of the related traps are described in the text.

  1. A unified analytical drain current model for Double-Gate Junctionless Field-Effect Transistors including short channel effects

    NASA Astrophysics Data System (ADS)

    Raksharam; Dutta, Aloke K.

    2017-04-01

    In this paper, a unified analytical model for the drain current of a symmetric Double-Gate Junctionless Field-Effect Transistor (DG-JLFET) is presented. The operation of the device has been classified into four modes: subthreshold, semi-depleted, accumulation, and hybrid; with the main focus of this work being on the accumulation mode, which has not been dealt with in detail so far in the literature. A physics-based model, using a simplified one-dimensional approach, has been developed for this mode, and it has been successfully integrated with the model for the hybrid mode. It also includes the effect of carrier mobility degradation due to the transverse electric field, which was hitherto missing in the earlier models reported in the literature. The piece-wise models have been unified using suitable interpolation functions. In addition, the model includes two most important short-channel effects pertaining to DG-JLFETs, namely the Drain Induced Barrier Lowering (DIBL) and the Subthreshold Swing (SS) degradation. The model is completely analytical, and is thus computationally highly efficient. The results of our model have shown an excellent match with those obtained from TCAD simulations for both long- and short-channel devices, as well as with the experimental data reported in the literature.

  2. Transforming Growth Factor-β Regulation of Epithelial Tight Junction Proteins Enhances Barrier Function and Blocks Enterohemorrhagic Escherichia coli O157:H7-Induced Increased Permeability

    PubMed Central

    Howe, Kathryn L.; Reardon, Colin; Wang, Arthur; Nazli, Aisha; McKay, Derek M.

    2005-01-01

    Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an enteric pathogen that causes potentially fatal symptoms after intimate adhesion, modulation of intestinal epithelial signal transduction, and alteration of epithelial function (eg, barrier disruption). Although the epithelial barrier is critical to gut homeostasis, only a few agents, such as transforming growth factor (TGF)-β, can enhance or protect epithelial barrier function. Our aims were to delineate the mechanism(s) behind TGF-β-induced barrier enhancement and to determine whether TGF-β could prevent EHEC-induced barrier disruption. Using monolayers of the human T84 colonic epithelial cell line, we found that TGF-β induced a significant increase in transepithelial electrical resistance (a measure of paracellular permeability) through activation of ERK MAPK and SMAD signaling pathways and up-regulation of the tight junction protein claudin-1. Additionally, TGF-β pretreatment of epithelia blocked the decrease in transepithelial electrical resistance and the increase in transepithelial passage of [3H]-mannitol caused by EHEC infection. EHEC infection was associated with reduced expression of zonula occludens-1, occludin, and claudin-2 (but not claudin-1 or claudin-4); TGF-β pretreatment prevented these changes. These studies provide insight into EHEC pathogenesis by illustrating the mechanisms underlying TGF-β-induced epithelial barrier enhancement and identifying TGF-β as an agent capable of blocking EHEC-induced increases in epithelial permeability via maintenance of claudin-2, occludin, and zonula occludens-1 levels. PMID:16314472

  3. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    PubMed

    Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  4. Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline.

    PubMed

    Ma, Xiaotang; Zhang, Huiting; Pan, Qunwen; Zhao, Yuhui; Chen, Ji; Zhao, Bin; Chen, Yanfang

    2013-01-01

    This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the permeability of HUVECs accompanied with down-regulation of occludens-1 (ZO-1) and occludin at both mRNA and protein levels. Similarly in bEnd.3s, hypoxia increased the permeability and decreased the expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased the permeability in these two models, which paralleled with elevated expression of TJPs. The data demonstrate that citicoline restores the barrier function of endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the expression of TJPs.

  5. Visualization and quantification of skin barrier perturbation induced by surfactant-humectant systems using two-photon fluorescence microscopy.

    PubMed

    Ghosh, Saswata; Kim, Daekeun; So, Peter; Blankschtein, Daniel

    2008-01-01

    In order to visualize the effects of aqueous surfactant-humectant systems on the skin barrier, an in vitro two-photon fluorescence microscopy (TPM) study, including dual-channel visualization, was carried out. TPM is a non-invasive imaging technique based on two-photon induced nonlinear excitations of fluorophores, with the capability for deep-tissue imaging (up to several hundred micrometers). The following aqueous solutions of surfactants, a humectant, and a surfactant+humectant mixture that contacted pig full-thickness skin (p-FTS) were studied: (i) a harsh surfactant solution-sodium dodecyl sulfate (SDS) (1 wt%); (ii) a harsh surfactant+humectant solution-SDS (1 wt%) + glycerol (10 wt%); (iii) a mild surfactant solution-sodium cocoyl isethionate (SCI) (1 wt%); (iv) a control solution-phosphate-buffered saline (PBS); and (v) a humectant solution-glycerol (10 wt%). Sulforhodamine B (SRB), a hydrophilic fluorescent probe, was used to visualize the effects of aqueous contacting solutions i-v on the skin barrier morphology. The results of the TPM visualization study revealed that SDS induces corneocyte damage by denaturing keratins and creating intracorneocyte penetration pathways. On the other hand, SDS+glycerol did not significantly induce corneocyte damage. The dual-channel TPM images corresponding to aqueous contacting solutions iii-v showed low SRB penetration into the corneocytes, as well as localization of the SRB probe within the lipid bilayers surrounding the corneocytes of the SC. Through a quantification of the amount of SRB that penetrated into the skin as a function of skin depth, we found that adding glycerol to an SDS aqueous contacting solution can significantly reduce the SDS-induced penetration depth of SRB, which provides evidence of the ability of glycerol to mitigate SDS-induced skin barrier perturbation. The distribution of SRB in the p-FTS samples was analyzed using a theoretical model that quantified changes in the skin aqueous pore

  6. Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity: comparison of acute corneal barrier dysfunction induced by travoprost Z and travoprost.

    PubMed

    Uematsu, Masafumi; Kumagami, Takeshi; Shimoda, Kenichiro; Kusano, Mao; Teshima, Mugen; To, Hideto; Kitahara, Takashi; Kitaoka, Takashi; Sasaki, Hitoshi

    2011-10-01

    To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives. Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay. Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC. Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.

  7. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

    PubMed Central

    Awad, Wageha A.; Hess, Claudia; Hess, Michael

    2017-01-01

    Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens

  8. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens.

    PubMed

    Awad, Wageha A; Hess, Claudia; Hess, Michael

    2017-02-10

    Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird's health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction's molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as "leaky gut". A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can

  9. Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis

    PubMed Central

    van den Bogaard, Ellen H.; Bergboer, Judith G.M.; Vonk-Bergers, Mieke; van Vlijmen-Willems, Ivonne M.J.J.; Hato, Stanleyson V.; van der Valk, Pieter G.M.; Schröder, Jens Michael; Joosten, Irma; Zeeuwen, Patrick L.J.M.; Schalkwijk, Joost

    2013-01-01

    Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte–mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine–mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD. PMID:23348739

  10. Spin orbit splitting of the photon induced Fano resonance in an oscillating graphene electrostatic barrier

    SciTech Connect

    Biswas, R.; Sinha, C.

    2014-04-07

    We investigate theoretically the effect of a time dependent oscillating potential on the transport property of the Dirac Fermion through a monolayer graphene electrostatic barrier under the influence of the Rashba spin orbit interaction. The time dependent problem is solved in the frame work of the non-perturbative Floquet approach. It is noted that the dynamic condition of the barrier may be controlled by tuning the Rashba parameter. Introduction of the spin orbit interaction causes splitting of the Fano resonance (FR), a characteristic feature in photon assisted tunneling. The separation between the spin split FR's gives an indirect measure of the fine structure of the quasi-hole bound state inside the barrier. The present findings on the Rashba splitting of the FR and its external control by tuning the oscillating field parameters might have potential for applications in spintronic devices, especially in the spin field effect transistors. The spin polarization of different Floquet sidebands is found to be quite sensitive to the spin-pseudospin interaction.

  11. SEEPAGE, a new MODFLOW DRAIN package.

    PubMed

    Batelaan, O; De Smedt, F

    2004-01-01

    The prediction of the location of ground water discharge areas is a key aspect for the protection and (re)development of ground water-dependent wetlands. Ground water discharge areas can be simulated with MODFLOW using the DRAIN package by setting the drain level equal to the topography, while the conductance is mostly set to an arbitrary high value. However, conceptual and practical problems arise in the calculation of the ground water discharge by the DRAIN package as calculated water tables above the land surface, difficult parameterization of the conductance, and large water balance errors. To overcome these problems, a new SEEPAGE package for MODFLOW is proposed. The basic idea of this package is an adaptable constant head cell. It has a variable head, unless the ground water rises above the seepage level, in which case it has a constant head cell. The estimation of the ground water discharge location along a homogeneous, isotropic, linear sloping profile is used to verify the model and to compare it to the DRAIN solution. In an application to three basins in Belgium, it is shown that the SEEPAGE package can be used in combination with the DRAIN package in situations where an upper boundary for a free water table and additional resistance for drainage is required. It is clearly demonstrated that the identification and delineation of regional ground water discharge areas is more accurate using the SEEPAGE package.

  12. Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo.

    PubMed

    He, Shasha; Liu, Fenghua; Xu, Lei; Yin, Peng; Li, Deyin; Mei, Chen; Jiang, Linshu; Ma, Yunfei; Xu, Jianqin

    2016-01-01

    Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague-Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction.

  13. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers

    PubMed Central

    Váradi, Judit; Harazin, András; Fenyvesi, Ferenc; Réti-Nagy, Katalin; Gogolák, Péter; Vámosi, György; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Vasvári, Gábor; Róka, Eszter; Haines, David; Deli, Mária A.; Vecsernyés, Miklós

    2017-01-01

    Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB) was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines. PMID:28103316

  14. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress

    PubMed Central

    Tong, Ling-chang; Wang, Yue; Wang, Zhi-bin; Liu, Wei-ye; Sun, Sheng; Li, Ling; Su, Ding-feng; Zhang, Li-chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7–14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  15. Cytokine expression and barrier disruption in human corneal epithelial cells induced by alarmin released from necrotic cells.

    PubMed

    Fukuda, Ken; Ishida, Waka; Miura, Yusaku; Kishimoto, Tatsuma; Fukushima, Atsuki

    2017-07-19

    Dying cells release endogenous molecules known as alarmins that signal danger to surrounding tissue. We investigated the effects of necrotic cell-derived alarmins on cytokine expression and barrier function in human corneal epithelial cells. The release of interleukin (IL)-6 and IL-8 from immortalized human corneal epithelial (HCE) cells in culture was measured with enzyme-linked immunosorbent assays. The abundance of IL-6 and 8 mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analysis. Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular localization of the p65 subunit of the transcription factor NF-κB was determined by immunofluorescence analysis, and phosphorylation of the endogenous NF-κB inhibitor IκBα was examined by immunoblot analysis. A necrotic cell supernatant prepared from HCE cells induced the up-regulation of IL-6 and 8 expression at both mRNA and protein levels as well as reduced TER in intact HCE cells. Among alarmins tested, only IL-1α (not IL-33 or HMGB1) mimicked these effects of the necrotic cell supernatant. Furthermore, IL-1 receptor antagonist (IL-1RA) and neutralizing antibodies to IL-1α (but not those to IL-1β) each attenuated the effects of the necrotic cell supernatant. Exposure of HCE cells to the necrotic cell supernatant also induced the phosphorylation and degradation of IκBα as well as translocation of the p65 subunit of NF-κB to the nucleus. IL-1α released from necrotic corneal epithelial cells may trigger inflammatory responses at the ocular surface, including cytokine production and barrier disruption.

  16. 21 CFR 868.5995 - Tee drain (water trap).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tee drain (water trap). 868.5995 Section 868.5995...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5995 Tee drain (water trap). (a) Identification. A tee drain (water trap) is a device intended to trap and drain water that collects in...

  17. 21 CFR 868.5995 - Tee drain (water trap).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tee drain (water trap). 868.5995 Section 868.5995...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5995 Tee drain (water trap). (a) Identification. A tee drain (water trap) is a device intended to trap and drain water that collects in...

  18. 3. DRAINING & DRYING BUILDING, REINFORCED CONCRETE MUSHROOM COLUMNS WITH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DRAINING & DRYING BUILDING, REINFORCED CONCRETE MUSHROOM COLUMNS WITH DROP PANELS SUPPORTING DRAINING BINS (IRON VALVES OF DRAINING BINS ARE EMBEDDED IN THE CEILING), VIEW LOOKING WEST - Mill "C" Complex, Sand Draining & Drying Building, South of Dee Bennet Road, near Illinois River, Ottawa, La Salle County, IL

  19. 7 CFR 52.3755 - Minimum drained weights.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Ripe Olives 1 Product Description, Types, Styles, and Grades § 52.3755 Minimum drained weights. (a... drained weight of canned ripe olives is determined by emptying the contents of the container upon a U.S... allow to drain for 2 minutes. The weight of drained olives is the weight of the sieve and product...

  20. 7 CFR 52.3755 - Minimum drained weights.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Ripe Olives 1 Product Description, Types, Styles, and Grades § 52.3755 Minimum drained weights. (a... drained weight of canned ripe olives is determined by emptying the contents of the container upon a U.S... allow to drain for 2 minutes. The weight of drained olives is the weight of the sieve and product...

  1. 14 CFR 23.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 23.1021 Section 23.1021... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Oil System § 23.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each...

  2. 14 CFR 125.159 - Vent and drain lines.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Vent and drain lines. 125.159 Section 125... Requirements § 125.159 Vent and drain lines. All vent and drain lines, and their fittings, that are located in... Administrator finds that the rupture or breakage of any vent or drain line may result in a fire hazard. ...

  3. 14 CFR 121.261 - Vent and drain lines.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Vent and drain lines. 121.261 Section 121... drain lines. All vent and drain lines and their fittings, that are located in a designated fire zone... the rupture or breakage of any vent or drain line may result in a fire hazard. ...

  4. 21 CFR 868.5995 - Tee drain (water trap).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tee drain (water trap). 868.5995 Section 868.5995...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5995 Tee drain (water trap). (a) Identification. A tee drain (water trap) is a device intended to trap and drain water that collects in...

  5. 21 CFR 868.5995 - Tee drain (water trap).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tee drain (water trap). 868.5995 Section 868.5995...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5995 Tee drain (water trap). (a) Identification. A tee drain (water trap) is a device intended to trap and drain water that collects in...

  6. Partial hepatectomy aggravates cyclosporin A-induced neurotoxicity by lowering the function of the blood-brain barrier in mice.

    PubMed

    Yamauchi, Atsushi; Dohgu, Shinya; Takata, Fuyuko; Watanabe, Takuya; Nishioku, Tsuyoshi; Matsumoto, Junich; Ohkubo, Yuka; Shuto, Hideki; Kataoka, Yasufumi

    2011-03-14

    Cyclosporin A, a calcineurin inhibitor, produces neurotoxicity with relatively high frequency in organ-transplanted patients. The aim of the present study was to clarify whether acute liver failure (ALF) simulated to the transient liver dysfunction at an early phase after liver transplantation increases the susceptibility to cyclosporin A-induced neurotoxicity through the blood-brain barrier (BBB) dysfunction. The right internal, left lateral and left internal lobes in male ddy mice were surgically excised under sodium pentobarbital anesthesia. Effect of cyclosporin A on harmine-induced tremors was examined and BBB permeability to (3)[H]cyclosporin A was assessed in partially (70%) hepatectomized mice at postoperative days 1, 3 and 7. Patrial hepatectomy aggravated harmine-induced tremors. Cyclosporin A (50mg/kg, i.p.) markedly augmented harmine-induced tremors in partially hepatectomized mice at postoperative day 1. Consistent with these behavioral findings, the brain uptake of (3)[H]cyclosporin A in mice injected with (3)[H]cyclosporin A into the jugular vein at postoperative day 1 was significantly increased by partial hepatectomy compared with sham operation. Our results indicate that ALF increases BBB permeability to cyclosporin A by lowering the function of P-glycoprotein and tight junctions, consequently leading to augmentation of cyclosporin A-induced neurotoxicity. The possibility that cyclosporin A increases the risk of neurotoxicity including tremors at an early phase of liver transplantation must be considered. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers.

    PubMed

    Elamin, Elhaseen E; Masclee, Ad A; Dekker, Jan; Pieters, Harm-Jan; Jonkers, Daisy M

    2013-12-01

    Short-chain fatty acids (SCFAs) have been shown to promote intestinal barrier function, but their protective effects against ethanol-induced intestinal injury and underlying mechanisms remain essentially unknown. The aim of the study was to analyze the influence of SCFAs on ethanol-induced barrier dysfunction and to examine the role of AMP-activated protein kinase (AMPK) as a possible mechanism using Caco-2 monolayers. The monolayers were treated apically with butyrate (2, 10, or 20 mmol/L), propionate (4, 20, or 40 mmol/L), or acetate (8, 40, or 80 mmol/L) for 1 h before ethanol (40 mmol/L) for 3 h. Barrier function was analyzed by measurement of transepithelial resistance and permeation of fluorescein isothiocyanate-labeled dextran. Distribution of the tight junction (TJ) proteins zona occludens-1, occludin, and filamentous-actin (F-actin) was examined by immunofluorescence. Metabolic stress was determined by measuring oxidative stress, mitochondrial function, and ATP using dichlorofluorescein diacetate, dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, and bioluminescence assay, respectively. AMPK was knocked down by small interfering RNA (siRNA), and its activity was assessed by a cell-based ELISA. Exposure to ethanol significantly impaired barrier function compared with controls (P < 0.0001), disrupted TJ and F-actin cytoskeleton integrity, and induced metabolic stress. However, pretreatment with 2 mmol/L butyrate, 4 mmol/L propionate, and 8 mmol/L acetate significantly alleviated the ethanol-induced barrier dysfunction, TJ and F-actin disruption, and metabolic stress compared with ethanol-exposed monolayers (P < 0.0001). The promoting effects on barrier function were abolished by inhibiting AMPK using either compound C or siRNA. These observations indicate that SCFAs exhibit protective effects against ethanol-induced barrier disruption via AMPK activation, suggesting a potential for SCFAs as prophylactic and/or therapeutic factors against ethanol-induced

  8. Deformation and orientation effects in the decay of 268Sg* formed in a 30Si-induced reaction across the Coulomb barrier

    NASA Astrophysics Data System (ADS)

    Sandhu, Kirandeep; Sharma, Manoj K.; Gupta, Raj K.

    2012-12-01

    The dynamical cluster decay model (DCM) is used to study the decay of the 268Sg* compound nucleus formed in the 30Si+238U reaction at above and below the Coulomb barrier energies. The neutron evaporation residues and fission cross sections are calculated in reference to the available data, including β2i-static deformations with ‘optimum' orientations. The role of spherical and the β2i-dynamic deformed choices of fragmentation are also studied explicitly at the highest 169 MeV energy. The fission fragment distribution is symmetric at above-barrier energies, where equatorial collisions are preferred, but becomes asymmetric when the nuclei approach in pole-to-pole configuration at sub-barrier energies. Therefore, at above-barrier energies the calculations are carried out by considering ‘hot fusion', equatorial collisions, whereas at sub-barrier energies the ‘cold fusion', polar configuration is considered. The asymmetric peaks at sub-barrier energies may be associated with some competing process, like quasifission. The analysis of polar and equatorial configurations suggests that larger barrier modification is required at sub-barrier energies for neutron evaporation residue and fission fragments, i.e., the contribution of barrier modification at sub-barrier energies is relatively higher for a cold elongated polar configuration as compared to a hot compact equatorial configuration. Finally, the potential energies surfaces for the Si-induced reaction are compared with the S-induced reaction on the 238U target, at comparable center of mass energies.

  9. Dressings and drains in posterior spine surgery and their effect on wound complications.

    PubMed

    Andrew Glennie, R; Dea, Nicolas; Street, John T

    2015-07-01

    The purpose of this study was to systematically search, critically appraise and summarize published randomized control trials (RCT) and non-RCT examining the effect of drains and dressings on wound healing rates and complications in posterior spine surgery. The use of post-operative drains and the type of post-operative dressing is at the discretion of the treating surgeon with no available clinical guidelines. Drains will theoretically decrease incidence of post-operative hematoma and therefore, potentially decrease the risk of neurologic compromise when the neural elements have been exposed. Occlusive dressings have more recently been advocated, potentially maintaining a sterile barrier for longer time periods post-operatively. A systematic review of databases from 1969-2013 was undertaken. All papers examining drains in spine surgery and dressings in primary healing of surgical wounds were included. Revman (version 5.2; The Nordic Cochrane Centre, The Cochrane Collaboration, Oxford, UK) was used to test for overall treatment effect, clinical heterogeneity and risk of bias. Of the papers identified, 1348 examined post-operative drains in spine surgery and 979 wound dressings for primary wound healing of all surgical wounds. Seven studies were included for analysis for post-operative drains and 10 studies were analyzed for primary wound healing. The use of a post-operative drain did not influence healing rates and had no effect secondarily on infection (odds ratio [OR] 1.33; 95% confidence interval [CI] 0.76-2.30). We were not able to establish whether surgical drains prevent hematomas causing neurologic compromise. There was a slight advantage to using occlusive dressings versus non-occlusive dressings in wound healing (OR 2.09; 95% CI 1.44-3.02). Incisional vacuum dressings as both an occlusive barrier and superficial drainage system have shown promise for wounds at risk of dehiscence. There is a relatively high risk of bias in the methodology of many of the

  10. Blood-brain barrier dysfunction-induced inflammatory signaling in brain pathology and epileptogenesis.

    PubMed

    Kim, Soo Young; Buckwalter, Marion; Soreq, Hermona; Vezzani, Annamaria; Kaufer, Daniela

    2012-11-01

    The protection of the brain from blood-borne toxins, proteins, and cells is critical to the brain's normal function. Accordingly, a compromise in the blood-brain barrier (BBB) function accompanies many neurologic disorders, and is tightly associated with brain inflammatory processes initiated by both infiltrating leukocytes from the blood, and activation of glial cells. Those inflammatory processes contribute to determining the severity and prognosis of numerous neurologic disorders, and can both cause, and result from BBB dysfunction. In this review we examine the role of BBB and inflammatory responses, in particular activation of transforming grown factor β (TGFβ) signaling, in epilepsy, stroke, and Parkinson's disease.

  11. Electrostatic potential barrier for electron emission at graphene edges induced by the nearly free electron states

    NASA Astrophysics Data System (ADS)

    Gao, Yanlin; Okada, Susumu

    2017-05-01

    Using the density functional theory, we studied the electronic structures of zigzag graphene nanoribbons with hydroxyl, H, ketone, aldehyde, or carboxyl terminations under a lateral electric field. The critical electric field for electron emission is proportional to the work function of the functionalized edges except the hydroxylated edge, which leads to the anomalous electric field outside the edge, owing to the electrons in the nearly free electron (NFE) state in the vacuum region. The strong electric field also causes a potential barrier for the electron emission from the H-terminated edge owing to the downward shift of the NFE state.

  12. Analysis of {alpha}-induced reactions on {sup 151}Eu below the Coulomb barrier

    SciTech Connect

    Avrigeanu, V.; Avrigeanu, M.

    2011-01-15

    Novel measurements of ({alpha},{gamma}) and ({alpha},n) reaction cross sections on the target nucleus {sup 151}Eu, close to the reaction thresholds, support the choice of recently proposed parameters of the {alpha}-particle optical model potential below the Coulomb barrier. A better understanding of the {alpha}-particle optical potential at these energies leads to a statistical model analysis of additional partial cross sections that were measured but not considered within a former model analysis. On this basis we have tentatively assigned a modified J{sup {pi}}=9{sup -} spin and parity to the 22.7-h isomer in {sup 154}Tb.

  13. A novel buried-drain DMOSFET structure

    NASA Astrophysics Data System (ADS)

    Fichtner, W.; Cooper, J. A., Jr.; Tretola, A. R.; Kahng, D.

    1982-11-01

    A novel buried-drain MOSFET (BDMOS) structure is presented which utilizes a double-implanted source region to achieve short-channel lengths. The fabrication sequence of a six-mask silicon-gate process shows the highlights of this new technology. Strong emphasis has been given on using process and device simulation tools, in order to optimize device performance. Experimental results on fabricated devices with source-drain distances between 0.5 and 3 microns and active channel lengths of 0.25 micron show the inherent potential of this new structure.

  14. VEGF-A165 potently induces human blood-nerve barrier endothelial cell proliferation, angiogenesis and wound healing in vitro

    PubMed Central

    Reddy, Chetan Lakshmana; Yosef, Nejla; Ubogu, Eroboghene E.

    2013-01-01

    Several mitogens such as vascular endothelial growth factor (VEGF) have been implicated in mammalian vascular proliferation and repair. However, the molecular mediators of human blood-nerve barrier (BNB) development and specialization are unknown. Primary human endoneurial endothelial cells (pHEndECs) were expanded in vitro and specific mitogen receptors detected by western blot. pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin. Non-radioactive cell proliferation, Matrigel™-induced angiogenesis and sterile micropipette injury wound healing assays were performed. Proliferation rates, number and total length of induced microvessels and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions. VEGF-A165 in the presence of heparin, was the most potent inducer of pHEndEC proliferation, angiogenesis and wound healing in vitro. 1.31 nM VEGF-A165 induced ~110% increase in cell proliferation relative to basal conditions (~51% without heparin). 2.62 pM VEGF-A165 induced a 3-fold increase in mean number of microvessels and 3.9-fold increase in total capillary length/field relative to basal conditions. In addition, 0.26 nM VEGF-A165 induced ~1.3-fold increased average rate of endothelial wound healing 4–18 hours after endothelial monolayer injury, mediated by increased cell migration. VEGF-A165 was the only mitogen capable of complete wound closure, occurring within 30 hours following injury via increased cell proliferation. This study demonstrates that VEGF-A165, in the presence of heparin, is a potent inducer of pHEndEC proliferation, angiogenesis and wound healing in vitro. VEGF-A165 may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injury. PMID:23712256

  15. CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

    PubMed

    Anidi, Ifeanyi U; Servinsky, Laura E; Rentsendorj, Otgonchimeg; Stephens, R Scott; Scott, Alan L; Pearse, David B

    2013-01-01

    Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT) and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb) compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS). To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC) from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER) from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our results demonstrate

  16. Photon induced Schottky barrier effects in inverse-extraordinary optoconductance structures

    NASA Astrophysics Data System (ADS)

    Tran, L.; Solin, S. A.; Gilbertson, A.; Cohen, L. F.

    2013-12-01

    We expand upon our previous work and characterize the photo-dependence of the effective Schottky barrier in EOC and I-EOC heterostructures by measuring the open circuit voltage and the change in the reverse bias resistance. Under full illumination by a 5 mW, 632.8 nm HeNe laser, the barrier is effectively eliminated and the Ti-GaAs interface becomes Ohmic. The reverse bias resistance changes by a factor of 209 over an illumination intensity change of 10-5:1. While this work illustrates the behavior of the Schottky interface upon illumination, it also demonstrates the effectiveness of the four-point, van der Pauw measurement fundamental to EOC/I-EOC phenomena at monitoring changes in the active region of the mesa. The resistance is largely unaffected by the photovoltaic, DC offset of the surrounding leads, as indicated by the radial symmetry of 2-D resistance maps obtained by rastering the laser across EOC/IEOC devices.

  17. The GaN/noble metal interface: metal induced gap states and Schottky barrier heights

    NASA Astrophysics Data System (ADS)

    Picozzi, Silvia; Continenza, Alessandra; Satta, Guido; Massidda, Sandro; Freeman, Arthur J.

    2000-03-01

    We present ab-initio FLAPW (E. Wimmer, H. Krakauer, M. Weinert and A.J. Freeman, Phys. Rev. B 24), 864 (1981) calculations on N-terminated [001] ordered GaN/Ag and GaN/Au interfaces. Our results show that the density of gap states is appreciable in the interface semiconductor layer; however, the gap states are efficiently screened and become negligible already in the sub-interface layer. The gap states' decay length in the semiconductor side is about 2.0 ± 0.1 Å\\: and seems to be independent of the deposited metal, therefore being, to a good approximation, a bulk GaN property. Our estimated Schottky barrier heights for the GaN/noble-metal interfaces are both smaller than that of the GaN/Al barrier, showing a large dispersion in the values - which seems to exclude the possibility of a Fermi level pinning within the gap. Finally, we investigate the role of atomic positions and of different chemical species at the interface region in determining the final value of the potential line-up.

  18. Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier

    SciTech Connect

    Zlokovic, B.V.; Segal, M.B.; Davson, H.; Jankov, R.M.

    1988-05-01

    Unidirectional flux of /sup 125/I-labeled DSIP at the blood-tissue interface of the blood-cerebrospinal fluid (CSF) barrier was studied in the perfused in situ choroid plexuses of the lateral ventricles of the sheep. Arterio-venous loss of /sup 125/I-radioactivity suggested a low-to-moderate permeability of the choroid epithelium to the intact peptide from the blood side. A saturable mechanism with Michaelis-Menten type kinetics with high affinity and very low capacity (approximate values: Kt = 5.0 +/- 0.4 nM; Vmax = 272 +/- 10 fmol.min-1) was demonstrated at the blood-tissue interface of the choroid plexus. The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

  19. Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood-brain barrier.

    PubMed

    Toborek, Michal; Seelbach, Melissa J; Rashid, Cetewayo S; András, Ibolya E; Chen, Lei; Park, Minseon; Esser, Karyn A

    2013-06-24

    There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood-brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock lab™ Analysis software. Controls included mice sedentary that did not have access to running wheels and/or injections with saline. METH induced oxidative stress in brain microvessels, resulting in up regulation of caveolae-associated NAD(P)H oxidase subunits, and phosphorylation of mitochondrial protein 66Shc. Treatment with METH disrupted also the expression and colocalization of tight junction proteins. Importantly, exercise markedly attenuated these effects and protected against METH-induced disruption of the BBB integrity. The obtained results indicate that exercise is an important modifiable behavioral factor that can protect against METH-induced cerebrovascular toxicity. These findings may provide new strategies in preventing the toxicity of drug of abuse.

  20. Improving thrust by pulse-induced breakdown enhancement in AC surface dielectric barrier discharge actuators for airflow control

    NASA Astrophysics Data System (ADS)

    Yan, Huijie; Yang, Liang; Qi, Xiaohua; Ren, Chunsheng

    2016-07-01

    The characteristics of a plate-to-plate AC surface dielectric barrier discharge (SDBD) actuator using the pulse-induced breakdown enhancing method are experimentally investigated. The encapsulated electrode is supplied with a sine high AC voltage, while the exposed electrode is feed by a synchronized pulse voltage. Based on the thrust force and power consumption measurements, a parametric study was performed using a positive pulse applied at the trough phase of the AC cycles in which the thrust force was observed to increase by about 100% to 300% and the efficiency up to about 100% compared with the AC-only supply conditions for different AC voltages within the tested range. The pulse-induced breakdown effect was analyzed from the electrical and light emission waveforms to reveal the underlying mechanism. The surface potential due to the charge deposition effect was also measured using a specially designed corona-like discharge potential probe. It is shown that the pulse-induced breakdown was able to cause a temporarily intensified local electric field to enhance the glow-like discharge and meanwhile increase the time-average surface potential in the region further downstream. The improvement in the force by the enhancement in the pulse-induced breakdown was mainly due to enhancements in the glow-like discharge and the surface potential increment, with the latter being more important when the AC voltage is higher.

  1. Radiation induces progenitor cell death, microglia activation, and blood-brain barrier damage in the juvenile rat cerebellum

    PubMed Central

    Zhou, Kai; Boström, Martina; Ek, C. Joakim; Li, Tao; Xie, Cuicui; Xu, Yiran; Sun, Yanyan; Blomgren, Klas; Zhu, Changlian

    2017-01-01

    Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies. PMID:28382975

  2. Voluntary exercise protects against methamphetamine-induced oxidative stress in brain microvasculature and disruption of the blood–brain barrier

    PubMed Central

    2013-01-01

    Background There is no effective therapeutic intervention developed targeting cerebrovascular toxicity of drugs of abuse, including methamphetamine (METH). We hypothesize that exercise protects against METH-induced disruption of the blood–brain barrier (BBB) by enhancing the antioxidant capacity of cerebral microvessels and modulating caveolae-associated signaling. Mice were subjected to voluntary wheel running for 5 weeks resembling the voluntary pattern of human exercise, followed by injection with METH (10 mg/kg). The frequency, duration, and intensity of each running session were monitored for each mouse via a direct data link to a computer and the running data are analyzed by Clock lab™ Analysis software. Controls included mice sedentary that did not have access to running wheels and/or injections with saline. Results METH induced oxidative stress in brain microvessels, resulting in up regulation of caveolae-associated NAD(P)H oxidase subunits, and phosphorylation of mitochondrial protein 66Shc. Treatment with METH disrupted also the expression and colocalization of tight junction proteins. Importantly, exercise markedly attenuated these effects and protected against METH-induced disruption of the BBB integrity. Conclusions The obtained results indicate that exercise is an important modifiable behavioral factor that can protect against METH-induced cerebrovascular toxicity. These findings may provide new strategies in preventing the toxicity of drug of abuse. PMID:23799892

  3. Contrast-Enhanced Ultrasound Imaging for the Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening

    PubMed Central

    Fan, Ching-Hsiang; Lin, Wun-Hao; Ting, Chien-Yu; Chai, Wen-Yen; Yen, Tzu-Chen; Liu, Hao-Li; Yeh, Chih-Kuang

    2014-01-01

    The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately, direct ultrasound imaging of BBB opening with MBs as contrast agent is not feasible, due to the inability of MBs to penetrate brain parenchyma. However, FUS-induced BBB opening is accompanied by changes in blood flow and perfusion, suggesting the possibility of perfusion-based ultrasound imaging. Here we evaluated the use of MB destruction-replenishment, which was originally developed for analysis of ultrasound perfusion kinetics, for verifying and quantifying FUS-induced BBB opening. MBs were intravenously injected and the BBB was disrupted by 2 MHz FUS with burst-tone exposure at 0.5-0.7 MPa. A perfusion kinetic map was estimated by MB destruction-replenishment time-intensity curve analysis. Our results showed that the scale and distribution of FUS-induced BBB opening could be determined at high resolution by ultrasound perfusion kinetic analysis. The accuracy and sensitivity of this approach was validated by dynamic contrast-enhanced MRI. Our successful demonstration of ultrasound imaging to monitor FUS-induced BBB opening provides a new approach to assess FUS-dependent brain drug delivery, with the benefit of high temporal resolution and convenient integration with the FUS device. PMID:25161701

  4. Source/drain technologies for the scaling of nanoscale CMOS device

    NASA Astrophysics Data System (ADS)

    Song, Yi; Zhou, Huajie; Xu, Qiuxia

    2011-02-01

    Continuous shrinking CMOS device into 21 nm technology node is facing fundamental challenges. The International Technology Roadmap for Semiconductors (ITRS) forecasts specific requirements to realize acceptable CMOS performance for the semiconductor industry. The innovations of various source/drain technologies are considered to be indispensable for the continuous scaling of CMOS device due to the requirements of high-performance and effective suppression of short channel effects. One of the key points is to realize ultra-shallow junction with steep concentration profile and low resistivity. There are many innovative solutions including advanced doping technologies and annealing technologies for ultra-shallow junction formation. Additionally, new source/drain structures such as raised source/drain and Schottky barrier metal source/drain, and advanced silicidation technologies also serve as the important options. The state-of-the-arts of these new technologies are extensively discussed from the view point of technical innovation and performance gain. Source/drain technologies are promising and active areas of device research down to 21 nm technology node and even beyond.

  5. Comparison of Postoperative Drain Insertion versus No Drain Insertion in Thyroidectomies

    PubMed Central

    Al-Habsi, Asma S.; Al-Sulaimani, Al-Anood K.; Taqi, Kadhim M.; Al-Qadhi, Hani A.

    2016-01-01

    Objectives A thyroidectomy is a frequently performed surgical procedure which can result in life-threatening complications. The insertion of a drain after a thyroidectomy has been suggested to prevent such complications. This study aimed to evaluate the use of surgical drains following thyroidectomies in relation to postoperative complications and mass sizes. Methods This retrospective case-control study included all thyroidectomies conducted at the Sultan Qaboos University Hospital, Muscat, Oman, from January 2011 to December 2013. Length of hospital stay, readmission, postoperative complications and mass size were evaluated. Results During the study period, 250 surgeries were carried out on 241 patients. The majority of patients were female (87.2%). Drains were inserted postoperatively after 202 surgeries (80.8%) compared to 48 surgeries (19.2%) without drains. A total of 32 surgeries (12.8%) were conducted on patients with thyroid masses <1 cm, 138 (55.2%) on those with masses between 1–4 cm and 80 (32.0%) on those with masses >4 cm. The association between drain use and mass size was not significant (P = 0.439). Although postoperative complications were more prevalent in patients with drains, the relationship between these factors was not significant (P >0.050). Length of hospital stay was significantly longer among patients with postoperative drains (P <0.010). Conclusion The routine insertion of drains after thyroid surgeries was found to result in longer hospital stays and did not reduce rates of post-thyroidectomy complications. Thyroid mass size should not be used as an indicator for the insertion of a drain after thyroidectomy. PMID:28003893

  6. Intentionally induced intestinal barrier dysfunction causes inflammation, affects metabolism, and reduces productivity in lactating Holstein cows.

    PubMed

    Kvidera, S K; Dickson, M J; Abuajamieh, M; Snider, D B; Fernandez, M V Sanz; Johnson, J S; Keating, A F; Gorden, P J; Green, H B; Schoenberg, K M; Baumgard, L H

    2017-03-22

    Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes. During period 2, control cows receiving sterile saline were pair-fed (PF) to the GSI-treated cows, and all cows were killed at the end of period 2. Administering GSI increased goblet cell area 218, 70, and 28% in jejunum, ileum, and colon, respectively. In the jejunum, GSI-treated cows had increased crypt depth and reduced villus height, villus height-to-crypt depth ratio, cell proliferation, and mucosal surface area. Plasma lipopolysaccharide binding protein increased with time, and tended to be increased 42% in GSI-treated cows relative to PF controls on d 5 to 7. Circulating haptoglobin and serum amyloid A concentrations increased (585- and 4.4-fold, respectively) similarly in both treatments. Administering GSI progressively reduced dry matter intake (66%) and, by design, the pattern and magnitude of decreased nutrient intake was similar in PF controls. A similar progressive decrease (42%) in milk yield occurred in both treatments, but we observed no treatment effects on milk components. Cows treated with GSI tended to have increased plasma insulin (68%) and decreased circulating nonesterified fatty acids (29%) compared with PF cows. For both treatments, plasma glucose decreased with time while β-hydroxybutyrate progressively increased. Liver triglycerides increased 221% from period 1 to sacrifice in both treatments. No differences were

  7. Src tyrosine kinase regulates the stem cell factor–induced breakdown of the blood–retinal barrier

    PubMed Central

    Im, Ji-Eun; Song, Sun-Hwa

    2016-01-01

    Purpose Stem cell factor (SCF) has been recently acknowledged as a novel endothelial permeability factor. However, the mechanisms by which SCF-induced activation of the SCF cognate receptor, cKit, enhances endothelial permeability have not been fully elucidated. This study aimed to investigate the role of Src in SCF-induced breakdown of the blood–retinal barrier (BRB). Methods In vitro endothelial permeability and in vivo retinal vascular permeability assays were performed to investigate the role of Src in SCF-induced breakdown of the BRB. Immunofluorescence staining experiments were performed to analyze the cellular distribution of phosphorylated Src and vascular endothelial (VE)-cadherin. Results SCF markedly reduced electric resistance across the human retinal vascular endothelial monolayer in vitro and enhanced extravasation of dyes in murine retinal vasculature in vivo. Inhibition of cKit activation using cKit mutant mice and chemical inhibitor substantially diminished the ability of SCF to increase endothelial permeability and retinal vascular leakage. In human retinal vascular endothelial cells, SCF induced strong phosphorylation of Src and distinct localization of phosphorylated Src in the plasma membrane. Inhibition of Src activation using chemical inhibitors abolished the SCF-induced hyperpermeability of human retinal vascular endothelial cells and retinal vascular leakage in mice. In addition, treatment with Src inhibitors restored junctional expression of VE-cadherin that disappeared in SCF-treated retinal endothelial cells and retinal vasculature. Conclusions These results showed the important role of Src in mediating SCF-induced breakdown of the BRB and retinal vascular leakage. Given that increased retinal vascular permeability is a common manifestation of various ocular diseases, the SCF/cKit/Src signaling pathway may be involved in the development of the hyperpermeable retinal vasculature in many ocular disorders. PMID:27746675

  8. UPA Fill Drain Valve Modification kit installation

    NASA Image and Video Library

    2016-01-25

    ISS046e023885 (01/25/2016) --- NASA astronaut Tim Kopra performs regular maintenance on the Urine Processing Assembly (UPA) aboard the International Space Station. The UPA is used by the crew to recycle water for use on the station. The image shows Tim replacing the brine filter from the UPA Fill Drain Valve enclosure.

  9. Effects of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on blood-brain barrier and dopaminergic neurons of rats with lipopolysaccharide-induced Parkinson's disease.

    PubMed

    Wu, Xiao-li; Wang, Ping; Liu, Yun-hui; Xue, Yi-xue

    2014-05-01

    Neuro-inflammation and dysfunction of blood-brain barrier play an important role in the occurrence, development, and neuronal degeneration of Parkinson's disease (PD). Studies have demonstrated that a variety of cytokines such as TNF-α and IL-1β destroy the structure and function of blood-brain barrier. The damage to blood-brain barrier results in death of dopaminergic neurons, while protection of blood-brain barrier slows down the progression of PD. Also, it has been shown that activation of poly (ADP-ribose) polymerase (PARP) plays an important role in causing damage to blood-brain barrier. In addition, the PARP inhibitor 3-AB has been shown to protect blood-brain barrier from damage and has neuroprotective effects. In this study, using a lipopolysaccharide (LPS)-induced PD rat model, we investigated whether 3-AB protects blood-brain barrier and dopaminergic neurons from functional damage. LPS significantly increased Evans blue content in the substantia nigra which peaked at 12 h, while administration of 3-AB significantly inhibited the LPS-induced increase in Evans blue content and also significantly increased the expression of the tight junction-associated proteins claudin-5, occludin and ZO-1. 3-AB also increased the number of tyrosine hydroxylase positive cells and reduced the IL-1β and TNF-α content significantly. According to western blot analysis, 3-AB significantly reduced the p-ERK1/2 expression, while the expression of p-p38MAPK increased. These results suggest that 3-AB protects the blood-brain barrier from functional damage in an LPS-induced PD rat model and dopaminergic neurons are protected from degeneration by upregulation of tight junction-associated proteins. These protective effects of 3-AB may be related to modulation of the ERK1/2 pathway.

  10. Dielectric Barrier Discharge Plasma-Induced Photocatalysis and Ozonation for the Treatment of Wastewater

    NASA Astrophysics Data System (ADS)

    Mok, Young Sun; Jo, Jin-Oh; Lee, Heon-Ju

    2008-02-01

    The physicochemical processes of dielectric barrier discharge (DBD) such as in-situ formation of chemically active species and emission of ultraviolet (UV)/visible light were utilized for the treatment of a simulated wastewater formed with Acid Red 4 as the model organic contaminant. The chemically active species (mostly ozone) produced in the DBD reactor were well distributed in the wastewater using a porous gas diffuser, thereby increasing the gas-liquid contact area. For the purpose of making the best use of the light emission, a titanium oxide-based photocatalyst was incorporated in the wastewater treating system. The experimental parameters chosen were the voltage applied to the DBD reactor, the initial pH of the wastewater, and the concentration of hydrogen peroxide added to the wastewater. The results have clearly shown that the present system capable of degrading organic contaminants in two ways (photocatalysis and ozonation) may be a promising wastewater treatment technology.

  11. Ultrathin epitaxial barrier layer to avoid thermally induced phase transformation in oxide heterostructures

    SciTech Connect

    Baek, David J.; Lu, Di; Hikita, Yasuyuki; Hwang, Harold Y.; Kourkoutis, Lena F.

    2016-12-22

    Incorporating oxides with radically different physical and chemical properties into heterostructures offers tantalizing possibilities to derive new functions and structures. Recently, we have fabricated freestanding 2D oxide membranes using the water-soluble perovskite Sr3Al2O6 as a sacrificial buffer layer. Here, with atomic-resolution spectroscopic imaging, we observe that direct growth of oxide thin films on Sr3Al2O6 can cause complete phase transformation of the buffer layer, rendering it water-insoluble. More importantly, we demonstrate that an ultrathin SrTiO3 layer can be employed as an effective barrier to preserve Sr3Al2O6 during subsequent growth, thus allowing its integration in a wider range of oxide heterostructures.

  12. Ultrathin epitaxial barrier layer to avoid thermally induced phase transformation in oxide heterostructures

    DOE PAGES

    Baek, David J.; Lu, Di; Hikita, Yasuyuki; ...

    2016-12-22

    Incorporating oxides with radically different physical and chemical properties into heterostructures offers tantalizing possibilities to derive new functions and structures. Recently, we have fabricated freestanding 2D oxide membranes using the water-soluble perovskite Sr3Al2O6 as a sacrificial buffer layer. Here, with atomic-resolution spectroscopic imaging, we observe that direct growth of oxide thin films on Sr3Al2O6 can cause complete phase transformation of the buffer layer, rendering it water-insoluble. More importantly, we demonstrate that an ultrathin SrTiO3 layer can be employed as an effective barrier to preserve Sr3Al2O6 during subsequent growth, thus allowing its integration in a wider range of oxide heterostructures.

  13. Effects of Barrier-Induced Nuclear Spin Magnetization Inhomogeneities on Diffusion-Attenuated MR Signal

    PubMed Central

    Sukstanskii, A.L.; Ackerman, J.J.H.; Yablonskiy, D.A.

    2007-01-01

    The spatial distribution of the transverse nuclear spin magnetization, appearing in a single compartment with impermeable boundaries in a Stejskal-Tanner gradient pulse MR experiment, is analyzed in detail. At short diffusion times the presence of diffusion-restrictive barriers (membranes) reduces effective diffusivity near the membranes and leads to an inhomogeneous spin magnetization distribution (the edge-enhancement effect). In this case, the signal reveals a quasi-two-compartment behavior and can be empirically modeled remarkably well by a biexponential function. The current results provide a framework for interpreting experimental MR data on various phenoma, including water diffusion in giant axons, metabolite diffusion in the brain, and hyperpolarized gas diffusion in lung airways. PMID:14523959

  14. Inducing injection barrier by covalent functionalization of multiwall carbon nanotubes acting as Moiré crystals

    NASA Astrophysics Data System (ADS)

    Bonnet, Roméo; Barraud, Clément; Martin, Pascal; Della Rocca, Maria Luisa; Lafarge, Philippe

    2016-10-01

    Covalent functionalization of multiwall carbon nanotubes is a direct method to suppress the conduction of the outermost shell, subject to interactions with the environment. The rehybridized sp3 external shell of the functionalized multiwall carbon nanotubes becomes naturally a hybrid injection barrier allowing the control of the contact resistances and the study of quantum transport in the more protected inner shells. Charge transport measurements performed on isolated multiwall carbon nanotubes of large diameter show an increase of the contact resistance and stabilization in the MΩ range. Electronic quantum properties of the inner shells are highlighted by the observation of superlattice structures in the conductance, recently attributed to the formation of a one-dimensional Moiré pattern.

  15. Absolute Cross Sections for Proton Induced Reactions on 147,149Sm Below the Coulomb Barrier

    NASA Astrophysics Data System (ADS)

    Gheorghe, I.; Filipescu, D.; Glodariu, T.; Bucurescu, D.; Cata-Danil, I.; Cata-Danil, G.; Deleanu, D.; Ghita, D.; Ivascu, M.; Lica, R.; Marginean, N.; Marginean, R.; Mihai, C.; Negret, A.; Sava, T.; Stroe, L.; Toma, S.; Sima, O.; Sin, M.

    2014-05-01

    Cross sections for 147,149Sm(p,n)147,149Eu and 147,149Sm(p, γ)148,150Eu were measured using the activation method. The results are compared to the predictions of the Hauser-Feshbach statistical model. Different γ-ray strength functions have been tested against the experimental values. In the case of 150Eu, in order to reproduce the experimental isomeric population cross sections, various scenarios for unknown branching ratios of certain discrete states have been discussed. The results provide constraints for the optical model parameters dedicated to this insufficiently known area of isotopes. Such cross sections for (p, γ) reactions at energies below the Coulomb barrier are valuable for p-process nucleosynthesis calculations.

  16. Ultrafine anaphase bridges, broken DNA and illegitimate recombination induced by a replication fork barrier

    PubMed Central

    Sofueva, Sevil; Osman, Fekret; Lorenz, Alexander; Steinacher, Roland; Castagnetti, Stefania; Ledesma, Jennifer; Whitby, Matthew C.

    2011-01-01

    Most DNA double-strand breaks (DSBs) in S- and G2-phase cells are repaired accurately by Rad51-dependent sister chromatid recombination. However, a minority give rise to gross chromosome rearrangements (GCRs), which can result in disease/death. What determines whether a DSB is repaired accurately or inaccurately is currently unclear. We provide evidence that suggests that perturbing replication by a non-programmed protein–DNA replication fork barrier results in the persistence of replication intermediates (most likely regions of unreplicated DNA) into mitosis, which results in anaphase bridge formation and ultimately to DNA breakage. However, unlike previously characterised replication-associated DSBs, these breaks are repaired mainly by Rad51-independent processes such as single-strand annealing, and are therefore prone to generate GCRs. These data highlight how a replication-associated DSB can be predisposed to give rise to genome rearrangements in eukaryotes. PMID:21576223

  17. Phytotoxicity induced in isolated zooxanthellae by herbicides extracted from Great Barrier Reef flood waters.

    PubMed

    Shaw, C M; Brodie, J; Mueller, J F

    2012-01-01

    To date there has been limited evidence anthropogenically sourced pollution from catchments reaching corals of the Great Barrier Reef (GBR). In this study, freshly isolated zooxanthellae were exposed to polar chemicals (chiefly herbicides) extracted from water samples collected in a flood plume in the GBR lagoon. Photosynthetic potential of the isolated zooxanthellae declined after exposure to concentrated extracts (10 times) from all but one of the sampling sites. Photosynthetic potential demonstrated a significant positive relationship with the concentration of diuron in the concentrated extracts and a significant inverse relationship with salinity measured at the sampling site. This study demonstrates that runoff from land based application of herbicides may reduce photosynthetic efficiency in corals of inshore reefs in the GBR. The ecological impacts of the chemicals in combination with other potential stressors on corals remain unclear. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Design and construction of a French drain for groundwater diversion in solid waste storage area six at the Oak Ridge National Laboratory

    SciTech Connect

    Davis, E.C.; Stansfield, R.G.

    1984-05-01

    Engineering modifiations or engineered barriers have been suggested as a possible means of improving the performance of low-level waste disposal sites located in the humid eastern United States. Design and construction of a passive French drain, located in Solid Waste Storage Area No. 6 at the Oak Ridge National Laboratory. The drain was designed to hydrologically isolate a 0.44-ha area that contains a group of 49 low-level waste trenches by separating it from upgradient groundwater recharge areas. The 252-m drain (maximum depth = 9 m) that surrounds the group of trenches on the north and east sides was excavated, lined with filter fabric, backfilled with crushed stone, and covered with a 0.6 m layer of excavated material at an estimated cost of $153,000. Of the 17 days it took to complete the work, about 5 days were spent excavating sidewall slide material that fell into the drain during excavation. Photography of the drain wall revealed the contorted structure of the weathered shale, which was responsible for many of the slides. Monitoring wells placed at intervals on the drain centerline indicate that groundwater is draining from the surrounding Maryville Formation (Conasauga Group); flows at catch basin No. 2 ranged from a base flow of 4 to 7 L/min to a maximum of 35 L/min, recorded on October 13. In response to groundwater flow in the drain, water levels in several monitoring wells adjacent to the drain have dropped by as much as 2.24 m to an elevation only slightly higher than the bottom of the French drain. In addition to the general lowering of the water table in the vicinity of the drain, water levels in three trenches began to subside, indicating that the drain is beginning to have an effect on the water in the trenches as well. Further monitoring of both drain discharge and water levels in monitoring wells across the site is continuing.

  19. Butyrate protects against disruption of the blood-milk barrier and moderates inflammatory responses in a model of mastitis induced by lipopolysaccharide.

    PubMed

    Wang, Jing-Jing; Wei, Zheng-Kai; Zhang, Xu; Wang, Ya-Nan; Fu, Yun-He; Yang, Zheng-Tao

    2017-08-11

    Short-chain fatty acids are fermentation end products produced by gut bacteria, which have been shown to ameliorate inflammatory bowel diseases and allergic asthma. However, the mechanism involved remains largely unknown. Here, we investigate the protective effects and mechanisms of sodium butyrate (SB) on LPS-induced mastitis model. Effects of increasing doses of SB on blood-milk barrier function and inflammation are studied in BALB/c mice with LPS-induced mastitis. The underlying mechanisms of anti-inflammatory effects of SB were further investigated in LPS-stimulated mouse mammary epithelial cells (mMECs). The results show that SB decreased LPS-induced disruption in mammary tissues, infiltration of inflammatory cells and the levels of TNF-α, IL-6 and IL-1β. SB up-regulated the tight junction proteins occludin and claudin-3 and reduced blood-milk barrier permeability in LPS-induced mastitis. Studies in vitro revealed that SB inhibited LPS-induced inflammatory response by inhibition of the NF-κB signalling pathway and histone deacetylases in LPS-stimulated mMECs. In our model, SB protected against LPS-induced mastitis by preserving blood-milk barrier function and depressing pro-inflammatory responses, suggesting the potential use of SB as a prophylactic agent to protect blood-milk barrier function in mastitis. © 2017 The British Pharmacological Society.

  20. Electrochemically induced dual reactive barriers for transformation of TCE and mixture of contaminants in groundwater

    PubMed Central

    Mao, Xuhui; Yuan, Songhu; Fallahpour, Noushin; Ciblak, Ali; Howard, Joniqua; Padilla, Ingrid; Loch-Caruso, Rita; Alshawabkeh, Akram N.

    2012-01-01

    A novel reactive electrochemical flow system consisting of iron anode and porous cathode is proposed for the remediation of mixture of contaminants in groundwater. The system consists of a series of sequentially arranged electrodes, a perforated iron anode, a porous copper cathode followed by a mesh-type mixed metal oxide anode. The iron anode generates ferrous species and a chemically reducing environment, the porous cathode provides a reactive electrochemically reducing barrier, and the inert anode provides proton and oxygen to neutralize the system. The redox conditions of the electrolyte flowing through this system can be regulated by controlling the distribution of the electric current. Column experiments are conducted to evaluate the process and study the variables. The electrochemical reduction on a copper foam cathode produced an electrode-based reductive potential capable of reducing TCE and nitrate. Rational electrodes arrangement, longer residence time of electrolytes and higher surface area of foam electrode improve the reductive transformation of TCE. More than 82.2% TCE removal efficiency is achieved for the case of low influent concentration (< 7.5 mg/L) and high current (> 45 mA). The ferrous species produced from the iron anode not only enhance the transformation of TCE on the cathode, but also facilitates transformation of other contaminants including dichromate, selenate and arsenite. Removal efficiencies greater than 80% are achieved for these contaminants from flowing contaminated water. The overall system, comprising the electrode-based and electrolyte-based barriers, can be engineered as a versatile and integrated remedial method for a relatively wide spectrum of contaminants and their mixtures. PMID:23067023

  1. Analysis of Ar plasma jets induced by single and double dielectric barrier discharges at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Judée, F.; Merbahi, N.; Wattieaux, G.; Yousfi, M.

    2016-09-01

    The aim is the comparison of different plasma parameters of single and double dielectric barrier discharge plasma jet configurations (S-DBD and D-DBD) which are potentially usable in biomedical applications. Both configurations are studied in terms of electric field distribution, electrical discharge characteristics, plasma parameters (estimated by optical emission spectroscopy analysis), and hydrodynamics of the plasma jet for electrical parameters of power supplies corresponding to an applied voltage of 10 kV, pulse duration of 1 μs, frequency of 9.69 kHz, and Ar flow of 2 l/min. We observed that the D-DBD configuration requires half the electrical power one needs to provide in the S-DBD case to generate a plasma jet with similar characteristics: excitation temperature around 4700 K, electron density around 2.5 × 1014 cm-3, gas temperature of about 320 K, a relatively high atomic oxygen concentration reaching up to 1000 ppm, the presence of reactive oxygen and nitrogen species (nitric oxide, hydroxyl radical, and atomic oxygen), and an irradiance in the UV-C range of about 20 μW cm-2. Moreover, it has been observed that D-DBD plasma jet is more sensitive to short pulse durations, probably due to the charge accumulation over the dielectric barrier around the internal electrode. This results in a significantly longer plasma length in the D-DBD configuration than in the S-DBD one up to a critical flow rate (2.25 l/min) before the occurrence of turbulence in the D-DBD case. Conversely, ionization wave velocities are significantly higher in the S-DBD setup (3.35 × 105 m/s against 1.02 × 105 m/s for D-DBD), probably due to the higher electrostatic field close to the high voltage electrode in the S-DBD plasma jet.

  2. Electrochemically induced dual reactive barriers for transformation of TCE and mixture of contaminants in groundwater.

    PubMed

    Mao, Xuhui; Yuan, Songhu; Fallahpour, Noushin; Ciblak, Ali; Howard, Joniqua; Padilla, Ingrid; Loch-Caruso, Rita; Alshawabkeh, Akram N

    2012-11-06

    A novel reactive electrochemical flow system consisting of an iron anode and a porous cathode is proposed for the remediation of mixture of contaminants in groundwater. The system consists of a series of sequentially arranged electrodes, a perforated iron anode, a porous copper cathode followed by a mesh-type mixed metal oxide anode. The iron anode generates ferrous species and a chemically reducing environment, the porous cathode provides a reactive electrochemically reducing barrier, and the inert anode provides protons and oxygen to neutralize the system. The redox conditions of the electrolyte flowing through this system can be regulated by controlling the distribution of the electric current. Column experiments are conducted to evaluate the process and study the variables. The electrochemical reduction on a copper foam cathode produced an electrode-based reductive potential capable of reducing TCE and nitrate. Rational electrodes arrangement, longer residence time of electrolytes and higher surface area of the foam electrode improve the reductive transformation of TCE. More than 82.2% TCE removal efficiency is achieved for the case of low influent concentration (<7.5 mg/L) and high current (>45 mA). The ferrous species produced from the iron anode not only enhance the transformation of TCE on the cathode, but also facilitates transformation of other contaminants including dichromate, selenate and arsenite. Removal efficiencies greater than 80% are achieved for these contaminants in flowing contaminated water. The overall system, comprising the electrode-based and electrolyte-based barriers, can be engineered as a versatile and integrated remedial method for a relatively wide spectrum of contaminants and their mixtures.

  3. Controlled aluminum-induced crystallization of an amorphous silicon thin film by using an oxide-layer diffusion barrier

    NASA Astrophysics Data System (ADS)

    Hwang, Ji-Hyun; Kwak, Hyunmin; Kwon, Myeung Hoi

    2014-03-01

    Aluminum-induced crystallization (AIC) of amorphous silicon with an Al2O3 diffusion barrier was investigated for controlling Si crystallization and preventing layer exchange during the annealing process. An Al2O3 layer was deposited between the a-Si and the Al films (a-Si/Al2O3/Al/Glass) and was blasted with an air spray gun with alumina beads to form diffusion channels between the Si and the Al layers. During the annealing process, small grain Si x Al seeds were formed at the channels. Then, the Al2O3 diffusion barrier was restructured to close the channels and prevent further diffusion of Al atoms into the a-Si layer. A polycrystalline Si film with (111), (220) and (311) crystallization peaks in the X-ray diffraction pattern was formed by annealing at 560 °C in a conventional furnace. That film showed a p-type semiconducting behavior with good crystallinity and a large grain size of up to 14.8 µm. No layer conversion occurred between the Si and the Al layers, which had been the fundamental obstacle to the applications in the crystallization of a-Si films by using the AIC method.

  4. Valence-band offsets and Schottky barrier heights of layered semiconductors explained by interface-induced gap states

    NASA Astrophysics Data System (ADS)

    Mönch, Winfried

    1998-04-01

    Many metal chalcogenides are layered semiconductors. They consist of chalcogen-metal-chalcogen layers that are themselves bound by van der Waals forces. Hence, heterostructures involving layered compounds are abrupt and strain-free. Experimental valence-band offsets of heterostructures between GaSe, InSe, SnS2, SnSe2, MoS2, MoTe2, WSe2, and CuInSe2 and between some of these compounds and ZnSe, CdS, and CdTe as well as barrier heights of Au contacts on GaSe, InSe, MoS2, MoTe2, WSe2, ZnSe, CdS, and CdTe are analyzed. The valence-band discontinuities of the heterostructures and the barrier heights of the Schottky contact compounds are consistently described by the continuum of interface-induced gap states as the primary mechanism that governs the band lineup at semiconductor interfaces.

  5. Clearance of albumin following ultrasound-induced blood-brain barrier opening is mediated by glial but not neuronal cells.

    PubMed

    Alonso, Angelika; Reinz, Eileen; Fatar, Marc; Hennerici, Michael G; Meairs, Stephen

    2011-09-09

    Ultrasound-mediated opening of the blood-brain barrier (BBB) in the presence of gas-filled microbubbles is a potential strategy for drug delivery across the blood-brain barrier to promote regeneration after ischemic stroke. However, related bioeffects and potential side-effects that could limit a translation into clinical application are poorly understood so far. We therefore examined the clearance of extravasated albumin following ultrasound-mediated BBB opening. Autofluorescence of albumin-bound Evans Blue dye indicated cellular albumin uptake as soon as 30min after insonation (2±0.72 cells/optical field). Cellular albumin uptake increased constantly over 24h (22±3.33 cells/optical field, p<0.05). Initially, the majority of albumin-positive cells were located in the periphery of brain capillaries. Most albumin phagocyting cells stained positive for CD163 and Iba-1, identifying them as activated microglia. Further, a small fraction of albumin-positive cells stained positive for the astroglial markers GFAP/S100B. Some perivascular cells with intracellular albumin were shown to express the endothelial marker protein EN4. Albumin uptaking cells stained negative for the neuronal TubulinIII. Thus, ultrasound-induced BBB opening leads to albumin extravasation which is phagocytized predominantly by activated microglia, astrocytes and endothelial cells. As albumin uptake into neurons has been shown to be neurotoxic, rapid albumin clearance by microglia might prevent neuronal cell death.

  6. Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

    PubMed

    Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

    2017-04-01

    Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

  7. Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity.

    PubMed

    Gil-Cardoso, Katherine; Ginés, Iris; Pinent, Montserrat; Ardévol, Anna; Blay, Mayte; Terra, Ximena

    2016-12-01

    Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

  8. Culture-induced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo.

    PubMed

    Lyck, Ruth; Ruderisch, Nadine; Moll, Anton G; Steiner, Oliver; Cohen, Clemens D; Engelhardt, Britta; Makrides, Victoria; Verrey, Francois

    2009-09-01

    Tight homeostatic control of brain amino acids (AA) depends on transport by solute carrier family proteins expressed by the blood-brain barrier (BBB) microvascular endothelial cells (BMEC). To characterize the mouse BMEC transcriptome and probe culture-induced changes, microarray analyses of platelet endothelial cell adhesion molecule-1-positive (PECAM1(+)) endothelial cells (ppMBMECs) were compared with primary MBMECs (pMBMEC) cultured in the presence or absence of glial cells and with b.End5 endothelioma cell line. Selected cell marker and AA transporter mRNA levels were further verified by reverse transcription real-time PCR. Regardless of glial coculture, expression of a large subset of genes was strongly altered by a brief culture step. This is consistent with the known dependence of BMECs on in vivo interactions to maintain physiologic functions, for example, tight barrier formation, and their consequent dedifferentiation in culture. Seven (4F2hc, Lat1, Taut, Snat3, Snat5, Xpct, and Cat1) of nine AA transporter mRNAs highly expressed in freshly isolated ppMBMECs were strongly downregulated for all cultures and two (Snat2 and Eaat3) were variably regulated. In contrast, five AA transporter mRNAs with low expression in ppMBMECs, including y(+)Lat2, xCT, and Snat1, were upregulated by culture. We hypothesized that the AA transporters highly expressed in ppMBMECs and downregulated in culture have a major in vivo function for BBB transendothelial transport.

  9. Neurothelin: an inducible cell surface glycoprotein of blood-brain barrier-specific endothelial cells and distinct neurons

    PubMed Central

    1990-01-01

    The blood-brain barrier is characterized by still poorly understood barrier and transport functions performed by specialized endothelial cells. Hybridoma technology has been used to identify a protein termed neurothelin that is specific for these endothelial cells. Neurothelin is defined by the species-specific mouse mAb 1W5 raised against lentil- lectin-binding proteins of neural tissue from embryonic chick. In the posthatch chick, neurothelin expression is found on endothelial cells within the brain but not on those of the systemic vascular system. Injection of the monoclonal antibody in vivo leads to labeling of brain capillaries, indicating that the corresponding antigen is expressed on the luminal surface of brain endothelial cells. Transplantation of embryonic mouse brain onto the chick chorioallantoic membrane results in rodent brain vascularization by the avian vascular system. Subsequently, normally mAb 1W5-negative endothelial cells, originating from blood vessels of the chick chorioallantoic membrane, are induced to express neurothelin when they are in contact with mouse neural tissue. In contrast to differentiated brain neurons that do not express neurothelin, neurons of the nonvascularized chick retina synthesize neurothelin. However, neurothelin is not found on retinal ganglion cell axons terminating on 1W5-negative brain cells. 1W5 immunoreactivity was also found in the pigment epithelium that forms the blood-eye barrier. Putting epithelial cells into culture results in concentration of neurothelin at cell-cell contact sites, leaving other cell surface areas devoid of antigen. Therefore, the distribution of neurothelin appears to be regulated by cell-cell interactions. In Western blot analysis, neurothelin was identified as a protein with a molecular mass of approximately 43 kD. The protein bears at least one intramolecular disulfide bridge and sulfated glucuronic acid as well as alpha-D- substituted mannose/glucose moieties. The exclusive

  10. Plasmin-dependent modulation of the blood–brain barrier: a major consideration during tPA-induced thrombolysis?

    PubMed Central

    Niego, Be'eri; Medcalf, Robert L

    2014-01-01

    Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood–brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process. PMID:24896566

  11. Destruction of Gaseous Styrene with a Low-Temperature Plasma Induced by a Tubular Multilayer Dielectric Barrier Discharge

    NASA Astrophysics Data System (ADS)

    Zhang, Jiahui; Liu, Juanjuan; Zhang, Renxi; Hou, Huiqi; Chen, Shanping; Zhang, Yi

    2015-01-01

    The destruction of gaseous styrene was studied using a low-temperature plasma induced by tubular multilayer dielectric barrier discharge (DBD). The results indicate that the applied voltage, gas flow rate, inlet styrene concentration and reactor configuration play important roles in styrene removal efficiency (ηstyrene) and energy yield (EY). Values of ηstyrene and EY reached 96% and 15567 mg/kWh when the applied voltage, gas flow rate, inlet styrene concentration and layers of quartz tubes were set at 10.8 kV, 5.0 m/s, 229 mg/m3 and 5 layers, respectively. A qualitative analysis of the byproducts and a detailed discussion of the reaction mechanism are also presented. The results could facilitate industrial applications of the new DBD reactor for waste gas treatment.

  12. Quantifying redox-induced Schottky barrier variations in memristive devices via in operando spectromicroscopy with graphene electrodes

    NASA Astrophysics Data System (ADS)

    Baeumer, Christoph; Schmitz, Christoph; Marchewka, Astrid; Mueller, David N.; Valenta, Richard; Hackl, Johanna; Raab, Nicolas; Rogers, Steven P.; Khan, M. Imtiaz; Nemsak, Slavomir; Shim, Moonsub; Menzel, Stephan; Schneider, Claus Michael; Waser, Rainer; Dittmann, Regina

    2016-08-01

    The continuing revolutionary success of mobile computing and smart devices calls for the development of novel, cost- and energy-efficient memories. Resistive switching is attractive because of, inter alia, increased switching speed and device density. On electrical stimulus, complex nanoscale redox processes are suspected to induce a resistance change in memristive devices. Quantitative information about these processes, which has been experimentally inaccessible so far, is essential for further advances. Here we use in operando spectromicroscopy to verify that redox reactions drive the resistance change. A remarkable agreement between experimental quantification of the redox state and device simulation reveals that changes in donor concentration by a factor of 2-3 at electrode-oxide interfaces cause a modulation of the effective Schottky barrier and lead to >2 orders of magnitude change in device resistance. These findings allow realistic device simulations, opening a route to less empirical and more predictive design of future memory cells.

  13. Quantifying redox-induced Schottky barrier variations in memristive devices via in operando spectromicroscopy with graphene electrodes

    PubMed Central

    Baeumer, Christoph; Schmitz, Christoph; Marchewka, Astrid; Mueller, David N.; Valenta, Richard; Hackl, Johanna; Raab, Nicolas; Rogers, Steven P.; Khan, M. Imtiaz; Nemsak, Slavomir; Shim, Moonsub; Menzel, Stephan; Schneider, Claus Michael; Waser, Rainer; Dittmann, Regina

    2016-01-01

    The continuing revolutionary success of mobile computing and smart devices calls for the development of novel, cost- and energy-efficient memories. Resistive switching is attractive because of, inter alia, increased switching speed and device density. On electrical stimulus, complex nanoscale redox processes are suspected to induce a resistance change in memristive devices. Quantitative information about these processes, which has been experimentally inaccessible so far, is essential for further advances. Here we use in operando spectromicroscopy to verify that redox reactions drive the resistance change. A remarkable agreement between experimental quantification of the redox state and device simulation reveals that changes in donor concentration by a factor of 2–3 at electrode-oxide interfaces cause a modulation of the effective Schottky barrier and lead to >2 orders of magnitude change in device resistance. These findings allow realistic device simulations, opening a route to less empirical and more predictive design of future memory cells. PMID:27539213

  14. Surgery-Induced Hippocampal Angiotensin II Elevation Causes Blood-Brain Barrier Disruption via MMP/TIMP in Aged Rats

    PubMed Central

    Li, Zhengqian; Mo, Na; Li, Lunxu; Cao, Yiyun; Wang, Wenming; Liang, Yaoxian; Deng, Hui; Xing, Rui; Yang, Lin; Ni, Cheng; Chui, Dehua; Guo, Xiangyang

    2016-01-01

    Reversible blood-brain barrier (BBB) disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD). Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), as well as three of their endogenous tissue inhibitors of MMP (TIMP-1, -2, -3), and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II) and Ang II receptor type 1 (AT1) after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1), as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB) activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor. PMID:27199659

  15. 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.

  16. Changes in the biomechanical properties of a single cell induced by nonthermal atmospheric pressure micro-dielectric barrier discharge plasma.

    PubMed

    Choi, Hyeongwon; Choi, Eun Ha; Kim, Kyung Sook

    2017-10-01

    Mechanical properties of a single cell are closely related to the fate and functions of the cell. Changes in mechanical properties may cause diseases or cell apoptosis. Selective cytotoxic effects of nonthermal atmospheric pressure micro-dielectric barrier discharge (DBD) plasma have been demonstrated on cancer cells. In this work, changes in the mechanical properties of a single cell induced by nonthermal atmospheric pressure micro-DBD plasma were investigated using atomic force microscopy (AFM). Two cervical cancer cell lines (HeLa and SiHa) and normal human fibroblast cells (HFBs) were exposed to micro-DBD plasma for various exposure times. The elasticity of a single cell was determined by force-distance curve measurement using AFM. Young's modulus was decreased by plasma treatment for all cells. The Young's modulus of plasma-treated HeLa cells was decreased by 75% compared to nontreated HeLa cells. In SiHa cells and HFBs, elasticity was decreased slightly. Chemical changes induced by the plasma treatment, which were observed by Raman spectroscopy, were also significant in HeLa cells compared to SiHa cells and HFBs. These results suggested that the molecular changes induced by micro-DBD plasma were related to cell mechanical changes. © 2017 Wiley Periodicals, Inc.

  17. Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood–brain barrier impairment

    PubMed Central

    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.

    2017-01-01

    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. PMID:28223486

  18. Interleukin-1β-induced barrier dysfunction is signaled through PKC-θ in human brain microvascular endothelium.

    PubMed

    Rigor, Robert R; Beard, Richard S; Litovka, Olesya P; Yuan, Sarah Y

    2012-05-15

    Blood-brain barrier dysfunction is a serious consequence of inflammatory brain diseases, cerebral infections, and trauma. The proinflammatory cytokine interleukin (IL)-1β is central to neuroinflammation and contributes to brain microvascular leakage and edema formation. Although it is well known that IL-1β exposure directly induces hyperpermeability in brain microvascular endothelium, the molecular mechanisms mediating this response are not completely understood. In the present study, we found that exposure of the human brain microvascular endothelium to IL-1β triggered activation of novel PKC isoforms δ, μ, and θ, followed by decreased transendothelial electrical resistance (TER). The IL-1β-induced decrease in TER was prevented by small hairpin RNA silencing of PKC-θ or by treatment with the isoform-selective PKC inhibitor Gö6976 but not by PKC inhibitors that are selective for all PKC isoforms other than PKC-θ. Decreased TER coincided with increased phosphorylation of regulatory myosin light chain and with increased proapoptotic signaling indicated by decreased uptake of mitotracker red in response to IL-1β treatment. However, neither of these observed effects were prevented by Gö6976 treatment, indicating lack of causality with respect to decreased TER. Instead, our data indicated that the mechanism of decreased TER involves PKC-θ-dependent phosphorylation of the tight junction protein zona occludens (ZO)-1. Because IL-1β is a central inflammatory mediator, our interpretation is that inhibition of PKC-θ or inhibition of ZO-1 phosphorylation could be viable strategies for preventing blood-brain barrier dysfunction under a variety of neuroinflammatory conditions.

  19. Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.

    PubMed

    Wang, Li-Feng; Li, Xiang; Gao, Ya-Bing; Wang, Shui-Ming; Zhao, Li; Dong, Ji; Yao, Bin-Wei; Xu, Xin-Ping; Chang, Gong-Min; Zhou, Hong-Mei; Hu, Xiang-Jun; Peng, Rui-Yun

    2015-08-01

    Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

  20. Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells.

    PubMed

    Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2016-09-01

    Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-ĸB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Heat stress-induced disruption of endothelial barrier function is via PAR1 signaling and suppressed by Xuebijing injection.

    PubMed

    Xu, Qiulin; Liu, Jingxian; Wang, Zhenglian; Guo, Xiaohua; Zhou, Gengbiao; Liu, Yanan; Huang, Qiaobing; Su, Lei

    2015-01-01

    Increased vascular permeability leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is central to the pathogenesis of heatstroke. Protease-activated receptor 1 (PAR1), the receptor for thrombin, plays a key role in disruption of endothelial barrier function in response to extracellular stimuli. However, the role of PAR1 in heat stress-induced endothelial hyper-permeability is unknown. In this study, we measured PAR1 protein expression in heat-stressed human umbilical venous endothelial cells (HUVECs), investigated the influences of PAR1 on endothelial permeability, F-actin rearrangement, and moesin phosphorylation by inhibiting PAR1 with its siRNA, neutralizing antibody (anti-PAR1), specific inhibitor(RWJ56110), and Xuebijing injection (XBJ), a traditional Chinese medicine used for sepsis treatment, and evaluated the role of PAR1 in heatstroke-related ALI/ARDS in mice by suppressing PAR1 with RWJ56110, anti-PAR1and XBJ. We found that heat stress induced PAR1 protein expression 2h after heat stress in endothelial cells, caused the release of endothelial matrix metalloprotease 1, an activator of PAR1, after 60 or 120 min of heat stimulation, as well as promoted endothelial hyper-permeability and F-actin rearrangement, which were inhibited by suppressing PAR1 with RWJ56110, anti-PAR1 and siRNA. PAR1 mediated moesin phosphorylation, which caused F-actin rearrangement and disruption of endothelial barrier function. To corroborate findings from in vitro experiments, we found that RWJ56110 and the anti-PAR1 significantly decreased lung edema, pulmonary microvascular permeability, protein exudation, and leukocytes infiltrations in heatstroke mice. Additionally, XBJ was found to suppress PAR1-moesin signal pathway and confer protective effects on maintaining endothelial barrier function both in vitro and in vivo heat-stressed model, similar to those observed above with the inhibition of PAR1. These results suggest that PAR1 is a potential

  2. Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.

    PubMed

    Kiyatkin, Eugene A; Sharma, Hari S

    2015-01-01

    Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure.

  3. Hypoxia-inducible factor-1α is involved in isoflurane-induced blood-brain barrier disruption in aged rats model of POCD.

    PubMed

    Cao, Yiyun; Li, Zhengqian; Li, Hongping; Ni, Cheng; Li, Lunxu; Yang, Ning; Shi, Chengmei; Zhong, Yanfeng; Cui, Dehua; Guo, Xiangyang

    2017-09-05

    Prolonged exposure to inhaled anesthetics may lead to postoperative cognitive dysfunction (POCD). Nevertheless, the underlying mechanisms are not known. Hypoxia-inducible factor-1α (HIF-1α) and its target gene vascular endothelial growth factor (VEGF) were shown to be activated by inhaled anesthetics. The aim of the present study was to determine the role of HIF-1α in isoflurane-induced blood-brain barrier (BBB) disruption and resultant cognitive impairment. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in vascular permeability, and disrupted BBB ultrastructure were accompanied by the degradation of tight junction proteins occludin and collagen type IV in brain blood vessels. Increases in HIF-1α and VEGF proteins and activation of MMP-2 in the hippocampus were also observed in the hippocamp of isoflurane-exposed rats compared with control rats. Pharmacological inhibition of HIF-1α activation by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) markedly suppressed the expression of HIF-1α, VEGF and MMP-2, and mitigated the severity of BBB disruption.YC-1 pretreatment also significantly attenuated isoflurane-induced cognitive deficits in the Morris water maze task. Overall, our results demonstrate that hippocampal HIF-1α/VEGF signaling seems to be the upstream mechanism of isoflurane-induced cognitive impairment, and provides apotential preventive and therapeutic target for POCD. Copyright © 2017. Published by Elsevier B.V.

  4. Plant-derived triterpene celastrol ameliorates oxygen glucose deprivation-induced disruption of endothelial barrier assembly via inducing tight junction proteins.

    PubMed

    Luo, Dan; Zhao, Jia; Rong, Jianhui

    2016-12-01

    The integrity and functions of blood-brain barrier (BBB) are regulated by the expression and organization of tight junction proteins. The present study was designed to explore whether plant-derived triterpenoid celastrol could regulate tight junction integrity in murine brain endothelial bEnd3 cells. We disrupted the tight junctions between endothelial bEnd3 cells by oxygen glucose deprivation (OGD). We investigated the effects of celastrol on the permeability of endothelial monolayers by measuring transepithelial electrical resistance (TEER). To clarify the tight junction composition, we analyzed the expression of tight junction proteins by RT-PCR and Western blotting techniques. We found that celastrol recovered OGD-induced TEER loss in a concentration-dependent manner. Celastrol induced occludin, claudin-5 and zonula occludens-1 (ZO-1) in endothelial cells. As a result, celastrol effectively maintained tight junction integrity and inhibited macrophage migration through endothelial monolayers against OGD challenge. Further mechanistic studies revealed that celastrol induced the expression of occludin and ZO-1) via activating MAPKs and PI3K/Akt/mTOR pathway. We also observed that celastrol regulated claudin-5 expression through different mechanisms. The present study demonstrated that celastrol effectively protected tight junction integrity against OGD-induced damage. Thus, celastrol could be a drug candidate for the treatment of BBB dysfunction in various diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Blood nerve barrier in rat and cellular mechanisms of lead-induced segmental demyelination

    SciTech Connect

    Dyck, P.J.; Windebank, A.J.; Low, P.A.; Baumann, W.J.

    1980-11-01

    Feeding of lead carbonate to rats causes widespread and reproducible segmental de- and remyelination of myelinated fibers (MFs) of peripheral nerve. Such segmental demyelination might be explained by increased permeability of endoneurial capillaries to serum containing protein-bound lead. The perineurium of control and lead nerves was impermeable to fluorescein-labeled bovine albumin (FBA) and to horseradish peroxidase (HRP). Epineurial capillaries in both conditions allowed HRP to pass freely between and, to a lesser extent, through endothelial cells. Contrary to expectation, flooding of the endoneurium with HRP was seen in only 1 of 36 tissue blocks of lead nerves from rats fed 4% lead carbonate for 7 1/2 and 12 weeks. Abundant HRP reaction product was seen in the epineurium in more than half of these tissue blocks. HRP was not generally found in endoneurial fluid, even in lead nerves with marked edema and widespread segmental de- and remyelination. These findings are against a massive breakdown of the blood nerve barrier. These studies suggest that there may be an increased transfer of HRP through endoneurial cells in lead neuropathy.

  6. Facilitating climate-change-induced range shifts across continental land-use barriers.

    PubMed

    Robillard, Cassandra M; Coristine, Laura E; Soares, Rosana N; Kerr, Jeremy T

    2015-12-01

    Climate changes impose requirements for many species to shift their ranges to remain within environmentally tolerable areas, but near-continuous regions of intense human land use stretching across continental extents diminish dispersal prospects for many species. We reviewed the impact of habitat loss and fragmentation on species' abilities to track changing climates and existing plans to facilitate species dispersal in response to climate change through regions of intensive land uses, drawing on examples from North America and elsewhere. We identified an emerging analytical framework that accounts for variation in species' dispersal capacities relative to both the pace of climate change and habitat availability. Habitat loss and fragmentation hinder climate change tracking, particularly for specialists, by impeding both propagule dispersal and population growth. This framework can be used to identify prospective modern-era climatic refugia, where the pace of climate change has been slower than surrounding areas, that are defined relative to individual species' needs. The framework also underscores the importance of identifying and managing dispersal pathways or corridors through semi-continental land use barriers that can benefit many species simultaneously. These emerging strategies to facilitate range shifts must account for uncertainties around population adaptation to local environmental conditions. Accounting for uncertainties in climate change and dispersal capabilities among species and expanding biological monitoring programs within an adaptive management paradigm are vital strategies that will improve species' capacities to track rapidly shifting climatic conditions across landscapes dominated by intensive human land use. © 2015 Society for Conservation Biology.

  7. Opening of brain blood barrier induced by red light and central analgesic improvement of cobra neurotoxin.

    PubMed

    Ye, Yong; Li, Yue; Fang, Fei

    2014-05-05

    Cobra neurotoxin (NT) has central analgesic effects, but it is difficult to pass through brain blood barrier (BBB). A novel method of red light induction is designed to help NT across BBB, which is based on photosensitizer activation by red light to generate reactive oxygen species (ROS) to open BBB. The effects were evaluated on cell models and animals in vivo with illumination by semiconductor laser at 670nm on photosensitizer pheophorbide isolated from silkworm excrement. Brain microvascular endothelial cells and astrocytes were co-cultured to build up BBB cell model. The radioactivity of (125)I-NT was measured in cells and tissues for NT permeation. Three ways of cranial irradiation, nasal cavity and intravascular irradiation were tested with combined injection of (125)I-NT 20μg/kg and pheophorbide 100μg/kg to rats, and organs of rats were separated and determined the radioactivity. Paw pressure test in rats, hot plate and writhing test in mice were applied to appraise the analgesic effects. NT across BBB cell model increased with time of illumination, and reached stable level after 60min. So did ROS in cells. NT mainly distributed in liver and kidney of rats, significantly increased in brain after illumination, and improved analgesic effects. Excitation of pheophorbide at red light produces ROS to open BBB, help NT enter brain, and enhance its central action. This research provides a new method for drug across BBB to improve its central role.

  8. Miniature Dielectric Barrier Discharge Nonthermal Plasma Induces Apoptosis in Lung Cancer Cells and Inhibits Cell Migration

    PubMed Central

    Eisenmann, Kathryn M.

    2017-01-01

    Traditional cancer treatments like radiotherapy and chemotherapy have drawbacks and are not selective for killing only cancer cells. Nonthermal atmospheric pressure plasmas with dielectric barrier discharge (DBD) can be applied to living cells and tissues and have emerged as novel tools for localized cancer therapy. The purpose of this study was to investigate the different effects caused by miniature DBD (mDBD) plasma to A549 lung cancer cells. In this study, A549 lung cancer cells cultured in 12 well plates were treated with mDBD plasma for specified treatment times to assess the changes in the size of the area of cell detachment, the viability of attached or detached cells, and cell migration. Furthermore, we investigated an innovative mDBD plasma-based therapy for localized treatment of lung cancer cells through apoptotic induction. Our results indicate that plasma treatment for 120 sec causes apoptotic cell death in 35.8% of cells, while mDBD plasma treatment for 60 sec, 30 sec, or 15 sec causes apoptotic cell death in 20.5%, 14.1%, and 6.3% of the cell population, respectively. Additionally, we observed reduced A549 cell migration in response to mDBD plasma treatment. Thus, mDBD plasma system can be a viable platform for localized lung cancer therapy. PMID:28243603

  9. Miniature Dielectric Barrier Discharge Nonthermal Plasma Induces Apoptosis in Lung Cancer Cells and Inhibits Cell Migration.

    PubMed

    Karki, Surya B; Yildirim-Ayan, Eda; Eisenmann, Kathryn M; Ayan, Halim

    2017-01-01

    Traditional cancer treatments like radiotherapy and chemotherapy have drawbacks and are not selective for killing only cancer cells. Nonthermal atmospheric pressure plasmas with dielectric barrier discharge (DBD) can be applied to living cells and tissues and have emerged as novel tools for localized cancer therapy. The purpose of this study was to investigate the different effects caused by miniature DBD (mDBD) plasma to A549 lung cancer cells. In this study, A549 lung cancer cells cultured in 12 well plates were treated with mDBD plasma for specified treatment times to assess the changes in the size of the area of cell detachment, the viability of attached or detached cells, and cell migration. Furthermore, we investigated an innovative mDBD plasma-based therapy for localized treatment of lung cancer cells through apoptotic induction. Our results indicate that plasma treatment for 120 sec causes apoptotic cell death in 35.8% of cells, while mDBD plasma treatment for 60 sec, 30 sec, or 15 sec causes apoptotic cell death in 20.5%, 14.1%, and 6.3% of the cell population, respectively. Additionally, we observed reduced A549 cell migration in response to mDBD plasma treatment. Thus, mDBD plasma system can be a viable platform for localized lung cancer therapy.

  10. Spontaneous versus induced hydrogen and deuterium helical shaped plasmas with electron internal transport barriers

    NASA Astrophysics Data System (ADS)

    Gobbin, M.; Franz, P.; Auriemma, F.; Lorenzini, R.; Marrelli, L.

    2015-09-01

    Electron internal transport barriers (eITBs) in high current plasmas with helical equilibria of the reversed field pinch experiment RFX-mod are analyzed and characterized in detail thanks to a high time resolution double filter diagnostic for the electron temperature spatial profile determination. The large amount of data provided by this diagnostic has required the development of dedicated algorithms and the identification of suitable parameters, reported and described in this paper, in order to perform automatic statistical studies. These numerical tools have been used to examine the effect of three dimensional (3D) magnetic fields applied by the RFX-mod 192 active coils in deuterium and hydrogen discharges with the aim to improve the sustainment and control of helical equilibria with eITBs. It is shown that 3D fields partially increase the occurring of helical states but with only a moderate effect on the eITBs duration; moreover, they have a different impact on the confinement properties in hydrogen and deuterium discharges. Numerical simulations, by the Hamiltonian guiding center code ORBIT, investigate the effect of magnetic topology in plasmas with and without the application of 3D fields on deuterium and hydrogen test ions transport. Results from numerical studies are in agreement with estimates of the particle confinement times showing that particle transport is reduced in deuterium plasmas but not significantly affected by the application of helical boundary conditions.

  11. Improved Ethanol Production from Xylose by Candida shehatae Induced by Dielectric Barrier Discharge Air Plasma

    NASA Astrophysics Data System (ADS)

    Chen, Huixia; Xiu, Zhilong; Bai, Fengwu

    2014-06-01

    Xylose fermentation is essential for ethanol production from lignocellulosic biomass. Exposure of the xylose-fermenting yeast Candida shehatae (C. shehatae) CICC1766 to atmospheric pressure dielectric barrier discharge (DBD) air plasma yields a clone (designated as C81015) with stability, which exhibits a higher ethanol fermentation rate from xylose, giving a maximal enhancement in ethanol production of 36.2% compared to the control (untreated). However, the biomass production of C81015 is lower than that of the control. Analysis of the NADH (nicotinamide adenine dinucleotide)- and NADPH (nicotinamide adenine dinucleotide phosphate)-linked xylose reductases and NAD+-linked xylitol dehydrogenase indicates that their activities are enhanced by 34.1%, 61.5% and 66.3%, respectively, suggesting that the activities of these three enzymes are responsible for improving ethanol fermentation in C81015 with xylose as a substrate. The results of this study show that DBD air plasma could serve as a novel and effective means of generating microbial strains that can better use xylose for ethanol fermentation.

  12. Understanding {sup 6}He induced reactions at energies around the Coulomb barrier

    SciTech Connect

    Moro, A. M.; Arias, J. M.; Acosta, L.; Martel, I.; Sanchez-Benitez, A. M.; Borge, M. J. G.; Escrig, D.; Tengblad, O.; Gomez-Camacho, J.; Rodriguez-Gallardo, M.

    2009-06-03

    Recent developments aimed to understand the observed features arising in the scattering of the Borromean nucleus {sup 6}He on heavy targets are discussed and compared with recent data for {sup 6}He+{sup 208}Pb measured at the RIB facility at Louvain-la-Neuve at energies around the Coulomb barrier. The analysis of the elastic scattering data in terms of the optical model, reveals the presence of a long range absorption mechanism, that manifests in the form of a large value of the imaginary diffuseness parameter. The elastic data have been also compared with three--body CDCC calculations, based on a di-neutron model of {sup 6}He, and four--body CDCC calculations, based on a more realistic three-body model of this nucleus. Finally, the angular and energy distribution of {alpha} particles emitted at backward angles are discussed and compared with different theoretical approaches. We find that these {alpha} particles are produced mainly by a two-neutron transfer mechanism to very excited states in the residual nucleus.

  13. Mechanisms involved in the blood-testis barrier increased permeability induced by EMP.

    PubMed

    Wang, Xiao-Wu; Ding, Gui-Rong; Shi, Chang-Hong; Zeng, Li-Hua; Liu, Jun-Ye; Li, Jing; Zhao, Tao; Chen, Yong-Bin; Guo, Guo-Zhen

    2010-09-30

    The blood-testis barrier (BTB) plays an important role in male reproductive system. Lots of environmental stimulations can increase the permeability of BTB and then result in antisperm antibody (AsAb) generation, which is a key step in male immune infertility. Here we reported the results of male mice exposed to electromagnetic pulse (EMP) by measuring the expression of tight-junction-associated proteins (ZO-1 and Occludin), vimentin microfilaments, and transforming growth factor-beta (TGF-beta3) as well as AsAb level in serum. Male BALB/c mice were sham exposed or exposed to EMP at two different intensities (200kV/m and 400kV/m) for 200 pulses. The testes were collected at different time points after EMP exposure. Immunofluorescence histocytochemistry, western blotting, laser confocal microscopy and RT-PCR were used in this study. Compared with sham group, the expression of ZO-1 and TGF-beta3 significantly decreased accompanied with unevenly stained vimentin microfilaments and increased serum AsAb levels in EMP-exposed mice. These results suggest a potential BTB injury and immune infertility in male mice exposed to a certain intensity of EMP. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Understanding age-induced alterations to the biomechanical barrier function of human stratum corneum.

    PubMed

    Biniek, Krysta; Kaczvinsky, Joseph; Matts, Paul; Dauskardt, Reinhold H

    2015-11-01

    The appearance and function of human skin are dramatically altered with aging, resulting in higher rates of severe xerosis and other skin complaints. The outermost layer of the epidermis, the stratum corneum (SC), is responsible for the biomechanical barrier function of skin and is also adversely transformed with age. With age the keratin filaments within the corneocytes are prone to crosslinking, the amount of intercellular lipids decreases resulting in fewer lipid bilayers, and the rate of corneocyte turnover decreases. The effect of these structural changes on the mechanical properties of the SC has not been determined. Here we determine how several aspects of the SC's mechanical properties are dramatically degraded with age. We performed a range of biomechanical experiments, including micro-tension, bulge, double cantilever beam, and substrate curvature testing on abdominal stratum corneum from cadaveric female donors ranging in age from 29 to 93 years old. We found that the SC stiffens with age, indicating that the keratin fibers stiffen, similarly to collagen fibers in the dermis. The cellular cohesion also increases with age, a result of the altered intercellular lipid structure. The kinetics of water movement through the SC is also decreased. Our results indicate that the combination of structural and mechanical property changes that occur with age are quite significant and may contribute to the prevalence of skin disorders among the elderly. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Wire-cylinder dielectric barrier discharge induced degradation of aqueous atrazine.

    PubMed

    Zhu, Dan; Jiang, Lin; Liu, Run-Long; Chen, Pei; Lang, Lin; Feng, Jing-Wei; Yuan, Shou-Jun; Zhao, Da-Yong

    2014-12-01

    The wire-cylinder dielectric barrier discharge reactor was adopted for removal of aqueous atrazine. The effect of different parameters on the degradation efficiency of atrazine was investigated, and the degradation mechanism of atrazine was studied. The experimental results showed that when the discharge power was 50 W and the air flow rate was 140 L h(-1), 93.7% of atrazine was degraded after 18 min of discharge time. The concentrations of generated O3 and H2O2 increased with increasing discharge time. The pH decreased from 6.80 to 2.50, 12.7% of TOC was removed after 18 min. The concentrations of generated Cl(-) and NO3(-) increased significantly during the degradation process of atrazine, and the decreasing toxicity trend was observed for the treated atrazine solution. The degradation byproducts of atrazine were identified using liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), which might be formed mainly in dechlorination hydroxylation, alkyl oxidation, dechlorination hydroxylation combined with alkyl oxidation and demethylation oxidation reactions.

  16. VE-cadherin involved in the pulmonary microvascular endothelial cell barrier injury induced by angiotensin II through modulating the cellular apoptosis and skeletal rearrangement

    PubMed Central

    Wu, Zhiyong; Liu, Huagang; Ren, Wei; Dai, Feifeng; Chang, Jinxing; Li, Bowen

    2016-01-01

    Objective: Angiotensin II (AngII) involved in the pathogenesis of pulmonary injury through impairing the integrity of pulmonary microvascular endothelial barrier, but the mechanism is still not clear. We aim to determine the roles of VE-cadherin, playing crucial roles in the adhesion of the vascular endothelial barrier and the barrier function, in the pulmonary microvascular endothelial cell (PMVEC) barrier injury mediated by AngII. Methods: Mice acute lung injury (ALI) model was induced through pumping of AngII. The infiltration of macrophages and neutrophils as well as the PMVEC permeability were determined in order to determine the barrier injury in vivo and in vitro. Knockdown of VE-cadherin was established using siRNA technique, and its roles in the apoptosis and skeletal rearrangement in the PMVECs were evaluated. Results: After AngII interference, the expression of VE-cadherin in the PMVECs and pulmonary tissues in mice was down-regulated. Upon VE-cadherin knockdown through siRNA technique, AngII induced susceptibility of PMVECs to apoptosis. Knockdown of VE-cadherin contributed to the skeletal rearrangement in the endothelial cells, together with increase of permeability. Conclusions: VE-cadherin expression is closely related to the apoptosis and skeletal rearrangement of PMVECs induced by AngII. PMID:27830014

  17. Drain Current Modulation of a Single Drain MOSFET by Lorentz Force for Magnetic Sensing Application

    PubMed Central

    Chatterjee, Prasenjit; Chow, Hwang-Cherng; Feng, Wu-Shiung

    2016-01-01

    This paper reports a detailed analysis of the drain current modulation of a single-drain normal-gate n channel metal-oxide semiconductor field effect transistor (n-MOSFET) under an on-chip magnetic field. A single-drain n-MOSFET has been fabricated and placed in the center of a square-shaped metal loop which generates the on-chip magnetic field. The proposed device designed is much smaller in size with respect to the metal loop, which ensures that the generated magnetic field is approximately uniform. The change of drain current and change of bulk current per micron device width has been measured. The result shows that the difference drain current is about 145 µA for the maximum applied magnetic field. Such changes occur from the applied Lorentz force to push out the carriers from the channel. Based on the drain current difference, the change in effective mobility has been detected up to 4.227%. Furthermore, a detailed investigation reveals that the device behavior is quite different in subthreshold and saturation region. A change of 50.24 µA bulk current has also been measured. Finally, the device has been verified for use as a magnetic sensor with sensitivity 4.084% (29.6 T−1), which is very effective as compared to other previously reported works for a single device. PMID:27589747

  18. Climate mitigation scenarios of drained peat soils

    NASA Astrophysics Data System (ADS)

    Kasimir Klemedtsson, Åsa; Coria, Jessica; He, Hongxing; Liu, Xiangping; Nordén, Anna

    2014-05-01

    The national inventory reports (NIR) submitted to the UNFCCC show Sweden - which as many other countries has wetlands where parts have been drained for agriculture and forestry purposes, - to annually emit 12 million tonnes carbon dioxide equivalents, which is more GHG'es than industrial energy use release in Sweden. Similar conditions can be found in other northern countries, having cool and wet conditions, naturally promoting peat accumulation, and where land use management over the last centuries have promoted draining activities. These drained peatland, though covering only 2% of the land area, have emissions corresponding to 20% of the total reported NIR emissions. This substantial emission contribution, however, is hidden within the Land Use Land Use Change and Forestry sector (LULUCF) where the forest Carbon uptake is even larger, which causes the peat soil emissions become invisible. The only drained soil emission accounted in the Swedish Kyoto reporting is the N2O emission from agricultural drained organic soils of the size 0.5 million tonnes CO2e yr-1. This lack of visibility has made incentives for land use change and management neither implemented nor suggested, however with large potential. Rewetting has the potential to decrease soil mineralization, why CO2 and N2O emissions are mitigated. However if the soil becomes very wet CH4 emission will increase together with hampered plant growth. By ecological modeling, using the CoupModel the climate change mitigation potential have been estimated for four different land use scenarios; 1, Drained peat soil with Spruce (business as usual scenario), 2, raised ground water level to 20 cm depth and Willow plantation, 3, raised ground water level to 10 cm depth and Reed Canary Grass, and 4, rewetting to an average water level in the soil surface with recolonizing wetland plants and mosses. We calculate the volume of biomass production per year, peat decomposition, N2O emission together with nitrate and DOC

  19. Lipopolysaccharide-Induced Middle Ear Inflammation Disrupts the cochlear Intra-Strial Fluid–Blood Barrier through Down-Regulation of Tight Junction Proteins

    PubMed Central

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid–blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid–blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid–blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid

  20. Lipopolysaccharide-induced middle ear inflammation disrupts the cochlear intra-strial fluid-blood barrier through down-regulation of tight junction proteins.

    PubMed

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid-blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid-blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid-blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid-blood barrier

  1. Polyinosinic:polycytidylic acid induces protein kinase D-dependent disassembly of apical junctions and barrier dysfunction in airway epithelial cells.

    PubMed

    Rezaee, Fariba; Meednu, Nida; Emo, Jason A; Saatian, Bahman; Chapman, Timothy J; Naydenov, Nayden G; De Benedetto, Anna; Beck, Lisa A; Ivanov, Andrei I; Georas, Steve N

    2011-12-01

    Disruption of the epithelial barrier might be a risk factor for allergen sensitization and asthma. Viral respiratory tract infections are strongly associated with asthma exacerbation, but the effects of respiratory viruses on airway epithelial barrier function are not well understood. Many viruses generate double-stranded RNA, which can lead to airway inflammation and initiate an antiviral immune response. We investigated the effects of the synthetic double-stranded RNA polyinosinic:polycytidylic acid (polyI:C) on the structure and function of the airway epithelial barrier in vitro. 16HBE14o- human bronchial epithelial cells and primary airway epithelial cells at an air-liquid interface were grown to confluence on Transwell inserts and exposed to polyI:C. We studied epithelial barrier function by measuring transepithelial electrical resistance and paracellular flux of fluorescent markers and structure of epithelial apical junctions by means of immunofluorescence microscopy. PolyI:C induced a profound decrease in transepithelial electrical resistance and increase in paracellular permeability. Immunofluorescence microscopy revealed markedly reduced junctional localization of zonula occludens-1, occludin, E-cadherin, β-catenin, and disorganization of junction-associated actin filaments. PolyI:C induced protein kinase D (PKD) phosphorylation, and a PKD antagonist attenuated polyI:C-induced disassembly of apical junctions and barrier dysfunction. PolyI:C has a powerful and previously unsuspected disruptive effect on the airway epithelial barrier. PolyI:C-dependent barrier disruption is mediated by disassembly of epithelial apical junctions, which is dependent on PKD signaling. These findings suggest a new mechanism potentially underlying the associations between viral respiratory tract infections, airway inflammation, and allergen sensitization. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  2. Polyinosinic:polycytidylic acid induces protein kinase D–dependent disassembly of apical junctions and barrier dysfunction in airway epithelial cells

    PubMed Central

    Rezaee, Fariba; Meednu, Nida; Emo, Jason A.; Saatian, Bahman; Chapman, Timothy J.; Naydenov, Nayden G.; De Benedetto, Anna; Beck, Lisa A.; Ivanov, Andrei I.; Georas, Steve N.

    2011-01-01

    Background Disruption of the epithelial barrier might be a risk factor for allergen sensitization and asthma. Viral respiratory tract infections are strongly associated with asthma exacerbation, but the effects of respiratory viruses on airway epithelial barrier function are not well understood. Many viruses generate double-stranded RNA, which can lead to airway inflammation and initiate an antiviral immune response. Objectives We investigated the effects of the synthetic double-stranded RNA polyinosinic:polycytidylic acid (polyI:C) on the structure and function of the airway epithelial barrier in vitro. Methods 16HBE14o- human bronchial epithelial cells and primary airway epithelial cells at an air-liquid interface were grown to confluence on Transwell inserts and exposed to polyI:C. We studied epithelial barrier function by measuring transepithelial electrical resistance and paracellular flux of fluorescent markers and structure of epithelial apical junctions by means of immunofluorescence microscopy. Results PolyI:C induced a profound decrease in transepithelial electrical resistance and increase in paracellular permeability. Immunofluorescence microscopy revealed markedly reduced junctional localization of zonula occludens-1, occludin, E-cadherin, β-catenin, and disorganization of junction-associated actin filaments. PolyI:C induced protein kinase D (PKD) phosphorylation, and a PKD antagonist attenuated polyI:C-induced disassembly of apical junctions and barrier dysfunction. Conclusions PolyI:C has a powerful and previously unsuspected disruptive effect on the airway epithelial barrier. PolyI:C-dependent barrier disruption is mediated by disassembly of epithelial apical junctions, which is dependent on PKD signaling. These findings suggest a new mechanism potentially underlying the associations between viral respiratory tract infections, airway inflammation, and allergen sensitization. PMID:21996340

  3. Viscosity-dependent drain current noise of AlGaN/GaN high electron mobility transistor in polar liquids

    SciTech Connect

    Fang, J. Y.; Hsu, C. P.; Kang, Y. W.; Fang, K. C.; Kao, W. L.; Yao, D. J.; Chen, C. C.; Li, S. S.; Yeh, J. A.; Wang, Y. L.; Lee, G. Y.; Chyi, J. I.; Hsu, C. H.; Huang, Y. F.; Ren, F.

    2013-11-28

    The drain current fluctuation of ungated AlGaN/GaN high electron mobility transistors (HEMTs) measured in different fluids at a drain-source voltage of 0.5 V was investigated. The HEMTs with metal on the gate region showed good current stability in deionized water, while a large fluctuation in drain current was observed for HEMTs without gate metal. The fluctuation in drain current for the HEMTs without gate metal was observed and calculated as standard deviation from a real-time measurement in air, deionized water, ethanol, dimethyl sulfoxide, ethylene glycol, 1,2-butanediol, and glycerol. At room temperature, the fluctuation in drain current for the HEMTs without gate metal was found to be relevant to the dipole moment and the viscosity of the liquids. A liquid with a larger viscosity showed a smaller fluctuation in drain current. The viscosity-dependent fluctuation of the drain current was ascribed to the Brownian motions of the liquid molecules, which induced a variation in the surface dipole of the gate region. This study uncovers the causes of the fluctuation in drain current of HEMTs in fluids. The results show that the AlGaN/GaN HEMTs may be used as sensors to measure the viscosity of liquids within a certain range of viscosity.

  4. Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium-induced colitis mouse model.

    PubMed

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2015-10-01

    Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.

  5. [Permeability of blood-brain barrier oxygen-glucose deprivation induced by tetramethylpyrazine-puerarin in vitro].

    PubMed

    Li, Jinhui; Che, Lingyan; Wang, Yu; Zhang, Yuyan; Wan, Haitong; Yang, Jiehong

    2010-10-01

    To explore permeability of artificial blood-brain barrier (aBBB) by oxygen-glucose deprivation combined (OGD)-induced using tetramethylpyrazine combined with puerarin in vitro. Rats were divided into normal control group, model group, tetramethylpyrazine group, puerarin group, tetramethylpyrazine-puerarin group and nimodipine group. Culture rat brain microvascular endothelial cells and astrocytes in vitro and build the OGD-induced aBBB damage model. Evaluate aBBB damage characteristics by TEER, gamma-GT, AKP and LDH. Determine contents of tetramethylpyrazine, puerarin, nimodipine and calculate drug permeating concentration of OGD-induced aBBB model by HPLC. Compared with the model, the level of TEER was lower than the control group with significant difference (P < 0.01). The levels of gamma-GT, AKP in tetramethylpyrazine group, tetramethylpyrazine-puerarin group and nimodipine group were higher than the model group, the differences were significant (P < 0.01). Compared with tetramethylpyrazine group or puerarin group, the level of AKP of tetramethylpyrazine-puerarin group increased significantly (P < 0.01). The differences of levels of TEER, gamma-GT, AKP and LDH between tetramethylpyrazine-puerarin group and nimodipinthe group were significant (P < 0.05). Tetramethylpyrazine-puerarin group has a synergistic effect of increasing TEER, gamma-GT, AKP and reducing LDH. The permeating rate in tetramethylpyrazine-puerarin group was higher than tetramethylpyrazine group and puerarin group. Tetramethylpyrazine-puerarin can permeate aBBB more easily and protect aBBB. The cause may relate to reducing the permeability of the OGD-induced aBBB.

  6. Nicotine Attenuates Disruption of Blood-Brain Barrier Induced by Saturated-Fat Feeding in Wild-Type Mice.

    PubMed

    Elahy, Mina; Lam, Virginie; Pallebage-Gamarallage, Menuka M; Giles, Corey; Mamo, John C L; Takechi, Ryusuke

    2015-12-01

    Emerging evidence suggests that integrity of blood-brain barrier (BBB) is pivotal to pathology and pathogenesis of vascular-based neurodegenerative disorders. We have recently reported BBB protective effects of nutraceutical agents with anti-inflammatory properties in an established dietary-induced BBB dysfunction model. Studies also reported that nicotine exhibits anti-oxidative/-inflammatory effects and improve cognitive impairment in Alzheimer's disease. However there has been no studies reporting the effect of nicotine on high-fat-induced BBB dysfunction. In the present study, we investigated the effect of nicotine on BBB integrity and neuro-inflammation in an established mouse model of BBB disruption induced by a diet enriched in saturated fatty acids (SFA). Wild-type C57BL/6J mice were fed chow enriched in SFA (23% w/w) with/without nicotine for 10 weeks. Compared to mice maintained on SFA-free and low-fat (LF) chow (4% w/w), capillary permeability indicated by the parenchymal extravasation of plasma derived IgG, was significantly greater in the SFA treatment group. Nicotine provided concomitantly with the SFA diet significantly attenuated IgG extravasation, however it remained significantly greater than LF-controls. Markers of neurovascular inflammation glial fibrillary acidic protein, cyclooxygenase-2, and glucose regulated protein 78 remained exaggerated in SFA+nicotine treated mice compared to LF-controls. Nicotine did however modestly, but not significantly, improve plasma total anti-oxidative status in SFA fed mice. Nicotine moderately attenuated BBB disruption induced by chronic ingestion of high-SFA diet, but had no significant effect on neuroinflammation per se. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Schottky barrier MOSFET systems and fabrication thereof

    DOEpatents

    Welch, J.D.

    1997-09-02

    (MOS) device systems-utilizing Schottky barrier source and drain to channel region junctions are disclosed. Experimentally derived results which demonstrate operation of fabricated N-channel and P-channel Schottky barrier (MOSFET) devices, and of fabricated single devices with operational characteristics similar to (CMOS) and to a non-latching (SRC) are reported. Use of essentially non-rectifying Schottky barriers in (MOS) structures involving highly doped and the like and intrinsic semiconductor to allow non-rectifying interconnection of, and electrical accessing of device regions is also disclosed. Insulator effected low leakage current device geometries and fabrication procedures therefore are taught. Selective electrical interconnection of drain to drain, source to drain, or source to source, of N-channel and/or P-channel Schottky barrier (MOSFET) devices formed on P-type, N-type and Intrinsic semiconductor allows realization of Schottky Barrier (CMOS), (MOSFET) with (MOSFET) load, balanced differential (MOSFET) device systems and inverting and non-inverting single devices with operating characteristics similar to (CMOS), which devices can be utilized in modulation, as well as in voltage controlled switching and effecting a direction of rectification. 89 figs.

  8. Schottky barrier MOSFET systems and fabrication thereof

    DOEpatents

    Welch, James D.

    1997-01-01

    (MOS) device systems-utilizing Schottky barrier source and drain to channel region junctions are disclosed. Experimentally derived results which demonstrate operation of fabricated N-channel and P-channel Schottky barrier (MOSFET) devices, and of fabricated single devices with operational characteristics similar to (CMOS) and to a non-latching (SRC) are reported. Use of essentially non-rectifying Schottky barriers in (MOS) structures involving highly doped and the like and intrinsic semiconductor to allow non-rectifying interconnection of, and electrical accessing of device regions is also disclosed. Insulator effected low leakage current device geometries and fabrication procedures therefore are taught. Selective electrical interconnection of drain to drain, source to drain, or source to source, of N-channel and/or P-channel Schottky barrier (MOSFET) devices formed on P-type, N-type and Intrinsic semiconductor allows realization of Schottky Barrier (CMOS), (MOSFET) with (MOSFET) load, balanced differential (MOSFET) device systems and inverting and non-inverting single devices with operating characteristics similar to (CMOS), which devices can be utilized in modulation, as well as in voltage controled switching and effecting a direction of rectification.

  9. Optimization of the Ultrasound-Induced Blood-Brain Barrier Opening

    PubMed Central

    Konofagou, Elisa E.

    2012-01-01

    Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly non-invasive, transient, and regionally selective brain drug delivery method. The brain is particularly difficult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions connecting adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy also constitute the cause of the tremendous obstacles posed in its pharmacological treatment. The BBB prevents most neurologically active drugs from entering the brain and, as a result, has been isolated as the rate-limiting factor in brain drug delivery. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. Over the past decade, methods that combine Focused Ultrasound (FUS) and microbubbles have been shown to offer the unique capability of noninvasively, locally and transiently open the BBB so as to treat central nervous system (CNS) diseases. Four of the main challenges that have been taken on by our group and discussed in this paper are: 1) assess its safety profile, 2) unveil the mechanism by which the BBB opens and closes, 3) control and predict the opened BBB properties and duration of the opening and 4) assess its premise in brain drug delivery. All these challenges will be discussed, findings in both small (mice) and large (non-human primates) animals are shown and finally the clinical potential for this technique is shown. PMID:23382778

  10. Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury

    PubMed Central

    Lucke-Wold, Brandon P.; Logsdon, Aric F.; Smith, Kelly E.; Turner, Ryan C.; Alkon, Daniel L.; Tan, Zhenjun; Naser, Zachary J.; Knotts, Chelsea M.; Huber, Jason D.

    2016-01-01

    Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the ‘signature injury’ of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague–Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan’s blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan’s blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t=4.808, p<0.05), and a reduction back toward control levels when bryostatin-1 was administered (t=5.113, p<0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t=4.559, p<0.01) and increased the neuroprotective isozyme PKCε (t=6.102, p<0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma. PMID:25301233

  11. Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury.

    PubMed

    Lucke-Wold, Brandon P; Logsdon, Aric F; Smith, Kelly E; Turner, Ryan C; Alkon, Daniel L; Tan, Zhenjun; Naser, Zachary J; Knotts, Chelsea M; Huber, Jason D; Rosen, Charles L

    2015-12-01

    Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t = 4.808, p < 0.05), and a reduction back toward control levels when bryostatin-1 was administered (t = 5.113, p < 0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t = 4.559, p < 0.01) and increased the neuroprotective isozyme PKCε (t = 6.102, p < 0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.

  12. Matrix Metalloproteinase-12 Induces Blood-Brain Barrier Damage After Focal Cerebral Ischemia.

    PubMed

    Chelluboina, Bharath; Klopfenstein, Jeffrey D; Pinson, David M; Wang, David Z; Vemuganti, Raghu; Veeravalli, Krishna Kumar

    2015-12-01

    Matrix metalloproteinases (MMPs) have a central role in compromising the integrity of the blood-brain barrier (BBB). The role of MMP-12 in brain damage after ischemic stroke remains unknown. The main objective of the current study is to investigate the effect of MMP-12 suppression at an early time point before reperfusion on the BBB damage in rats. Sprague-Dawley rats were subjected to middle cerebral artery occlusion and reperfusion. MMP-12 shRNA-expressing plasmids formulated as nanoparticles were administered at a dose of 1 mg/kg body weight. The involvement of MMP-12 on BBB damage was assessed by performing various techniques, including Evans blue dye extravasation, 2,3,5-triphenyltetrazolium chloride staining, immunoblot, gelatin zymography, and immunofluorescence analysis. MMP-12 is upregulated ≈31-, 47-, and 66-fold in rats subjected 1-, 2-, or 4-hour ischemia, respectively, followed by 1-day reperfusion. MMP-12 suppression protected the BBB integrity by inhibiting the degradation of tight-junction proteins. Either intravenous or intra-arterial delivery of MMP-12 shRNA-expressing plasmid significantly reduced the percent Evans blue dye extravasation and infarct size. Furthermore, MMP-12 suppression reduced the endogenous levels of other proteases, such as tissue-type plasminogen activator and MMP-9, which are also known to be the key players involved in BBB damage. These results demonstrate the adverse role of MMP-12 in acute brain damage that occurs after ischemic stroke and, thereby, suggesting that MMP-12 suppression could be a promising therapeutic target for cerebral ischemia. © 2015 American Heart Association, Inc.

  13. Internally drained condenser for spacecraft thermal management

    NASA Technical Reports Server (NTRS)

    Valenzuela, Javier A.; Drew, Brian C.

    1989-01-01

    This paper presents the results obtained to date in a program to develop a high heat flux condenser for use in two-phase spacecraft thermal management loops. The objective is to obtain a several fold increase in condensation heat transfer coefficient over those which can be achieved with shear-controlled or capillary-wick condensers. The internally drained condenser relies on shaped fins to develop a capillary pressure gradient over the surface of the fins and drive the condensate toward narrow drainage grooves separating the fins. The condensate then flows through a drainage network embedded in the condenser walls. Heat transfer coefficients of up to 8 W/sq cm C were measured in steam, providing a heat transfer enhancement ratio greater than a factor of 8. In the paper the proof-of-concept experiments are described and simplified models to predict the performance of the internally drained condenser are presented.

  14. Denaturated proteins: Draining effect and molecular dimensions

    NASA Astrophysics Data System (ADS)

    Dondos, A.

    2010-09-01

    Using equations derived from the synthetic macromolecules, we calculate the dimensions in solution of the denaturated proteins. For these calculations, we use a value for the Flory’s parameter Φ obtained from an equation established for the polymers presenting a draining effect, and which is lower than the value of 2.6×10 23 (cgs) generally used. The obtained values for the dimensions of the denaturated proteins (end to end distance, statistical segment length and relation from the end to end distance and the number of residue) using the method proposed here are in good agreement with the values obtained from Flory and co-workers. On the contrary, the values obtained in this work are different from the values proposed by other authors who do not take into account the draining effect and use a value for Φ equal to 2.6×10 23.

  15. Protection of blood-brain barrier breakdown by nifedipine in adrenaline-induced acute hypertension.

    PubMed

    Nukhet Turkel, A; Ziya Ziylan, Y

    2004-04-01

    The question of whether influxes of ionic Ca+2 into cerebral endothelium plays an important role in increased vascular permeability consequent to an acute hypertension is not accurately resolved. We tested the effect of nifedipine, a calcium entry blocker, on the cerebrovascular permeability for proteins in adrenalin-induced acute hypertension. The experiments were carried out on male Wistar rats. The experimental groups consisted of normotensive saline controls, adrenaline-induced hypertensive rats, and adrenalin-induced hypertensive rats as pre-treated or post-treated with a bolus of nifedipine. Brains of hypertensive rats showed increased permeability to Evans Blue-Albumin complex, when blood pressure elevated rapidly to more than 170 mmHg. The number and size of areas of Evans-Blue extravasation were smaller if an increase in blood pressure was prevented. The short lasting elevation of blood pressure did not result in protein extravasation in brains of hypertensive rats. The results suggest that nifedipine can modify the permeability disruptions observed in acutely hypertensive rats. The data also support the hypothesis that Ca+2 may be responsible for the changes in permeability of BBB in hypertension by mediating the contraction of vascular muscles.

  16. Using Smoke Injection in Drains to Identify Potential Preferential Pathways in a Drained Arable Field

    NASA Astrophysics Data System (ADS)

    Nielsen, M. H.; Petersen, C. T.; Hansen, S.

    2014-12-01

    Macropores forming a continuous pathway between the soil surface and subsurface drains favour the transport of many contaminants from agricultural fields to surface waters. The smoke injection method presented by Shipitalo and Gibbs (2000) used for demonstrating and quantifying such pathways has been further developed and used on a drained Danish sandy loam. In order to identify the preferential pathways to drains, smoke was injected in three 1.15 m deep tile drains (total drain length 93 m), and smoke emitting macropores (SEMP) at the soil surface were counted and characterized as producing either strong or weak plumes compared to reference plumes from 3 and 6 mm wide tubes. In the two situations investigated in the present study - an early spring and an autumn situation, smoke only penetrated the soil surface layer via earthworm burrows located in a 1.0 m wide belt directly above the drain lines. However, it is known from previous studies that desiccation fractures in a dry summer situation also can contribute to the smoke pattern. The distance between SEMP measured along the drain lines was on average 0.46 m whereas the average spacing between SEMP with strong plumes was 2.3 m. Ponded water was applied in 6 cm wide rings placed above 52 burrows including 17 reference burrows which did not emit smoke. Thirteen pathways in the soil were examined using dye tracer and profile excavation. SEMP with strong plumes marked the entrance of highly efficient transport pathways conducting surface applied water and dye tracer into the drain. However, no single burrow was traced all the way from the surface into the drain, the dye patterns branched off in a network of other macropores. Water infiltration rates were significantly higher (P < 0.05) in SEMP with strong plumes (average rate: 247 mL min-1 n = 19) compared to SEMP with weak plumes (average rate: 87 mL min-1 n = 16) and no plumes (average rate: 56 mL min-1 n = 17). The results suggest that the smoke injection method

  17. Percutaneous Retrieval of a Retained Jackson-Pratt Drain Fragment

    SciTech Connect

    Namyslowski, Jan; Halin, Neil J.; Greenfield, Alan J.

    1996-11-15

    A retained intraabdominal Jackson-Pratt drain fragment was percutaneously retrieved using an inflated angioplasty balloon that had been maneuvered inside of the drain lumen over a hydrophilic-coated steerable guidewire.

  18. Bulk Friction Angles in Dry, Drained, and Saturated Gravel Beds

    NASA Astrophysics Data System (ADS)

    Holo, S.; Palucis, M. C.; Lamb, M. P.

    2015-12-01

    We examined the effect of capillary action and lubrication of grains on bulk friction angles through tilting chute experiments. In each experiment, we screed a bed of 5mm gravels in 65cm long x 18cm wide tilting chute with fixed roughness and slowly tilted the chute until a granular avalanche occurred. We performed these experiments under three conditions: with dry grains, with a bed that had been submerged and subsequently drained such that no water occupied the pore space, and with the entire apparatus submerged under water such that the bed is saturated. In addition, for each of these cases, we performed experiments with 5, 10, and 15cm bed thicknesses. In the dry case, the bed failed at ~ 41º, and bed thickness did not have a significant effect on failure angle. In the drained case, friction angles increased from 46.5º to 50.9º with increasing bed thickness. In the submerged case, the bed failed at angles not significantly different than those from the dry case, and they did not vary with bed thickness. The increase in friction angles between the dry and drained cases suggests that addition of the water induces a cohesive effect on the grains. Because the pore pressure from the saturated bed removes capillary effects but retains lubrication effects, the submerged case data suggest that capillary action is primarily responsible for the observed increases in friction angle and effects from grain lubrication are negligible. Further study is ongoing to fully understand the effect of capillary action on bulk friction angles in unsaturated gravel and why it appears to increase with bed thickness.

  19. Nanoscale-Barrier Formation Induced by Low-Dose Electron-Beam Exposure in Ultrathin MoS2 Transistors.

    PubMed

    Matsunaga, Masahiro; Higuchi, Ayaka; He, Guanchen; Yamada, Tetsushi; Krüger, Peter; Ochiai, Yuichi; Gong, Yongji; Vajtai, Robert; Ajayan, Pulickel M; Bird, Jonathan P; Aoki, Nobuyuki

    2016-10-05

    Utilizing an innovative combination of scanning-probe and spectroscopic techniques, supported by first-principles calculations, we demonstrate how electron-beam exposure of field-effect transistors, implemented from ultrathin molybdenum disulfide (MoS2), may cause nanoscale structural modifications that in turn significantly modify the electrical operation of these devices. Quite surprisingly, these modifications are induced by even the relatively low electron doses used in conventional electron-beam lithography, which are found to induce compressive strain in the atomically thin MoS2. Likely arising from sulfur-vacancy formation in the exposed regions, the strain gives rise to a local widening of the MoS2 bandgap, an idea that is supported both by our experiment and by the results of first-principles calculations. A nanoscale potential barrier develops at the boundary between exposed and unexposed regions and may cause extrinsic variations in the resulting electrical characteristics exhibited by the transistor. The widespread use of electron-beam lithography in nanofabrication implies that the presence of such strain must be carefully considered when seeking to harness the potential of atomically thin transistors. At the same time, this work also promises the possibility of exploiting the strain as a means to achieve "bandstructure engineering" in such devices.

  20. Permeability assessment of the focused ultrasound-induced blood-brain barrier opening using dynamic contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Vlachos, F.; Tung, Y.-S.; Konofagou, E. E.

    2010-09-01

    Focused ultrasound (FUS) in conjunction with microbubbles has been shown to successfully open the blood-brain barrier (BBB) in the mouse brain. In this study, we compute the BBB permeability after opening in vivo. The spatial permeability of the BBB-opened region was assessed using dynamic contrast-enhanced MRI (DCE-MRI). The DCE-MR images were post-processed using the general kinetic model (GKM) and the reference region model (RRM). Permeability maps were generated and the Ktrans values were calculated for a predefined volume of interest in the sonicated and the control area for each mouse. The results demonstrated that Ktrans in the BBB-opened region (0.02 ± 0.0123 for GKM and 0.03 ± 0.0167 min-1 for RRM) was at least two orders of magnitude higher when compared to the contra-lateral (control) side (0 and 8.5 × 10-4 ± 12 × 10-4 min-1, respectively). The permeability values obtained with the two models showed statistically significant agreement and excellent correlation (R2 = 0.97). At histological examination, it was concluded that no macroscopic damage was induced. This study thus constitutes the first permeability assessment of FUS-induced BBB opening using DCE-MRI, supporting the fact that the aforementioned technique may constitute a safe, non-invasive and efficacious drug delivery method.

  1. Variations of Morphologic Changes induced by Tropical Storm Debby along Three Barrier Island, West-Central Florida, USA

    NASA Astrophysics Data System (ADS)

    Wang, P.; Roberts, T.

    2012-12-01

    Tropical Storm Debby generated sustained high waves and elevated water levels for nearly three days from June 24th to 26th, 2012, inducing substantial changes in beach and nearshore morphology. In addition, the storm winds and high waves approached the coast from a highly oblique angle from the south, driving substantial northward longshore sand transport, opposite to the regional net annual southward transport. A total of 145 beach and nearshore profiles along 3 adjacent barrier islands were surveyed 2 weeks before and one week after the storm impact. Overall, dune, beach, intertidal, and immediate subtidal areas suffered erosion, while deposition was measured over the nearshore bar. Beach recovery in the form of ridge and runnel development occurred as the storm energy subsided. Substantial longshore variations of storm-induced beach changes were measured, including both severe dune/beach/berm erosion and storm berm accretion, and both onshore and offshore migration of nearshore bar. Factors controlling these longshore variations include: 1) the oblique approaching of the storm forcing, 2) pre-storm beach morphology and chronic erosional or accretional trends, 3) sediment supply, and 4) tidal inlet and beach interactions. Wide spreading dune scarping occurred along the 30-km studied coast. Based on the pre- and post-storm survey data, a balanced sediment budget is obtained accounting for sand volume loss from dune, beach, intertidal, and subtidal zones, and sand gains over the nearshore bar and along the northern sections of the beach.

  2. Transendothelial permeability changes induced by free radicals in an in vitro model of the blood-brain barrier.

    PubMed

    Lagrange, P; Romero, I A; Minn, A; Revest, P A

    1999-09-01

    In the present study, we investigated the changes in blood-brain barrier (BBB) permeability following brain endothelial cell exposure to different xenobiotics able to promote free radical generation during their metabolism. Our in vitro BBB model consisted of confluent monolayers of immortalized rat brain capillary endothelial cells (RBE4) grown on collagen-coated filters in the presence of C6 glioma cells grown in the lower compartment. We have recently shown that a range of xenobiotics, including menadione, nitrofurazone, and methylviologen (paraquat) may undergo monoelectronic redox cycling in isolated brain capillaries, giving rise to reactive oxygen species. In this study, addition of 100 microM menadione to the culture medium for 30 min significantly increased the permeability of endothelial cell monolayers to radiolabeled sucrose. The effect on endothelial permeability induced by menadione was dose-dependent and reversible. These permeability changes preceded the onset of cell death, as assessed by the Trypan blue exclusion method. Pre-incubation with superoxide dismutase and catalase blocked changes in sucrose permeability to control levels in a dose-dependent manner, suggesting the involvement of reactive oxygen species in menadione-induced BBB opening.

  3. Eosinophilic esophagitis–linked calpain 14 is an IL-13–induced protease that mediates esophageal epithelial barrier impairment

    PubMed Central

    Davis, Benjamin P.; Stucke, Emily M.; Khorki, M. Eyad; Litosh, Vladislav A.; Rymer, Jeffrey K.; Rochman, Mark; Travers, Jared; Kottyan, Leah C.

    2016-01-01

    We recently identified a genome-wide genetic association of eosinophilic esophagitis (EoE) at 2p23 spanning the calpain 14 (CAPN14) gene, yet the causal mechanism has not been elucidated. We now show that recombinant CAPN14 cleaves a calpain-specific substrate and is inhibited by 4 classical calpain inhibitors: MDL-28170, acetyl-calpastatin, E-64, and PD151746. CAPN14 is specifically induced (>100-fold) in esophageal epithelium after IL-13 treatment. Epithelial cells overexpressing CAPN14 display impaired epithelial architecture, characterized by acantholysis, epidermal clefting, and epidermolysis. CAPN14 overexpression impairs epithelial barrier function, as demonstrated by decreased transepithelial resistance (2.1-fold) and increased FITC-dextran flux (2.6-fold). Epithelium with gene-silenced CAPN14 demonstrates increased dilated intercellular spaces (5.5-fold) and less organized basal cell layering (1.5-fold) following IL-13 treatment. Finally, CAPN14 overexpression results in loss of desmoglein 1 (DSG1) expression, whereas the IL-13–induced loss of DSG1 is normalized by CAPN14 gene silencing. Importantly, these findings were specific to CAPN14, as they were not observed with modulation of CAPN1 expression. These results, along with the potent induction of CAPN14 by IL-13 and genetic linkage of EoE to the CAPN14 gene locus, demonstrate a molecular and cellular pathway that contributes to T helper type 2 responses in mucosal epithelium. PMID:27158675

  4. Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior for Patlak Model

    PubMed Central

    Fang, Ruogu; Karlsson, Kolbeinn; Chen, Tsuhan; Sanelli, Pina C.

    2014-01-01

    Blood-brain-barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. PMID:24200529

  5. Resveratrol attenuates lipopolysaccharide-induced dysfunction of blood-brain barrier in endothelial cells via AMPK activation

    PubMed Central

    2016-01-01

    Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. The blood-brain barrier (BBB), formed by specialized brain endothelial cells that are interconnected by tight junctions, strictly regulates paracellular permeability to maintain an optimal extracellular environment for brain homeostasis. The aim of this study was to elucidate the effects of resveratrol and the role of AMPK in BBB dysfunction induced by lipopolysaccharide (LPS). Exposure of human brain microvascular endothelial cells (HBMECs) to LPS (1 µg/ml) for 4 to 24 hours week dramatically increased the permeability of the BBB in parallel with lowered expression levels of occluding and claudin-5, which are essential to maintain tight junctions in HBMECs. In addition, LPS significantly increased the reactive oxygen species (ROS) productions. All effects induced by LPS in HBVMCs were reversed by adenoviral overexpression of superoxide dismutase, inhibition of NAD(P) H oxidase by apocynin or gain-function of AMPK by adenoviral overexpression of constitutively active mutant (AMPK-CA) or by resveratrol. Finally, upregulation of AMPK by either AMPK-CA or resveratrol abolished the levels of LPS-enhanced NAD(P)H oxidase subunits protein expressions. We conclude that AMPK activation by resveratrol improves the integrity of the BBB disrupted by LPS through suppressing the induction of NAD(P)H oxidase-derived ROS in HBMECs. PMID:27382348

  6. A Conserved Behavioral State Barrier Impedes Transitions between Anesthetic-Induced Unconsciousness and Wakefulness: Evidence for Neural Inertia

    PubMed Central

    Friedman, Eliot B.; Sun, Yi; Moore, Jason T.; Hung, Hsiao-Tung; Meng, Qing Cheng; Perera, Priyan; Joiner, William J.; Thomas, Steven A.; Eckenhoff, Roderic G.; Sehgal, Amita; Kelz, Max B.

    2010-01-01

    One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these transitions. Induction of anesthesia is commonly attributed to drug-induced global modulation of neuronal function, while emergence from anesthesia has been thought to occur passively, paralleling elimination of the anesthetic from its sites in the central nervous system (CNS). If this were true, then CNS anesthetic concentrations on induction and emergence would be indistinguishable. By generating anesthetic dose-response data in both insects and mammals, we demonstrate that the forward and reverse paths through which anesthetic-induced unconsciousness arises and dissipates are not identical. Instead they exhibit hysteresis that is not fully explained by pharmacokinetics as previously thought. Single gene mutations that affect sleep-wake states are shown to collapse or widen anesthetic hysteresis without obvious confounding effects on volatile anesthetic uptake, distribution, or metabolism. We propose a fundamental and biologically conserved concept of neural inertia, a tendency of the CNS to resist behavioral state transitions between conscious and unconscious states. We demonstrate that such a barrier separates wakeful and anesthetized states for multiple anesthetics in both flies and mice, and argue that it contributes to the hysteresis observed when the brain transitions between conscious and unconscious states. PMID:20689589

  7. Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases.

    PubMed

    Rahbari, Nuh N; Kedrin, Dmitriy; Incio, Joao; Liu, Hao; Ho, William W; Nia, Hadi T; Edrich, Christina M; Jung, Keehoon; Daubriac, Julien; Chen, Ivy; Heishi, Takahiro; Martin, John D; Huang, Yuhui; Maimon, Nir; Reissfelder, Christoph; Weitz, Jurgen; Boucher, Yves; Clark, Jeffrey W; Grodzinsky, Alan J; Duda, Dan G; Jain, Rakesh K; Fukumura, Dai

    2016-10-12

    The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition. The density of these matrix components correlated with increased tumor stiffness after anti-VEGF therapy. Treatment-induced tumor hypoxia appeared to be the driving force for the remodeling of the extracellular matrix. In preclinical models, we show that enzymatic depletion of HA partially rescued the compromised perfusion in liver mCRCs after anti-VEGF therapy and prolonged survival in combination with anti-VEGF therapy and chemotherapy. These findings suggest that extracellular matrix components such as HA could be a potential therapeutic target for reducing physical barriers to systemic treatments in patients with mCRC who receive anti-VEGF therapy.

  8. Targeted gene delivery to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption.

    PubMed

    Huang, Qin; Deng, Jinmu; Wang, Feng; Chen, Song; Liu, Yingjiang; Wang, Zhibiao; Wang, Zhigang; Cheng, Yuan

    2012-01-01

    This study aimed to investigate the feasibility of targeted gene transfer into central nervous system (CNS) by MRI-guided focused ultrasound-induced blood-brain barrier (BBB) disruption. Before each sonication, T2-weighted images were obtained to select the target region. Followed by injecting DNA-loaded microbubbles into the tail vein, sonication was performed. The state of local BBB, distribution of plasmid DNA through the opened BBB, the ultrastructural changes of neurons and BDNF expression were detected. The results showed that MRI-guided focused ultrasound (FUS) could accomplish noninvasive, transient, and local BBB disruption, at 1h after sonication, plasmid DNA across the opened BBB had been internalized into the neurons presenting heterogeneous distribution and numerous transparent vesicles were observed in the cytoplasm of the neurons at the sonicated region, suggesting vesicle-mediated endocytosis. At 48 h after sonication, the expressions of exogenous gene pBDNF-EGFP were observed in the cytoplasm of some neurons, and BDNF expressions were markedly enhanced by the combination of ultrasound and pBDNF-EGFP-loaded microbubbles about 20-fold than that of the control group (P<0.01). The method by using MRI-guided FUS to induce the local BBB disruption could accomplish effective targeted exogenous gene transfer in CNS. This technique may provide a new option for the treatment of various CNS diseases.

  9. Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

    PubMed

    Yang, Feng-Yi; Lin, Yi-Li; Chou, Fong-In; Lin, Yu-Chuan; Hsueh Liu, Yen-Wan; Chang, Lun-Wei; Hsieh, Yu-Ling

    2014-01-01

    The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

  10. Modified Pulsatilla decoction attenuates oxazolone-induced colitis in mice through suppression of inflammation and epithelial barrier disruption

    PubMed Central

    Wang, Xuewei; Fan, Fugang; Cao, Qin

    2016-01-01

    Inflammatory bowel diseases (IBDs) are chronic inflammatory gastrointestinal disorders caused by a dysregulated mucosal immune response and epithelial barrier disruption. Conventional treatment of IBD is currently limited to overcoming patient symptoms and is often associated with severe adverse effects from the drugs used. Modified Pulsatilla decoction has been used previously to treat ulcerative colitis (UC) in clinical practice in China, however, the underlying mechanism in the treatment of UC remains to be elucidated. In the present study, the efficiency and mechanisms of modified Pulsatilla decoction in the treatment of oxazolone-induced colitis were investigated. Assessment of clinical colitis and histological examination found that the administration of modified Pulsatilla decoction attenuated the severity of oxazolone-induced colitis in mice. Measurement of cytokine concentration, western blotting and reverse transcription-quantitative polymerase chain reaction demonstrated modified Pulsatilla decoction treatment significantly reduced the secretion of pro-inflammatory cytokines and restored alterations in tight junction proteins in the colon tissues. In addition, modified Pulsatilla decoction suppressed the activation of the nuclear factor-κB signaling pathway. Thus, the findings of the present study demonstrated that modified Pulsatilla decoction offers an effective therapeutic approach for the treatment of IBD and revealed the underlying mechanisms of action offered by modified Pulsatilla decoction. PMID:27278299

  11. Nonthermal dielectric-barrier discharge plasma-induced inactivation involves oxidative DNA damage and membrane lipid peroxidation in Escherichia coli.

    PubMed

    Joshi, Suresh G; Cooper, Moogega; Yost, Adam; Paff, Michelle; Ercan, Utku K; Fridman, Gregory; Friedman, Gary; Fridman, Alexander; Brooks, Ari D

    2011-03-01

    Oxidative stress leads to membrane lipid peroxidation, which yields products causing variable degrees of detrimental oxidative modifications in cells. Reactive oxygen species (ROS) are the key regulators in this process and induce lipid peroxidation in Escherichia coli. Application of nonthermal (cold) plasma is increasingly used for inactivation of surface contaminants. Recently, we reported a successful application of nonthermal plasma, using a floating-electrode dielectric-barrier discharge (FE-DBD) technique for rapid inactivation of bacterial contaminants in normal atmospheric air (S. G. Joshi et al., Am. J. Infect. Control 38:293-301, 2010). In the present report, we demonstrate that FE-DBD plasma-mediated inactivation involves membrane lipid peroxidation in E. coli. Dose-dependent ROS, such as singlet oxygen and hydrogen peroxide-like species generated during plasma-induced oxidative stress, were responsible for membrane lipid peroxidation, and ROS scavengers, such as α-tocopherol (vitamin E), were able to significantly inhibit the extent of lipid peroxidation and oxidative DNA damage. These findings indicate that this is a major mechanism involved in FE-DBD plasma-mediated inactivation of bacteria.

  12. Acute effects of focused ultrasound-induced increases in blood-brain barrier permeability on rat microvascular transcriptome

    PubMed Central

    McMahon, Dallan; Bendayan, Reina; Hynynen, Kullervo

    2017-01-01

    Therapeutic treatment options for central nervous system diseases are greatly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), in conjunction with circulating microbubbles, can be used to induce a targeted and transient increase in BBB permeability, providing a unique approach for the delivery of drugs from the systemic circulation into the brain. While preclinical research has demonstrated the utility of FUS, there remains a large gap in our knowledge regarding the impact of sonication on BBB gene expression. This work is focused on investigating the transcriptional changes in dorsal hippocampal rat microvessels in the acute stages following sonication. Microarray analysis of microvessels was performed at 6 and 24 hrs post-FUS. Expression changes in individual genes and bioinformatic analysis suggests that FUS may induce a transient inflammatory response in microvessels. Increased transcription of proinflammatory cytokine genes appears to be short-lived, largely returning to baseline by 24 hrs. This observation may help to explain some previously observed bioeffects of FUS and may also be a driving force for the angiogenic processes and reduced drug efflux suggested by this work. While further studies are necessary, these results open up intriguing possibilities for novel FUS applications and suggest possible routes for pharmacologically modifying the technique. PMID:28374753

  13. Improving low-dose blood-brain barrier permeability quantification using sparse high-dose induced prior for Patlak model.

    PubMed

    Fang, Ruogu; Karlsson, Kolbeinn; Chen, Tsuhan; Sanelli, Pina C

    2014-08-01

    Blood-brain barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis.

  14. DNA Persistence in a Sink Drain Environment

    SciTech Connect

    Winder, Eric M.; Bonheyo, George T.

    2015-07-31

    Biofilms are organized structures composed mainly of cells and extracellular polymeric substances produced by the constituent microorganisms. Ubiquitous in nature, biofilms have an innate ability to capture and retain passing material and may therefore act as natural collectors of contaminants or signatures of upstream activities. To determine the persistence and detectability of DNA passing through a sink drain environment, Bacillus anthracis strain Ames35 was cultured (6.35 x 107 CFU/mL), sterilized, and disposed of by addition to a sink drain apparatus with an established biofilm. The sink drain apparatus was sampled before and for several days after the addition of the sterilized B. anthracis culture to detect the presence of B. anthracis DNA. Multiple PCR primer pairs were used to screen for chromosomal and plasmid DNA with primers targeting shorter sequences showing greater amplification efficiency and success. PCR amplification and detection of target sequences indicate persistence of chromosomal DNA and plasmid DNA in the biofilm for 5 or more and 14 or more days, respectively.

  15. DNA Persistence in a Sink Drain Environment

    DOE PAGES

    Winder, Eric M.; Bonheyo, George T.

    2015-07-31

    Biofilms are organized structures composed mainly of cells and extracellular polymeric substances produced by the constituent microorganisms. Ubiquitous in nature, biofilms have an innate ability to capture and retain passing material and may therefore act as natural collectors of contaminants or signatures of upstream activities. To determine the persistence and detectability of DNA passing through a sink drain environment, Bacillus anthracis strain Ames35 was cultured (6.35 x 107 CFU/mL), sterilized, and disposed of by addition to a sink drain apparatus with an established biofilm. The sink drain apparatus was sampled before and for several days after the addition of themore » sterilized B. anthracis culture to detect the presence of B. anthracis DNA. Multiple PCR primer pairs were used to screen for chromosomal and plasmid DNA with primers targeting shorter sequences showing greater amplification efficiency and success. PCR amplification and detection of target sequences indicate persistence of chromosomal DNA and plasmid DNA in the biofilm for 5 or more and 14 or more days, respectively.« less

  16. Subarachnoid hemorrhage due to retained lumbar drain.

    PubMed

    Guppy, Kern H; Silverthorn, James W; Akins, Paul T

    2011-12-01

    Intrathecal spinal catheters (lumbar drains) are indicated for several medical and surgical conditions. In neurosurgical procedures, they are used to reduce intracranial and intrathecal pressures by diverting CSF. They have also been placed for therapeutic access to administer drugs, and more recently, vascular surgeons have used them to improve spinal cord perfusion during the treatment of thoracic aortic aneurysms. Insertion of these lumbar drains is not without attendant complications. One complication is the shearing of the distal end of the catheter with a resultant retained fragment. The authors report the case of a 65-year-old man who presented with a subarachnoid hemorrhage due to the migration of a retained lumbar drain that sheared off during its removal. To the best of the authors' knowledge, this is the first case of rostral migration of a retained intrathecal catheter causing subarachnoid hemorrhage. The authors review the literature on retained intrathecal spinal catheters, and their findings support either early removal of easily accessible catheters or close monitoring with serial imaging.

  17. DNA Persistence in a Sink Drain Environment

    PubMed Central

    Winder, Eric M.; Bonheyo, George T.

    2015-01-01

    Biofilms are organized structures composed mainly of cells and extracellular polymeric substances produced by the constituent microorganisms. Ubiquitous in nature, biofilms have an innate ability to capture and retain passing material and may therefore act as natural collectors of contaminants or signatures of upstream activities. To determine the persistence and detectability of DNA passing through a sink drain environment, Bacillus anthracis strain Ames35 was cultured (6.35 x 107 CFU/mL), sterilized, and disposed of by addition to a sink drain apparatus with an established biofilm. The sink drain apparatus was sampled before and for several days after the addition of the sterilized B. anthracis culture to detect the presence of B. anthracis DNA. Multiple PCR primer pairs were used to screen for chromosomal and plasmid DNA with primers targeting shorter sequences showing greater amplification efficiency and success. PCR amplification and detection of target sequences indicate persistence of chromosomal DNA and plasmid DNA in the biofilm for 5 or more and 14 or more days, respectively. PMID:26230525

  18. Mycotoxin detoxifiers attenuate deoxynivalenol-induced pro-inflammatory barrier insult in porcine enterocytes as an in vitro evaluation model of feed mycotoxin reduction.

    PubMed

    Park, Seong-Hwan; Kim, Juil; Kim, Dongwook; Moon, Yuseok

    2017-02-01

    Deoxynivalenol (DON), the most prevalent mycotoxin worldwide, leads to economic losses for animal food production. Swine is a most sensitive domestic animal to DON due to rapid absorption and low detoxification by gut microbiota. Specifically, DON can severely damage pig intestinal tissue by disrupting the intestinal barrier and inducing inflammatory responses. We evaluated the effects of several mycotoxin detoxifiers including bentonites, yeast cell wall components, and mixture-typed detoxifier composed of mineral, microorganisms, and phytogenic substances on DON-insulted intestinal barrier and pro-inflammatory responses using in vitro porcine enterocyte culture model. DON-induced disruption of the in vitro gut barrier was attenuated by all three mycotoxin detoxifiers in dose-dependent manners. These mycotoxin detoxifiers also suppressed DON-induced pro-inflammatory chemokine expression to different degrees, which was mediated by downregulation of mitogen-activated kinases and early growth response-1. Of note, the mixture-typed detoxifier was the most prominent mitigating agent at the cellular levels whereas the high dose of bentonite clay also had suppressive action against DON-induced pro-inflammatory insult. The in vitro porcine enterocyte-based assessment of intestinal barrier integrity and inflammatory signals provides sensitive and simplified alternative bioassay of feed additives such as detoxifiers against enteropathogenic mycotoxins with comprehensive mechanistic confirmation.

  19. Reaction Mechanisms in Collisions Induced by Halo and/or Weakly Bound Nuclei Around the Barrier: the 13N+9Be and 6He+64Zn Collisions

    SciTech Connect

    Figuera, P.; Cardella, G.; Di Pietro, A.; Lu, J.; Marchetta, C.; Papa, M.; Tian, W.; Amorini, F.; Cherubini, S.; Lattuada, M.; Musumarra, A.; Pizzone, R. G.; Rizzo, F.; Scuderi, V.; Angulo, C.; Casarejos, E.; Pellegriti, M. G.; Raabe, R.; Sida, J. L.

    2006-08-14

    The study of reaction mechanisms in collisions induced by halo and/or weakly bound nuclei around the barrier has recently been the subject of many theoretical and experimental papers. Here we discuss our recent results concerning the study of the systems 13N+9Be and 6He+64Zn.

  20. Bed drain cover assembly for a fluidized bed

    DOEpatents

    Comparato, Joseph R.; Jacobs, Martin

    1982-01-01

    A loose fitting movable cover plate (36), suitable for the severe service encountered in a fluidized bed combustor (10), restricts the flow of solids into the combustor drain lines (30) during shutdown of the bed. This cover makes it possible to empty spent solids from the bed drain lines which would otherwise plug the piping between the drain and the downstream metering device. This enables use of multiple drain lines each with a separate metering device for the control of solids flow rate.

  1. Transport and performance of a zero-Schottky barrier and doped contacts graphene nanoribbon transistors

    NASA Astrophysics Data System (ADS)

    Alam, Khairul

    2009-01-01

    The transport physics and performance of a top gate graphene nanoribbon (GNR) on an insulator transistor are studied for both the MOSFET like doped source-drain and the zero-Schottky barrier source-drain contacts. A voltage controlled tunnel barrier is the device transport physics. The doped source-drain contact device has a higher gate capacitance, higher transconductance, higher on/off current ratio and higher on-state current. The higher on-state current results in a lower switching delay of 17 fs, and the higher transconductance results in a higher intrinsic cut-off frequency of 27 THz in the doped source-drain contact device. The gate voltage, beyond the source-channel flat band condition, modulates both the tunnel and the thermal barrier in the doped source-drain contact devices and the tunnel barrier only in the Schottky contact devices. This limits the on-state current of Schottky contact devices.

  2. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier

    PubMed Central

    Santos, Margarida A.; Faryabi, Robert B.; Ergen, Aysegul V.; Day, Amanda M.; Malhowski, Amy; Canela, Andres; Onozawa, Masahiro; Lee, Ji-Eun; Callen, Elsa; Gutierrez-Martinez, Paula; Chen, Hua-Tang; Wong, Nancy; Finkel, Nadia; Deshpande, Aniruddha; Sharrow, Susan; Rossi, Derrick J.; Ito, Keisuke; Ge, Kai; Aplan, Peter D.; Armstrong, Scott A.; Nussenzweig, André

    2015-01-01

    Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells1. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks2–4, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma5,6, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL–AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4−/− MLL–AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL–AF9 blasts, which requires cyclin-dependent kinase inhibitor p21Cip1 (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia. PMID:25079327

  3. Moisture-Induced Delamination Video of an Oxidized Thermal Barrier Coating

    NASA Technical Reports Server (NTRS)

    Smialek, James L.; Zhu, Dongming; Cuy, Michael D.

    2008-01-01

    PVD TBC coatings were thermally cycled to near-failure at 1150 C. Normal failure occurred after 200-300 1-hr cycles with only moderate weight gains (0.5 mg/cm2). Delamination and buckling was often delayed until well after cooldown (desktop spallation), but could be instantly induced by the application of water drops, as shown in an accompanying video-recording. Moisture therefore plays a primary role in delayed desktop TBC failure. Hydrogen embrittlement is proposed as the underlying mechanism.

  4. Moisture-Induced Delamination Video of an Oxidized Thermal Barrier Coating

    NASA Technical Reports Server (NTRS)

    Smialek, James L.; Zhu, Dongming; Cuy, Michael D.

    2008-01-01

    PVD TBC coatings were thermally cycled to near-failure at 1150 C. Normal failure occurred after 200 to 300 1-hr cycles with only moderate weight gains (0.5 mg/sq cm). Delamination and buckling was often delayed until well after cooldown (desktop spallation), but could be instantly induced by the application of water drops, as shown in a video clip which can be viewed by clicking on figure 2 of this report. Moisture therefore plays a primary role in delayed desktop TBC failure. Hydrogen embrittlement is proposed as the underlying mechanism.

  5. Barriers to Rural Induced Abortion Services in Canada: Findings of the British Columbia Abortion Providers Survey (BCAPS)

    PubMed Central

    Norman, Wendy V.; Soon, Judith A.; Maughn, Nanamma; Dressler, Jennifer

    2013-01-01

    Background Rural induced abortion service has declined in Canada. Factors influencing abortion provision by rural physicians are unknown. This study assessed distribution, practice, and experiences among rural compared to urban abortion providers in the Canadian province of British Columbia (BC). Methods We used mixed methods to assess physicians on the BC registry of abortion providers. In 2011 we distributed a previously-published questionnaire and conducted semi-structured interviews. Results Surveys were returned by 39/46 (85%) of BC abortion providers. Half were family physicians, within both rural and urban cohorts. One-quarter (17/67) of rural hospitals offer abortion service. Medical abortions comprised 14.7% of total reported abortions. The three largest urban areas reported 90% of all abortions, although only 57% of reproductive age women reside in the associated health authority regions. Each rural physician provided on average 76 (SD 52) abortions annually, including 35 (SD 30) medical abortions. Rural physicians provided surgical abortions in operating rooms, often using general anaesthesia, while urban physicians provided the same services primarily in ambulatory settings using local anaesthesia. Rural providers reported health system barriers, particularly relating to operating room logistics. Urban providers reported occasional anonymous harassment and violence. Conclusions Medical abortions represented 15% of all BC abortions, a larger proportion than previously reported (under 4%) for Canada. Rural physicians describe addressable barriers to service provision that may explain the declining accessibility of rural abortion services. Moving rural surgical abortions out of operating rooms and into local ambulatory care settings has the potential to improve care and costs, while reducing logistical challenges facing rural physicians. PMID:23840578

  6. Iontophoresis itself on hairless mouse skin induces the loss of the epidermal calcium gradient without skin barrier impairment.

    PubMed

    Lee, S H; Choi, E H; Feingold, K R; Jiang, S; Ahn, S K

    1998-07-01

    Iontophoresis increases the delivery of drugs across the stratum corneum, but the pathway by which ionized drugs transit the stratum corneum is unknown. In this study we examined the effect of iontophoresis on the skin barrier and the epidermal calcium gradient. Hairless mice were subjected to iontophoresis for 5-120 min and skin specimens were prepared for electron microscopy. Neither positive nor negative iontophoresis affected transepidermal water loss. Lacunar dilatation and partial distention of the intercellular layers of the stratum corneum were observed in rough proportion to applied time in iontophoresis skin as well as control skin. Additionally, using calcium capture cytochemistry, we demonstrated that both positive and negative iontophoresis caused the disappearance of the epidermal calcium gradient with marked decrease in calcium content in the upper epidermis. Positive iontophoresis was associated with increased calcium in the stratum basale and dermis, whereas negative iontophoresis increased calcium in the stratum corneum. Moreover, as previously shown after barrier disruption and sonophoresis, the decrease in calcium content in the upper epidermis was associated with an increase in lamellar body secretion and the build up of lamellar material at the stratum corneum-stratum granulosum interface. In conclusion, iontophoresis on the skin of hairless mice may induce the change of ionized molecules in the epidermis, as the loss of the calcium gradient, which causes the decrease of skin impedence, gives charged drugs the ability to cross the skin more easily. Also, the structural changes, such as lacunar dilatation, whether they result from hydration or occlusion, may help the transport of charged drugs across the stratum corneum.

  7. Barriers to rural induced abortion services in Canada: findings of the British Columbia Abortion Providers Survey (BCAPS).

    PubMed

    Norman, Wendy V; Soon, Judith A; Maughn, Nanamma; Dressler, Jennifer

    2013-01-01

    Rural induced abortion service has declined in Canada. Factors influencing abortion provision by rural physicians are unknown. This study assessed distribution, practice, and experiences among rural compared to urban abortion providers in the Canadian province of British Columbia (BC). We used mixed methods to assess physicians on the BC registry of abortion providers. In 2011 we distributed a previously-published questionnaire and conducted semi-structured interviews. Surveys were returned by 39/46 (85%) of BC abortion providers. Half were family physicians, within both rural and urban cohorts. One-quarter (17/67) of rural hospitals offer abortion service. Medical abortions comprised 14.7% of total reported abortions. The three largest urban areas reported 90% of all abortions, although only 57% of reproductive age women reside in the associated health authority regions. Each rural physician provided on average 76 (SD 52) abortions annually, including 35 (SD 30) medical abortions. Rural physicians provided surgical abortions in operating rooms, often using general anaesthesia, while urban physicians provided the same services primarily in ambulatory settings using local anaesthesia. Rural providers reported health system barriers, particularly relating to operating room logistics. Urban providers reported occasional anonymous harassment and violence. Medical abortions represented 15% of all BC abortions, a larger proportion than previously reported (under 4%) for Canada. Rural physicians describe addressable barriers to service provision that may explain the declining accessibility of rural abortion services. Moving rural surgical abortions out of operating rooms and into local ambulatory care settings has the potential to improve care and costs, while reducing logistical challenges facing rural physicians.

  8. The safest parameters for FUS-induced blood-brain barrier opening without effects on the opening volume

    NASA Astrophysics Data System (ADS)

    Tung, Yao-Sheng; Olumolade, Yemi; Wang, Shutao; Wu, Shih-Ying; Konofagou, Elisa E.

    2012-11-01

    Acoustic cavitation has been identified as the main physical mechanism for the focused ultrasound (FUS) induced blood-brain barrier (BBB) opening. In this paper, the mechanism of stable cavitation (SC) and inertial cavitation (IC) responsible for BBB opening was investigated. Thirty-three (n=33) mice were intravenously injected with bubbles of 4-5 μm in diameter. The right hippocampus was then sonicated using focused 1.5-MHz ultrasound and three different studies were carried out. First, pulse lengths (PLs) of 0.1, 0.5, 2, and 5 ms at 0.18- MPa peak rarefactional pressure with 5-Hz pulse repetition frequency (PRF) and 5-minute duration were used to identify the threshold of PL using SC. Second, the effects of the duty cycle and exposure time were investigated. Third, the BBB opening size was compared between the SC and the IC. In the case of IC-induced BBB opening, a burst sequence (3-cycles PL; 5-Hz burst repetition frequency (BRF); 30 s duration) at 0.45 MPa was applied. Passive cavitation detection was performed with each sonication to detect whether a broadband response was obtained, i.e., if IC occurred, during BBB opening. The properties of BBB opening were measured through MRI. The threshold of PL for BBB opening was identified between 0.1 and 0.5 ms using SC, but the BBB can be opened in few cycles using IC. The BBB opening volume and normalized intensity increased with the PL, but reached saturation when the PL was above 2 ms. Once the PL threshold was reached, the same exposure time induced a similar BBB opening volume, but longer sonication duration induced higher MR intensity. The duty cycle was found not to play an important role on the BBB opening. Comparable BBB opening volume (20-25 mm3) could be reached between long PL (7500 cycles, i.e., 5 ms) at 0.18 MPa and 3 cycles at 0.45 MPa. 3-kDa fluorescently tagged dextran may be able to diffuse to the parenchyma after IC-induced BBB opening at 0.45 MPa but not after SC-induced BBB opening at 0.18 MPa.

  9. 14 CFR 23.999 - Fuel system drains.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Fuel system drains. 23.999 Section 23.999... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Fuel System Components § 23.999 Fuel system drains. (a) There must be at least one drain to allow safe drainage of the...

  10. 14 CFR 25.999 - Fuel system drains.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Fuel system drains. 25.999 Section 25.999... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Fuel System Components § 25.999 Fuel system drains. (a) Drainage of the fuel system must be accomplished by the use of fuel strainer and fuel tank sump drains....

  11. 14 CFR 27.999 - Fuel system drains.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Fuel system drains. 27.999 Section 27.999... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Fuel System Components § 27.999 Fuel system drains. (a) There must be at least one accessible drain at the lowest point in each fuel system to completely...

  12. 14 CFR 125.139 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Oil system drains. 125.139 Section 125.139....139 Oil system drains. Accessible drains incorporating either a manual or automatic means for positive locking in the closed position must be provided to allow safe drainage of the entire oil system. ...

  13. 14 CFR 125.139 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Oil system drains. 125.139 Section 125.139....139 Oil system drains. Accessible drains incorporating either a manual or automatic means for positive locking in the closed position must be provided to allow safe drainage of the entire oil system. ...

  14. 14 CFR 125.139 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Oil system drains. 125.139 Section 125.139....139 Oil system drains. Accessible drains incorporating either a manual or automatic means for positive locking in the closed position must be provided to allow safe drainage of the entire oil system. ...

  15. 14 CFR 125.139 - Oil system drains.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Oil system drains. 125.139 Section 125.139....139 Oil system drains. Accessible drains incorporating either a manual or automatic means for positive locking in the closed position must be provided to allow safe drainage of the entire oil system. ...

  16. 46 CFR 45.157 - Scuppers and gravity drains.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Scuppers and gravity drains. 45.157 Section 45.157 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.157 Scuppers and gravity drains. Scuppers and gravity deck drains from spaces...

  17. 46 CFR 45.157 - Scuppers and gravity drains.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Scuppers and gravity drains. 45.157 Section 45.157 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.157 Scuppers and gravity drains. Scuppers and gravity deck drains from spaces...

  18. 46 CFR 45.157 - Scuppers and gravity drains.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Scuppers and gravity drains. 45.157 Section 45.157 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.157 Scuppers and gravity drains. Scuppers and gravity deck drains from spaces...

  19. 46 CFR 45.157 - Scuppers and gravity drains.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Scuppers and gravity drains. 45.157 Section 45.157 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.157 Scuppers and gravity drains. Scuppers and gravity deck drains from spaces...

  20. 46 CFR 45.157 - Scuppers and gravity drains.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Scuppers and gravity drains. 45.157 Section 45.157 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Conditions of Assignment § 45.157 Scuppers and gravity drains. Scuppers and gravity deck drains from spaces...

  1. 14 CFR 23.999 - Fuel system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Fuel system drains. 23.999 Section 23.999... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant Fuel System Components § 23.999 Fuel system drains. (a) There must be at least one drain to allow safe drainage of the entire...

  2. 1. SAND DRAINING & DRYING BUILDING (RIGHT), COVERED INCLINE CONVEYOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. SAND DRAINING & DRYING BUILDING (RIGHT), COVERED INCLINE CONVEYOR (LOWER RIGHT) THAT EXTENDS TO THE SAND-SORTING BUILDING, AND REMAINS OF ORIGINAL (1917) WASHING, DRAINING & DRYING BUILDING (LEFT), VIEW LOOKING WEST FROM TOP OF SAND-SORTING BUILDING - Mill "C" Complex, Sand Draining & Drying Building, South of Dee Bennet Road, near Illinois River, Ottawa, La Salle County, IL

  3. 14 CFR 125.139 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Oil system drains. 125.139 Section 125.139....139 Oil system drains. Accessible drains incorporating either a manual or automatic means for positive locking in the closed position must be provided to allow safe drainage of the entire oil system....

  4. 21 CFR 868.5995 - Tee drain (water trap).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tee drain (water trap). 868.5995 Section 868.5995 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5995 Tee drain (water trap). (a) Identification. A tee drain (water trap) is a...

  5. Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal barrier

    PubMed Central

    Kamekura, Ryuta; Nava, Porfirio; Feng, Mingli; Quiros, Miguel; Nishio, Hikaru; Weber, Dominique A.; Parkos, Charles A.; Nusrat, Asma

    2015-01-01

    Desmosomal cadherins mediate intercellular adhesion and control epithelial homeostasis. Recent studies show that proteinases play an important role in the pathobiology of cancer by targeting epithelial intercellular junction proteins such as cadherins. Here we describe the proinflammatory cytokine-induced activation of matrix metalloproteinase 9 and a disintegrin and metalloproteinase domain–containing protein 10, which promote the shedding of desmosomal cadherin desmoglein-2 (Dsg2) ectodomains in intestinal epithelial cells. Epithelial exposure to Dsg2 ectodomains compromises intercellular adhesion by promoting the relocalization of endogenous Dsg2 and E-cadherin from the plasma membrane while also promoting proliferation by activation of human epidermal growth factor receptor 2/3 signaling. Cadherin ectodomains were detected in the inflamed intestinal mucosa of mice with colitis and patients with ulcerative colitis. Taken together, our findings reveal a novel response pathway in which inflammation-induced modification of columnar epithelial cell cadherins decreases intercellular adhesion while enhancing cellular proliferation, which may serve as a compensatory mechanism to promote repair. PMID:26224314

  6. Is Drain Tip Culture Prognostic of Surgical Site Infection? Results of 1380 Drain Tip Cultures in Total Hip Arthroplasty.

    PubMed

    Takada, Ryohei; Jinno, Tetsuya; Koga, Daisuke; Hirao, Masanobu; Muneta, Takeshi; Okawa, Atsushi

    2015-08-01

    The purpose of this study was to evaluate a prognostic value of drain tip culture for surgical site infection (SSI) after total hip arthroplasty. A total of 1380 closed suction drain tips cultured after removal in primary total hip arthroplasty were included in this study. Drains were removed in 12-72 hours after surgery. Drain tip cultures were positive in 11 cases (0.8%). SSI was found in 4 cases (0.3%), where the drain tip cultures were all negative. The sensitivity of drain tip culture for infection after surgery was 0%, and the specificity was 99.7%. We concluded that, drain tip culture cannot be prognostic for SSI after total hip arthroplasty. Routine use of drain tip culture is not supported.

  7. Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo.

    PubMed

    Choi, James J; Feshitan, Jameel A; Baseri, Babak; Wang, Shougang; Tung, Yao-Sheng; Borden, Mark A; Konofagou, Elisa E

    2010-01-01

    The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood-brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1-10 microm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1-2 and 4-5 microm in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice (n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1-2 microm bubbles and between 0.15 and 0.30 MPa in the 4-5 microm case. At every pressure studied, the fluorescence was greater with the 4-5 mum than with the 1-2 microm bubbles. At 0.61 MPa, in the 1-2 microm bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted.

  8. Microbubble-Size Dependence of Focused Ultrasound-Induced Blood–Brain Barrier Opening in Mice In Vivo

    PubMed Central

    Choi, James J.; Feshitan, Jameel A.; Baseri, Babak; Wang, Shougang; Tung, Yao-Sheng; Borden, Mark A.; Konofagou, Elisa E.

    2014-01-01

    The therapeutic efficacy of neurological agents is severely limited, because large compounds do not cross the blood–brain barrier (BBB). Focused ultrasound (FUS) sonication in the presence of microbubbles has been shown to temporarily open the BBB, allowing systemically administered agents into the brain. Until now, polydispersed microbubbles (1–10 μm in diameter) were used, and, therefore, the bubble sizes better suited for inducing the opening remain unknown. Here, the FUS-induced BBB opening dependence on microbubble size is investigated. Bubbles at 1–2 and 4–5 μm in diameter were separately size-isolated using differential centrifugation before being systemically administered in mice (n = 28). The BBB opening pressure threshold was identified by varying the peak-rarefactional pressure amplitude. BBB opening was determined by fluorescence enhancement due to systemically administered, fluorescent-tagged, 3-kDa dextran. The identified threshold fell between 0.30 and 0.46 MPa in the case of 1–2 μm bubbles and between 0.15 and 0.30 MPa in the 4–5 μm case. At every pressure studied, the fluorescence was greater with the 4–5 μm than with the 1–2 μm bubbles. At 0.61 MPa, in the 1–2 μm bubble case, the fluorescence amount and area were greater in the thalamus than in the hippocampus. In conclusion, it was determined that the FUS-induced BBB opening was dependent on both the size distribution in the injected microbubble volume and the brain region targeted. PMID:19846365

  9. Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

    PubMed Central

    Squadrito, Francesco; Micali, Antonio; Rinaldi, Mariagrazia; Irrera, Natasha; Marini, Herbert; Puzzolo, Domenico; Pisani, Antonina; Lorenzini, Cesare; Valenti, Andrea; Laurà, Rosaria; Germanà, Antonino; Bitto, Alessandra; Pizzino, Gabriele; Pallio, Giovanni; Altavilla, Domenica; Minutoli, Letteria

    2017-01-01

    Cadmium (Cd) impairs blood-testis barrier (BTB). Polydeoxyribonucleotide (PDRN), an adenosine A2A agonist, has positive effects on male reproductive system. We investigated the effects of PDRN on the morphological and functional changes induced by Cd in mice testes. Adult Swiss mice were divided into four groups: controls administered with 0.9% NaCl (1 ml/kg, i.p., daily) or with PDRN (8 mg/kg, i.p. daily), animals challenged with Cd chloride (CdCl2; 2 mg/kg, i.p, daily) and animals challenged with CdCl2 (2 mg/kg, i.p., daily) and treated with PDRN (8 mg/kg, i.p., daily). Experiments lasted 14 days. Testes were processed for biochemical, structural, and ultrastructural evaluation and hormones were assayed in serum. CdCl2 increased pERK 1/2 expression and Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels; it decreased testosterone (TE) and inhibin-B levels and induced structural damages in extratubular compartment and in seminiferous epithelium, with ultrastructural features of BTB disruption. Many TUNEL-positive germ cells were present. CdCl2 increased tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin, and N-cadherin immunoreactivity. PDRN administration reduced pERK 1/2 expression, FSH, and LH levels; it increased TE and inhibin-B levels, ameliorated germinal epithelium changes and protected BTB ultrastructure. Few TUNEL-positive germ cells were present and the extratubular compartment was preserved. Furthermore, PDRN decreased TGF-β3 immunoreactivity and enhanced claudin-11, occludin, and N-cadherin immunoreactivity. We demonstrate a protective effect of PDRN on Cd-induced damages of BTB and suggest that PDRN may play an important role against Cd, particularly against its harmful effects on gametogenesis. PMID:28119612

  10. Effect of atropine sulfate on soman-induced blood-brain barrier (BBB) opening

    SciTech Connect

    Carpentier, P.; Lallement, G.; Tarricone, A.; Blanchet, G.

    1993-05-13

    Using Evans-Blue (EB) labeled serum albumin, it was recently shown that soman may produce seizure-related and reversible BBB opening in rats. Topographically, whereas hippocampus was never damaged, protein leakage was most frequent in the thalamus, and to a lesser degree, in certain basal formations (hypothalamus, amygdala, preoptic area, corpus mammillare) and lateral septum. In the present study, the distribution of soman-induced BBB opening was similar when intoxicated rats were pretreated by atropine methyl nitrate (AMN) a muscarinic blocker which does not penetrate the BBB. On the other hand, when AMN was substituted by atropine sulfate (AS), which is known to readily cross the BBB, thalamic nuclei became totally devoid of any vascular lesions whereas EB leakage still remained in the other normally damaged brain structures listed above. Therefore, the muscarinic cholinergic system appears to play a more prominent role on BBB control in the thalamus than in other cerebral regions.

  11. Overexpression of actin-depolymerizing factor blocks oxidized low-density lipoprotein-induced mouse brain microvascular endothelial cell barrier dysfunction.

    PubMed

    Wang, Jun; Sun, Lu; Si, Yan-Fang; Li, Bao-Min

    2012-12-01

    The aim of present work was to elucidate the role of actin-depolymerizing factor (ADF), an important regulator of actin cytoskeleton, in the oxidized low-density lipoprotein (ox-LDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to ox-LDL. Treatment with LDL served as control. It was found that ADF mRNA level and protein expression were decreased when exposed to ox-LDL in MBMECs. Then, we investigated the influence of ADF overexpression on ox-LDL-treated MBMECs. Structurally, overexpression of ADF inhibited ox-LDL-induced F-actin formation. Functionally, overexpression of ADF attenuated ox-LDL-induced disruption of endothelial barrier marked by restoration of transendothelial electrical resistance, permeability of Evans Blue and expression of tight junction-associated proteins including ZO-1 and occludin, and blocked ox-LDL-induced oxidative stress marked by inhibition of reactive oxygen species (ROS) formation and activity of NADPH oxidase and Nox2 expression. However, overexpression of ADF in control cells had no significant effect on endothelial permeability and ROS formation. In conclusion, overexpression of ADF blocks ox-LDL-induced disruption of endothelial barrier. In addition, siRNA-mediated downregulation of ADF expression aggravated ox-LDL-induced disruption of endothelial barrier and ROS formation. These findings identify ADF as a key signaling molecule in the regulation of BBB integrity and suggest that ADF might be used as a target to modulate diseases accompanied by ox-LDL-induced BBB compromise.

  12. Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.

    PubMed

    Schankin, Christoph J; Maniyar, Farooq H; Seo, Youngho; Kori, Shashidar; Eller, Michael; Chou, Denise E; Blecha, Joseph; Murphy, Stephanie T; Hawkins, Randall A; Sprenger, Till; VanBrocklin, Henry F; Goadsby, Peter J

    2016-07-01

    SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

  13. Restructuring brain drain: strengthening governance and financing for health worker migration.

    PubMed

    Mackey, Tim K; Liang, Bryan A

    2013-01-15

    Health worker migration from resource-poor countries to developed countries, also known as ''brain drain'', represents a serious global health crisis and a significant barrier to achieving global health equity. Resource-poor countries are unable to recruit and retain health workers for domestic health systems, resulting in inadequate health infrastructure and millions of dollars in healthcare investment losses. Using acceptable methods of policy analysis, we first assess current strategies aimed at alleviating brain drain and then propose our own global health policy based solution to address current policy limitations. Although governments and private organizations have tried to address this policy challenge, brain drain continues to destabilise public health systems and their populations globally. Most importantly, lack of adequate financing and binding governance solutions continue to fail to prevent health worker brain drain. In response to these challenges, the establishment of a Global Health Resource Fund in conjunction with an international framework for health worker migration could create global governance for stable funding mechanisms encourage equitable migration pathways, and provide data collection that is desperately needed.

  14. Protective Effect of Huoxiang Zhengqi Oral Liquid on Intestinal Mucosal Mechanical Barrier of Rats with Postinfectious Irritable Bowel Syndrome Induced by Acetic Acid

    PubMed Central

    Liu, Yao; Liu, Wei; Peng, Qiu-Xian; Peng, Jiang-Li; Yu, Lin-Zhong; Hu, Jian-Lan

    2014-01-01

    In this study, a rat model with acetic acid-induced PI-IBS was used to study the role of HXZQ oral liquid in repairing the colonic epithelial barrier and reducing intestinal permeability. Pathomorphism of colonic tissue, epithelial ultrastructure, DAO activity in serum, and the protein expression of ZO-1 and occludin were examined to investigate protective effect mechanisms of HXZQ on intestinal mucosa barrier and then present experimental support for its use for prevention and cure of PI-IBS. PMID:25254052

  15. All-Manganite Tunnel Junctions with Interface-Induced Barrier Magnetism

    NASA Astrophysics Data System (ADS)

    Sefrioui, Zouhair

    2011-03-01

    The recent discovery of several unexpected phases at complex oxide interfaces is providing new insights into the physics of strongly correlated electron systems. The possibility of tailoring the electronic structure of such interfaces has triggered a great technological drive to functionalize them into devices. In this communication, we describe an alternative strategy to produce spin filtering by inducing a ferromagnetic insulating state in an ultrathin antiferromagnetic layer in contact with a ferromagnetic layer. This artificially induced spin filtering persists up to relatively high temperatures and operates at high applied bias voltages. The results suggest that after playing a key role in exchange-bias for spin-valves, uncompensated moments at engineered antiferromagnetic interfaces represent a novel route for generating highly spin-polarized currents with antiferromagnets. Work done in collaboration with M. Bibes, C. Carrétéro, A. Barthélémy (Unité Mixte de Physique CNRS/Thales, Campus de Polytechnique, 1, Avenue A. Fresnel, 91767 Palaiseau (France) and Université Paris-Sud, 91045 Orsay (France)), F.A. Cuellar, C. Visani, A. Rivera-Calzada, , C. León, J. Santamaria (Grupo de Física de Materiales Complejos, Universidad Complutense de Madrid, 28040 Madrid (Spain)), M.J. Calderón, L. Brey (Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain)), K. March, M. Walls, D. Imhoff (Laboratoire de Physique des Solides, CNRS, Université Paris-Sud, 91405 Orsay (France)), R. Lopez Anton, T.R. Charlton (ISIS, Rutherford Appleton Laboratory, Chilton, Oxon OX11 0QX (United Kingdom)), E. Iborra (Universidad Politécnica de Madrid, Escuela Técnica Superior de Ingenieros de Telecomunicaciones, 28040 Madrid (Spain)), F. Ott (Léon Brillouin, CEA/CNRS, UMR 12, 91191 Gif-sur-Yvette (France)). This work was supported by the Spanish Ministry for Science and Education programs MAT2008 06517, and the Réseau Thématique de Recherche Avanc

  16. Ferulate protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in tert-butyl hydroperoxide-induced Caco-2 cells.

    PubMed

    Kim, Hyun Jung; Lee, Eun Kyeong; Park, Min Hi; Ha, Young Mi; Jung, Kyung Jin; Kim, Min-Sun; Kim, Mi Kyung; Yu, Byung Pal; Chung, Hae Young

    2013-03-01

    Epithelial barrier function is determined by both transcellular and paracellular permeability, the latter of which is mainly influenced by tight junctions (TJs) and apoptotic leaks within the epithelium. We investigated the protective effects of ferulate on epithelial barrier integrity by examining permeability, TJ protein expression, and apoptosis in Caco-2 cells treated with tert-butyl hydroperoxide (t-BHP), a strong reactive species inducer. Caco-2 cells pretreated with ferulate (5 or 15 μM) were exposed to t-BHP (100 μM), and ferulate suppressed the t-BHP-mediated increases in reactive species and epithelial permeability in Caco-2 cells. Moreover, ferulate inhibited epithelial cell leakage induced by t-BHP, which was accompanied by decreased expression of the TJ proteins zonula occludens-1 and occludin. In addition, pretreatment with ferulate markedly protected cells against t-BHP-induced apoptosis, as evidenced by decreased nuclear condensation, cytochrome c release, and caspase-3 cleavage and an increased Bax/Bcl-2 ratio. These results suggest that ferulate protects the epithelial barrier of Caco-2 cells against oxidative stress, which results in increased epithelial permeability, decreased TJ protein expression, and increased apoptosis. The most significant finding of our study is the demonstration of protective, ferulate-mediated antioxidant effects on barrier integrity, with a particular focus on intracellular molecular mechanisms.

  17. Effect of hyperthermia and endotoxin induced fever on the blood-brain barrier

    SciTech Connect

    Gustafson, A.N.

    1987-01-01

    The purpose of this study was to determine the effect of hyperthermia and fever, on the permeability characteristics of the BBB. A group of rats were maintained in a warm environment until their body temperature became elevated by 1.5/sup 0/C. The permeability of the BBB was determined by injecting the rats with /sup 14/C-sucrose (MW 340) and /sup 3/H-dextran (MW 70,000) and calculating the permeability-surface area product. When hyperthermic animals were compared to controls maintained in a neutral environment it was found that BBB permeability was increased for the smaller radioisotope only. A third group of animals was injected with endotoxin to induce fever. Body temperature was elevated by 1.4/sup 0/C which was similar to the hyperthermic group. BBB permeability to both radioisotopes was not significantly different from control animals. Another group of animals was given a higher dose of endotoxin which produced shock. It was found that BBB permeability was increased for /sup 14/C-sucrose in all brain regions and also for /sup 3/H-dextran in the cerebellum.

  18. Process-based model predictions of hurricane induced morphodynamic change on low-lying barrier islands

    USGS Publications Warehouse

    Plant, Nathaniel G.; Thompson, David M.; Elias, Edwin; Wang, Ping; Rosati, Julie D.; Roberts, Tiffany M.

    2011-01-01

    Using Delft3D, a Chandeleur Island model was constructed to examine the sediment-transport patterns and morphodynamic change caused by Hurricane Katrina and similar storm events. The model setup included a coarse Gulf of Mexico domain and a nested finer-resolution Chandeleur Island domain. The finer-resolution domain resolved morphodynamic processes driven by storms and tides. A sensitivity analysis of the simulated morphodynamic response was performed to investigate the effects of variations in surge levels. The Chandeleur morphodynamic model reproduced several important features that matched observed morphodynamic changes. A simulation of bathymetric change driven by storm surge alone (no waves) along the central portion of the Chandeleur Islands showed (1) a general landward retreat and lowering of the island chain and (2) multiple breaches that increased the degree of island dissection. The locations of many of the breaches correspond with the low-lying or narrow sections of the initial bathymetry. The major part of the morphological change occurred prior to the peak of the surge when overtopping of the islands produced a strong water-level gradient and induced significant flow velocities.

  19. Simulation and comparative study of tunneling field effect transistors with dopant-segregated Schottky source/drain

    NASA Astrophysics Data System (ADS)

    Zhang, Yi Bo; Sun, Lei; Xu, Hao; Han, Jing Wen

    2016-04-01

    Dopant-segregated Schottky source/drain tunneling field effect transistors (STFET) are investigated in this paper. The working mechanisms of STFET and the influence of device parameters are studied with Synopsys Sentaurus. Schottky source/drain MOSFETs possess several advantages over conventional MOSFETs, and dopant segregation can be feasibly achieved within current silicidation process. With dopant segregation, highly doped regions can be obtained after silicidation, which is necessary for band-to-band tunneling. With proper parameter setting, STFET can achieve comparable performance as TFET. High segregation doping for STFET is required to increase band-to-band tunneling probability and suppress bipolar behaviors. Increasing the electron barrier height at source side helps to provide larger drive current and higher on/off ratio. It is also found that STFET’s on-state performance is irrelevant to the segregation length when the segregation length is larger than a certain value. Furthermore, STFET is also insensitive to the Schottky barrier at drain side when the Schottky barrier at source side is fixed, which would relax the requirement for source/drain fabrication.

  20. Optimal design of small-diameter silicone chest drain devices.

    PubMed

    Chung, Juhyun; Li, John K-J

    2006-03-01

    To overcome the complications due to the use of noncompliant large diameter conventional chest drain devices, a flexible small diameter chest drain device was designed and simulated based on computational fluid dynamics (CFD) techniques. It was clearly shown that the pressure drop and velocity increase of the most distal drainage holes, which are located near the suction end, are dominant over other drainage holes. A conventional chest drain device with circular side holes showed higher mass flow rate due to larger cross sectional area. It also showed less dependency on the side hole placement compared to open channel, closed cavity chest drain with rectangular side holes. When all holes are opened the conventional chest drain showed 6% increase in flow rate while the open channel, closed cavity drain device showed 47% increase in flow rate reflecting a better design performance. These results provide an insight into the CFD-based optimal design of chest drain devices for potential applications in clinical intraoperative procedures.

  1. Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization.

    PubMed

    Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

    2016-08-10

    Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca(2+)) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium-dependent redistribution of occludin tight junctions. Thus, ketamine has the potential for maintaining the BBB in critically ill patients with severe brain disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Cysteinyl leukotriene receptor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain barrier dysfunction.

    PubMed

    Lenz, Q F; Arroyo, D S; Temp, F R; Poersch, A B; Masson, C J; Jesse, A C; Marafiga, J R; Reschke, C R; Iribarren, P; Mello, C F

    2014-09-26

    Current evidence suggests that inflammation plays a role in the pathophysiology of seizures. In line with this view, selected pro-inflammatory arachidonic acid derivatives have been reported to facilitate seizures. Kainate-induced seizures are accompanied by leukotriene formation, and are reduced by inhibitors of LOX/COX pathway. Moreover, LTD4 receptor blockade and LTD4 synthesis inhibition suppress pentylenetetrazol (PTZ)-induced kindling and pilocarpine-induced recurrent seizures. Although there is convincing evidence supporting that blood-brain-barrier (BBB) dysfunction facilitates seizures, no study has investigated whether the anticonvulsant effect of montelukast is associated with its ability to maintain BBB integrity. In this study we investigated whether montelukast and other CysLT receptor antagonists decrease PTZ-induced seizures, as well as whether these antagonists preserve BBB during PTZ-induced seizures. Adult male albino Swiss mice were stereotaxically implanted with a cannula into the right lateral ventricle, and two electrodes were placed over the parietal cortex along with a ground lead positioned over the nasal sinus for electroencephalography (EEG) recording. The effects of montelukast (0.03 or 0.3 μmol/1 μL, i.c.v.), pranlukast (1 or 3 μmol/1 μL, i.c.v.), Bay u-9773 (0.3, 3 or 30 nmol/1 μL, i.c.v.), in the presence or absence of the agonist LTD4 (0.2, 2, 6 or 20 pmol/1 μL, i.c.v.), on PTZ (1.8 μmol/2 μL)-induced seizures and BBB permeability disruption were determined. The animals were injected with the antagonists, agonist or vehicle 30 min before PTZ, and monitored for additional 30 min for the appearance of seizures by electrographic and behavioral methods. BBB permeability was assessed by sodium fluorescein method and by confocal microscopy for CD45 and IgG immunoreactivity. Bay-u9973 (3 and 30 nmol), montelukast (0.03 and 0.3 μmol) and pranlukast (1 and 3 μmol), increased the latency to generalized seizures and decreased the

  3. Viscous fingering of a draining suspension

    NASA Astrophysics Data System (ADS)

    Chen, Yun; Malambri, Frank; Lee, Sungyon

    2016-11-01

    The Saffman-Taylor viscous fingering arises when a viscous oil is withdrawn from a Hele-Shaw cell that is filled with a less viscous fluid. When particles are introduced into the draining fluid, new behaviors emerge, which are unobserved in the well-established pure oil case. We experimentally investigate the particle-modified inward fingering for varying particle concentrations. In particular, the fingering growth rate and number of fingers are experimentally quantified and are shown to be directly affected by the presence of particles. The physical mechanism of the particle-modified fingering is also discussed.

  4. Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.

    PubMed

    Parikh, Neil U; Aalinkeel, R; Reynolds, J L; Nair, B B; Sykes, D E; Mammen, M J; Schwartz, S A; Mahajan, S D

    2015-10-22

    Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

  5. Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction

    PubMed Central

    Jones, Letitia D.; Jackson, Joseph W.; Maggirwar, Sanjay B.

    2016-01-01

    The number of HIV-1 positive individuals developing some form of HIV-associated neurocognitive disorder (HAND) is increasing. In these individuals, the integrity of the blood-brain barrier (BBB) is compromised due to an increase in exposure to pro-inflammatory mediators, viral proteins, and virus released from infected cells. It has been shown that soluble CD40L (sCD40L) is released upon platelet activation and is an important mediator of the pathogenesis of HAND but the underlying mechanisms are unclear, emphasizing the need of an effective animal model. Here, we have utilized a novel animal model in which wild-type (WT) mice were infected with EcoHIV; a derivative of HIV-1 that contains a substitution of envelope protein gp120 with that of gp80 derived from murine leukemia virus-1 (MuLV-1). As early as two-weeks post-infection, EcoHIV led to increased permeability of the BBB associated with decreased expression of tight junction protein claudin-5, in CD40L and platelet activation-dependent manner. Treatment with an antiplatelet drug, eptifibatide, in EcoHIV-infected mice normalized BBB function, sCD40L release and platelet activity, thus implicating platelet activation and platelet-derived CD40L in virally induced BBB dysfunction. Our results also validate and underscore the importance of EcoHIV infection mouse model as a tool to explore therapeutic targets for HAND. PMID:26986758

  6. Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood–brain barrier opening

    PubMed Central

    Cho, Eunice E; Drazic, Jelena; Ganguly, Milan; Stefanovic, Bojana; Hynynen, Kullervo

    2011-01-01

    Blood–brain barrier (BBB) disruption can be achieved with ultrasound (US) and circulating microbubble (MB) contrast agent. Using dorsal US sonication and Definity, an MB contrast agent, responses of the cortical cerebral vasculature to BBB opening were observed with varying acoustic peak negative pressure (0.071 to 0.25 MPa) under two-photon microscope. Wistar rats with a craniotomy were sonicated with a single piezoelectric transducer following the intravenous injection of Texas Red for visualization of vasculature and leakage from BBB opening. Based on time-dependent intensity change in the extravascular area, the leakage was classified into three types: fast, sustained, and slow. Fast leakage was characterized by a rapid increase to peak intensity during sonication, but a decrease afterwards, occurring at all pressures and vessels sizes analyzed in our study. Sustained leakage was indicated by a similar, immediate increase to peak intensity but one that remained elevated for the duration of imaging, occurring at low-to-intermediate pressures. Slow leakage began 5 to 15 minutes after sonication, dominating at low pressures, and was more prevalent among smaller vessels than fast and sustained leakage. Our study showed the possibility of controlling leakage type and vessel size in US-induced BBB opening through varying acoustic pressure. PMID:21505473

  7. Barrier-free intermolecular proton transfer in the uracil-glycine complex induced by excess electron attachment

    NASA Astrophysics Data System (ADS)

    Gutowski, M.; Dąbkowska, I.; Rak, J.; Xu, S.; Nilles, J. M.; Radisic, D.; Bowen, K. H., Jr.

    2002-09-01

    The photoelectron spectra (PES) of anions of uracil-glycine and uracil-phenylalanine complexes reveal broad features with maxima at 1.8 and 2.0 eV. The results of ab initio density functional B3LYP and second order Møller-Plesset theory calculations indicate that the excess electron occupies a π^* orbital localized on uracil. The excess electron attachment to the complex can induce a barrier-free proton transfer (BFPT) from the carboxylic group of glycine to the O8 atom of uracil. As a result, the four most stable structures of the anion of uracil-glycine complex can be characterized as the neutral radical of hydrogenated uracil solvated by the anion of deprotonated glycine. The similarity between the PES spectra for the uracil complexes with glycine and phenylalanine suggests that the BFPT is also operative in the case of the latter anionic species. The BFPT to the O8 atom of uracil may be related to the damage of nucleic acid bases by low energy electrons because the O8 atom is involved in a hydrogen bond with adenine in the standard Watson-Crick pairing scheme.

  8. Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.

    PubMed

    Wei, Kuo-Chen; Chu, Po-Chun; Wang, Hay-Yan Jack; Huang, Chiung-Yin; Chen, Pin-Yuan; Tsai, Hong-Chieh; Lu, Yu-Jen; Lee, Pei-Yun; Tseng, I-Chou; Feng, Li-Ying; Hsu, Peng-Wei; Yen, Tzu-Chen; Liu, Hao-Li

    2013-01-01

    The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

  9. Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier.

    PubMed

    Zhou, Da; Pan, Qin; Xin, Feng-Zhi; Zhang, Rui-Nan; He, Chong-Xin; Chen, Guang-Yu; Liu, Chang; Chen, Yuan-Wen; Fan, Jian-Gao

    2017-01-07

    To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation- or metabolism-associated genes were quantified by real-time PCR. NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-α, IL-1, IL-2, IL-6 and IFN-γ in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.

  10. The Dependence of the Ultrasound-Induced Blood-Brain Barrier Opening Characteristics on Microbubble Size In Vivo

    NASA Astrophysics Data System (ADS)

    Choi, James J.; Feshitan, Jameel A.; Wang, Shougang; Tung, Yao-Sheng; Baseri, Babak; Borden, Mark A.; Konofagou, Elisa E.

    2009-04-01

    Recent neuropharmaceutical developments have led to potent disease-modifying drugs. In spite of these advancements, most agents cannot traverse the blood-brain barrier (BBB) and deposit in the brain. Focused ultrasound (FUS) with microbubbles has been shown to induce noninvasive, localized, and transient BBB opening. Although promising, safety and efficacy concerns still remain. Previously reported experiments used conventional imaging contrast agents that have a wide size distribution. In this study, we hypothesize that BBB opening characteristics are dependent on bubble diameter. A 25 μl bolus of in-house manufactured, lipid-shelled bubbles with either 1-2 or 4-5 μm diameter ranges was injected intravenously. Pulsed FUS (frequency: 1.5 MHz, peak-negative pressure: 146-607 kPa, duty cycle: 20%, duration: 1-min) was then applied to the left hippocampus of mice (n = 16) in vivo through the intact skin and skull. MRI or fluorescence microscopy was used to determine BBB opening. Contrast-enhanced (Omniscan™; 0.75 mL; molecular weight: 574 Da) MRI (9.4-T) was acquired on multiple days after sonication to determine BBB opening and closing. Fluorescence microscopy was also used to determine the feasibility of delivering large, 3 kDa dextran compounds through the BBB. The BBB opening acoustic pressure threshold for the 4-5μm bubbles was in the 146-304 kPa range while the threshold for the 1-2μm bubbles was higher. In conclusion, FUS-induced BBB opening and closing was shown to be dependent on the bubble diameter indicati