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Sample records for epidermal permeability barrier

  1. Acute Modulations in Permeability Barrier Function Regulate Epidermal Cornification

    PubMed Central

    Demerjian, Marianne; Hachem, Jean-Pierre; Tschachler, Erwin; Denecker, Geertrui; Declercq, Wim; Vandenabeele, Peter; Mauro, Theodora; Hupe, Melanie; Crumrine, Debra; Roelandt, Truus; Houben, Evi; Elias, Peter M.; Feingold, Kenneth R.

    2008-01-01

    Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier function, we hypothesized that corneocyte formation could also be regulated by barrier function. Barrier abrogation by two unrelated methods initiated a wave of cornification, assessed as TdT-mediated dUTP nick end-labeling-positive cells in stratum granulosum and newly cornified cells by electron microscopy. Because cornification was blocked by occlusion, corneocytes formed specifically in response to barrier, rather than injury or cell replacement, requirements. SP inhibitors and hyperacidification (which decreases SP activity) blocked cornification after barrier disruption. Similarly, cornification was delayed in PAR2−/− mice. Although classical markers of apoptosis [poly(ADP-ribose)polymerase and caspase (Casp)-3] remained unchanged, barrier disruption activated Casp-14. Moreover, the pan-Casp inhibitor Z-VAD-FMK delayed cornification, and corneocytes were structurally aberrant in Casp14−/− mice. Thus, permeability barrier requirements coordinately drive both the generation of the stratum corneum lipid-enriched extracellular matrix and the transformation of granular cells into corneocytes, in an SP- and Casp-14-dependent manner, signaled by PAR2. PMID:18156206

  2. Epidermal Permeability Barrier Defects and Barrier Repair Therapy in Atopic Dermatitis

    PubMed Central

    Lee, Hae-Jin

    2014-01-01

    Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g., Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD. PMID:24991450

  3. Co-Regulation and Interdependence of the Mammalian Epidermal Permeability and Antimicrobial Barriers

    PubMed Central

    Aberg, Karin M.; Man, Mao-Qiang; Gallo, Richard L.; Ganz, Tomas; Crumrine, Debra; Brown, Barbara E.; Choi, Eung-Ho; Kim, Dong-Kun; Schröder, Jens M.; Feingold, Kenneth R.; Elias, Peter M.

    2009-01-01

    Human epidermis elaborates two small cationic, highly hydrophobic antimicrobial peptides (AMP), β-defensin 2 (hBD2), and the carboxypeptide cleavage product of human cathelicidin (hCAP18), LL-37, which are co-packaged along with lipids within epidermal lamellar bodies (LBs) before their secretion. Because of their colocalization, we hypothesized that AMP and barrier lipid production could be coregulated by altered permeability barrier requirements. mRNA and immunostainable protein levels for mBD3 and cathelin-related antimicrobial peptide (CRAMP) (murine homologues of hBD2 and LL-37, respectively) increase 1–8 hours after acute permeability barrier disruption and normalize by 24 hours, kinetics that mirror the lipid metabolic response to permeability barrier disruption. Artificial permeability barrier restoration, which inhibits the lipid-synthetic response leading to barrier recovery, blocks the increase in AMP mRNA/protein expression, further evidence that AMP expression is linked to permeability barrier function. Conversely, LB-derived AMPs are also important for permeability barrier homeostasis. Despite an apparent increase in mBD3 protein, CRAMP−/− mice delayed permeability barrier recovery, attributable to defective LB contents and abnormalities in the structure of the lamellar membranes that regulate permeability barrier function. These studies demonstrate that (1) the permeability and antimicrobial barriers are coordinately regulated by permeability barrier requirements and (2) CRAMP is required for permeability barrier homeostasis. PMID:17943185

  4. Epidermal Permeability Barrier Recovery Is Delayed in Vitiligo-Involved Sites

    PubMed Central

    Liu, J.; Man, W.Y.; Lv, C.Z.; Song, S.P.; Shi, Y.J.; Elias, P.M.; Man, M.Q.

    2010-01-01

    Background/Objectives Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. Methods A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13–51 years (mean age: 27.91 ± 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. Results In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 ± 5.39% vs. 58.30 ± 4.71%; t = 2.441; p < 0.02). Conclusion Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo. PMID:20185976

  5. Mesotrypsin and caspase-14 participate in prosaposin processing: potential relevance to epidermal permeability barrier formation.

    PubMed

    Yamamoto-Tanaka, Mami; Motoyama, Akira; Miyai, Masashi; Matsunaga, Yukiko; Matsuda, Junko; Tsuboi, Ryoji; Hibino, Toshihiko

    2014-07-18

    A proteomics-based search for molecules interacting with caspase-14 identified prosaposin and epidermal mesotrypsin as candidates. Prosaposin is a precursor of four sphingolipid activator proteins (saposins A-D) that are essential for lysosomal hydrolysis of sphingolipids. Thus, we hypothesized that caspase-14 and mesotrypsin participate in processing of prosaposin. Because we identified a saposin A sequence as an interactor with these proteases, we prepared a specific antibody to saposin A and focused on saposin A-related physiological reactions. We found that mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models. Saposin A was localized in granular cells, whereas prosaposin was present in the upper layer of human epidermis. The proximity ligation assay confirmed interaction between prosaposin, caspase-14, and mesotrypsin in the granular layer. Oil Red staining showed that the lipid envelope was significantly reduced in the cornified layer of skin from saposin A-deficient mice. Ultrastructural studies revealed severely disorganized cornified layer structure in both prosaposin- and saposin A-deficient mice. Overall, our results indicate that epidermal mesotrypsin and caspase-14 work cooperatively in prosaposin processing. We propose that they thereby contribute to permeability barrier formation in vivo. PMID:24872419

  6. Hyaluronan Participates in the Epidermal Response to Disruption of the Permeability Barrier in Vivo

    PubMed Central

    Maytin, Edward V.; Chung, Helen H.; Seetharaman, V. Mani

    2004-01-01

    Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular matrix of tissues that plays a role in cellular migration, proliferation and differentiation. Injury to the stratum corneum elicits an epidermal hyperproliferative response, a pathogenic feature in many cutaneous diseases including eczema and psoriasis. Because HA is abundant in the matrix between keratinocytes, we asked whether the presence of HA is required for epidermal hyperplasia to occur in response to barrier injury. Disruption of the stratum corneum, by acetone application on the skin of hairless mice, led to a marked accumulation of HA in the matrix between epidermal basal and spinous keratinocytes, and also within keratinocytes of the upper epidermis. To test whether HA may have a functional role in epidermal hyperplasia, we used Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA and blunt the accumulation of epidermal HA after acetone. StrepH signficantly reduced epidermal HA levels, and also significantly inhibited the development of epidermal hyperplasia. This reduction in epidermal thickness was not attributable to any decrease in keratinocyte proliferation, but rather to an apparent acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin expression). Overall, the data show that HA is a significant participant in the epidermal response to barrier injury. PMID:15466397

  7. Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model

    SciTech Connect

    Ajani, Gati; Sato, Nobuyuki; Mack, Judith A.; Maytin, Edward V. . E-mail: maytine@ccf.org

    2007-08-15

    Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposures to acetone then were fixed and paraffin-sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened transglutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes.

  8. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model.

    PubMed Central

    Ghadially, R; Brown, B E; Sequeira-Martin, S M; Feingold, K R; Elias, P M

    1995-01-01

    Aged epidermis displays altered drug permeability, increased susceptibility to irritant contact dermatitis, and often severe xerosis, suggesting compromise of the aged epidermal barrier. To delineate the functional, structural, and lipid biochemical basis of epidermal aging, we compared barrier function in young (20-30 yr) vs aged (> 80 yr) human subjects, and in a murine model. Baseline transepidermal water loss in both aged humans and senescent mice was subnormal. However, the aged barrier was perturbed more readily with either acetone or tape stripping (18 +/- 2 strippings vs 31 +/- 5 strippings in aged vs young human subjects, respectively). Moreover, after either acetone treatment or tape stripping, the barrier recovered more slowly in aged than in young human subjects (50 and 80% recovery at 24 and 72 h, respectively, in young subjects vs 15% recovery at 24 h in aged subjects), followed by a further delay over the next 6 d. Similar differences in barrier recovery were seen in senescent vs young mice. Although the total lipid content was decreased in the stratum corneum of aged mice (approximately 30%), the distribution of ceramides (including ceramide 1), cholesterol, and free fatty acids was unchanged. Moreover, a normal complement of esterified, very long-chain fatty acids was present. Finally, stratum corneum lamellar bilayers displayed normal substructure and dimensions, but were focally decreased in number, with decreased secretion of lamellar body contents. Thus, assessment of barrier function in aged epidermis under basal conditions is misleading, since both barrier integrity and barrier repair are markedly abnormal. These functional changes can be attributed to a global deficiency in all key stratum corneum lipids, resulting in decreased lamellar bilayers in the stratum corneum interstices. This constellation of findings may explain the increased susceptibility of intrinsically aged skin to exogenous and environmental insults. Images PMID:7738193

  9. 3D In Vitro Model of a Functional Epidermal Permeability Barrier from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

    PubMed Central

    Petrova, Anastasia; Celli, Anna; Jacquet, Laureen; Dafou, Dimitra; Crumrine, Debra; Hupe, Melanie; Arno, Matthew; Hobbs, Carl; Cvoro, Aleksandra; Karagiannis, Panagiotis; Devito, Liani; Sun, Richard; Adame, Lillian C.; Vaughan, Robert; McGrath, John A.; Mauro, Theodora M.; Ilic, Dusko

    2014-01-01

    Summary Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, a suitable in vitro model for studying normal barrier function and barrier defects is still lacking. Here, we demonstrate the generation of human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are structurally similar to native epidermis, with a functional permeability barrier. We exposed a pure population of hESC/iPSC-derived keratinocytes, whose transcriptome corresponds to the gene signature of normal primary human keratinocytes (NHKs), to a sequential high-to-low humidity environment in an air/liquid interface culture. The resulting HEEs had all of the cellular strata of the human epidermis, with skin barrier properties similar to those of normal skin. Such HEEs generated from disease-specific iPSCs will be an invaluable tool not only for dissecting molecular mechanisms that lead to epidermal barrier defects but also for drug development and screening. PMID:24936454

  10. Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2.

    PubMed

    Demerjian, Marianne; Hachem, Jean-Pierre; Tschachler, Erwin; Denecker, Geertrui; Declercq, Wim; Vandenabeele, Peter; Mauro, Theodora; Hupe, Melanie; Crumrine, Debra; Roelandt, Truus; Houben, Evi; Elias, Peter M; Feingold, Kenneth R

    2008-01-01

    Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier function, we hypothesized that corneocyte formation could also be regulated by barrier function. Barrier abrogation by two unrelated methods initiated a wave of cornification, assessed as TdT-mediated dUTP nick end-labeling-positive cells in stratum granulosum and newly cornified cells by electron microscopy. Because cornification was blocked by occlusion, corneocytes formed specifically in response to barrier, rather than injury or cell replacement, requirements. SP inhibitors and hyperacidification (which decreases SP activity) blocked cornification after barrier disruption. Similarly, cornification was delayed in PAR2(-/-) mice. Although classical markers of apoptosis [poly(ADP-ribose)polymerase and caspase (Casp)-3] remained unchanged, barrier disruption activated Casp-14. Moreover, the pan-Casp inhibitor Z-VAD-FMK delayed cornification, and corneocytes were structurally aberrant in Casp14(-/-) mice. Thus, permeability barrier requirements coordinately drive both the generation of the stratum corneum lipid-enriched extracellular matrix and the transformation of granular cells into corneocytes, in an SP- and Casp-14-dependent manner, signaled by PAR2. PMID:18156206

  11. CHOLINERGIC REGULATION OF KERATINOCYTE INNATE IMMUNITY AND PERMEABILITY BARRIER INTEGRITY: NEW PERSPECTIVES IN EPIDERMAL IMMUNITY AND DISEASE

    PubMed Central

    Curtis, Brenda J.; Radek, Katherine A.

    2015-01-01

    Several cutaneous inflammatory diseases and their clinical phenotypes are recapitulated in animal models of skin disease. However, the identification of shared pathways for disease progression is limited by the ability to delineate the complex biochemical processes fundamental for development of the disease. Identifying common signaling pathways that contribute to cutaneous inflammation and immune function will facilitate better scientific and therapeutic strategies to span a variety of inflammatory skin diseases. Aberrant antimicrobial peptide (AMP) expression and activity is one mechanism behind the development and severity of several inflammatory skin diseases and directly influences the susceptibility of skin to microbial infections. Our studies have recently exposed a newly identified pathway for negative regulation of AMPs in the skin by the cholinergic anti-inflammatory pathway via acetylcholine (ACh). The role of ACh in AMP regulation of immune and permeability barrier function in keratinocytes is reviewed, and the importance for a better comprehension of cutaneous disease progression by cholinergic signaling is discussed. PMID:21918536

  12. Lowered Humidity Produces Human Epidermal Equivalents with Enhanced Barrier Properties

    PubMed Central

    Sun, Richard; Celli, Anna; Crumrine, Debra; Hupe, Melanie; Adame, Lillian C.; Pennypacker, Sally D.; Park, Kyungho; Uchida, Yoshikazu; Feingold, Kenneth R.; Elias, Peter M.; Ilic, Dusko

    2015-01-01

    Multilayered human keratinocyte cultures increasingly are used to model human epidermis. Until now, studies utilizing human epidermal equivalents (HEEs) have been limited because previous preparations do not establish a normal epidermal permeability barrier. In this report, we show that reducing environmental humidity to 50% relative humidity yields HEEs that closely match human postnatal epidermis and have enhanced repair of the permeability barrier. These cultures display low transepidermal water loss and possess a calcium and pH gradient that resembles those seen in human epidermis. These cultures upregulate glucosylceramide synthase and make normal-appearing lipid lamellar bilayers. The epidermal permeability barrier of these cultures can be perturbed, using the identical tools previously described for human skin, and recover in the same time course seen during in vivo barrier recovery. These cultures will be useful for basic and applied studies on epidermal barrier function. PMID:24803151

  13. From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome.

    PubMed

    García, Isaac E; Bosen, Felicitas; Mujica, Paula; Pupo, Amaury; Flores-Muñoz, Carolina; Jara, Oscar; González, Carlos; Willecke, Klaus; Martínez, Agustín D

    2016-03-01

    The keratitis-ichthyosis-deafness (KID) syndrome is characterized by corneal, skin, and hearing abnormalities. KID has been linked to heterozygous dominant missense mutations in the GJB2 and GJB6 genes, encoding connexin26 and 30, respectively. In vitro evidence indicates that KID mutations lead to hyperactive (open) hemichannels, which in some cases is accompanied by abnormal function of gap junction channels. Transgenic mouse models expressing connexin26 KID mutations reproduce human phenotypes and present impaired epidermal calcium homeostasis and abnormal lipid composition of the stratum corneum affecting the water barrier. Here we have compiled relevant data regarding the KID syndrome and propose a mechanism for the epidermal aspects of the disease. PMID:26777423

  14. Effects of in Utero Exposure of C57BL/6J Mice to 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Epidermal Permeability Barrier Development and Function

    PubMed Central

    Muenyi, Clarisse S.; Carrion, Sandra Leon; Jones, Lynn A.; Kennedy, Lawrence H.; Slominski, Andrzej T.

    2014-01-01

    Background: Development of the epidermal permeability barrier (EPB) is essential for neonatal life. Defects in this barrier are found in many skin diseases such as atopic dermatitis. Objective: We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development and function of the EPB. Methods: Timed-pregnant C57BL/6J mice were gavaged with corn oil or TCDD (10 μg/kg body weight) on gestation day 12. Embryos were harvested on embryonic day (E) 15, E16, E17, and postnatal day (PND) 1. Results: A skin permeability assay showed that TCDD accelerated the development of the EPB, beginning at E15. This was accompanied by a significant decrease in transepidermal water loss (TEWL), enhanced stratification, and formation of the stratum corneum (SC). The levels of several ceramides were significantly increased at E15 and E16. PND1 histology revealed TCDD-induced acanthosis and epidermal hyperkeratosis. This was accompanied by disrupted epidermal tight junction (TJ) function, with increased dye leakage at the terminal claudin-1–staining TJs of the stratum granulosum. Because the animals did not have enhanced rates of TEWL, a commonly observed phenotype in animals with TJ defects, we performed tape-stripping. Removal of most of the SC resulted in a significant increase in TEWL in TCDD-exposed PND1 pups compared with their control group. Conclusions: These findings demonstrate that in utero exposure to TCDD accelerates the formation of an abnormal EPB with leaky TJs, warranting further study of environmental exposures, epithelial TJ integrity, and atopic disease. Citation: Muenyi CS, Leon Carrion S, Jones LA, Kennedy LH, Slominski AT, Sutter CH, Sutter TR. 2014. Effects of in utero exposure of C57BL/6J mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin on epidermal permeability barrier development and function. Environ Health Perspect 122:1052–1058; http://dx.doi.org/10.1289/ehp.1308045 PMID:24904982

  15. The "caveolae brake hypothesis" and the epidermal barrier.

    PubMed

    Roelandt, Truus; Giddelo, Christina; Heughebaert, Carol; Denecker, Geertrui; Hupe, Melanie; Crumrine, Debra; Kusuma, Andy; Haftek, Marek; Roseeuw, Diane; Declercq, Wim; Feingold, Kenneth R; Elias, Peter M; Hachem, Jean-Pierre

    2009-04-01

    Epidermal permeability barrier formation depends upon lamellar body (LB) secretion/fusion with the apical plasma membrane (APM) of outermost stratum granulosum (SG) cell, creating cholesterol/glycosphingolipid-enriched lipid rafts-like domains. We found that the dimensions of these domains are comparable to lipid raft in other cell types; and that acute barrier disruption regulates their size and dynamics. To assess the function of these LB-derived raft-like domains, we assessed APM dynamics and barrier recovery in methyl-beta-cyclodextrin (MbetaCD)-treated hairless mice and caveolin-1 knockouts (cav-1(-/-)). MbetaCD treatment impaired APM raft-like domain formation and barrier recovery. Accelerated barrier recovery is observed in cav-1(-/-) in parallel with expansion of raft-like domains. Barrier abrogation of normal epidermis resulted in translocation of cav-1 from the cytoplasm to raft-like membrane domains, restricting further raft-like domain formation and initiating terminal differentiation. Inhibition of LB secretion by monensin and absence of cav-1 delayed terminal differentiation. Furthermore, cav-1(-/-) mice exhibited an increased propensity to develop experimentally induced epidermal hyperplasia correlating with lipid raft persistence. Finally, the epidermal hyperplasia in psoriasis and Netherton syndrome is paralleled by increased lipid raft formation. These studies demonstrate that cav-1 delivery to the APM by LB trafficking to APM "brakes" further LB secretion, signals terminal differentiation, and regulates epidermal hyperproliferation. PMID:19005485

  16. Epidermal Growth Factor and Intestinal Barrier Function.

    PubMed

    Tang, Xiaopeng; Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng; Fang, Rejun

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  17. Epidermal Growth Factor and Intestinal Barrier Function

    PubMed Central

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  18. Nrf2 links epidermal barrier function with antioxidant defense.

    PubMed

    Schäfer, Matthias; Farwanah, Hany; Willrodt, Ann-Helen; Huebner, Aaron J; Sandhoff, Konrad; Roop, Dennis; Hohl, Daniel; Bloch, Wilhelm; Werner, Sabine

    2012-05-01

    The skin provides an efficient permeability barrier and protects from microbial invasion and oxidative stress. Here, we show that these essential functions are linked through the Nrf2 transcription factor. To test the hypothesis that activation of Nrf2 provides skin protection under stress conditions, we determined the consequences of pharmacological or genetic activation of Nrf2 in keratinocytes. Surprisingly, mice with enhanced Nrf2 activity in keratinocytes developed epidermal thickening, hyperkeratosis and inflammation resembling lamellar ichthyosis. This resulted from upregulation of the cornified envelope proteins small proline-rich proteins (Sprr) 2d and 2h and of secretory leukocyte peptidase inhibitor (Slpi), which we identified as novel Nrf2 targets in keratinocytes. Since Sprrs are potent scavengers of reactive oxygen species and since Slpi has antimicrobial activities, their upregulation contributes to Nrf2's protective function. However, it also caused corneocyte fragility and impaired desquamation, followed by alterations in the epidermal lipid barrier, inflammation and overexpression of mitogens that induced keratinocyte hyperproliferation. These results identify an unexpected role of Nrf2 in epidermal barrier function, which needs to be considered for pharmacological use of Nrf2 activators. PMID:22383093

  19. Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient.

    PubMed

    Jiang, Shao Jun; Chu, Ai Wu; Lu, Zhen Feng; Pan, Min Hong; Che, Dun Fa; Zhou, Xiao Jun

    2007-12-01

    Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation. PMID:18031457

  20. Psychological stress and epidermal barrier function.

    PubMed

    Orion, Edith; Wolf, Ronni

    2012-01-01

    The skin is the organ that acts as a barrier between the outer and inner environments of the body. It is thus exposed not only to a wide variety of physical, chemical, and thermal insults from the outside world but also to inner endogenous stimuli. Stress, once an abstract psychologic phenomenon, has taken research's center stage in recent years. The "mind-body connection" is now less of an obscure New Age term and more of an elaborate physiologic pathway by which bilateral communication occurs between body and brain. Dermatologists and dermatologic patients have long acknowledged the effect of stress on the skin and its capability to initiate, maintain, or exacerbate several skin diseases. Because disruption of epidermal barrier integrity may be important in the development of some common skin diseases, it is crucial to understand its vulnerability to psychologic stress. PMID:22507042

  1. Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans

    PubMed Central

    ELIAS, PETER M.; MENON, GOPINATHAN; WETZEL, BRUCE K.; WILLIAMS, JOHN (JACK) W.

    2011-01-01

    Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have “driven” the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [≈1.5–0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed ≈1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor⇒KIT; FOXn1⇒FGF2; IL-1α, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. PMID:20209486

  2. Permeability Barrier Generation in the Martian Lithosphere

    NASA Astrophysics Data System (ADS)

    Schools, Joe; Montési, Laurent

    2015-11-01

    Permeability barriers develop when a magma produced in the interior of a planet rises into the cooler lithosphere and crystallizes more rapidly than the lithosphere can deform (Sparks and Parmentier, 1991). Crystallization products may then clog the porous network in which melt is propagating, reducing the permeability to almost zero, i.e., forming a permeability barrier. Subsequent melts cannot cross the barrier. Permeability barriers have been useful to explain variations in crustal thickness at mid-ocean ridges on Earth (Magde et al., 1997; Hebert and Montési, 2011; Montési et al., 2011). We explore here under what conditions permeability barriers may form on Mars.We use the MELTS thermodynamic calculator (Ghiorso and Sack, 1995; Ghiorso et al., 2002; Asimow et al., 2004) in conjunction with estimated Martian mantle compositions (Morgan and Anders, 1979; Wänke and Dreibus, 1994; Lodders and Fegley, 1997; Sanloup et al., 1999; Taylor 2013) to model the formation of permeability barriers in the lithosphere of Mars. In order to represent potential past and present conditions of Mars, we vary the lithospheric thickness, mantle potential temperature (heat flux), oxygen fugacity, and water content.Our results show that permeability layers can develop in the thermal boundary layer of the simulated Martian lithosphere if the mantle potential temperature is higher than ~1500°C. The various Martian mantle compositions yield barriers in the same locations, under matching variable conditions. There is no significant difference in barrier location over the range of accepted Martian oxygen fugacity values. Water content is the most significant influence on barrier development as it reduces the temperature of crystallization, allowing melt to rise further into the lithosphere. Our lower temperature and thicker lithosphere model runs, which are likely the most similar to modern Mars, show no permeability barrier generation. Losing the possibility of having a permeability

  3. Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

    PubMed

    Mishra, Rangnath; Foster, Daniel; Vasu, Vihas T; Thaikoottathil, Jyoti V; Kosmider, Beata; Chu, Hong Wei; Bowler, Russell P; Finigan, James H

    2016-06-01

    The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete. We have previously identified that the receptor tyrosine kinase human epidermal receptor (HER) 2 growth factor is activated by the ligand neuregulin-1 and increases epithelial permeability in models of inflammatory acute lung injury. We hypothesized that CS activates HER2 and that CS-mediated changes in barrier function would be HER2 dependent in airway epithelial cells. We determined that HER2 was activated in whole lung, as well as isolated epithelial cells, from smokers, and that acute CS exposure resulted in HER2 activation in cultured bronchial epithelial cells. Mechanistic studies determined that CS-mediated HER2 activation is independent of neuregulin-1 but required upstream activation of the epidermal growth factor receptor. HER2 was required for CS-induced epithelial permeability as knockdown of HER2 blocked increases in permeability after CS. CS caused an increase in IL-6 production by epithelial cells that was dependent on HER2-mediated extracellular signal-regulated kinases (Erk) activation. Finally, blockade of IL-6 attenuated CS-induced epithelial permeability. Our data indicate that CS activates pulmonary epithelial HER2 and that HER2 is a central mediator of CS-induced epithelial barrier dysfunction. PMID:26600084

  4. Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier

    PubMed Central

    Xin, Shujun; Ye, Li; Lv, Chengzhi; Elias, Peter M.

    2016-01-01

    Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers. PMID:27437403

  5. Heavy Cigarette Smokers in a Chinese Population Display a Compromised Permeability Barrier.

    PubMed

    Xin, Shujun; Ye, Li; Man, George; Lv, Chengzhi; Elias, Peter M; Man, Mao-Qiang

    2016-01-01

    Cigarette smoking is associated with various cutaneous disorders with defective permeability. Yet, whether cigarette smoking influences epidermal permeability barrier function is largely unknown. Here, we measured skin biophysical properties, including permeability barrier homeostasis, stratum corneum (SC) integrity, SC hydration, skin surface pH, and skin melanin/erythema index, in cigarette smokers. A total of 99 male volunteers were enrolled in this study. Smokers were categorized as light-to-moderate (<20 cigarettes/day) or heavy smokers (≥20 cigarettes/day). An MPA5 was used to measure SC hydration and skin melanin/erythema index on the dorsal hand, forehead, and cheek. Basal transepidermal water loss (TEWL) and barrier recovery rates were assessed on the forearm. A Skin-pH-Meter pH900 was used to measure skin surface pH. Our results showed that heavy cigarette smokers exhibited delayed barrier recovery after acute abrogation (1.02% ± 13.06 versus 16.48% ± 6.07), and barrier recovery rates correlated negatively with the number of daily cigarettes consumption (p = 0.0087). Changes in biophysical parameters in cigarette smokers varied with body sites. In conclusion, heavy cigarette smokers display compromised permeability barrier homeostasis, which could contribute, in part, to the increased prevalence of certain cutaneous disorders characterized by defective permeability. Thus, improving epidermal permeability barrier should be considered for heavy cigarette smokers. PMID:27437403

  6. Epidermal Differentiation in Barrier Maintenance and Wound Healing.

    PubMed

    Wikramanayake, Tongyu Cao; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-03-01

    Significance: The epidermal barrier prevents water loss and serves as the body's first line of defense against toxins, chemicals, and infectious microbes. Disruption of the barrier, either through congenital disorders of barrier formation or through wounds, puts the individual at risk for dehydration, hypersensitivity, infection, and prolonged inflammation. Epidermal barrier disorders affect millions of patients in the United States, causing loss of productivity and diminished quality of life for patients and their families, and represent a burden to the health-care system and society. Recent Advances: The genetic basis of many congenital barrier disorders has been identified in recent years, and great advances have been made in the molecular mechanisms of the formation and homeostasis of epidermal barrier, as well as acute and chronic wound healing. Progress in stem cell (SC) biology, particularly in induced pluripotent stem cells (iPSCs) and allogeneic mesenchymal stem cells (MSCs), has opened new doors for cell-based therapy of chronic wounds. Critical Issues: Understanding of the molecular mechanisms of barrier homeostasis in health and disease, as well as contributions of iPSCs and allogeneic MSCs to wound healing, will lead to the identification of novel targets for developing therapeutics for congenital barrier and wound healing disorders. Future Directions: Future studies should focus on better understanding of molecular mechanisms leading to disrupted homeostasis of epidermal barrier to identify potential therapeutic targets to combat its associated diseases. PMID:24669361

  7. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

    PubMed Central

    Elias, Peter M.; Williams, Mary L.; Holleran, Walter M.; Jiang, Yan J.; Schmuth, Matthias

    2010-01-01

    Many of the ichthyoses are associated with inherited disorders of lipid metabolism. These disorders have provided unique models to dissect physiologic processes in normal epidermis and the pathophysiology of more common scaling conditions. In most of these disorders, a permeability barrier abnormality “drives” pathophysiology through stimulation of epidermal hyperplasia. Among primary abnormalities of nonpolar lipid metabolism, triglyceride accumulation in neutral lipid storage disease as a result of a lipase mutation provokes a barrier abnormality via lamellar/nonlamellar phase separation within the extracellular matrix of the stratum corneum (SC). Similar mechanisms account for the barrier abnormalities (and subsequent ichthyosis) in inherited disorders of polar lipid metabolism. For example, in recessive X-linked ichthyosis (RXLI), cholesterol sulfate (CSO4) accumulation also produces a permeability barrier defect through lamellar/nonlamellar phase separation. However, in RXLI, the desquamation abnormality is in part attributable to the plurifunctional roles of CSO4 as a regulator of both epidermal differentiation and corneodesmosome degradation. Phase separation also occurs in type II Gaucher disease (GD; from accumulation of glucosylceramides as a result of to β-glucocerebrosidase deficiency). Finally, failure to assemble both lipids and desquamatory enzymes into nascent epidermal lamellar bodies (LBs) accounts for both the permeability barrier and desquamation abnormalities in Harlequin ichthyosis (HI). The barrier abnormality provokes the clinical phenotype in these disorders not only by stimulating epidermal proliferation, but also by inducing inflammation. PMID:18245815

  8. EVALUATION OF PERMEABLE REACTIVE BARRIER PERFORMANCE

    EPA Science Inventory

    The permeable reactive barrier (PRB) technology represents a passive option for long-term treatment of ground-water contamination. PRBs are a potentially more cost-effective treatment option for a variety of dissolved contaminants, such as certain types of chlorinated solvents, ...

  9. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

    PubMed Central

    Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

    2012-01-01

    Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

  10. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    PubMed

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. PMID:26967476

  11. TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation.

    PubMed

    Hayez, Aurélie; Roegiers, Edith; Malaisse, Jérémy; Balau, Benoit; Sterpin, Christiane; Achouri, Younes; De Rouvroit, Catherine Lambert; Poumay, Yves; Michiels, Carine; De Backer, Olivier

    2016-01-01

    TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study. PMID:26785122

  12. TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation

    PubMed Central

    Malaisse, Jérémy; Balau, Benoit; Sterpin, Christiane; Achouri, Younes; Lambert De Rouvroit, Catherine; Poumay, Yves; Michiels, Carine; De Backer, Olivier

    2016-01-01

    TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study. PMID:26785122

  13. Specific binding of Clostridium perfringens enterotoxin fragment to Claudin-b and modulation of zebrafish epidermal barrier.

    PubMed

    Zhang, Jingjing; Ni, Chen; Yang, Zhenguo; Piontek, Anna; Chen, Huapu; Wang, Sijie; Fan, Yiming; Qin, Zhihai; Piontek, Joerg

    2015-08-01

    Claudins (Cldn) are the major components of tight junctions (TJs) sealing the paracellular cleft in tissue barriers of various organs. Zebrafish Cldnb, the homolog of mammalian Cldn4, is expressed at epithelial cell-cell contacts and is important for regulating epidermal permeability. The bacterial toxin Clostridium perfringens enterotoxin (CPE) has been shown to bind to a subset of mammalian Cldns. In this study, we used the Cldn-binding C-terminal domain of CPE (194-319 amino acids, cCPE 194-319 ) to investigate its functional role in modulating zebrafish larval epidermal barriers. In vitro analyses show that cCPE 194-319 removed Cldn4 from epithelial cells and disrupted the monolayer tightness, which could be rescued by the removal of cCPE 194-319. Incubation of zebrafish larvae with cCPE 194-319 removed Cldnb specifically from the epidermal cell membrane. Dye diffusion analysis with 4-kDa fluorescent dextran indicated that the permeability of the epidermal barrier increased due to cCPE 194-319 incubation. Electron microscopic investigation revealed reversible loss of TJ integrity by Cldnb removal. Collectively, these results suggest that cCPE 194-319 could be used as a Cldnb modulator to transiently open the epidermal barrier in zebrafish. In addition, zebrafish might be used as an in vivo system to investigate the capability of cCPE to enhance drug delivery across tissue barriers. PMID:25869230

  14. Clamshell excavation of a permeable reactive barrier

    NASA Astrophysics Data System (ADS)

    Molfetta, Antonio Di; Sethi, Rajandrea

    2006-06-01

    Nowadays, permeable reactive barriers (PRB) are one of the most widespread techniques for the remediation of contaminated aquifers. Over the past 10 years, the use of iron-based PRBs has evolved from innovative to accepted standard practice for the treatment of a variety of groundwater contaminants (ITRC in: Permeable reactive barriers: lessons learned/new directions. The Interstate Technology and Regulatory Council, Permeable Reactive Barriers Team 2005). Although, a variety of excavation methods have been developed, backhoe excavators are often used for the construction of PRBs. The aim of this study is to describe the emplacement of a full-scale PRB and the benefits deriving from the use of a crawler crane equipped with a hydraulic grab (also known as clamshell excavator) in the excavation phases. The studied PRB was designed to remediate a chlorinated hydrocarbons plume at an old industrial landfill site, in Avigliana, near the city of Torino, in Italy. The continuous reactive barrier was designed to be 120 m long, 13 m deep, and 0.6 m thick. The installation of the barrier was accomplished using a clamshell for the excavation of the trench and a guar-gum slurry to support the walls. The performance of this technique was outstanding and allowed the installation of the PRB in 7 days. The degree of precision of the excavation was very high because of the intrinsic characteristics of this excavation tool and of the use of a concrete curb to guide the hydraulic grab. Moreover, the adopted technique permitted a saving of bioslurry thus minimizing the amount of biocide required.

  15. pH-Regulated Mechanisms Account for Pigment-Type Differences in Epidermal Barrier Function

    PubMed Central

    Gunathilake, Roshan; Schurer, Nanna Y.; Shoo, Brenda A.; Celli, Anna; Hachem, Jean-Pierre; Crumrine, Debra; Sirimanna, Ganga; Feingold, Kenneth R.; Mauro, Theodora M.; Elias, Peter M.

    2009-01-01

    To determine whether pigment type determines differences in epidermal function, we studied stratum corneum (SC) pH, permeability barrier homeostasis, and SC integrity in three geographically disparate populations with pigment type I–II versus IV–V skin (Fitzpatrick I–VI scale). Type IV–V subjects showed: (i) lower surface pH (≈0.5 U); (ii) enhanced SC integrity (transepidermal water loss change with sequential tape strippings); and (iii) more rapid barrier recovery than type I–II subjects. Enhanced barrier function could be ascribed to increased epidermal lipid content, increased lamellar body production, and reduced acidity, leading to enhanced lipid processing. Compromised SC integrity in type I–II subjects could be ascribed to increased serine protease activity, resulting in accelerated desmoglein-1 (DSG-1)/corneodesmosome degradation. In contrast, DSG-1-positive CDs persisted in type IV–V subjects, but due to enhanced cathepsin-D activity, SC thickness did not increase. Adjustment of pH of type I–II SC to type IV–V levels improved epidermal function. Finally, dendrites from type IV–V melanocytes were more acidic than those from type I–II subjects, and they transfer more melanosomes to the SC, suggesting that melanosome secretion could contribute to the more acidic pH of type IV–V skin. These studies show marked pigment-type differences in epidermal structure and function that are pH driven. PMID:19177137

  16. sPLA2 and the epidermal barrier

    PubMed Central

    Ilic, Dusko; Bollinger, James M.; Gelb, Michael; Mauro, Theodora M.

    2015-01-01

    The mammalian epidermis provides both an interface and a protective barrier between the organism and its environment. Lipid, processed into water-impermeable bilayers between the outermost layers of the epidermal cells, forms the major barrier that prevents water from exiting the organism, and also prevents toxins and infectious agents from entering. The secretory phospholipase 2 (sPLA2) enzymes control important processes in skin and other organs, including inflammation and differentiation. sPLA2 activity contributes to epidermal barrier formation and homeostasis by generating free fatty acids, which are required both for formation of lamellar membranes and also for acidification of the stratum corneum (SC). sPLA2 is especially important in controlling SC acidification and establishment of an optimum epidermal barrier during the first postnatal week. Several sPLA2 isoforms are present in the epidermis. We find that two of these isoforms, sPLA2 IIA and sPLA2 IIF, localize to the upper stratum granulosum and increase in response to experimental barrier perturbation. sPLA2F−/− mice also demonstrate a more neutral SC pH than do their normal littermates, and their initial recovery from barrier perturbation is delayed. These findings confirm that sPLA2 enzymes perform important roles in epidermal development, and suggest that the sPLA2IIF isoform may be central to SC acidification and barrier function. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. PMID:24269828

  17. Quantitative proteogenomic profiling of epidermal barrier formation in vitro

    PubMed Central

    Winget, Jason M.; Watts, Julian D.; Hoopmann, Michael R.; DiColandrea, Teresa; Robinson, Michael K.; Huggins, Tom; Bascom, Charles C.; Isfort, Robert J.; Moritz, Robert L.

    2015-01-01

    Background The barrier function of the epidermis is integral to personal well-being, and defects in the skin barrier are associated with several widespread diseases. Currently there is a limited understanding of system-level proteomic changes during epidermal stratification and barrier establishment. Objective Here we report the quantitative proteogenomic profile of an in vitro reconstituted epidermis at three time points of development in order to characterize protein changes during stratification. Methods The proteome was measured using data-dependent “shotgun” mass spectrometry and quantified with statistically validated label-free proteomic methods for 20 replicates at each of three time points during the course of epidermal development. Results Over 3600 proteins were identified in the reconstituted epidermis, with more than 1200 of these changing in abundance over the time course. We also collected and discuss matched transcriptomic data for the three time points, allowing alignment of this new dataset with previously published characterization of the reconstituted epidermis system. Conclusion These results represent the most comprehensive epidermal-specific proteome to date, and therefore reveal several aspects of barrier formation and skin composition. The limited correlation between transcript and protein abundance underscores the importance of proteomic analysis in developing a full understanding of epidermal maturation. PMID:25862149

  18. Blood-ocular barrier permeability in monkeys.

    PubMed Central

    Yoshida, A; Ishiko, S; Kojima, M; Lipsky, S N

    1992-01-01

    The permeability of the blood-ocular barrier was investigated in five monkeys using vitreous fluorophotometry (VFP). Inward permeability (Pin) of the blood-retinal barrier was calculated by a computer simulation method. Kinetic VFP was performed after intravitreal injection of fluorescein (F) or fluorescein monoglucuronide (FG). The estimated mean value of Pin (x10(-6) cm/min) was 4.8 (SD 1.2). The mean rates of loss (per hour) of F from the anterior chamber (Ka) and the vitreous (Kv) were 0.11 (SD 0.01) and 0.13 (SD 0.03), respectively, which were approximately three and four times greater than those of FG (0.04 (SD 0.01) and 0.03 (SD 0.01), respectively). Probenecid administered intraperitoneally decreased both the Ka and the Kv of F significantly but had no effect on the Ka or the Kv of FG, suggesting that F was excreted from the eye with the aid of the active transport mechanism. The results of comparative studies of the rates of loss of F from the anterior chamber (Ka) and from the vitreous (Kv) suggested that active transport was more predominant in the blood-retinal barrier than in the blood-aqueous barrier. PMID:1739721

  19. Using FLIM in the study of permeability barrier function of aged and young skin

    NASA Astrophysics Data System (ADS)

    Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

    2006-02-01

    Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

  20. EPA/ITRC-RTDF permeable reactive barrier short course. Permeable reactive barriers: Application and deployment

    SciTech Connect

    Not Available

    1999-01-01

    This report focuses on the following: Permeable Reactive Barriers: Application and Deployment; Introduction to Permeable Reactive Barriers (PRBs) for Remediating and Managing Contaminated Groundwater in Situ; Collection and Interpretation of Design Data 1: Site Characterization for PRBs; Reactive Materials: Zero-Valent Iron; Collection and Interpretation of Design Data 2: Laboratory and Pilot Scale Tests; Design Calculations; Compliance Monitoring, Performance Monitoring and Long-Term Maintenance for PRBs; PRB Emplacement Techniques; PRB Permitting and Implementation; Treatment of Metals; Non-Metallic Reactive Materials; Economic Considerations for PRB Deployment; and Bibliography.

  1. EPA/ITRC-RTDF permeable reactive barrier short course. Permeable reactive barriers: Application and deployment

    SciTech Connect

    1999-11-01

    This report focuses on the following: Permeable Reactive Barriers: Application and Deployment; Introduction to Permeable Reactive Barriers (PRBs) for Remediating and Managing Contaminated Groundwater in Situ; Collection and Interpretation of Design Data 1: Site Characterization for PRBs; Reactive Materials: Zero-Valent Iron; Collection and Interpretation of Design Data 2: Laboratory and Pilot Scale Tests; Design Calculations; Compliance Monitoring, Performance Monitoring and Long-Term Maintenance for PRBs; PRB Emplacement Techniques; PRB Permitting and Implementation; Treatment of Metals; Non-Metallic Reactive Materials; Economic Considerations for PRB Deployment; and Bibliography.

  2. Induced epidermal permeability modulates resistance and susceptibility of wheat seedlings to herbivory by Hessian fly larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salivary secretions of neonate Hessian fly larvae initiate epidermal permeability in wheat plants, resulting in the two-way exchange of molecules. This permeability allows larval elicitors to enter the plant where they can trigger plant processes leading to resistance or susceptibility. The rapid in...

  3. The Role of Impaired Epidermal Barrier Function in Atopic Dermatitis.

    PubMed

    Jurakić Tončić, Ružica; Marinović, Branka

    2016-06-01

    Atopic dermatitis (AD) is a chronic, inflammatory, pruritic skin disease with increasing prevalence. The etiopathogenesis of atopic dermatitis is multifactorial and involves a complex interplay of environmental and genetic factors that induce derangements in the structure and function of the epidermal barrier and immune system. Due to great heterogeneity of etiopathogenesis, there is also great variability of clinical presentation, and diagnosis can sometimes be challenging and difficult. Diagnosis mostly relies on clinical features and laboratory tests, but morphology alone cannot reliably establish the diagnosis, so the spectrum of features associated with AD must be considered. Traditionally, patients with AD have been separated into two different subgroups, i.e. intrinsic and extrinsic. Today, most of authors prefer the outside to inside and back to outside hypothesis, suggesting that the primary disorder lies in epidermal structure and function, resulting in inflammation and immunological downstream activation which further provokes secondary barrier abnormalities. In this review, we discuss the structure and function of the epidermal barrier and the role of impaired barrier function in etiopathogenesis of atopic dermatitis. PMID:27477169

  4. Detergent-induced epidermal barrier dysfunction and its prevention.

    PubMed

    Okuda, Minehiro; Yoshiike, Takashi; Ogawa, Hideoki

    2002-12-01

    Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function. PMID:12443839

  5. The diffusion-active permeable reactive barrier

    NASA Astrophysics Data System (ADS)

    Schwarz, Alex O.; Rittmann, Bruce E.

    2010-03-01

    Using the biogeochemical model CCBATCH, which we expanded to include transport processes, we study a novel approach for the treatment of aquifers contaminated with toxic concentrations of metals, the diffusion-active permeable reactive barrier (DAPRB), which is based on generation of sulfide by Sulfate Reducing Bacteria (SRB) as the groundwater moves through a layered treatment zone. In the DAPRB, layers of low conductivity (low-K) containing reactive materials are intercalated between layers of high conductivity (high-K) that transport the groundwater across the barrier. Because diffusion dominates transport in the reactive layers, microbial communities can take advantage there of the chemical-gradient mechanism for protection from toxicants. The ideal sulfidic DAPRB design includes particulate organic matter (POM) and solid sulfate mineral inside the reactive (low-K) layer. This leads to sulfate reduction and the formation of sulfide ligands that complex with toxic metals, such as Zn 2+ in the high-K layer. We perform a theoretical biogeochemical analysis of the ideal configuration of a DAPRB for treatment of Zn-contaminated groundwater. Our analysis using the expanded CCBATCH confirms the gradient-resistance mechanism for bio-protection, with the ZnS bio-sink forming at the intersection of the Zn and sulfide plumes inside the high-K layers of the DAPRB. The detailed DAPRB analysis also shows that total alkalinity and pH distributions are representative footprints of the two key biogeochemical processes taking place, sulfidogenesis and Zn immobilization as sulfide mineral. This is so because these two reactions consume or produce acidic hydrogen and alkalinity. Additionally, because Zn immobilization is due to ZnS mineral precipitation, the ZnS mineral distribution is a good indicator for the bio-sink. Bio-sinks are located for the most part within the high-K layers, and their exact position depends on the relative magnitude of metal and sulfide fluxes. Finally

  6. TREATMENT OF INORGANIC CONTAMINANTS USING PERMEABLE REACTIVE BARRIERS

    EPA Science Inventory

    Permeable reactive barriers are an emerging alternative to traditional pump and treat systems for groundwater remediation. This technique has progressed rapidly over the past decade from laboratory bench-scale studies to full-scale implementation. Laboratory studies indicate the ...

  7. PERMEABLE REACTIVE BARRIER TECHNOLOGIES FOR CONTAMINANT REMEDIATION

    EPA Science Inventory

    Environmental scientists are generally familiar with the concept of barriers for restricting the movement of contaminant plumes in ground water. Such barriers are typically constructed of highly impermeable emplacements of materials such as grouts, slurries, or sheet pilings to ...

  8. Review of potential subsurface permeable barrier emplacement and monitoring technologies

    SciTech Connect

    Riggsbee, W.H.; Treat, R.L.; Stansfield, H.J.; Schwarz, R.M.; Cantrell, K.J.; Phillips, S.J.

    1994-02-01

    This report focuses on subsurface permeable barrier technologies potentially applicable to existing waste disposal sites. This report describes candidate subsurface permeable barriers, methods for emplacing these barriers, and methods used to monitor the barrier performance. Two types of subsurface barrier systems are described: those that apply to contamination.in the unsaturated zone, and those that apply to groundwater and to mobile contamination near the groundwater table. These barriers may be emplaced either horizontally or vertically depending on waste and site characteristics. Materials for creating permeable subsurface barriers are emplaced using one of three basic methods: injection, in situ mechanical mixing, or excavation-insertion. Injection is the emplacement of dissolved reagents or colloidal suspensions into the soil at elevated pressures. In situ mechanical mixing is the physical blending of the soil and the barrier material underground. Excavation-insertion is the removal of a soil volume and adding barrier materials to the space created. Major vertical barrier emplacement technologies include trenching-backfilling; slurry trenching; and vertical drilling and injection, including boring (earth augering), cable tool drilling, rotary drilling, sonic drilling, jetting methods, injection-mixing in drilled holes, and deep soil mixing. Major horizontal barrier emplacement technologies include horizontal drilling, microtunneling, compaction boring, horizontal emplacement, longwall mining, hydraulic fracturing, and jetting methods.

  9. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    PubMed Central

    Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola

    2016-01-01

    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function. PMID:26985171

  10. Calmodulin 4 is dispensable for epidermal barrier formation and wound healing in mice.

    PubMed

    Lessard, Juliane C; Kalinin, Alexandr; Bible, Paul W; Morasso, Maria I

    2015-01-01

    Calcium-mediated signals play important roles in epidermal barrier formation, skin homoeostasis and wound repair. Calmodulin 4 (Calm4) is a small, Ca2+ -binding protein with strong expression in suprabasal keratinocytes. In mice, Calm4 first appears in the skin at the time of barrier formation, and its expression increases in response to epidermal barrier challenges. In this study, we report the generation of Calm4 knockout mice and provide evidence that Calm4 is dispensable for epidermal barrier formation, maintenance and repair. PMID:25316000

  11. 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. PMID:26027835

  12. Controlling ferrofluid permeability across the blood–brain barrier model.

    PubMed

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

    2014-02-21

    In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB). PMID:24457539

  13. Controlling ferrofluid permeability across the blood-brain barrier model

    NASA Astrophysics Data System (ADS)

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J.

    2014-02-01

    In the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood-brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood-brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood-brain barrier (e.g. CPB).

  14. Test device for measuring permeability of a barrier material

    DOEpatents

    Reese, Matthew; Dameron, Arrelaine; Kempe, Michael

    2014-03-04

    A test device for measuring permeability of a barrier material. An exemplary device comprises a test card having a thin-film conductor-pattern formed thereon and an edge seal which seals the test card to the barrier material. Another exemplary embodiment is an electrical calcium test device comprising: a test card an impermeable spacer, an edge seal which seals the test card to the spacer and an edge seal which seals the spacer to the barrier material.

  15. The effect of Psoroptes ovis infestation on ovine epidermal barrier function

    PubMed Central

    2013-01-01

    Sheep scab is an intensively pruritic, exudative and allergic dermatitis of sheep caused by the ectoparasitic mite Psoroptes ovis. The purpose of the present study was to investigate the effect of P. ovis infestation on different components of the ovine epidermal barrier within the first 24 hours post-infestation (hpi). To achieve this, the expression of epidermal differentiation complex (EDC) genes and epidermal barrier proteins, the nature and severity of epidermal pathology and transepidermal water loss (TEWL) were evaluated. By 1 hpi a significant dermal polymorphonuclear infiltrate and a significant increase in TEWL with maximal mean TEWL (598.67 g/m2h) were observed. Epidermal pathology involving intra-epidermal pustulation, loss of epidermal architecture and damage to the basement membrane was seen by 3 hpi. Filaggrin and loricrin protein levels in the stratum corneum declined significantly in the first 24 hpi and qPCR validation confirmed the decrease in expression of the key EDC genes involucrin, filaggrin and loricrin observed by microarray analysis, with 5.8-fold, 4.5-fold and 80-fold decreases, respectively by 24 hpi. The present study has demonstrated that early P. ovis infestation disrupts the ovine epidermal barrier causing significant alterations in the expression of critical barrier components, epidermal pathology, and TEWL. Many of these features have also been documented in human and canine atopic dermatitis suggesting that sheep scab may provide a model for the elucidation of events occurring in the early phases of atopic sensitisation. PMID:23398847

  16. Evolutionary origin and diversification of epidermal barrier proteins in amniotes.

    PubMed

    Strasser, Bettina; Mlitz, Veronika; Hermann, Marcela; Rice, Robert H; Eigenheer, Richard A; Alibardi, Lorenzo; Tschachler, Erwin; Eckhart, Leopold

    2014-12-01

    The evolution of amniotes has involved major molecular innovations in the epidermis. In particular, distinct structural proteins that undergo covalent cross-linking during cornification of keratinocytes facilitate the formation of mechanically resilient superficial cell layers and help to limit water loss to the environment. Special modes of cornification generate amniote-specific skin appendages such as claws, feathers, and hair. In mammals, many protein substrates of cornification are encoded by a cluster of genes, termed the epidermal differentiation complex (EDC). To provide a basis for hypotheses about the evolution of cornification proteins, we screened for homologs of the EDC in non-mammalian vertebrates. By comparative genomics, de novo gene prediction and gene expression analyses, we show that, in contrast to fish and amphibians, the chicken and the green anole lizard have EDC homologs comprising genes that are specifically expressed in the epidermis and in skin appendages. Our data suggest that an important component of the cornified protein envelope of mammalian keratinocytes, that is, loricrin, has originated in a common ancestor of modern amniotes, perhaps during the acquisition of a fully terrestrial lifestyle. Moreover, we provide evidence that the sauropsid-specific beta-keratins have evolved as a subclass of EDC genes. Based on the comprehensive characterization of the arrangement, exon-intron structures and conserved sequence elements of EDC genes, we propose new scenarios for the evolutionary origin of epidermal barrier proteins via fusion of neighboring S100A and peptidoglycan recognition protein genes, subsequent loss of exons and highly divergent sequence evolution. PMID:25169930

  17. TOPICAL ANTIHISTAMINES DISPLAY POTENT ANTI-INFLAMMATORY ACTIVITY LINKED IN PART TO ENHANCED PERMEABILITY BARRIER FUNCTION

    PubMed Central

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P.; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R.; Elias, Peter M.

    2012-01-01

    Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective, if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by: i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and ii) enhanced epidermal lipid synthesis and secretion. Since barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamine. In four immunologically-diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis), or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, while H1/2r antagonists improved inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly-systemic to a topical approach. PMID:23014339

  18. 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases the expression of genes in the human epidermal differentiation complex and accelerates epidermal barrier formation.

    PubMed

    Sutter, Carrie Hayes; Bodreddigari, Sridevi; Campion, Christina; Wible, Ryan S; Sutter, Thomas R

    2011-11-01

    Chloracne is commonly observed in people exposed to dioxins, yet the mechanism of toxicity is not well understood. The pathology of chloracne is characterized by hyperkeratinization of the interfollicular squamous epithelium, hyperproliferation and hyperkeratinization of hair follicle cells as well as a metaplastic response of the ductular sebum secreting sebaceous glands. In vitro studies using normal human epidermal keratinocytes to model interfollicular human epidermis demonstrate a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated acceleration of differentiation and increase in gene expression of several prodifferentiation genes, including filaggrin (FLG). Here, we demonstrated that the TCDD-activated aryl hydrocarbon receptor (AHR) bound a small fragment of DNA upstream of the transcriptional start sites of the FLG gene, containing one of two candidate xenobiotic response elements (XREs). Reporter assays using the promoter region of FLG containing the two putative XREs indicated that the increase in this messenger RNA (mRNA) was due to TCDD-mediated enhanced transcription, which was lost when both XREs were mutated. As FLG is part of the human epidermal differentiation complex (EDC) found on chromosome 1, we measured mRNAs from an additional 18 EDC genes for their regulation by TCDD. Of these genes, 14 were increased by TCDD. Immunoblot assays demonstrated that the proteins of FLG as well as that of another prodifferentiation gene, small proline rich protein 2, were increased by TCDD. In utero exposure to TCDD accelerated the formation of the epidermal barrier in the developing mouse fetus by approximately 1 day. These results indicate that the epidermal permeability barrier is a functional target of the TCDD-activated AHR. PMID:21835898

  19. Epidermal Permeability Barrier in the Treatment of Keratosis Pilaris

    PubMed Central

    Kootiratrakarn, Tanawatt; Kampirapap, Kowit; Chunhasewee, Chakkrapong

    2015-01-01

    Objectives. To evaluate and compare the efficacy, safety, hydrating properties, and tolerability of 10% lactic acid (LA) and 5% salicylic acid (SA) in the therapy of keratosis pilaris (KP). Material and Method. Patients with KP were randomized for treatment with either 10% LA or 5% SA creams being applied twice daily for 3 months. The patients were clinically assessed at baseline and after 4, 8, and 12 weeks of treatment and 4 weeks after treatment. The functional properties of the stratum corneum (SC) were determined before treatment, 12 weeks, and follow-up phase by high-frequency conductance and transepidermal water loss (TEWL). Results. At the end of the trial, the mean reduction of the lesions from baseline was statistically significant for 10% LA (66%) and 5% SA (52%). During the treatment, higher conductance values were found on both group and this improvement was maintained until the follow up period. No significant differences in transepidermal water loss were observed after treatment. The adverse effects were limited to mild irritation localized on the skin without systemic side effect. Conclusion. The study demonstrated that 10% LA and 5% SA are beneficial to treat KP with the significantly clearance and marked improvement as by instrumental evaluation. PMID:25802513

  20. Epidermal permeability barrier in the treatment of keratosis pilaris.

    PubMed

    Kootiratrakarn, Tanawatt; Kampirapap, Kowit; Chunhasewee, Chakkrapong

    2015-01-01

    Objectives. To evaluate and compare the efficacy, safety, hydrating properties, and tolerability of 10% lactic acid (LA) and 5% salicylic acid (SA) in the therapy of keratosis pilaris (KP). Material and Method. Patients with KP were randomized for treatment with either 10% LA or 5% SA creams being applied twice daily for 3 months. The patients were clinically assessed at baseline and after 4, 8, and 12 weeks of treatment and 4 weeks after treatment. The functional properties of the stratum corneum (SC) were determined before treatment, 12 weeks, and follow-up phase by high-frequency conductance and transepidermal water loss (TEWL). Results. At the end of the trial, the mean reduction of the lesions from baseline was statistically significant for 10% LA (66%) and 5% SA (52%). During the treatment, higher conductance values were found on both group and this improvement was maintained until the follow up period. No significant differences in transepidermal water loss were observed after treatment. The adverse effects were limited to mild irritation localized on the skin without systemic side effect. Conclusion. The study demonstrated that 10% LA and 5% SA are beneficial to treat KP with the significantly clearance and marked improvement as by instrumental evaluation. PMID:25802513

  1. Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis.

    PubMed

    Clark, Jessica A; Gan, Heng; Samocha, Alexandr J; Fox, Amy C; Buchman, Timothy G; Coopersmith, Craig M

    2009-09-01

    Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion. PMID:19571236

  2. Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis

    PubMed Central

    Clark, Jessica A.; Gan, Heng; Samocha, Alexandr J.; Fox, Amy C.; Buchman, Timothy G.; Coopersmith, Craig M.

    2009-01-01

    Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes (IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion. PMID:19571236

  3. Foamed gel barriers in porous media: Breakdown and permeability evolution

    SciTech Connect

    Miller, M.J.; Fogler, H.S.

    1995-11-01

    Foamed gel has begun to play an important role in permeability modification applications because of the reduced chemical requirements. Foamed gels create impermeable barriers in porous media; however, once a critical pressure differential is exceeded, the permeability increases with increasing pressure. A two-dimensional network model was developed to estimate foamed gel barrier performance in terms of the maximum pressure a barrier can withstand and the evolution of the foamed gel barrier`s permeability. The formation of conductive pathways and the accompanying permeability increase were estimated for a model of the pressure-induced deformation and rupture of individual lenses. The evolution of conductive pathways changed from invasion percolation (high elastic modulus, rigid gel) to a lens rupture chain reaction initiated by the rupture of a single lens (low elastic modulus gel) as the elastic modulus of the gel was decreased. The apparent fractal dimension of the first conductive channel ranged from 1.89 to 1.06 for high and low elastic modulus gels., respectively. This dependency of breakthrough and breakdown is unique and produces a large range of breakdown behavior for any degree of microscopic heterogeneity.

  4. Japanese Cedar (Cryptomeria japonica) pollen allergen induces elevation of intracellular calcium in human keratinocytes and impairs epidermal barrier function of human skin ex vivo.

    PubMed

    Kumamoto, Junichi; Tsutsumi, Moe; Goto, Makiko; Nagayama, Masaharu; Denda, Mitsuhiro

    2016-01-01

    Cry j1 is the major peptide allergen of Japanese cedar (Sugi), Cryptomeria japonica. Since some allergens disrupt epidermal permeability barrier homeostasis, we hypothesized that Cry j1 might have a similar effect. Intracellular calcium level in cultured human keratinocytes was measured with a ratiometric fluorescent probe, Fura-2 AM. Application of Cry j1 significantly increased the intracellular calcium level of keratinocytes, and this increase was inhibited by trypsin inhibitor or a protease-activated receptor 2 (PAR-2) antagonist. We found that Cry j1 itself did not show protease activity, but application of Cry j1 to cultured keratinocytes induced a rapid (within 30 s) and transient increase of protease activity in the medium. This transient increase was blocked by trypsin inhibitor or PAR-2 antagonist. The effect of Cry j1 on transepidermal water loss (TEWL) of cultured human skin was measured in the presence and absence of a trypsin inhibitor and PAR-2 antagonist. Cry j1 significantly impaired the barrier function of human skin ex vivo, and this action was blocked by co-application of trypsin inhibitor or PAR-2 antagonist. Our results suggested that interaction of Cry j1 with epidermal keratinocytes leads to the activation of PAR-2, which induces elevation of intracellular calcium and disruption of barrier function. Blocking the interaction of Cry j1 with epidermal keratinocytes might ameliorate allergic reaction and prevent disruption of epidermal permeability barrier homeostasis. PMID:26498292

  5. PERMEABLE REACTIVE BARRIERS FOR REMEDIATION OF INORGANIC CONTAMINANTS

    EPA Science Inventory

    The permeable reactive barrier (PRB) technology is an in-situ approach for groundwater remediation that couples subsurface flow management with a passive chemical or biochemical treatment zone. The development and application of the PRB technology has progressed over the last de...

  6. Permeable Reactive Barriers for Treatment of Cr6

    EPA Science Inventory

    Several options are available for treatment of hexavalent chromium (Cr(VI)) in groundwater using the permeable reactive barrier (PRB) approach. They include conventional trench-and-fill systems, chemical redox curtains, and organic carbon redox curtains. Each of these PRB syste...

  7. MICROBIAL CHARACTERIZATION OF MANURE BASED PERMEABLE REACTIVE BARRIER

    EPA Science Inventory

    The implementation of permeable reactive barriers (PRB) provides a viable option for the remediation of contaminants of environmental significance such as dissolved metals (i.e., chromium), chlorinated solvents, and nitrate/ammonia. The designs of PRBs are usually based on the a...

  8. LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS: LESSONS LEARNED

    EPA Science Inventory

    This presentation will provide an overview of research efforts at EPA on the application, monitoring, and performance of Permeable Reactive Barriers (PRBs) for groundwater restoration. Over the past 10 years, research projects conducted by research staff at EPA's National Risk M...

  9. COLLECTION OF DESIGN DATA: SITE CHARACTERIZATION FOR PERMEABLE REACTIVE BARRIERS

    EPA Science Inventory

    Permeable reactive barriers (PRBs) for the restoration of contaminated ground water are no longer innovative. PRBs have evolved from innovative to accepted, standard practice, for the containment and treatment of a variety of contaminants in ground water. Like any remedial tech...

  10. Tjp3/zo-3 is critical for epidermal barrier function in zebrafish embryos.

    PubMed

    Kiener, Tanja K; Selptsova-Friedrich, Inna; Hunziker, Walter

    2008-04-01

    TJP3/ZO-3 is a scaffolding protein that tethers tight junction integral membrane proteins to the actin cytoskeleton and links the conserved Crumbs polarity complex to tight junctions. The physiological function of TJP3/ZO-3 is not known and mice lacking TJP3/ZO-3 show no apparent phenotype. Here we show that Tjp3/Zo-3 is a component of tight junctions present in the enveloping cell layer of zebrafish embryos. Silencing tjp3/zo-3 using morpholinos leads to edema, loss of blood circulation and tail fin malformations in the embryos. The ultrastructure of tight junctions of the enveloping cell layer is disrupted, without affecting the asymmetric distribution of plasma membrane proteins. Morphants show a loss of the epidermal barrier, as assessed by an increased permeability of the enveloping cell layer to low molecular weight tracers and a higher sensitivity of the embryos to osmotic stress. Subjecting wild-type embryos to osmotic stress mimicks the morphant phenotype, consistent with the phenotype being a direct consequence of failed osmoregulation. Thus, Tjp3/Zo-3 is critical for barrier function of the enveloping cell layer and osmoregulation in early stages of zebrafish development. PMID:18275946

  11. Modeling Fe0 permeable reactive barriers for groundwater remediation

    NASA Astrophysics Data System (ADS)

    Carniato, Luca; Schoups, Gerrit; Seuntjens, Piet; Bastiaens, Leen

    2010-05-01

    Remediation of groundwater pollution has traditionally been achieved by energy-intensive and drastic methods such as pump and treat (P&T) systems. Recently, more economically viable and less invasive methods such as permeable reactive barriers have been used to clean up a wide variety of groundwater pollutants (volatile organic compounds, VOCl). Permeable reactive barriers are installed in the subsurface and the naturally present hydraulic gradient makes the groundwater flow through the barrier where the contaminants are removed by different removal processes (biodegradation, sorption, precipitation, chemical destruction). Effective application of these techniques requires a solid understanding of the site-specific hydrogeological and biochemical conditions, as well as a predictive assessment of long-term remediation efficiency. For example, secondary mineral precipitation has been shown to reduce reactivity and efficiency of permeable reactive barriers and the interactions between biological and chemical processes may also influence the long-term efficiency of such systems. In this study a multi-component transport model based on PHAST USGS has been developed to simulate the removal processes in the barrier and to make quantitative predictions about the long-term efficiency of the system. In particular the modelling approach will be presented together with the model application in lab-scale experiments and in field.

  12. Endocannabinoids modulate human blood–brain barrier permeability in vitro

    PubMed Central

    Hind, William H; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J; O'Sullivan, Saoirse E

    2015-01-01

    Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Key Results Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. Conclusion and Implication The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. PMID:25651941

  13. TIMP-1 attenuates blood–brain barrier permeability in mice with acute liver failure

    PubMed Central

    Chen, Feng; Radisky, Evette S; Das, Pritam; Batra, Jyotica; Hata, Toshiyuki; Hori, Tomohide; Baine, Ann-Marie T; Gardner, Lindsay; Yue, Mei Y; Bu, Guojun; del Zoppo, Gregory; Patel, Tushar C; Nguyen, Justin H

    2013-01-01

    Blood–brain barrier (BBB) dysfunction in acute liver failure (ALF) results in increased BBB permeability that often precludes the patients from obtaining a life-saving liver transplantation. It remains controversial whether matrix metalloproteinase-9 (MMP-9) from the injured liver contributes to the deregulation of BBB function in ALF. We selectively upregulated a physiologic inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute liver failure was induced with tumor necrosis factor-α and 𝒟-(+)-galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein (NaF) extravasation. We found a significant increase in TIMP-1 within the central nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a reduction in activation of epidermal growth factor receptor and p38 mitogen-activated protein kinase signals, and a restoration of the tight junction protein occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar protection against BBB permeability in mice with ALF. Our results provided a proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and suggests a potential therapeutic role of TIMP-1 in ALF. PMID:23532086

  14. Monitoring Permeable Reactive Barriers using Electrical Resistance Tomography

    SciTech Connect

    Ramirez, A; Bratton, W; Maresca, J; Daily, W; Dickerson, W

    2003-12-08

    An electrical resistivity tomography (ERT) method is being evaluated as a measurement tool to determine the integrity of permeable reactive barriers (PRBs) during and after construction of the barrier and as a monitoring tool to determine the long-term operational health of the barrier. The method is novel because it inserts the electrodes directly into the barrier itself. Numerical modeling calculations indicate that the ERT method can detect flaws (voids) in the barrier as small as 0.11 m{sup 2} (0.33 m x 0.33 m) when the aspect ratio of the electrodes are 2:1. Laboratory measurements indicate that the change in resistance over time of the iron-filling mixture used to create the PRB is sufficient for ERT to monitor the long-term health of the barrier. The use of this ERT method allows for the cost-effective installation of the barrier, especially when the vadose zone is large, because borehole installation methods, rather than trenching methods, can be used.

  15. Dietary constituents are able to play a beneficial role in canine epidermal barrier function.

    PubMed

    Watson, Adrian L; Fray, Tim R; Bailey, Julie; Baker, Claire B; Beyer, Sally A; Markwell, Peter J

    2006-01-01

    Epidermal barrier function is a critical attribute of mammalian skin. The barrier is responsible for preventing skin-associated pathologies through controlling egress of water and preventing ingress of environmental agents. Maintaining the quality and integrity of the epidermal barrier is therefore of considerable importance. Structurally, the barrier is composed of two main parts, the corneocytes and the intercellular lamellar lipid. The epidermal lamellar lipid comprises mainly ceramides, sterols and fatty acids. Twenty-seven nutritional components were screened for their ability to upregulate epidermal lipid synthesis. Seven of the 27 nutritional components (pantothenate, choline, nicotinamide, histidine, proline, pyridoxine and inositol) were subsequently retested using an in vitro transepidermal diffusion experimental model, providing a functional assessment of barrier properties. Ultimately, the best performing five nutrients were fed to dogs at supplemented concentrations in a 12-week feeding study. Barrier function was measured using transepidermal water loss (TEWL). It was found that a combination of pantothenate, choline, nicotinamide, histidine and inositol, when fed at supplemented concentrations, was able to significantly reduce TEWL in dogs after 9 weeks. PMID:16364034

  16. Freeze-fracture electron microscopic and osmotic water permeability studies of epidermal lipid liposomes derived from stratum corneum lipids of porcine epidermis.

    PubMed

    Mandal, T K; Downing, D T

    1993-02-01

    Freeze-fracture electron microscopic studies revealed that the liposomal membrane morphology was intact before and after osmotic treatment. This finding suggested that water leakage from the liposomes was not due to fusion of two or more lipid vesicles, but rather to the osmotic salt effect. A stop-flow spectrophotometric study revealed that epidermal lipid liposomes derived from stratum corneum lipids of porcine skin underwent increases of the absorbances with decreases of volume of the vesicles. The initial rate at which the changes in optical density occurs is a measure of the water permeability through the liposomes. The reciprocal of the changes in the absorbance at the equilibrium at different salt osmotic shocks showed a linear dependence on the reciprocal of the osmotic pressure gradient, indicating that epidermal lipid liposomes are an ideal osmometer. The present investigation reports that lignoceric acid is a potent water barrier. Present findings suggest that the initial rate of water penetration decreased in the liposomes made from 30-45% (wt% ratio) of cholesterol and ceramides. Oleic acid as drug penetration enhancer facilitated the water diffusion of the stratum corneum lipid liposomes by a fluidizing effect on the liposomal membranes. Furthermore, ceramides are important in the water barrier properties of the skin. The permeability of water depends upon the amount (wt%) and the type of lipid of the membrane. PMID:8095743

  17. Activated Protein C Enhances Human Keratinocyte Barrier Integrity via Sequential Activation of Epidermal Growth Factor Receptor and Tie2*

    PubMed Central

    Xue, Meilang; Chow, Shu-Oi; Dervish, Suat; Chan, Yee-Ka Agnes; Julovi, Sohel M.; Jackson, Christopher J.

    2011-01-01

    Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, significantly increased the barrier impedance of keratinocyte monolayers, measured by electric cell substrate impedance sensing and FITC-dextran flux. In response to APC, Tie2, a tyrosine kinase receptor, was rapidly activated within 30 min, and relocated to cell-cell contacts. APC also increased junction proteins zona occludens, claudin-1 and VE-cadherin. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA abolished the barrier protective effect of APC. Interestingly, APC did not activate Tie2 through its major ligand, angiopoietin-1, but instead acted by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor. Furthermore, when activation of Akt, but not ERK, was inhibited, the barrier protective effect of APC on keratinocytes was abolished. Thus, APC activates Tie2, via a mechanism requiring, in sequential order, the receptors, endothelial protein C receptor, protease-activated receptor-1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance junctional complexes and reduce keratinocyte permeability. PMID:21173154

  18. Automated Impedance Tomography for Monitoring Permeable Reactive Barrier Health

    SciTech Connect

    LaBrecque, D J; Adkins, P L

    2009-07-02

    The objective of this research was the development of an autonomous, automated electrical geophysical monitoring system which allows for near real-time assessment of Permeable Reactive Barrier (PRB) health and aging and which provides this assessment through a web-based interface to site operators, owners and regulatory agencies. Field studies were performed at four existing PRB sites; (1) a uranium tailing site near Monticello, Utah, (2) the DOE complex at Kansas City, Missouri, (3) the Denver Federal Center in Denver, Colorado and (4) the Asarco Smelter site in East Helena, Montana. Preliminary surface data over the PRB sites were collected (in December, 2005). After the initial round of data collection, the plan was modified to include studies inside the barriers in order to better understand barrier aging processes. In September 2006 an autonomous data collection system was designed and installed at the EPA PRB and the electrode setups in the barrier were revised and three new vertical electrode arrays were placed in dedicated boreholes which were in direct contact with the PRB material. Final data were collected at the Kansas City, Denver and Monticello, Utah PRB sites in the fall of 2007. At the Asarco Smelter site in East Helena, Montana, nearly continuous data was collected by the autonomous monitoring system from June 2006 to November 2007. This data provided us with a picture of the evolution of the barrier, enabling us to examine barrier changes more precisely and determine whether these changes are due to installation issues or are normal barrier aging. Two rounds of laboratory experiments were carried out during the project. We conducted column experiments to investigate the effect of mineralogy on the electrical signatures resulting from iron corrosion and mineral precipitation in zero valent iron (ZVI) columns. In the second round of laboratory experiments we observed the electrical response from simulation of actual field PRBs at two sites: the

  19. Long-Term Monitoring of Permeable Reactive Barriers - Progress Report

    SciTech Connect

    Liang, L.

    2001-04-12

    The purpose of this project is to conduct collaborative research to evaluate and maximize the effectiveness of permeable reactive barriers (PRBs) with a broad-based working group including representatives from the U.S. Department of Energy (DOE), U.S. Department of Defense (DoD), and the U.S. Environmental Protection Agency (EPA). The Naval Facilities Engineering Service Center (NFESC) and its project partner, Battelle, are leading the DoD effort with funding from DoD's Environmental Security Technology Certification Program (ESTCP) and Strategic Environmental Research and Development Program (SERDP). Oak Ridge National Laboratory (ORNL) is coordinating the DOE effort with support from Subsurface Contaminant Focus Area (SCFA), a research program under DOEs Office of Science and Technology. The National Risk Management Research Laboratory's Subsurface Protection and Remediation Division is leading EPA's effort. The combined effort of these three agencies allows the evaluation of a large number of sites. Documents generated by this joint project will be reviewed by the participating agencies' principal investigators, the Permeable Barriers Group of the Remediation Technologies Development Forum (RTDF), and the Interstate Technology and Regulatory Cooperation (ITRC). The technical objectives of this project are to collect and review existing field data at selected PRB sites, identify data gaps, conduct additional measurements, and provide recommendations to DOE users on suitable long-term monitoring strategies. The specific objectives are to (1) evaluate geochemical and hydraulic performance of PRBs, (2) develop guidelines for hydraulic and geochemical characterization/monitoring, and (3) devise and implement long-term monitoring strategies through the use of hydrological and geochemical models. Accomplishing these objectives will provide valuable information regarding the optimum configuration and lifetime of barriers at specific sites. It will also permit

  20. Treatment of inorganic contaminants using permeable reactive barriers

    NASA Astrophysics Data System (ADS)

    Blowes, David W.; Ptacek, Carol J.; Benner, Shawn G.; McRae, Che W. T.; Bennett, Timothy A.; Puls, Robert W.

    2000-09-01

    Permeable reactive barriers are an emerging alternative to traditional pump and treat systems for groundwater remediation. This technique has progressed rapidly over the past decade from laboratory bench-scale studies to full-scale implementation. Laboratory studies indicate the potential for treatment of a large number of inorganic contaminants, including As, Cd, Cr, Cu, Hg, Fe, Mn, Mo, Ni, Pb, Se, Tc, U, V, NO 3, PO 4 and SO 4. Small-scale field studies have demonstrated treatment of Cd, Cr, Cu, Fe, Ni, Pb, NO 3, PO 4 and SO 4. Permeable reactive barriers composed of zero-valent iron have been used in full-scale installations for the treatment of Cr, U, and Tc. Solid-phase organic carbon in the form of municipal compost has been used to remove dissolved constituents associated with acid-mine drainage, including SO 4, Fe, Ni, Co and Zn. Dissolved nutrients, including NO 3 and PO 4, have been removed from domestic septic-system effluent and agricultural drainage.

  1. Acyl lipidation of a peptide: effects on activity and epidermal permeability in vitro

    PubMed Central

    Rocco, Daniel; Ross, James; Murray, Paul E; Caccetta, Rima

    2016-01-01

    Short-chain lipid conjugates can increase permeability of a small peptide across human epidermis; however, the emerging lipoaminoacid (LAA) conjugation technique is costly and can deliver mixed synthetic products of varied biological potential. LAA conjugation using a racemic mixture produces a mixture of D- and L-stereoisomers. Individual enantiomers can be produced at an extra cost. We investigated an affordable technique that produces only one synthetic product: short-chain (C7–C8) acyl lipidation. Acyl lipidation of Ala-Ala-Pro-Val, an inhibitor of human neutrophil elastase (HNE; believed to lead to abnormal tissue destruction and disease development), was investigated as an alternative to LAA conjugation. The current study aimed to assess the effects of acyl lipidation (either at the N-terminal or at the C-terminal) on neutrophil elastase activity in vitro and on transdermal delivery ex vivo. The inhibitory capacity of the acyl conjugates was compared to LAA conjugates (conjugated at the N-terminal) of the same peptide. The L-stereoisomer appears to rapidly degrade, but it represents a significantly (P<0.05) better inhibitor of HNE than the parent peptide (Ala-Ala-Pro-Val). Although the D-stereoisomer appears to permeate human epidermal skin sections in a better fashion than the L-stereoisomer, it is not a significantly better inhibitor of HNE than the parent peptide. Acyl lipidation (with a C7 lipid chain) at either end of the peptide substantially enhances the permeability of the peptide across human skin epidermis as well as significantly (P<0.005) increases its elastase inhibitory potential. Therefore, our current study indicates that acyl lipidation of a peptide is a more economical and effective alternative to LAA conjugation. PMID:27468224

  2. Evidence of multiple permeability barriers in sarcolemmal (SL) aortic vesicles

    SciTech Connect

    Kaufman, L.J.; Kahn, A.M.; Allen, J.C.

    1986-03-05

    SL vesicles from canine aorta were prepared using Mg aggregation and differential centrifugation. Na/sup +/, K/sup +/-ATPase (NKA) and K/sup +/-Phosphatase (K-Pase) were determined in native and SDS treated SL with either 0.4 mM ouabain (OB) or the lipophilic inhibitor, digitoxigenin (DG). Native SL: OB inhibited NKA=0, DG inhibited NKA=7.7 ..mu..m/mg/hr; SDS treated SL: OB inhibited NKA=4.6, DG inhibited NKA=9.5; Native SL: OB inhibited K-Pase = 177nm/mg/hr, DG inhibited K-Pase = 285, SDS treated SL: OB inhibited K-Pase = 217, DG inhibited K- Pase = 283. Thus, native SL, primarily unbroken and both right side- and inside-out, may be impermeable to ATP and OB. Specific /sup 3/H-OB binding (Mg, P/sub i/) to SL was 5.0 pm/mg in native and 9.6 pm/mg in SL treated with the Mg chelator, CDTA. Altered binding was due to increased B/sub max/, not K/sub m/. Thus, in addition to the permeability barrier of SL, the Mg-bound basement membrane may present another barrier by obscuring OB binding sites. Gel filtration revealed that only the higher molecular weight fractions demonstrated specific OB binding which decreased with decreasing molecular weight, a finding consistent with varying vesicular size. These data indicate that SL prepared by Mg aggregation contain vesicles of differing size with at least two permeability barriers, SL and basement membrane.

  3. Directed site exploration for permeable reactive barrier design

    USGS Publications Warehouse

    Lee, J.; Graettinger, A.J.; Moylan, J.; Reeves, H.W.

    2009-01-01

    Permeable reactive barriers (PRBs) are being employed for in situ site remediation of groundwater that is typically flowing under natural gradients. Site characterization is of critical importance to the success of a PRB. A design-specific site exploration approach called quantitatively directed exploration (QDE) is presented. The QDE approach employs three spatially related matrices: (1) covariance of input parameters, (2) sensitivity of model outputs, and (3) covariance of model outputs to identify the most important location to explore based on a specific design. Sampling at the location that most reduces overall site uncertainty produces a higher probability of success of a particular design. The QDE approach is demonstrated on the Kansas City Plant, Kansas City, MO, a case study where a PRB was installed and failed. It is shown that additional quantitatively directed site exploration during the design phase could have prevented the remedial failure that was caused by missing a geologic body having high hydraulic conductivity at the south end of the barrier. The most contributing input parameter approach using head uncertainty clearly indicated where the next sampling should be made toward the high hydraulic conductivity zone. This case study demonstrates the need to include the specific design as well as site characterization uncertainty when choosing the sampling locations. ?? 2008 Elsevier B.V.

  4. Wave scattering by a permeable barrier over undulating bed topography

    NASA Astrophysics Data System (ADS)

    Choudhary, A.; Martha, S. C.

    2016-06-01

    The scattering of surface water waves by bottom undulation in the presence of a permeable vertical barrier is investigated for its solution. A mixed boundary value problem (BVP) arises here in a natural way while examining this physical problem. Regular perturbation analysis is employed to determine the solution of the BVP. By utilizing this analysis the given BVP reduces to two different BVPs up to first order. The solution of the zeroth order BVP is obtained with the aid of eigenfunction expansion method in conjunction with least-squares approximation. The first order BVP is solved with the help of the Green's integral theorem and the physical quantities, namely the reflection and transmission coefficients, are obtained in the form of integrals which involve the bottom undulation and the solution of the zeroth order BVP. A particular form of the bottom undulation which closely resembles to some obstacles made by nature due to sedimentation and ripple growth of sand, is considered to evaluate these integrals. The variation of these coefficients is examined for different values of the porous effect parameter, barrier length, number of ripples and ripple amplitude.

  5. ECONOMICS ANALYSIS OF THE IMPLEMENTATION OF PERMEABLE REACTIVE BARRIERS FOR REMEDIATION OF CONTAMINATED GROUND WATER

    EPA Science Inventory

    This report presents an analysis of the cost of using permeable reactive barriers to remediate contaminated ground water. When possible, these costs are compared with the cost of pump-and-treat technology for similar situations. Permeable reactive barriers are no longer perceiv...

  6. Surface altered zeolites as permeable barriers for in situ treatment of contaminated groundwater

    SciTech Connect

    1996-11-01

    The authors characterized surfactant-modified zeolite (SMZ) for its ability to sorb organic and inorganic contaminants from water. The ultimate objective is to use SMZ as a permeable barrier to prevent migration of contaminants in groundwater. This report summarizes results under Phase 1 of a three-phase project leading to a full-scale field demonstration of SMZ permeable- barrier technology.

  7. SURFACE-ALTERED ZEOLITES AS PERMEABLE BARRIERS FOR IN SITU TREATMENT OF CONTAMINATED GROUNDWATER

    SciTech Connect

    Robert S. Bowman; Zhaohui Li; Stephen J. Roy; Todd Burt; Timothy L. Johnson; Richard L. Johnson

    1999-08-30

    The overall objective of this effort is to develop and test a zeolite-based permeable barrier system for containing and remediating contaminated groundwater. The projected product is an engineered and tested permeable barrier system that can be adopted by the commercial sector.

  8. Zeolite in horizontal permeable reactive barriers for artificial groundwater recharge

    NASA Astrophysics Data System (ADS)

    Leal, María; Martínez-Hernández, Virtudes; Lillo, Javier; Meffe, Raffaella; de Bustamante, Irene

    2013-04-01

    The Spanish Water Reuse Royal Decree 1620/2007 considers groundwater recharge as a feasible use of reclaimed water. To achieve the water quality established in the above-mentioned legislation, a tertiary wastewater treatment is required. In this context, the infiltration of effluents generated by secondary wastewater treatments through a Horizontal Permeable Reactive Barrier (HPRB) may represent a suitable regeneration technology. Some nutrients (phosphate and ammonium) and some Pharmaceutical and Personal Care Products (PPCPs) are not fully removed in conventional wastewater treatment plants. To avoid groundwater contamination when effluents of wastewater treatments plants are used in artificial recharge activities, these contaminants have to be removed. Due to its sorption capacities, zeolite is among the most used reactive materials in Permeable Reactive Barrier (PRB). Therefore, the main goal of this study is to evaluate the zeolite retention effectiveness of nutrients and PPCPs occurring in treated wastewater. Batch sorption experiments using synthetic wastewater (SWW) and zeolite were performed. A 1:4 zeolite/SWW ratio was selected due to the high sorption capacity of the reactive material.The assays were carried out by triplicate. All the bottles containing the SWW-zeolite mixture were placed on a mechanical shaker during 24 hours at 140 rpm and 25 °C. Ammonium and phosphate, as main nutrients, and a group of PPCPs were selected as compounds to be tested during the experiments. Nutrients were analyzed by ion chromatography. For PPCPs determination, Solid Phase Extraction (SPE) was applied before their analysis by liquid chromatography-mass spectrometry time of flight (LC-MS/ TOF). The experimental data were fitted to linearized Langmuir and Freundlich isotherm equations to obtain sorption parameters. In general, Freundlich model shows a greater capability of reproducing experimental data. To our knowledge, sorption of the investigated compounds on zeolite

  9. Dynamic and Physical Clustering of Gene Expression during Epidermal Barrier Formation in Differentiating Keratinocytes

    PubMed Central

    Copley, Richard; Taylor, Martin S.; Hayden, Patrick J.; Stolper, Gina; Mott, Richard; Hein, Jotun; Moffatt, Miriam F.; Cookson, William O. C. M.

    2009-01-01

    The mammalian epidermis is a continually renewing structure that provides the interface between the organism and an innately hostile environment. The keratinocyte is its principal cell. Keratinocyte proteins form a physical epithelial barrier, protect against microbial damage, and prepare immune responses to danger. Epithelial immunity is disordered in many common diseases and disordered epithelial differentiation underlies many cancers. In order to identify the genes that mediate epithelial development we used a tissue model of the skin derived from primary human keratinocytes. We measured global gene expression in triplicate at five times over the ten days that the keratinocytes took to fully differentiate. We identified 1282 gene transcripts that significantly changed during differentiation (false discovery rate <0.01%). We robustly grouped these transcripts by K-means clustering into modules with distinct temporal expression patterns, shared regulatory motifs, and biological functions. We found a striking cluster of late expressed genes that form the structural and innate immune defences of the epithelial barrier. Gene Ontology analyses showed that undifferentiated keratinocytes were characterised by genes for motility and the adaptive immune response. We systematically identified calcium-binding genes, which may operate with the epidermal calcium gradient to control keratinocyte division during skin repair. The results provide multiple novel insights into keratinocyte biology, in particular providing a comprehensive list of known and previously unrecognised major components of the epidermal barrier. The findings provide a reference for subsequent understanding of how the barrier functions in health and disease. PMID:19888454

  10. Application of controlled nutrient release to permeable reactive barriers.

    PubMed

    Freidman, Benjamin L; Gras, Sally L; Snape, Ian; Stevens, Geoff W; Mumford, Kathryn A

    2016-03-15

    The application of controlled release nutrient (CRN) materials to permeable reactive barriers to promote biodegradation of petroleum hydrocarbons in groundwater was investigated. The longevity of release, influence of flow velocity and petroleum hydrocarbon concentration on nutrient release was assessed using soluble and ion exchange CRN materials; namely Polyon™ and Zeopro™. Both CRN materials, assessed at 4 °C and 23 °C, demonstrated continuing release of nitrogen, phosphorus and potassium (N-P-K) at 3500 bed volumes passing, with longer timeframes of N-P-K release at 4 °C. Zeopro™-activated carbon mixtures demonstrated depletion of N-P-K prior to 3500 bed volumes passing. Increased flow velocity was shown to lower nutrient concentrations in Polyon™ flow cells while nutrient release from Zeopro™ was largely unchanged. The presence of petroleum hydrocarbons, at 1.08 mmol/L and 3.25 mmol/L toluene, were not shown to alter nutrient release from Polyon™ and Zeopro™ across 14 days. These findings suggest that Polyon™ and Zeopro™ may be suitable CRN materials for application to PRBs in low nutrient environments. PMID:26735866

  11. Simplified, noninvasive PET measurement of blood-brain barrier permeability

    SciTech Connect

    Iannotti, F.; Fieschi, C.; Alfano, B.; Picozzi, P.; Mansi, L.; Pozzilli, C.; Punzo, A.; Del Vecchio, G.; Lenzi, G.L.; Salvatore, M.

    1987-05-01

    Blood-brain barrier (BBB) permeability to (/sup 68/Ga)EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the (/sup 68/Ga)EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes.

  12. Ascorbate Reverses High Glucose- and RAGE-induced Leak of the Endothelial Permeability Barrier

    PubMed Central

    Meredith, M. Elizabeth; Qu, Zhi-chao; May, James M.

    2014-01-01

    High glucose concentrations due to diabetes increase leakage of plasma constituents across the endothelial permeability barrier. We sought to determine whether vitamin C, or ascorbic acid (ascorbate), could reverse such high glucose-induced increases in endothelial barrier permeability. Human umbilical vein endothelial cells and two brain endothelial cell lines cultured at 25 mM glucose showed increases in endothelial barrier permeability to radiolabeled inulin compared to cells cultured at 5 mM glucose. Acute loading of the cells for 30–60 min with ascorbate before the permeability assay prevented the high glucose-induced increase in permeability and decreased basal permeability at 5 mM glucose. High glucose-induced barrier leakage was mediated largely by activation of the receptor for advanced glycation end products (RAGE), since it was prevented by RAGE blockade and mimicked by RAGE ligands. Intracellular ascorbate completely prevented RAGE ligand-induced increases in barrier permeability. The high glucose-induced increase in endothelial barrier permeability was also acutely decreased by several cell-penetrant antioxidants, suggesting that at least part of the ascorbate effect could be due to its ability to act as an antioxidant. PMID:24472555

  13. Stress does not increase blood-brain barrier permeability in mice.

    PubMed

    Roszkowski, Martin; Bohacek, Johannes

    2016-07-01

    Several studies have reported that exposure to acute psychophysiological stressors can lead to an increase in blood-brain barrier permeability, but these findings remain controversial and disputed. We thoroughly examined this issue by assessing the effect of several well-established paradigms of acute stress and chronic stress on blood-brain barrier permeability in several brain areas of adult mice. Using cerebral extraction ratio for the small molecule tracer sodium fluorescein (NaF, 376 Da) as a sensitive measure of blood-brain barrier permeability, we find that neither acute swim nor restraint stress lead to increased cerebral extraction ratio. Daily 6-h restraint stress for 21 days, a model for the severe detrimental impact of chronic stress on brain function, also does not alter cerebral extraction ratio. In contrast, we find that cold forced swim and cold restraint stress both lead to a transient, pronounced decrease of cerebral extraction ratio in hippocampus and cortex, suggesting that body temperature can be an important confounding factor in studies of blood-brain barrier permeability. To additionally assess if stress could change blood-brain barrier permeability for macromolecules, we measured cerebral extraction ratio for fluorescein isothiocyanate-dextran (70 kDa). We find that neither acute restraint nor cold swim stress affected blood-brain barrier permeability for macromolecules, thus corroborating our findings that various stressors do not increase blood-brain barrier permeability. PMID:27146513

  14. Effects of High-Intensity Endurance Exercise on Epidermal Barriers against Microbial Invasion

    PubMed Central

    Eda, Nobuhiko; Shimizu, Kazuhiro; Suzuki, Satomi; Lee, Eunjae; Akama, Takao

    2013-01-01

    For athletes, preventing infectious disease on skin is important. Examination measurement of epidermal barriers could provide valuable information on the risk of skin infections. The aim of this study was to determine the effects of high-intensity endurance exercise on epidermal barriers. Six healthy adult males (age; 22.3 ± 1.6 years) performed bicycle exercise at 75%HRmax for 60 min from 18:30 to 19:30. Skin surface samples were measured 18:30 (pre), 19:30 (post), 20:30 (60 min), and 21:30 (120 min). Secretory immunoglobulin A (SIgA) and human β-defensin 2 (HBD-2) concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). SIgA concentration at pre was significantly higher than at post, 60 min and 120 min (p < 0.05). HBD-2 concentration at post and 120 min was significantly higher than at pre (p < 0. 05). Moisture content of the stratum corneum was significantly higher at post than at pre, 60 min, and 120 min (p < 0.05). On the chest, moisture content of the stratum corneum was significantly lower at 120 min than at pre (p < 0.05). The number of staphylococci was significantly higher at post than at pre (p < 0.05), and tended to be higher at 60 min than at pre on the chest (p = 0. 08). High-intensity endurance exercise might depress the immune barrier and physical barrier and enhance the risk of skin infection. On the other hand, the biochemical barrier increases after exercise, and our findings suggest that this barrier might supplement the compromised function of other skin barriers. Key points The immune barrier and physical barrier might be depressed and the risk of skin infection might be enhanced by high-intensity endurance exercise. The biochemical barrier increases after high-intensity endurance exercise and might supplement the compromised function of other skin barriers. We recommend that athletes maintain their skin surface in good condition, for example, by showering immediately after sports activities and using moisturizers

  15. Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin*

    PubMed Central

    Plichta, Jennifer K.; Droho, Steve; Curtis, Brenda J.; Patel, Parita; Gamelli, Richard L.; Radek, Katherine A.

    2014-01-01

    Objectives Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue. Design Experimental mouse scald burn injury. Setting University Research Laboratory. Subjects C57/Bl6 Male mice, 8–12 weeks old. Interventions To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn. Measurements and Main Results Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients. Conclusions These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs

  16. Mast Cells Regulate Epidermal Barrier Function and the Development of Allergic Skin Inflammation.

    PubMed

    Sehra, Sarita; Serezani, Ana P M; Ocaña, Jesus A; Travers, Jeffrey B; Kaplan, Mark H

    2016-07-01

    Atopic dermatitis is a chronic inflammatory skin disease characterized by infiltration of eosinophils, T helper cells, and mast cells. The role of mast cells in atopic dermatitis is not completely understood. To define the effects of mast cells on skin biology, we observed that mast cells regulate the homeostatic expression of epidermal differentiation complex and other skin genes. Decreased epidermal differentiation complex gene expression in mice that genetically lack mast cells (Kit(W-sh/W-sh) mice) is associated with increased uptake of protein antigens painted on the skin by dendritic cells (DCs) compared with similarly treated wild-type mice, suggesting a protective role for mast cells in exposure to nominal environmental allergens. To test this further, we crossed Kit(W-sh/W-sh) mice with signal transducer and activator of transcription 6 (i.e., Stat6) VT transgenic mice that develop spontaneous atopic dermatitis-like disease that is dependent on T helper cell 2 cytokines and is associated with high serum concentrations of IgE. We observed that Stat6VT × Kit(W-sh/W-sh) mice developed more frequent and more severe allergic skin inflammation than Stat6VT transgenic mice that had mast cells. Together, these studies suggest that mast cells regulate epidermal barrier function and have a potential protective role in the development of atopic dermatitis-like disease. PMID:27021404

  17. 'You shall not pass!': quantifying barrier permeability and proximity avoidance by animals.

    PubMed

    Beyer, Hawthorne L; Gurarie, Eliezer; Börger, Luca; Panzacchi, Manuela; Basille, Mathieu; Herfindal, Ivar; Van Moorter, Bram; R Lele, Subhash; Matthiopoulos, Jason

    2016-01-01

    Impediments to animal movement are ubiquitous and vary widely in both scale and permeability. It is essential to understand how impediments alter ecological dynamics via their influence on animal behavioural strategies governing space use and, for anthropogenic features such as roads and fences, how to mitigate these effects to effectively manage species and landscapes. Here, we focused primarily on barriers to movement, which we define as features that cannot be circumnavigated but may be crossed. Responses to barriers will be influenced by the movement capabilities of the animal, its proximity to the barriers, and habitat preference. We developed a mechanistic modelling framework for simultaneously quantifying the permeability and proximity effects of barriers on habitat preference and movement. We used simulations based on our model to demonstrate how parameters on movement, habitat preference and barrier permeability can be estimated statistically. We then applied the model to a case study of road effects on wild mountain reindeer summer movements. This framework provided unbiased and precise parameter estimates across a range of strengths of preferences and barrier permeabilities. The quality of permeability estimates, however, was correlated with the number of times the barrier is crossed and the number of locations in proximity to barriers. In the case study we found that reindeer avoided areas near roads and that roads are semi-permeable barriers to movement. There was strong avoidance of roads extending up to c. 1 km for four of five animals, and having to cross roads reduced the probability of movement by 68·6% (range 3·5-99·5%). Human infrastructure has embedded within it the idea of networks: nodes connected by linear features such as roads, rail tracks, pipelines, fences and cables, many of which divide the landscape and limit animal movement. The unintended but potentially profound consequences of infrastructure on animals remain poorly understood

  18. PERFORMANCE OF PERMEABLE REACTIVE BARRIER AT U.S. COAST GUARD SITE, ELIZABETH CITY, NC

    EPA Science Inventory

    Permeable reactive barriers are innovative and cost-effective remedial technologies and are becoming more desirable methods for in-situ passive remediation of ground water contaminated with chlorinated hydrocarbons and redox-sensitive metals. As contaminated water passes through ...

  19. PERFORMANCE MONITORING OF PERMEABLE REACTIVE BARRIERS TO REMEDIATE CONTAMINATED GROUND WATER

    EPA Science Inventory

    Permeable reactive barriers (PRB's) are an emerging, alternative in-situ approach for remediating groundwater contamination that combine subsurface fluid flow management with a passive chemical treatment zone. Removal of contaminants from the groundwater plume is achieved by alt...

  20. APPLICATION OF THE PERMEABLE REACTIVE BARRIER TECHNOLOGY FOR THE TREATMENT OF ARSENIC IN GROUND WATER

    EPA Science Inventory

    The research approach will involve hydrogeological and geochemical studies to provide information needed in order to select an appropriate design configuration and to evaluate the performance of a pilot-scale subsurface permeable reactive barrier to remediate arsenic-contaminated...

  1. LONG-TERM PERFORMANCE ASSESSMENT OF PERMEABLE REACTIVE BARRIERS TO REMEDIATE CONTAMINATED GROUND WATER

    EPA Science Inventory

    Permeable reactive barriers (PRBs) are an emerging, alternative in-situ approach for remediating groundwater contamination that combine subsurface fluid flow management with a passive chemical treatment zone. The few pilot and commercial installations which have been implemented ...

  2. PERMEABLE REACTIVE BARRIER STRATEGIES FOR REMEDIATION OF ARSENIC-CONTAMINATED GROUNDWATER: ABSTRACT

    EPA Science Inventory

    NRMRL-ADA-01152 Wilkin*, R.T., and Paul*, C.J. "Permeable Reactive Barrier Strategies for Remediation of Arsenic- Contaminated Groundwater." In: Geological Society of America, Abstracts with programs., Geological Society of America Annua...

  3. BIFUNCTIONAL ALUMINUN: A PERMEABLE BARRIER MATERIAL FOR THE DEGRADATION OF MTBE

    EPA Science Inventory

    Bifunctional aluminum is an innovative remedial material for the treatment of gasoline oxygenates in permeable reactive barriers (PRBs). PRBs represent a promising environmental technology for remediation of groundwater contamination. Although zero-valent metals (ZVM) have been...

  4. PERMEABLE REACTIVE BARRIERS FOR IN-SITU TREATMENT OF ARSENIC-CONTAMINATED GROUNDWATER

    EPA Science Inventory

    Laboratory and field research has shown that permeable reactive barriers (PRBs) containing a variety of materials can treat arsenic (As) contaminated groundwater. Sites where these PRBs are located include a mine tailings facility, fertilizer and chemical manufacturing sites, a...

  5. Performance Assessment of a Permeable Reactive Barrier for Ground Water Remediation Fifteen Years After Installation

    EPA Science Inventory

    The fifteen-year performance of a granular iron, permeable reactive barrier (PRB; Elizabeth City, North Carolina) is reviewed with respect to contaminanttreatment (hexavalent chromium and trichloroethylene) and hydraulic performance. Due to in-situ treatment of the chromium sourc...

  6. Iron Hydroxy Carbonate Formation in Zerovalent Iron Permeable Reactive Barriers: Characterization and Evaluation of Phase Stability

    EPA Science Inventory

    Predicting the long-term potential of permeable reactive barriers for treating contaminated groundwater relies on understanding the endpoints of biogeochemical reactions between influent groundwater and the reactive medium. Iron hydroxy carbonate (chukanovite) is frequently obs...

  7. COST ANALYSIS OF PERMEABLE REACTIVE BARRIERS FOR REMEDIATION OF GROUND WATER

    EPA Science Inventory

    ABSTRACT

    Permeable reactive barriers (PRB's) are an emerging, alternative in-situ approach for remediating contaminated groundwater that combine subsurface fluid flow management with a passive chemical treatment zone. PRB's are a potentially more cost effective treatment...

  8. Rab3Gap1 mediates exocytosis of Claudin-1 and tight junction formation during epidermal barrier acquisition

    PubMed Central

    Youssef, G.; Gerner, L.; Naeem, A.S.; Ralph, O.; Ono, M.; O’Neill, C.A.; O’Shaughnessy, R.F.L.

    2013-01-01

    Epidermal barrier acquisition during late murine gestation is accompanied by an increase in Akt kinase activity and cJun dephosphorlyation. The latter is directed by the Ppp2r2a regulatory subunit of the Pp2a phosphatase. This was accompanied by a change of Claudin-1 localisation to the cell surface and interaction between Occludin and Claudin-1 which are thought to be required for tight junction formation. The aim of this study was to determine the nature of the barrier defect caused by the loss of AKT/Ppp2r2a function. There was a paracellular barrier defect in rat epidermal keratinocytes expressing a Ppp2r2a siRNA. In Ppp2r2a knockdown cells, Claudin-1 was located to the cytoplasm and its expression was increased. Inhibiting cJun phosphorylation restored barrier function and plasma membrane localisation of Claudin-1. Expression of the Rab3 GTPase activating protein, Rab3Gap1, was restored in Ppp2r2a siRNA cells when cJun phosphorylation was inhibited. During normal mouse epidermal development, Claudin-1 plasma membrane localisation and Rab3Gap1 cell surface expression were co-incident with Akt activation in mouse epidermis, strongly suggesting a role of Rab3Gap1 in epidermal barrier acquisition. Supporting this hypothesis, siRNA knockdown of Rab3Gap1 prevented plasma membrane Claudin-1 expression and the formation of a barrier competent epithelium. Replacing Rab3Gap1 in Ppp2r2a knockdown cells was sufficient to rescue Claudin-1 transport to the cell surface. Therefore these data suggest Rab3Gap1 mediated exocytosis of Claudin-1 is an important component of epidermal barrier acquisition during epidermal development. PMID:23685254

  9. New biomimetic barrier Permeapad™ for efficient investigation of passive permeability of drugs.

    PubMed

    di Cagno, Massimiliano; Bibi, Hanady A; Bauer-Brandl, Annette

    2015-06-20

    In this work the suitability of a newly invented physical patch comprising a biomimetic barrier (named Permeapad™) for drug permeability tests has been investigated. Exemplars of Permeapad™ were adapted to Franz diffusion cells and apparent permeability (Papp) of a series of drugs were measured and compared with calculated partition coefficients (logPcal) of the investigated drugs as well as literature reference values obtained from Parallel Artificial Membrane Permeation Assay (PAMPA) and the cellular based method Caco-2. Moreover, tightness of the barrier to hydrophilic marker's permeation, resistance of these barriers to proton permeation (pH changes) and shelf-life functionality were also investigated. Comparison with the published data indicated a good correlation between the permeability values measured and partition coefficients (logPcal). Moreover, a good correlation between the permeabilities measured with the new barrier and well-established in vitro permeability methods (PAMPA and Caco-2 respectively) was found for both highly absorbed and poorly permeable compounds. Permeapad™ also proved to maintain high integrity over time and in different pH environments. In conclusion, Permeapad™ as an innovative barrier appears to be a promising tool for fast, cost effective and reliable screening of drugs and chemical entities' passive permeability. PMID:25840123

  10. Comparison study of ferrofluid and powder iron oxide nanoparticle permeability across the blood-brain barrier.

    PubMed

    Hoff, Dan; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

    2013-01-01

    In the present study, the permeability of 11 different iron oxide nanoparticle (IONP) samples (eight fluids and three powders) was determined using an in vitro blood-brain barrier model. Importantly, the results showed that the ferrofluid formulations were statistically more permeable than the IONP powder formulations at the blood-brain barrier, suggesting a role for the presently studied in situ synthesized ferrofluid formulations using poly(vinyl) alcohol, bovine serum albumin, collagen, glutamic acid, graphene, and their combinations as materials which can cross the blood-brain barrier to deliver drugs or have other neurological therapeutic efficacy. Conversely, the results showed the least permeability across the blood-brain barrier for the IONP with collagen formulation, suggesting a role as a magnetic resonance imaging contrast agent but limiting IONP passage across the blood-brain barrier. Further analysis of the data yielded several trends of note, with little correlation between permeability and fluid zeta potential, but a larger correlation between permeability and fluid particle size (with the smaller particle sizes having larger permeability). Such results lay the foundation for simple modification of iron oxide nanoparticle formulations to either promote or inhibit passage across the blood-brain barrier, and deserve further investigation for a wide range of applications. PMID:23426527

  11. Increased symplasmic permeability in barley root epidermal cells correlates with defects in root hair development.

    PubMed

    Marzec, M; Muszynska, A; Melzer, M; Sas-Nowosielska, H; Kurczynska, E U

    2014-03-01

    It is well known that the process of plant cell differentiation depends on the symplasmic isolation of cells. Before starting the differentiation programme, the individual cell or group of cells should restrict symplasmic communication with neighbouring cells. We tested the symplasmic communication between epidermal cells in the different root zones of parental barley plants Hordeum vulgare L., cv. 'Karat' with normal root hair development, and two root hairless mutants (rhl1.a and rhl1.b). The results clearly show that symplasmic communication was limited during root hair differentiation in the parental variety, whereas in both root hairless mutants epidermal cells were still symplasmically connected in the corresponding root zone. This paper is the first report on the role of symplasmic isolation in barley root cell differentiation, and additionally shows that a disturbance in the restriction of symplasmic communication is present in root hairless mutants. PMID:23927737

  12. Increased symplasmic permeability in barley root epidermal cells correlates with defects in root hair development

    PubMed Central

    Marzec, M; Muszynska, A; Melzer, M; Sas-Nowosielska, H; Kurczynska, E U; Wick, S

    2014-01-01

    It is well known that the process of plant cell differentiation depends on the symplasmic isolation of cells. Before starting the differentiation programme, the individual cell or group of cells should restrict symplasmic communication with neighbouring cells. We tested the symplasmic communication between epidermal cells in the different root zones of parental barley plants Hordeum vulgare L., cv. ‘Karat’ with normal root hair development, and two root hairless mutants (rhl1.a and rhl1.b). The results clearly show that symplasmic communication was limited during root hair differentiation in the parental variety, whereas in both root hairless mutants epidermal cells were still symplasmically connected in the corresponding root zone. This paper is the first report on the role of symplasmic isolation in barley root cell differentiation, and additionally shows that a disturbance in the restriction of symplasmic communication is present in root hairless mutants. PMID:23927737

  13. Large-scale identification of human genes implicated in epidermal barrier function

    PubMed Central

    Toulza, Eve; Mattiuzzo, Nicolas R; Galliano, Marie-Florence; Jonca, Nathalie; Dossat, Carole; Jacob, Daniel; de Daruvar, Antoine; Wincker, Patrick; Serre, Guy; Guerrin, Marina

    2007-01-01

    Background During epidermal differentiation, keratinocytes progressing through the suprabasal layers undergo complex and tightly regulated biochemical modifications leading to cornification and desquamation. The last living cells, the granular keratinocytes (GKs), produce almost all of the proteins and lipids required for the protective barrier function before their programmed cell death gives rise to corneocytes. We present here the first analysis of the transcriptome of human GKs, purified from healthy epidermis by an original approach. Results Using the ORESTES method, 22,585 expressed sequence tags (ESTs) were produced that matched 3,387 genes. Despite normalization provided by this method (mean 4.6 ORESTES per gene), some highly transcribed genes, including that encoding dermokine, were overrepresented. About 330 expressed genes displayed less than 100 ESTs in UniGene clusters and are most likely to be specific for GKs and potentially involved in barrier function. This hypothesis was tested by comparing the relative expression of 73 genes in the basal and granular layers of epidermis by quantitative RT-PCR. Among these, 33 were identified as new, highly specific markers of GKs, including those encoding a protease, protease inhibitors and proteins involved in lipid metabolism and transport. We identified filaggrin 2 (also called ifapsoriasin), a poorly characterized member of the epidermal differentiation complex, as well as three new lipase genes clustered with paralogous genes on chromosome 10q23.31. A new gene of unknown function, C1orf81, is specifically disrupted in the human genome by a frameshift mutation. Conclusion These data increase the present knowledge of genes responsible for the formation of the skin barrier and suggest new candidates for genodermatoses of unknown origin. PMID:17562024

  14. REMEDIATION OF TCE-CONTAMINATED GROUNDWATER BY A PERMEABLE REACTIVE BARRIER FILLED WITH PLANT MULCH (BIOWALL)

    EPA Science Inventory

    A pilot-scale permeable reactive barrier filled with plant mulch was installed at Altus Air Force Base (in Oklahoma, USA) to treat trichloroethylene (TCE) contamination in ground water emanating from a landfill. The barrier was constructed in June 2002. It was 139 meters long, 7 ...

  15. Activation of epidermal toll-like receptor 2 enhances tight junction function: implications for atopic dermatitis and skin barrier repair.

    PubMed

    Kuo, I-Hsin; Carpenter-Mendini, Amanda; Yoshida, Takeshi; McGirt, Laura Y; Ivanov, Andrei I; Barnes, Kathleen C; Gallo, Richard L; Borkowski, Andrew W; Yamasaki, Kenshi; Leung, Donald Y; Georas, Steve N; De Benedetto, Anna; Beck, Lisa A

    2013-04-01

    Atopic dermatitis (AD) is characterized by epidermal tight junction (TJ) defects and a propensity for Staphylococcus aureus skin infections. S. aureus is sensed by many pattern recognition receptors, including Toll-like receptor 2 (TLR2). We hypothesized that an effective innate immune response will include skin barrier repair, and that this response is impaired in AD subjects. S. aureus-derived peptidoglycan (PGN) and synthetic TLR2 agonists enhanced TJ barrier and increased expression of TJ proteins, claudin-1 (CLDN1), claudin-23 (CLDN23), occludin, and Zonulae occludens 1 (ZO-1) in primary human keratinocytes. A TLR2 agonist enhanced skin barrier recovery in human epidermis wounded by tape stripping. Tlr2(-/-) mice had a delayed and incomplete barrier recovery following tape stripping. AD subjects had reduced epidermal TLR2 expression as compared with nonatopic subjects, which inversely correlated (r=-0.654, P=0.0004) with transepidermal water loss (TEWL). These observations indicate that TLR2 activation enhances skin barrier in murine and human skin and is an important part of a wound repair response. Reduced epidermal TLR2 expression observed in AD patients may have a role in their incompetent skin barrier. PMID:23223142

  16. SURFACE-ALTERED ZEOLITES AS PERMEABLE BARRIERS FOR IN SITU TREATMENT OF CONTAMINATED GROUNDWATER

    SciTech Connect

    Robert S. Bowman; Pengfei Zhang; Xian Tao

    2002-03-01

    This report summarizes experiments to develop and test surfactant-modified zeolite/zero-valent iron (SMZ/ZVI) pellets for permeable reactive barriers to treat groundwater contamination. Coating a glass foam core with a mixture of hexadecyltrimethylammonium surfactant, zeolite, and ZVI produced a high hydraulic conductivity, mechanically stable pellet. Laboratory experiments showed that the pellets completely removed soluble chromate from aqueous solution, and reduced perchloroethylene (PCE) concentrations more than pellets that lacked surfactant. Based upon the laboratory results, they predicted a 1-m-wide SMZ/ZVI barrier that would reduce PCE concentrations by four orders of magnitude. Thirteen cubic meters (470 cubic feet) of SMZ/ZVI pellets were manufactured and emplaced in a permeable barrier test facility. A controlled plume of chromate and PCE was allowed to contact the barrier for four weeks. The entire plume was captured by the barrier. No chromate was detected downgradient of the barrier. The PCE broke through the barrier after four weeks, and downgradient concentrations ultimately exceeded 10% of the influent PCE. The less-than-expected PCE reduction was attributed to insufficient surfactant content, the large size, and pH-altering characteristics of the bulk-produced pellets. The pellets developed here can be improved to yield a performance- and cost-competitive permeable barrier material.

  17. Permeability of the blood–brain barrier predicts conversion from optic neuritis to multiple sclerosis

    PubMed Central

    Modvig, Signe; Simonsen, Helle J.; Frederiksen, Jette L.; Larsson, Henrik B. W.

    2015-01-01

    Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood–brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood–brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison with cerebrospinal fluid markers of inflammation, cellular trafficking and blood–brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood–brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2 years after optic neuritis onset. Logistic regression analysis showed that baseline permeability in normal-appearing white matter significantly improved prediction of multiple sclerosis conversion (according to the 2010 revised McDonald diagnostic criteria) within 2 years compared to T2 lesion count alone. There was no correlation between permeability and T2 lesion count. An increase in permeability in normal-appearing white matter of 0.1 ml/100 g/min increased the risk of multiple sclerosis 8.5 times whereas having more than nine T2 lesions increased the risk 52.6 times. Receiver operating characteristic curve analysis of permeability in normal-appearing white matter gave a cut-off of 0.13 ml/100 g/min, which predicted conversion to multiple sclerosis with a

  18. Postnatal requirement of the epithelial sodium channel for maintenance of epidermal barrier function.

    PubMed

    Charles, Roch-Philippe; Guitard, Marjorie; Leyvraz, Céline; Breiden, Bernadette; Haftek, Marek; Haftek-Terreau, Zofia; Stehle, Jean-Christophe; Sandhoff, Konrad; Hummler, Edith

    2008-02-01

    In skin, the physiological consequence of an epithelial sodium channel (ENaC) deficiency is not obvious directly at birth. Nevertheless, within hours after birth, mice deficient for the alpha-subunit of the highly amiloride-sensitive epithelial sodium channel (alphaENaC/Scnn1a) suffer from a significant increased dehydration. This is characterized by a loss of body weight (by 6% in 6 h) and an increased transepidermal water loss, which is accompanied by a higher skin surface pH in 1-day-old pups. Although early and late differentiation markers, as well as tight junction protein distribution and function, seem unaffected, deficiency of alphaENaC severely disturbs the stratum corneum lipid composition with decreased ceramide and cholesterol levels, and increased pro-barrier lipids, whereas covalently bound lipids are drastically reduced. Ultrastructural analysis revealed morphological changes in the formation of intercellular lamellar lipids and the lamellar body secretion. Extracellular formation of the lamellar lipids proved to be abnormal in the knockouts. In conclusion, ENaC deficiency results in progressive dehydration and, consequently, weight loss due to severe impairment of lipid formation and secretion. Our data demonstrate that ENaC expression is required for the postnatal maintenance of the epidermal barrier function but not for its generation. PMID:18039670

  19. Keratin 16 regulates innate immunity in response to epidermal barrier breach

    PubMed Central

    Lessard, Juliane C.; Piña-Paz, Sylvia; Rotty, Jeremy D.; Hickerson, Robyn P.; Kaspar, Roger L.; Balmain, Allan; Coulombe, Pierre A.

    2013-01-01

    Mutations in the type I keratin 16 (Krt16) and its partner type II keratin 6 (Krt6a, Krt6b) cause pachyonychia congenita (PC), a disorder typified by dystrophic nails, painful hyperkeratotic calluses in glabrous skin, and lesions involving other epithelial appendages. The pathophysiology of these symptoms and its relationship to settings in which Krt16 and Krt6 are induced in response to epidermal barrier stress are poorly understood. We report that hyperkeratotic calluses arising in the glabrous skin of individuals with PC and Krt16 null mice share a gene expression signature enriched in genes involved in inflammation and innate immunity, in particular damage-associated molecular patterns. Transcriptional hyper-activation of damage-associated molecular pattern genes occurs following de novo chemical or mechanical irritation to ear skin and in spontaneously arising skin lesions in Krt16 null mice. Genome-wide expression analysis of normal mouse tail skin and benign proliferative lesions reveals a tight, context-dependent coregulation of Krt16 and Krt6 with genes involved in skin barrier maintenance and innate immunity. Our results uncover a role for Krt16 in regulating epithelial inflammation that is relevant to genodermatoses, psoriasis, and cancer and suggest a avenue for the therapeutic management of PC and related disorders. PMID:24218583

  20. Modulation of Blood–Brain Barrier Permeability in Mice Using Synthetic E-Cadherin Peptide

    PubMed Central

    2015-01-01

    The present work characterizes the effects of synthetic E-cadherin peptide (HAV) on blood–brain barrier (BBB) integrity using various techniques including magnetic resonance imaging (MRI) and near-infrared fluorescent imaging (NIRF). The permeability of small molecular weight permeability marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRDye 800CW PEG, and the P-glycoprotein (P-gp) efflux transporter contrast agent, rhodamine 800 (R800), were examined in the presence and absence of HAV peptide. The results consistently demonstrated that systemic iv administration of HAV peptide resulted in a reversible disruption of BBB integrity and enhanced the accumulation of all the dyes examined. The magnitude of increase ranged from 2-fold to 5-fold depending on the size and the properties of the permeability markers. The time frame for BBB disruption with HAV peptide was rapid, occurring within 3–6 min following injection of the peptide. Furthermore, modulation of BBB permeability was reversible with the barrier integrity being restored within 60 min of the injection. The increased BBB permeability observed following HAV peptide administration was not attributable to changes in cerebral blood flow. These studies support the potential use of cadherin peptides to rapidly and reversibly modulate BBB permeability of a variety of therapeutic agents. PMID:24495091

  1. Bacillus cereus Induces Permeability of the Blood Ocular Barrier During Experimental Endophthalmitis

    PubMed Central

    Moyer, A. L.; Ramadan, R. T.; Novosad, B.; Astley, R.; Callegan, M. C.

    2010-01-01

    Purpose The purpose of this study was to determine to what extent blood retina barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. Methods Mice were intravitreally injected with 100 CFU B. cereus and eyes were analyzed at specific times postinfection 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 RPE. Results B. cereus-induced leakage of albumin and fibrin into the aqueous and vitreous humor by 8 h postinfection. BRB permeability occurred as early as 4 h and increased 13.30-fold compared to uninfected controls by 8 h. Production of proinflammatory cytokines IL-6, MIP-1α, IL-1β, and KC increased over the course of infection. In the retina, ZO-1 disruption begins by 4 h, followed by decreasing occludin and ZO-1 expression at 4 and 8 h, respectively. Tubulin condensation and RPE65 degradation occurred by 12 h. A quorum sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Both wild-type and mutant B. cereus sterile supernatants induced blood ocular barrier permeability similarly to that of wild-type infection. Conclusions These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 h postinfection. Disruption of tight junctions at the level of the RPE may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability. PMID:19264886

  2. Mapping the Fluid Pathways and Permeability Barriers of a Large Gas Hydrate Reservoir

    NASA Astrophysics Data System (ADS)

    Campbell, A.; Zhang, Y. L.; Sun, L. F.; Saleh, R.; Pun, W.; Bellefleur, G.; Milkereit, B.

    2012-12-01

    An understanding of the relationship between the physical properties of gas hydrate saturated sedimentary basins aids in the detection, exploration and monitoring one of the world's upcoming energy resources. A large gas hydrate reservoir is located in the MacKenzie Delta of the Canadian Arctic and geophysical logs from the Mallik test site are available for the gas hydrate stability zone (GHSZ) between depths of approximately 850 m to 1100 m. The geophysical data sets from two neighboring boreholes at the Mallik test site are analyzed. Commonly used porosity logs, as well as nuclear magnetic resonance, compressional and Stoneley wave velocity dispersion logs are used to map zones of elevated and severely reduced porosity and permeability respectively. The lateral continuity of horizontal permeability barriers can be further understood with the aid of surface seismic modeling studies. In this integrated study, the behavior of compressional and Stoneley wave velocity dispersion and surface seismic modeling studies are used to identify the fluid pathways and permeability barriers of the gas hydrate reservoir. The results are compared with known nuclear magnetic resonance-derived permeability values. The aim of investigating this heterogeneous medium is to map the fluid pathways and the associated permeability barriers throughout the gas hydrate stability zone. This provides a framework for an understanding of the long-term dissociation of gas hydrates along vertical and horizontal pathways, and will improve the knowledge pertaining to the production of such a promising energy source.

  3. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium

    PubMed Central

    Lie, Pearl P. Y.; Mruk, Dolores D.; Lee, Will M.; Cheng, C. Yan

    2009-01-01

    In the seminiferous epithelium, Eps8 is localized to actin-based cell junctions at the blood-testis barrier (BTB) and the apical ectoplasmic specialization (ES) in stage V–VI tubules but is considerably diminished in stage VIII tubules. Eps8 down-regulation coincides with the time of BTB restructuring and apical ES disassembly, implicating the role of Eps8 in cell adhesion. Its involvement in Sertoli-germ cell adhesion was substantiated in studies using an in vivo animal model by treating rats with 1-(2,4-dichlorobenzy)-1H-indazole-3-carbohydrazide (adjudin) to induce anchoring junction restructuring, during which Eps8 disappeared at the apical ES before germ cell departure. In Sertoli cell cultures with established permeability barrier mimicking the BTB in vivo, the knockdown of Eps8 by RNAi led to F-actin disorganization and the mislocalization of the tight junction proteins occludin and ZO-1, suggesting the function of Eps8 in maintaining BTB integrity. In vivo knockdown of Eps8 in the testis caused germ cell sloughing and BTB damage, concomitant with occludin mislocalization, further validating that Eps8 is a novel regulator of cell adhesion and BTB integrity in the seminiferous epithelium.—Lie, P. P. Y., Mruk, D. D., Lee, W. M., Cheng, C. Y. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium. PMID:19293393

  4. Focal Adhesion Kinase Controls pH-Dependent Epidermal Barrier Homeostasis by Regulating Actin-Directed Na+/H+ Exchanger 1 Plasma Membrane Localization

    PubMed Central

    Ilic, Dusko; Mao-Qiang, Man; Crumrine, Debra; Dolganov, Gregory; Larocque, Nicholas; Xu, Pu; Demerjian, Marianne; Brown, Barbara E.; Lim, Ssang-Taek; Ossovskaya, Valeria; Schlaepfer, David D.; Fisher, Susan J.; Feingold, Kenneth R.; Elias, Peter M.; Mauro, Theodora M.

    2007-01-01

    Ubiquitously expressed focal adhesion kinase (FAK), linked to multiple intracellular signaling pathways, has previously been shown to control cell motility, invasion, proliferation, and survival. Using mice with a keratinocyte-restricted deletion of fak (FAKK5 KO), we report here a novel role for FAK: maintenance of adult epidermal permeability barrier homeostasis. Abundant lacunae of unprocessed lipids in stratum corneum (SC) of FAKK5 KO mice and delayed barrier recovery pointed to malfunction of pH-dependent enzymes active in extracellular space of SC. Measuring the SC pH gradient showed significantly more neutral pH values in FAKK5 KO mice, suggesting the importance of FAK for acidification. Moreover, normal functions were restored when FAKK5 KO mice were exposed to a surface pH typical of mouse SC (pH = 5.5). Baseline levels and response to barrier disruption of secretory phospholipase A2 isoforms, enzymes that mediate generation of free fatty acids in epidermis, appeared similar in both FAKK5 KO and control littermates. We found that the critical SC acidification regulator Na+/H+ exchanger 1 failed to localize to the plasma membrane in FAK-deficient keratinocytes both in vivo and in vitro. Thus, for plasma membrane localization in terminally differentiated keratinocytes, Na+/H+ exchanger 1 requires an intact actin cytoskeleton, which is impaired in FAK-deficient cells. PMID:17525272

  5. A framework for understanding semi-permeable barrier effects on migratory ungulates

    USGS Publications Warehouse

    Sawyer, Hall; Kauffman, Matthew J.; Middleton, Arthur D.; Morrison, Thomas A.; Nielson, Ryan M.; Wyckoff, Teal B.

    2013-01-01

    1. Impermeable barriers to migration can greatly constrain the set of possible routes and ranges used by migrating animals. For ungulates, however, many forms of development are semi-permeable, and making informed management decisions about their potential impacts to the persistence of migration routes is difficult because our knowledge of how semi-permeable barriers affect migratory behaviour and function is limited. 2. Here, we propose a general framework to advance the understanding of barrier effects on ungulate migration by emphasizing the need to (i) quantify potential barriers in terms that allow behavioural thresholds to be considered, (ii) identify and measure behavioural responses to semi-permeable barriers and (iii) consider the functional attributes of the migratory landscape (e.g. stopovers) and how the benefits of migration might be reduced by behavioural changes. 3. We used global position system (GPS) data collected from two subpopulations of mule deer Odocoileus hemionus to evaluate how different levels of gas development influenced migratory behaviour, including movement rates and stopover use at the individual level, and intensity of use and width of migration route at the population level. We then characterized the functional landscape of migration routes as either stopover habitat or movement corridors and examined how the observed behavioural changes affected the functionality of the migration route in terms of stopover use. 4. We found migratory behaviour to vary with development intensity. Our results suggest that mule deer can migrate through moderate levels of development without any noticeable effects on migratory behaviour. However, in areas with more intensive development, animals often detoured from established routes, increased their rate of movement and reduced stopover use, while the overall use and width of migration routes decreased. 5. Synthesis and applications. In contrast to impermeable barriers that impede animal movement

  6. Zinc modulates cytokine-induced lung epithelial cell barrier permeability.

    PubMed

    Bao, Shenying; Knoell, Daren L

    2006-12-01

    Apoptosis plays a causative role in acute lung injury in part due to epithelial cell loss. We recently reported that zinc protects the lung epithelium during inflammatory stress whereas depletion of intracellular zinc enhances extrinsic apoptosis. In this investigation, we evaluated the relationship between zinc, caspase-3, and cell-to-cell contact via proteins that form the adherens junction complex. Cell adhesion proteins are directly responsible for formation of the mechanical barrier of the lung epithelium. We hypothesized that exposure to inflammatory cytokines, in conjunction with zinc deprivation, would induce caspase-3, leading to degradation of junction proteins, loss of cell-to-cell contact, and compromised barrier function. Primary human upper airway and type I/II alveolar epithelial cultures were obtained from multiple donors and exposed to inflammatory stimuli that provoke extrinsic apoptosis in addition to depletion of intracellular zinc. We observed that zinc deprivation combined with tumor necrosis factor-alpha, interferon-gamma, and Fas receptor ligation accelerates caspase-3 activation, proteolysis of E-cadherin and beta-catenin, and cellular apoptosis, leading to increased paracellular leak across monolayers of both upper airway and alveolar lung epithelial cultures. Zinc supplementation inhibited apoptosis and paracellular leak, whereas caspase inhibition was less effective. We conclude that zinc is a vital factor in the lung epithelium that protects against death receptor-mediated apoptosis and barrier dysfunction. Furthermore, our findings suggest that although caspase-3 inhibition reduces lung epithelial apoptosis it does not prevent mechanical dysfunction. These findings facilitate future studies aimed at developing therapeutic strategies to prevent acute lung injury. PMID:16844947

  7. Spatiotemporal Dysfunction of the Vascular Permeability Barrier in Transgenic Mice with Sickle Cell Disease

    PubMed Central

    Ghosh, Samit; Tan, Fang; Ofori-Acquah, Solomon F.

    2012-01-01

    Sickle cell disease (SCD) is characterized by chronic intravascular hemolysis that generates excess cell-free hemoglobin in the blood circulation. Hemoglobin causes multiple endothelial dysfunctions including increased vascular permeability, impaired reactivity to vasoactive agonists, and increased adhesion of leukocytes to the endothelium. While the adhesive and vasomotor defects of SCD associated with cell-free hemoglobin are well defined, the vascular permeability phenotype remains poorly appreciated. We addressed this issue in two widely used and clinically relevant mouse models of SCD. We discovered that the endothelial barrier is normal in most organs in the young but deteriorates with aging particularly in the lung. Indeed, middle-aged sickle mice developed pulmonary edema revealing for the first time similarities in the chronic permeability phenotypes of the lung in mice and humans with SCD. Intravenous administration of lysed red blood cells into the circulation of sickle mice increased vascular permeability significantly in the lung without impacting permeability in other organs. Thus, increased vascular permeability is an endothelial dysfunction of SCD with the barrier in the lung likely the most vulnerable to acute inflammation. PMID:22778926

  8. A PERMEABLE REACTIVE BARRIER FOR TREATMENT OF HEAVY METALS: JOURNAL ARTICLE

    EPA Science Inventory

    NRMRL-ADA-00327 Ludwig*, R., McGregor, R.G., Blowes, D.W., Benner, S.G., and Mountjoy, K. A Permeable Reactive Barrier for Treatment of Heavy Metals. Ground Water 40 (1):59-66 (2002) Historical storage of ore concentrate containing sulfid...

  9. LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS TO REMEDIATE CONTAMINATED GROUND WATER

    EPA Science Inventory

    This research brief presents findings over the past four years at two sites where detailed investigations by the U.S. Environmental Protection Agency (U.S. EPA) have focused on the long-term performance of PRBs under a Tri-Agency Permeable Reactive Barrier Initiative (TRI). This ...

  10. CHROMIUM REMOVAL PROCESSES DURING GROUNDWATER REMEDIATION BY A ZEROVALENT IRON PERMEABLE REACTIVE BARRIER

    EPA Science Inventory

    Solid-phase associations of chromium were examined in core materials collected from a full-scale, zerovalent iron, permeable reactive barrier (PRB) at the U.S. Coast Guard Support Center located near Elizabeth City (NC). The PRB was installed in 1996 to treat groundwater contami...

  11. Blood-Brain Barrier Permeability and Monocyte Infiltration in Experimental Allergic Encephalomyelitis

    ERIC Educational Resources Information Center

    Floris, S.; Blezer, E. L. A.; Schreibelt, G.; Dopp, E.; van der Pol, S. M. A.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E.

    2004-01-01

    Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive…

  12. A clay permeable reactive barrier to remove Cs-137 from groundwater: Column experiments.

    PubMed

    De Pourcq, K; Ayora, C; García-Gutiérrez, M; Missana, T; Carrera, J

    2015-11-01

    Clay minerals are reputed sorbents for Cs-137 and can be used as a low-permeability material to prevent groundwater flow. Therefore, clay barriers are employed to seal Cs-137 polluted areas and nuclear waste repositories. This work is motivated by cases where groundwater flow cannot be impeded. A permeable and reactive barrier to retain Cs-137 was tested. The trapping mechanism is based on the sorption of cesium on illite-containing clay. The permeability of the reactive material is provided by mixing clay on a matrix of wood shavings. Column tests combined with reactive transport modeling were performed to check both reactivity and permeability. Hydraulic conductivity of the mixture (10(-4) m/s) was sufficient to ensure an adequate hydraulic performance of an eventual barrier excavated in most aquifers. A number of column experiments confirmed Cs retention under different flow rates and inflow solutions. A 1D reactive transport model based on a cation-exchange mechanism was built. It was calibrated with batch experiments for high concentrations of NH4+ and K+ (the main competitors of Cs in the exchange positions). The model predicted satisfactorily the results of the column experiments. Once validated, it was used to investigate the performance and duration of a 2 m thick barrier under different scenarios (flow, clay content, Cs-137 and K concentration). PMID:26197347

  13. ACCUMULATION RATE OF MICROBIAL BIOMASS AT TWO PERMEABLE REACTIVE BARRIER SITES

    EPA Science Inventory

    Accumulation of mineral precipitates and microbial biomass are key factors that impact the long-term performance of in-situ Permeable Reactive Barriers for treating contaminated groundwater. Both processes can impact remedial performance by decreasing zero-valent iron reactivity...

  14. PERMEABLE REACTIVE BARRIERS RESEARCH AT THE ENVIRONMENTAL PROTECTION AGENCY'S NATIONAL RISK MANAGEMENT RESEARCH LABORATORY

    EPA Science Inventory

    This presentation will provide an overview of research efforts at EPA on the application, monitoring, and performance of Permeable Reactive Barriers (PRBs) for groundwater restoration. Over the past 10 years, research projects conducted by research staff at EPA's National Risk M...

  15. COST ANALYSIS OF PERMEABLE REACTIVE BARRIERS FOR REMEDIATION OF GROUND WATER

    EPA Science Inventory

    The U. S. Environmental Protection Agency's Office of Research and Development and its contractor have evaluated cost data from 22 sites where permeable reactive barriers (PRBs) have been utilized to remediate contaminated ground water resources. Most of the sites evaluated wer...

  16. AMELIORATION OF ACID MINE DRAINAGE USING REACTIVE MIXTURES IN PERMEABLE REACTIVE BARRIERS

    EPA Science Inventory

    The generation and release of acidic drainage from mine wastes is an environmental problem of international scale. The use of zero-valent iron and/or iron mixtures in subsurface Permeable Reactive Barriers (PRB) presents a possible passive alternative for remediating acidic grou...

  17. Dexou low pH plume baseline permeable reactive barrier options

    SciTech Connect

    Phifer, M.A.

    2000-06-20

    The current Environmental Restoration Department (ERD) Permeable Reactive Barrier (PRB) baseline configuration consists of a limestone trench and a granular cast iron trench in series. This report provides information relative to the use of PRB technology for the remediation of the D-Area low pH groundwater plumes.

  18. EVALUATION OF PERMEABLE REACTIVE BARRIER PERFORMANCE: A TRI-AGENCY INITIATIVE

    EPA Science Inventory

    The permeable reactive barrier (PRB) technology represents a passive option for long-term treatment of ground-water contamination. PRBs are a potentially more cost-effective treatment option for a variety of dissolved contaminants, such as certain types of chlorinated solvents, ...

  19. SPATIAL DISTRIBUTION OF CARBON AND SULFUR PRECIPITATING WITHIN PERMEABLE REACTIVE BARRIERS: DEVELOPMENT OF ANALYTICAL METHODS

    EPA Science Inventory

    A permeable reactive barrier (PRB) is a wall of porous reactive material placed in the path of a dissolved contaminant plume for the purpose of removing contaminants from ground water. Chemical processes within these reactive materials remove both inorganic and organic contamina...

  20. LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS: LESSONS LEARNED, FUTURE DIRECTIONS

    EPA Science Inventory

    Recently, a synthesis of research findings by EPA has been prepared and presented in an EPA report titled Capstone Report on the Application, Monitoring, and Performance of Permeable Reactive Barriers for Ground-Water Remediation (EPA/600/R-03/045 a,b). Another report has also be...

  1. A Tracer Test to Characterize Treatment of TCE in a Permeable Reactive Barrier

    EPA Science Inventory

    A tracer test was conducted to characterize the flow of ground water surrounding a permeable reactive barrier constructed with plant mulch (a biowall) at the OU-1 site on Altus Air Force Base, Oklahoma. This biowall is intended to intercept and treat ground water contaminated by ...

  2. IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function

    PubMed Central

    Singh, Brijendra; Jegga, Anil G.; Shanmukhappa, Kumar S.; Edukulla, Ramakrishna; Khurana, Gurjit H.; Medvedovic, Mario; Dillon, Stacey R.; Madala, Satish K.

    2016-01-01

    Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis. However, the molecular mechanisms involved in IL31-driven pathological remodeling in skin diseases remain largely unknown. Here, we studied the role of IL-31 in skin damage as a result of intradermal administration of recombinant IL-31 into mice. Notably, IL-31 was sufficient to increase epidermal basal-cell proliferation and thickening of the epidermal skin layer. Our findings demonstrate a progressive increase in transepidermal water loss with chronic administration of IL-31 into the skin. Further, analysis of the skin transcriptome indicates a significant increase in the transcripts involved in epidermal-cell proliferation, epidermal thickening, and mechanical integrity. In summary, our findings demonstrate an important role for IL-31 signaling in epidermal cell proliferation and thickening that together may lead to impaired skin-barrier function in pathological remodeling of the skin. PMID:27556734

  3. The gut microbiota influences blood-brain barrier permeability in mice.

    PubMed

    Braniste, Viorica; Al-Asmakh, Maha; Kowal, Czeslawa; Anuar, Farhana; Abbaspour, Afrouz; Tóth, Miklós; Korecka, Agata; Bakocevic, Nadja; Ng, Lai Guan; Guan, Ng Lai; Kundu, Parag; Gulyás, Balázs; Halldin, Christer; Hultenby, Kjell; Nilsson, Harriet; Hebert, Hans; Volpe, Bruce T; Diamond, Betty; Pettersson, Sven

    2014-11-19

    Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life. PMID:25411471

  4. The acyl-CoA binding protein is required for normal epidermal barrier function in mice.

    PubMed

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt; Neess, Ditte; Brewer, Jonathan; Hannibal-Bach, Hans Kristian; Helledie, Torben; Fenger, Christina; Due, Marianne; Berzina, Zane; Neubert, Reinhard; Chemnitz, John; Finsen, Bente; Clemmensen, Anders; Wilbertz, Johannes; Saxtorph, Henrik; Knudsen, Jens; Bagatolli, Luis; Mandrup, Susanne

    2012-10-01

    The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling with age. Morphology and development of skin and appendages are normal in ACBP(-/-) mice; however, the stratum corneum display altered biophysical properties with reduced proton activity and decreased water content. Mass spectrometry analyses of lipids from epidermis and stratum corneum of ACBP(+/+) and ACBP(-/-) mice showed very similar composition, except for a significant and specific decrease in the very long chain free fatty acids (VLC-FFA) in stratum corneum of ACBP(-/-) mice. This finding indicates that ACBP is critically involved in the processes that lead to production of stratum corneum VLC-FFAs via complex phospholipids in the lamellar bodies. Importantly, we show that ACBP(-/-) mice display a ∼50% increased transepidermal water loss compared with ACBP(+/+) mice. Furthermore, skin and fur sebum monoalkyl diacylglycerol (MADAG) levels are significantly increased, suggesting that ACBP limits MADAG synthesis in sebaceous glands. In summary, our study shows that ACBP is required for production of VLC-FFA for stratum corneum and for maintaining normal epidermal barrier function. PMID:22829653

  5. Redox-active media for permeable reactive barriers

    SciTech Connect

    Sivavec, T.M.; Mackenzie, P.D.; Horney, D.P.; Baghel, S.S.

    1997-12-31

    In this paper, three classes of redox-active media are described and evaluated in terms of their long-term effectiveness in treating TCE-contaminated groundwater in permeable reactive zones. Zero-valent iron, in the form of recycled cast iron filings, the first class, has received considerable attention as a reactive media and has been used in about a dozen pilot- and full-scale subsurface wall installations. Criteria used in selecting commercial sources of granular iron, will be discussed. Two other classes of redox-active media that have not yet seen wide use in pilot- or full-scale installations will also be described: Fe(II) minerals and bimetallic systems. Fe(II) minerals, including magnetite (Fe{sub 3}O{sub 4}), and ferrous sulfide (troilite, FeS), are redox-active and afford TCE reduction rates and product distributions that suggest that they react via a reductive mechanism similar to that which operates in the FeO system. Fe(II) species within the passive oxide layer coating the iron metal may act as electron transfer mediators, with FeO serving as the bulk reductant. Bimetallic systems, the third class of redox-active media, are commonly prepared by plating a second metal onto zero-valent iron (e.g., Ni/Fe and Pd/Fe) and have been shown to accelerate solvent degradation rates relative to untreated iron metal. The long-term effectiveness of this approach, however, has not yet been determined in groundwater treatability tests. The results of a Ni-plated iron column study using site groundwater indicate that a change in reduction mechanism (to catalytic dehydrohalogenation/hydrogenation) accounts for the observed rate enhancement. A significant loss in media reactivity was observed over time, attributable to Ni catalyst deactivation or poisoning. Zero-valent iron systems have not shown similar losses in reactivity in long-term laboratory, pilot or field investigations.

  6. Measurement of blood-brain barrier permeability with positron emission tomography and (68Ga)EDTA

    SciTech Connect

    Kessler, R.M.; Goble, J.C.; Bird, J.H.; Girton, M.E.; Doppman, J.L.; Rapoport, S.I.; Barranger, J.A.

    1984-09-01

    Positron emission tomography (PET) was employed to examine time-dependent changes in blood-brain barrier (BBB) permeability to (68Ga)ethylenediaminetetraacetate (EDTA) in the rhesus monkey, following reversible barrier opening by intracarotid infusion of a hypertonic mannitol solution. The PET technique, when combined with measurements of plasma radioactivity, provided a quantitative measure of the cerebrovascular permeability-area product (PA) at different times following mannitol infusion. Hypertonic mannitol treatment reversibly increased PA to (68Ga)EDTA more than 10-fold; much of the barrier effect was over by 10 min after mannitol treatment. The results show that PET can be used to measure transient changes in BBB integrity in specific brain regions, under in vivo, noninvasive conditions.

  7. Anthrax lethal toxin disrupts the endothelial permeability barrier through blocking p38 signaling.

    PubMed

    Liu, Tiegang; Milia, Erica; Warburton, Rod R; Hill, Nicholas S; Gaestel, Matthias; Kayyali, Usamah S

    2012-04-01

    Exposure to anthrax causes life-threatening disease through the action of the toxin produced by the Bacillus anthracis bacteria. Lethal factor (LF), an anthrax toxin component which causes severe vascular leak and edema, is a protease which specifically degrades MAP kinase kinases (MKK). We have recently shown that p38 MAP kinase activation leading to HSP27 phosphorylation augments the endothelial permeability barrier. We now show that treatment of rat pulmonary microvascular endothelial cells with anthrax lethal toxin (LeTx), which is composed of LF and the protective antigen, increases endothelial barrier permeability and gap formation between endothelial cells through disrupting p38 signaling. LeTx treatment increases MKK3b degradation and in turn decreases p38 activity at baseline as well as after activation of p38 signaling. Consequently, LeTx treatment decreases activation of the p38 substrate kinase, MK2, and the phosphorylation of the latter's substrate, HSP27. LeTx treatment disrupts other signaling pathways leading to suppression of Erk-mediated signaling, but these effects do not correlate with LeTx-induced barrier compromise. Overexpressing phosphomimicking (pm)HSP27, which protects the endothelial permeability barrier against LeTx, blocks LeTx inactivation of p38 and MK2, but it does not block MKK3b degradation or Erk inactivation. Our results suggest that LeTx might cause vascular leak through inactivating p38-MK2-HSP27 signaling and that activating HSP27 phosphorylation specifically restores p38 signaling and blocks anthrax LeTx toxicity. The fact that barrier integrity could be restored by pmHSP27 overexpression without affecting degradation of MKK3b, or inactivation of Erk, suggests a specific and central role for p38-MK2-HSP27 in endothelial barrier permeability regulation. PMID:21618534

  8. Epidermal growth factor attenuates blood-spinal cord barrier disruption via PI3K/Akt/Rac1 pathway after acute spinal cord injury.

    PubMed

    Zheng, Binbin; Ye, Libing; Zhou, Yulong; Zhu, Sipin; Wang, Qingqing; Shi, Hongxue; Chen, Daqing; Wei, Xiaojie; Wang, Zhouguang; Li, Xiaokun; Xiao, Jian; Xu, Huazi; Zhang, Hongyu

    2016-06-01

    After spinal cord injury (SCI), disruption of blood-spinal cord barrier (BSCB) elicits blood cell infiltration such as neutrophils and macrophages, contributing to permanent neurological disability. Previous studies show that epidermal growth factor (EGF) produces potent neuroprotective effects in SCI models. However, little is known that whether EGF contributes to the integrity of BSCB. The present study is performed to explore the mechanism of BSCB permeability changes which are induced by EGF treatment after SCI in rats. In this study, we demonstrate that EGF administration inhibits the disruption of BSCB permeability and improves the locomotor activity in SCI model rats. Inhibition of the PI3K/Akt pathways by a specific inhibitor, LY294002, suppresses EGF-induced Rac1 activation as well as tight junction (TJ) and adherens junction (AJ) expression. Furthermore, the protective effect of EGF on BSCB is related to the activation of Rac1 both in vivo and in vitro. Blockade of Rac1 activation with Rac1 siRNA downregulates EGF-induced TJ and AJ proteins expression in endothelial cells. Taken together, our results indicate that EGF treatment preserves BSCB integrity and improves functional recovery after SCI via PI3K-Akt-Rac1 signalling pathway. PMID:26769343

  9. Use of jet grouting to create a low permeability horizontal barrier below an incinerator ash landfill

    SciTech Connect

    Furth, A.J.; Burke, G.K.; Deutsch, W.L. Jr.

    1997-12-31

    The City of Philadelphia`s Division of Aviation (DOA) has begun construction of a new commuter runway, designated as Runway 8-26, at the Philadelphia International Airport. A portion of this runway will be constructed over a former Superfund site known as the Enterprise Avenue Landfill, which for many years was used to dispose of solid waste incinerator ash and other hazardous materials. The site was clay capped in the 1980`s, but in order for the DOA to use the site, additional remediation was needed to meet US EPA final closure requirements. One component of the closure plan included installation of a low permeability horizontal barrier above a very thin (approximately 0.61 to 0.91 meters) natural clay stratum which underlies an approximately 1020 m{sup 2} area of the landfill footprint so as to insure that a minimum 1.52 meter thick low permeability barrier exists beneath the entire 150,000 m{sup 2} landfill. The new barrier was constructed using jet grouting techniques to achieve remote excavation and replacement of the bottom 0.91 meters of the waste mass with a low permeability grout. The grout was formulated to meet the low permeability, low elastic modulus and compressive strength requirements of the project design. This paper will discuss the advantages of using jet grouting for the work and details the development of the grout mixture, modeling of the grout zone under load, field construction techniques, performance monitoring and verification testing.

  10. Permeable Adsorptive Barrier (PAB) for the remediation of groundwater simultaneously contaminated by some chlorinated organic compounds.

    PubMed

    Erto, A; Bortone, I; Di Nardo, A; Di Natale, M; Musmarra, D

    2014-07-01

    In this paper, a Permeable Reactive Barrier (PRB) made with activated carbon, namely a Permeable Adsorptive Barrier (PAB), is put forward as an effective technique for the remediation of aquifers simultaneously contaminated by some chlorinated organic compounds. A design procedure, based on a computer code and including different routines, is presented as a tool to accurately describe mass transport within the aquifer and adsorption/desorption phenomena occurring inside the barrier. The remediation of a contaminated aquifer near a solid waste landfill in the district of Napoli (Italy), where Tetrachloroethylene (PCE) and Trichloroethylene (TCE) are simultaneously present, is considered as a case study. A complete hydrological and geotechnical site characterization, as well as a number of dedicated adsorption laboratory tests for the determination of activated carbon PCE/TCE adsorption capacity in binary systems, are carried out to support the barrier design. By means of a series of numerical simulations it is possible to determine the optimal barrier location, orientation and dimensions. PABs appear to be an effective remediation tool for the in-situ treatment of an aquifer contaminated by PCE and TCE simultaneously, as the concentration of both compounds flowing out of the barrier is everywhere lower than the regulatory limits on groundwater quality. PMID:24747934

  11. Nitric Oxide and Airway Epithelial Barrier Function: Regulation of Tight Junction Proteins and Epithelial Permeability

    PubMed Central

    Olson, Nels; Greul, Anne-Katrin; Hristova, Milena; Bove, Peter F.; Kasahara, David I.; van der Vliet, Albert

    2008-01-01

    Acute airway inflammation is associated with enhanced production of nitric oxide (NO•) and altered airway epithelial barrier function, suggesting a role of NO• or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity. PMID:19100237

  12. Major translocation of calcium upon epidermal barrier insult: imaging and quantification via FLIM/Fourier vector analysis

    PubMed Central

    Sanchez, Susana; Barry, Nicholas P.; Kirschner, Nina; Meyer, Wilfried; Mauro, Theodora M.; Moll, Ingrid; Gratton, Enrico

    2015-01-01

    Calcium controls an array of key events in keratinocytes and epidermis: localized changes in Ca2+ concentrations and their regulation are therefore especially important to assess when observing epidermal barrier homeostasis and repair, neonatal barrier establishment, in differentiation, signaling, cell adhesion, and in various pathological states. Yet, tissue- and cellular Ca2+ concentrations in physiologic and diseased states are only partially known, and difficult to measure. Prior observations on the Ca2+ distribution in skin were based on Ca2+ precipitation followed by electron microscopy, or proton-induced X-ray emission. Neither cellular and/or subcellular localization could be determined through these approaches. In cells in vitro, fluorescent dyes have been used extensively for ratiometric measurements of static and dynamic Ca2+ concentrations, also assessing organelle Ca2+ concentrations. For lack of better methods, these findings together build the basis for the current view of the role of Ca2+ in epidermis, their limitations notwithstanding. Here we report a method using Calcium Green 5N as the calcium sensor and the phasor-plot approach to separate raw lifetime components. Thus, fluorescence lifetime imaging (FLIM) enables us to quantitatively assess and visualize dynamic changes of Ca2+ at light-microscopic resolution in ex vivo biopsies of unfixed epidermis, in close to in vivo conditions. Comparing undisturbed epidermis with epidermis following a barrier insult revealed major shifts, and more importantly, a mobilization of high amounts of Ca2+ shortly following barrier disruption, from intracellular stores. These results partially contradict the conventional view, where barrier insults abrogate a Ca2+ gradient towards the stratum granulosum. Ca2+ FLIM overcomes prior limitations in the observation of epidermal Ca2+ dynamics, and will allow further insights into basic epidermal physiology. PMID:21193994

  13. Permeability changes in the blood-brain barrier: causes and consequences.

    PubMed

    Pardridge, W M; Connor, J D; Crawford, I L

    1975-01-01

    1. Generalized changes in blood-brain barrier (BBB) permeability are accompanied by extravasation of plasma proteins; thus, they are readily studied with protein markers or protein-dye complexes. Selective changes in permeability involve alterations in BBB transport systems; they are best studied with techniques which detect the qualitative hallmarks of carrier-mediated transport, namely saturation, competition, and stereospecificity. 2. Quantitative assessments of the selective permeability of the BBB can be made from the saturation data expressed in terms of Michaelis-Menten kinetics. The advantages of the latter are twofold: (a) alterations elicited by modified barrier affinity (Km) can be distinguished from alterations in carrier capacity (Vmax); (b) the relative rates of flux of a metabolite across the BBB can be placed in the perspective of cerebral metabolism. Kinetic data on transport processes in the BBB are obtained by either constant infusion or single injection techniques. Results obtained with both methodologies have been comparable. 3. Independent transport systems for glucose, neutral amino acids, basic amino acids, and monocarboxylic acids have been identified in the BBB. The description of these transport systems in kinetic terms provides a background of information on intact mechanisms to which altered transport can be compared. 4. Experimental evidence indicates that the availability of key metabolic substrates, such as glucose or essential amino acids, may be rate-limiting in cerebral metabolism. A working hypothesis was developed that the consequences of a selective change in barrier permeability to one or more of these essential substrates are directly related to altered rates of reaction in substrate-limited pathways, e.g., cerebral protein or neuro-transmitter biosynthesis. 5. Toxicological causes of generalized changes in BBB permeability include hypertonic solutions, organic solvents, surface-active agents, enzymes, and heavy metals. Some

  14. Surfactant-modified zeolites as permeable barriers to organic and inorganic groundwater contaminants

    SciTech Connect

    Bowman, R.S.; Sullivan, E.J.

    1995-10-01

    We have shown in laboratory experiments that natural zeolites treated with hexadecyltrimethylammonium (HDTMA) are effective sorbents for nonpolar organics, inorganic cations, and inorganic anions. Due to their low cost ({approximately}$0.75/kg) and granular nature, HDTMA-zeolites appear ideal candidates for reactive, permeable subsurface barriers. The HDTMA-zeolites are stable over a wide range of pH (3-13), ionic strength (1 M Cs{sup +} or Ca{sup 2+}), and in organic solvents. Surfactant-modified zeolites sorb nonpolar organics (benzene, toluene, xylene, chlorinated aliphatics) via a partitioning mechanism, inorganic cations (Pb{sup 2+}) via ion exchange and surface complexation, and inorganic anions (CrO{sub 4}{sup 2-}, SeO{sub 4}{sup 2-}, SO{sub 4}{sup 2-}) via surface precipitation.The goal of this work is to demonstrate the use of surfactant-modified zeolite as a permeable barrier to ground water contaminants.

  15. Permeability barrier of Gram-negative cell envelopes and approaches to bypass it

    DOE PAGESBeta

    Zgurskaya, Helen I.; López, Cesar A.; Gnanakaran, Sandrasegaram

    2015-09-18

    Gram-negative bacteria are intrinsically resistant to many antibiotics. Species that have acquired multidrug resistance and cause infections that are effectively untreatable present a serious threat to public health. The problem is broadly recognized and tackled at both the fundamental and applied levels. This article summarizes current advances in understanding the molecular bases of the low permeability barrier of Gram-negative pathogens, which is the major obstacle in discovery and development of antibiotics effective against such pathogens. Gaps in knowledge and specific strategies to break this barrier and to achieve potent activities against difficult Gram-negative bacteria are also discussed.

  16. Oxidation of trichloroethylene, toluene, and ethanol vapors by a partially saturated permeable reactive barrier

    NASA Astrophysics Data System (ADS)

    Mahmoodlu, Mojtaba G.; Hassanizadeh, S. Majid; Hartog, Niels; Raoof, Amir

    2014-08-01

    The mitigation of volatile organic compound (VOC) vapors in the unsaturated zone largely relies on the active removal of vapor by ventilation. In this study we considered an alternative method involving the use of solid potassium permanganate to create a horizontal permeable reactive barrier for oxidizing VOC vapors. Column experiments were carried out to investigate the oxidation of trichloroethylene (TCE), toluene, and ethanol vapors using a partially saturated mixture of potassium permanganate and sand grains. Results showed a significant removal of VOC vapors due to the oxidation. We found that water saturation has a major effect on the removal capacity of the permeable reactive layer. We observed a high removal efficiency and reactivity of potassium permanganate for all target compounds at the highest water saturation (Sw = 0.6). A change in pH within the reactive layer reduced oxidation rate of VOCs. The use of carbonate minerals increased the reactivity of potassium permanganate during the oxidation of TCE vapor by buffering the pH. Reactive transport of VOC vapors diffusing through the permeable reactive layer was modeled, including the pH effect on the oxidation rates. The model accurately described the observed breakthrough curve of TCE and toluene vapors in the headspace of the column. However, miscibility of ethanol in water in combination with produced water during oxidation made the modeling results less accurate for ethanol. A linear relationship was found between total oxidized mass of VOC vapors per unit volume of permeable reactive layer and initial water saturation. This behavior indicates that pH changes control the overall reactivity and longevity of the permeable reactive layer during oxidation of VOCs. The results suggest that field application of a horizontal permeable reactive barrier can be a viable technology against upward migration of VOC vapors through the unsaturated zone.

  17. Applications of permeable barrier technology to ground water contamination at the Shiprock, NM, UMTRA site

    SciTech Connect

    Thomson, B.M.; Henry, E.J.; Thombre, M.S.

    1996-12-31

    The Shiprock uranium mill tailings pile in far northwestern New Mexico consists of approximately 1.5 million tons of uranium mill tailings from an acid leach mill which operated from 1954 to 1968. Located on land owned by the Navajo Nation, it was one of the first tailings piles stabilized under the Uranium Mill Tailings Remedial Action (UMTRA) project. Stabilization activities were completed in 1986 and consisted principally of consolidating the tailings, contouring the pile to achieve good drainage, and covering the pile with a multi-layer cap to control infiltration of water, radon emanation, and surface erosion. No ground water protection or remediation measures were implemented other than limiting infiltration of water through the pile, although a significant ground water contamination plume exists in the flood plain adjacent to the San Juan River. The major contaminants at the Shiprock site include high concentrations of sulfate, nitrate, arsenic, and uranium. One alternative for remediation may be the use of a permeable barrier in the flood plain aquifer. As proposed for the Shiprock site, the permeable barrier would be a trench constructed in the flood plain that would be backfilled with a media that is permeable to ground water, but would intercept or degrade the pollutants. Work to date has focused on use of a mixed microbial population of sulfate and nitrate reducing organisms. These organisms would produce strongly reducing conditions which would result in precipitation of the metal contaminants (i.e., Se(IV) and U(IV)) in the barrier. One of the first considerations in designing a permeable barrier is developing an understanding of ground water flow at the site. Accordingly, a steady state numerical model of the ground water flow at the site was developed using the MODFLOW code.

  18. Hydraulic performance of a permeable reactive barrier at Casey Station, Antarctica.

    PubMed

    Mumford, K A; Rayner, J L; Snape, I; Stevens, G W

    2014-12-01

    A permeable bio-reactive barrier (PRB) was installed at Casey Station, Antarctica in 2005/06 to intercept, capture and degrade petroleum hydrocarbons from a decade old fuel spill. A funnel and gate configuration was selected and implemented. The reactive gate was split into five separate cells to enable the testing of five different treatment combinations. Although different treatment materials were used in each cell, each treatment combination contained the following reactive zones: a zone for the controlled release of nutrients to enhance degradation, a zone for hydrocarbon capture and enhanced degradation, and a zone to capture excess nutrients. The materials selected for each of these zones had other requirements, these included; not having any adverse impact on the environment, being permeable enough to capture the entire catchment flow, and having sufficient residence time to fully capture migrating hydrocarbons. Over a five year period the performance of the PRB was extensively monitored and evaluated for nutrient concentration, fuel retention and permeability. At the end of the five year test period the material located within the reactive gate was excavated, total petroleum hydrocarbon concentrations present on the material determined and particle size analysis conducted. This work found that although maintaining media reactivity is obviously important, the most critical aspect of PRB performance is preserving the permeability of the barrier itself, in this case by maintaining appropriate particle size distribution. This is particularly important when PRBs are installed in regions that are subject to freeze thaw processes that may result in particle disintegration over time. PMID:25078614

  19. Accumulation Rate of Microbial Biomass at Two Permeable Reactive Barrier Sites

    NASA Astrophysics Data System (ADS)

    Wilkin, R.; Sewell, G.; Puls, R.

    2001-12-01

    Accumulation of mineral precipitates and microbial biomass are key factors that impact the long term performance of in situ Permeable Reactive Barriers for treating contaminated groundwater. Both processes can impact remedial performance by decreasing zero valent iron reactivity and permeability. Results are presented from solid phase and groundwater monitoring studies conducted at two Permeable Reactive Barrier sites, U.S. Coast Guard Support Center (Elizabeth City, North Carolina) and the Denver Federal Center (Lakewood, Colorado). At both sites barrier installations have been in place for approximately five years. Over this period, consistent patterns of spatially heterogeneous microbial biomass accumulation are observed at these sites. The iron-aquifer interface witnesses the greatest accumulation of microbial biomass and mineral precipitates. There accumulation rates are a factor of 3 to 10 times greater than midwall or downgradient regions. Estimates of porosity loss due to mineral and biomass buildup range from about 1 to 5 percent per year of the initial available volume. Phospholipid fatty acid profiles indicate that the PRB biomass is dominated by biomarkers indicative of anaerobic sulfate reducing or iron reducing bacteria. This result is in agreement with acid volatile sulfide concentrations that strongly correlate with biomass concentrations. Upgradient groundwater chemistry and flow rate appear to be the main factors that control the rate (and type) of mineral precipitate formation as well as the rate of biomass accumulation. Notice, this is an abstract of a proposed presentation and does not necessarily reflect EPA policy.

  20. Hypomyelination, memory impairment, and blood-brain barrier permeability in a model of sleep apnea.

    PubMed

    Kim, Lenise Jihe; Martinez, Denis; Fiori, Cintia Zappe; Baronio, Diego; Kretzmann, Nélson Alexandre; Barros, Helena Maria Tannhauser

    2015-02-01

    We investigated the effect of intermittent hypoxia, mimicking sleep apnea, on axonal integrity, blood-brain barrier permeability, and cognitive function of mice. Forty-seven C57BL mice were exposed to intermittent or sham hypoxia, alternating 30s of progressive hypoxia and 30s of reoxigenation, during 8h/day. The axonal integrity in cerebellum was evaluated by transmission electron microscopy. Short- and long-term memories were assessed by novel object recognition test. The levels of endothelin-1 were measured by ELISA. Blood-brain barrier permeability was quantified by Evans Blue dye. After 14 days, animals exposed to intermittent hypoxia showed hypomyelination in cerebellum white matter and higher serum levels of endothelin-1. The short and long-term memories in novel object recognition test was impaired in the group exposed to intermittent hypoxia as compared to controls. Blood-brain barrier permeability was similar between the groups. These results indicated that hypomyelination and impairment of short- and long-term working memories occurred in C57BL mice after 14 days of intermittent hypoxia mimicking sleep apnea. PMID:25482664

  1. The mechanisms and quantification of the selective permeability in transport across biological barriers: the example of kyotorphin.

    PubMed

    Serrano, Isa D; Freire, Joao M; Carvalho, Miguel V; Neves, Mafalda; Melo, Manuel N; Castanho, Miguel A R B

    2014-02-01

    This paper addresses the mechanisms behind selective endothelial permeability and their regulations. The singular properties of each of the seven blood-tissues barriers. Then, it further revisits the physical, quantitative meaning of permeability, and the way it should be measured based on sound physical chemistry reasoning and methodologies. Despite the relevance of permeability studies one often comes across inaccurate determinations, mostly from oversimplified data analyses. To worsen matters, the exact meaning of permeability is being lost along with this loss of accuracy. The importance of proper permeability calculation is illustrated with a family of derivatives of kyotorphin, an analgesic dipeptide. PMID:24456269

  2. Plasma From Patients With HELLP Syndrome Increases Blood–Brain Barrier Permeability

    PubMed Central

    Tremble, Sarah M.; Owens, Michelle Y.; Morris, Rachael; Cipolla, Marilyn J.

    2015-01-01

    Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood–brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction. PMID:25194151

  3. Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest.

    PubMed

    Tress, Erika E; Clark, Robert S B; Foley, Lesley M; Alexander, Henry; Hickey, Robert W; Drabek, Tomas; Kochanek, Patrick M; Manole, Mioara D

    2014-08-22

    Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9 min was induced in 16-18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24 h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24 h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9 min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB. PMID:24937271

  4. Iron Sulfide as a Sustainable Reactive Material for Permeable Reactive Barriers

    NASA Astrophysics Data System (ADS)

    Henderson, A. D.; Demond, A. H.

    2012-12-01

    Permeable reactive barriers (PRBs) are gaining acceptance for groundwater remediation, as they operate in situ and do not require continuous energy input. The majority of PRBs use zero-valent iron (ZVI). However, some ZVI PRBs have hydraulically failed [1,2], due to the fact that ZVI may reduce not only contaminants but also water and non-contaminant solutes. These reactions may form precipitates or gas phases that reduce permeability. Therefore, there is a need to assess the hydraulic suitability of possible alternatives, such as iron sulfide (FeS). The capability of FeS to remove both metals and halogenated organics from aqueous systems has been demonstrated previously [3,4], and FeS formed in situ within a ZVI PRB has been linked to contaminant removal [5]. These results suggest possible applications in groundwater remediation as a permeable reactive barrier (PRB) material. However, the propensity of FeS for permeability loss, due to solids and gas production, must be evaluated in order to address its suitability for PRBs. The reduction in permeability for FeS-coated sands under the anoxic conditions often encountered at contaminated groundwater sites was examined through column experiments and geochemical modeling under conditions of high calcium and nitrate, which have been previously shown to cause significant permeability reduction in zero-valent iron (ZVI) systems [6]. The column experiments showed negligible production of both solids and gases. The geochemical model was used to estimate solid and gas volumes generated under conditions of varying FeS concentration. Then, the Kozeny-Carman equation and a power-law relationship was used to predict permeability reduction, with a maximum reduction in permeability of 1% due to solids and about 30% due to gas formation under conditions for which a complete loss of permeability was predicted for ZVI systems. This difference in permeability reduction is driven by the differences in thermodynamic stability of ZVI

  5. A calcite permeable reactive barrier for the remediation of Fluoride from spent potliner (SPL) contaminated groundwater

    NASA Astrophysics Data System (ADS)

    Turner, Brett D.; Binning, Philip J.; Sloan, Scott W.

    2008-01-01

    The use of calcite (CaCO 3) as a substrate for a permeable reactive barrier (PRB) for removing fluoride from contaminated groundwater is proposed and is illustrated by application to groundwater contaminated by spent potliner leachate (SPL), a waste derived from the aluminium smelting process. The paper focuses on two issues in the implementation of calcite permeable reactive barriers for remediating fluoride contaminated water: the impact of the groundwater chemical matrix and CO 2 addition on fluoride removal. Column tests comparing pure NaF solutions, synthetic SPL solutions, and actual SPL leachate indicate that the complex chemical matrix of the SPL leachate can impact fluoride removal significantly. For SPL contaminant mixtures, fluoride removal is initially less than expected from idealized, pure, solutions. However, with time, the effect of other contaminants on fluoride removal diminishes. Column tests also show that pH control is important for optimizing fluoride removal with the mass removed increasing with decreasing pH. Barrier pH can be regulated by CO 2 addition with the point of injection being critical for optimising the remediation performance. Experimental and model results show that approximately 99% of 2300 mg/L fluoride can be removed when CO 2 is injected directly into the barrier. This can be compared to approximately 30-50% removal when the influent solution is equilibrated with atmospheric CO 2 before contact with calcite.

  6. A calcite permeable reactive barrier for the remediation of Fluoride from spent potliner (SPL) contaminated groundwater.

    PubMed

    Turner, Brett D; Binning, Philip J; Sloan, Scott W

    2008-01-28

    The use of calcite (CaCO3) as a substrate for a permeable reactive barrier (PRB) for removing fluoride from contaminated groundwater is proposed and is illustrated by application to groundwater contaminated by spent potliner leachate (SPL), a waste derived from the aluminium smelting process. The paper focuses on two issues in the implementation of calcite permeable reactive barriers for remediating fluoride contaminated water: the impact of the groundwater chemical matrix and CO2 addition on fluoride removal. Column tests comparing pure NaF solutions, synthetic SPL solutions, and actual SPL leachate indicate that the complex chemical matrix of the SPL leachate can impact fluoride removal significantly. For SPL contaminant mixtures, fluoride removal is initially less than expected from idealized, pure, solutions. However, with time, the effect of other contaminants on fluoride removal diminishes. Column tests also show that pH control is important for optimizing fluoride removal with the mass removed increasing with decreasing pH. Barrier pH can be regulated by CO2 addition with the point of injection being critical for optimising the remediation performance. Experimental and model results show that approximately 99% of 2300 mg/L fluoride can be removed when CO2 is injected directly into the barrier. This can be compared to approximately 30-50% removal when the influent solution is equilibrated with atmospheric CO2 before contact with calcite. PMID:17913284

  7. LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS: AN UPDATE ON A U.S. MULTI-AGENCY INITIATIVE

    EPA Science Inventory

    Permeable reactive barriers (PRB's) are an emerging, alternative in-situ approach for remediating contaminated groundwater that combine subsurface fluid flow management with a passive chemical treatment zone. PRB's are a potentially more cost effective treatment option at seve...

  8. CARBON AND SULFUR ACCUMULATION AND IRON MINERAL TRANSFORMATION IN PERMEABLE REACTIVE BARRIERS CONTAINING ZERO-VALENT IRON

    EPA Science Inventory

    Permeable reactive barrier technology is an in-situ approach for remediating groundwater contamination that combines subsurface fluid flow management with passive chemical treatment. Factors such as the buildup of mineral precipitates, buildup of microbial biomass (bio-fouling...

  9. The effect of a tin barrier layer on the permeability of hydrogen through mild steel and ferritic stainless steel

    SciTech Connect

    Bowker, J.; Piercy, G.R.

    1984-11-01

    Experiments were performed to measure the effectiveness of a commercially electroplated tin layer as a barrier to hydrogen, and to see how this altered when the tin layer was converted to FeSn. The authors measured the permeability of hydrogen through AISI 410 ferritic stainless steel and determined the effectiveness of tin as a surface barrier on it. The measured values for the permeability of hydrogen in iron and ferritic stainless steel are shown.

  10. Barrier permeability at cut axonal ends progressively decreases until an ionic seal is formed.

    PubMed Central

    Eddleman, C S; Bittner, G D; Fishman, H M

    2000-01-01

    After axonal severance, a barrier forms at the cut ends to rapidly restrict bulk inflow and outflow. In severed crayfish axons we used the exclusion of hydrophilic, fluorescent dye molecules of different sizes (0.6-70 kDa) and the temporal decline of ionic injury current to levels in intact axons to determine the time course (0-120 min posttransection) of barrier formation and the posttransection time at which an axolemmal ionic seal had formed, as confirmed by the recovery of resting and action potentials. Confocal images showed that the posttransection time of dye exclusion was inversely related to dye molecular size. A barrier to the smallest dye molecule formed more rapidly (<60 min) than did the barrier to ionic entry (>60 min). These data show that axolemmal sealing lacks abrupt, large changes in barrier permeability that would be expected if a seal were to form suddenly, as previously assumed. Rather, these data suggest that a barrier forms gradually and slowly by restricting the movement of molecules of progressively smaller size amid injury-induced vesicles that accumulate, interact, and form junctional complexes with each other and the axolemma at the cut end. This process eventually culminates in an axolemmal ionic seal, and is not complete until ionic injury current returns to baseline levels measured in an undamaged axon. PMID:11023894

  11. Separation methods that are capable of revealing blood-brain barrier permeability.

    PubMed

    Dash, Alekha K; Elmquist, William F

    2003-11-25

    The objective of this review is to emphasize the application of separation science in evaluating the blood-brain barrier (BBB) permeability to drugs and bioactive agents. Several techniques have been utilized to quantitate the BBB permeability. These methods can be classified into two major categories: in vitro or in vivo. The in vivo methods used include brain homogenization, cerebrospinal fluid (CSF) sampling, voltametry, autoradiography, nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), intracerebral microdialysis, and brain uptake index (BUI) determination. The in vitro methods include tissue culture and immobilized artificial membrane (IAM) technology. Separation methods have always played an important role as adjunct methods to the methods outlined above for the quantitation of BBB permeability and have been utilized the most with brain homogenization, in situ brain perfusion, CSF sampling, intracerebral microdialysis, in vitro tissue culture and IAM chromatography. However, the literature published to date indicates that the separation method has been used the most in conjunction with intracerebral microdialysis and CSF sampling methods. The major advantages of microdialysis sampling in BBB permeability studies is the possibility of online separation and quantitation as well as the need for only a small sample volume for such an analysis. Separation methods are preferred over non-separation methods in BBB permeability evaluation for two main reasons. First, when the selectivity of a determination method is insufficient, interfering substances must be separated from the analyte of interest prior to determination. Secondly, when large number of analytes is to be detected and quantitated by a single analytical procedure, the mixture must be separated to each individual component prior to determination. Chiral separation in particular can be essential to evaluate the stereo-selective permeation and distribution of agents into the

  12. Targeted skin overexpression of the mineralocorticoid receptor in mice causes epidermal atrophy, premature skin barrier formation, eye abnormalities, and alopecia.

    PubMed

    Sainte Marie, Yannis; Toulon, Antoine; Paus, Ralf; Maubec, Eve; Cherfa, Aicha; Grossin, Maggy; Descamps, Vincent; Clemessy, Maud; Gasc, Jean-Marie; Peuchmaur, Michel; Glick, Adam; Farman, Nicolette; Jaisser, Frederic

    2007-09-01

    The mineralocorticoid receptor (MR) is a transcription factor of the nuclear receptor family, activation of which by aldosterone enhances salt reabsorption in the kidney. The MR is also expressed in nonclassical aldosterone target cells (brain, heart, and skin), in which its functions are incompletely understood. To explore the functional importance of MR in mammalian skin, we have generated a conditional doxycycline-inducible model of MR overexpression, resulting in double-transgenic (DT) mice [keratin 5-tTa/tetO-human MR (hMR)], targeting the human MR specifically to keratinocytes of the epidermis and hair follicle (HF). Expression of hMR throughout gestation resulted in early postnatal death that could be prevented by antagonizing MR signaling. DT mice exhibited premature epidermal barrier formation at embryonic day 16.5, reduced HF density and epidermal atrophy, increased keratinocyte apoptosis at embryonic day 18.5, and premature eye opening. When hMR expression was initiated after birth to overcome mortality, DT mice developed progressive alopecia and HF cysts, starting 4 months after hMR induction, preceded by dystrophy and cycling abnormalities of pelage HF. In contrast, interfollicular epidermis, vibrissae, and footpad sweat glands in DT mice were normal. This new mouse model reveals novel biological roles of MR signaling and offers an instructive tool for dissecting nonclassical functions of MR signaling in epidermal, hair follicle, and ocular physiology. PMID:17675581

  13. Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies.

    PubMed

    Franz-Montan, Michelle; Serpe, Luciano; Martinelli, Claudia Cristina Maia; da Silva, Camila Batista; Santos, Cleiton Pita Dos; Novaes, Pedro Duarte; Volpato, Maria Cristina; de Paula, Eneida; Lopez, Renata Fonseca Vianna; Groppo, Francisco Carlos

    2016-01-01

    The objective of the present study was to investigate the influence of preparation and storage conditions on the histology and permeability of different parts of porcine oral mucosa used for in vitro studies of transbuccal formulations. Fresh and frozen (-20°C and -80°C, with or without cryoprotectant) epithelia of porcine palatal, gingival, dorsum of the tongue, and buccal mucosa were submitted for histological analyses to determine the effects of storage conditions on barrier integrity. Permeation of lidocaine hydrochloride (used as a hydrophilic model drug) across fresh and previously frozen oral epithelium was measured in order to evaluate the barrier function. Histological evaluation demonstrated that the oral epithelium was successfully separated from the connective tissue, except for gingival mucosa. After storage under different conditions, all tissues presented desquamation of superficial layers and spherical spaces induced by the freezing process. The permeability of lidocaine hydrochloride varied among the fresh oral mucosa and generally increased after freezing. In conclusion, fresh epithelium from the buccal and dorsum of the tongue mucosa should be used for in vitro studies investigating hydrophilic drug transport when these are the desired clinical application sites. However, when the palate is the target site, both fresh and frozen (for up to 4weeks, without addition of cryoprotectant) samples could be used. The addition of glycerol as a cryoprotectant should be avoided due to increased lidocaine hydrochloride permeability. PMID:26435216

  14. 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

  15. Vascular Endothelial Growth Factors Enhance the Permeability of the Mouse Blood-brain Barrier

    PubMed Central

    Jiang, Shize; Xia, Rui; Jiang, Yong; Wang, Lei; Gao, Fabao

    2014-01-01

    The blood-brain barrier (BBB) impedes entry of many drugs into the brain, limiting clinical efficacy. A safe and efficient method for reversibly increasing BBB permeability would greatly facilitate central nervous system (CNS) drug delivery and expand the range of possible therapeutics to include water soluble compounds, proteins, nucleotides, and other large molecules. We examined the effect of vascular endothelial growth factor (VEGF) on BBB permeability in Kunming (KM) mice. Human VEGF165 was administered to treatment groups at two concentrations (1.6 or 3.0 µg/mouse), while controls received equal-volume saline. Changes in BBB permeability were measured by parenchymal accumulation of the contrast agent Gd-DTPA as assessed by 7 T magnetic resonance imaging (MRI). Mice were then injected with Evans blue, sacrificed 0.5 h later, and perfused transcardially. Brains were removed, fixed, and sectioned for histological study. Both VEGF groups exhibited a significantly greater signal intensity from the cerebral cortex and basal ganglia than controls (P<0.001). Evans blue fluorescence intensity was higher in the parenchyma and lower in the cerebrovasculature of VEGF-treated animals compared to controls. No significant brain edema was observed by diffusion weighted MRI (DWI) or histological staining. Exogenous application of VEGF can increase the permeability of the BBB without causing brain edema. Pretreatment with VEGF may be a feasible method to facilitate drug delivery into the CNS. PMID:24551038

  16. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

    PubMed Central

    Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

  17. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    SciTech Connect

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-05-15

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  18. Improvement of epidermal differentiation and barrier function in reconstructed human skin after grafting onto athymic nude mice.

    PubMed

    Higounenc, I; Démarchez, M; Régnier, M; Schmidt, R; Ponec, M; Shroot, B

    1994-01-01

    To determine whether epidermis reconstructed in vitro at the air-liquid interface on de-epidermized dermis has the capacity to normalize the expression of differentiation-specific markers, its lipid composition and stratum corneum barrier properties, human skin equivalents were transplanted onto athymic nude mice and investigated at different stages ranging from 1 to 4 months after grafting. Indirect immunofluorescence with species- or non-species-specific antibodies revealed that as early as 1 month after transplantation keratinization, and involucrin, loricrin and transglutaminase patterns were normalized. Human melanocytes were observed in the basal layer of the pigmented graft. As revealed by high-performance thin-layer chromatography and transmission electron microscopy after ruthenium tetroxide fixation, the lipid profile and the intracellular lamellar organization were similar to those found in natural epidermis. Transepidermal water loss measurements and penetration studies showed that the barrier properties of the reconstructed epidermis after transplantation were comparable to those of normal human skin. PMID:8154923

  19. Quantification of pore clogging characteristics in potential permeable reactive barrier (PRB) substrates using image analysis

    NASA Astrophysics Data System (ADS)

    Wantanaphong, J.; Mooney, S. J.; Bailey, E. H.

    2006-08-01

    Permeable reactive barriers (PRBs) are now an established approach for groundwater remediation. However, one concern is the deterioration of barrier material performance due to pore clogging. This study sought to quantify the effect of pore clogging on the alteration of the physical porous architecture of two novel potential PRB materials (clinoptilolite and calcified seaweed) using image analysis of SEM-derived images. Results after a water treatment contaminated with heavy metals over periods of up to 10 months identified a decrease in porosity from c. 22% to c. 15% for calcified seaweed and from c. 22% to c. 18% for clinoptilolite. Porosity was reduced by as much as 37% in a calcified seaweed column that clogged. The mean pore size (2D) of both materials slightly decreased after water treatment with c. 11% reduction in calcified seaweed and c. 7% reduction in clinoptilolite. An increase in the proportion of crack-shaped pores was observed in both materials after the contaminated water treatment, most noticeably in the bottom of columns where contaminated water first reacted with the material. The distribution of pores (within a given image) derived from the distance transform indicated the largest morphological differences in materials was recorded in calcified seaweed columns, which is likely to impact significantly on their performance as barrier materials. The magnitude of porosity reduction over a short time period in relation to predicted barrier longevity suggest these and similar materials may be unsuited for barrier installation in their present form.

  20. Epidermal barrier abnormalities in exfoliative ichthyosis with a novel homozygous loss-of-function mutation in CSTA.

    PubMed

    Moosbrugger-Martinz, V; Jalili, A; Schossig, A S; Jahn-Bassler, K; Zschocke, J; Schmuth, M; Stingl, G; Eckl, K M; Hennies, H C; Gruber, R

    2015-06-01

    Autosomal recessive exfoliative ichthyosis (AREI) results from mutations in CSTA, encoding cysteine protease inhibitor A (cystatin A). We present a 25-year-old man from Iran with consanguineous parents, who presented with congenital erythroderma, hyperhidrosis and diffuse hyperkeratosis with coarse palmoplantar peeling of the skin, aggravated by exposure to water and by occlusion. Candidate gene analysis revealed a previously unknown homozygous loss-of-function mutation c.172C>T (p.Arg58Ter) in CSTA, and immunostaining showed absence of epidermal cystatin A, confirming the diagnosis of AREI. Ultrastructural analysis by transmission electron microscopy showed normal degradation of corneodesmosomes, mild intercellular oedema in the spinous layer but not in the basal layer, normal-appearing desmosomes, and prominent keratin filaments within basal keratinocytes. Thickness of cornified envelopes was reduced, lamellar lipid bilayers were disturbed, lamellar body secretion occurred prematurely and processing of secreted lamellar body contents was delayed. These barrier abnormalities were reminiscent of (albeit less severe than in) Netherton syndrome, which results from a deficiency of the serine protease inhibitor LEKTI. This work describes ultrastructural findings with evidence of epidermal barrier abnormalities in AREI. PMID:25400170

  1. LONG-TERM GEOCHEMICAL BEHAVIOR OF A ZEROVALENT IRON PERMEABLE REACTIVE BARRIER FOR THE TREATMENT OF HEXAVALENT CHROMIUM IN GROUNDWATER

    EPA Science Inventory

    Passive, in-situ reactive barriers have proven to be viable, cost-effective systems for the remediation of Cr-contaminated groundwater at some sites. Permeable reactive barriers (PRBs) are installed in the flow-path of groundwater, most typically as vertical treatment walls. Re...

  2. Long-Term Blood-Brain Barrier Permeability Changes in Binswanger’s Disease

    PubMed Central

    Huisa, Branko N; Caprihan, Arvind; Thompson, Jeffrey; Prestopnik, Jillian; Qualls, Clifford R; Rosenberg, Gary A

    2015-01-01

    Background and Purpose The blood brain-barrier (BBB) is disrupted in small vessel disease (SVD) patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM (NAWM) and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger’s disease (BD). Methods We selected a subset of 22 BD subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice over several years using dynamic contrast-enhanced MRI (DCEMRI). WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were co-registered. WM was divided into 3 regions: NAWM, WMH ring and WMH core. The ring was defined as 2mm on each side of the WMH border. WMP was calculated in each of the three specific regions. We used paired t-test, ANOVA and Fisher’s exact test to compare individual changes. Results WMP was significantly higher in subjects than controls (p<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the NAWM, and 52% within the WMH ring (p<0.001; ANOVA). Conclusions Increased BBB permeability in NAWM and close to the WMH borders supports a relationship between BBB disruption and development of WMHs. PMID:26205374

  3. In vitro blood-brain barrier permeability predictions for GABAA receptor modulating piperine analogs.

    PubMed

    Eigenmann, Daniela Elisabeth; Dürig, Carmen; Jähne, Evelyn Andrea; Smieško, Martin; Culot, Maxime; Gosselet, Fabien; Cecchelli, Romeo; Helms, Hans Christian Cederberg; Brodin, Birger; Wimmer, Laurin; Mihovilovic, Marko D; Hamburger, Matthias; Oufir, Mouhssin

    2016-06-01

    The alkaloid piperine from black pepper (Piper nigrum L.) and several synthetic piperine analogs were recently identified as positive allosteric modulators of γ-aminobutyric acid type A (GABAA) receptors. In order to reach their target sites of action, these compounds need to enter the brain by crossing the blood-brain barrier (BBB). We here evaluated piperine and five selected analogs (SCT-66, SCT-64, SCT-29, LAU397, and LAU399) regarding their BBB permeability. Data were obtained in three in vitro BBB models, namely a recently established human model with immortalized hBMEC cells, a human brain-like endothelial cells (BLEC) model, and a primary animal (bovine endothelial/rat astrocytes co-culture) model. For each compound, quantitative UHPLC-MS/MS methods in the range of 5.00-500ng/mL in the corresponding matrix were developed, and permeability coefficients in the three BBB models were determined. In vitro predictions from the two human BBB models were in good agreement, while permeability data from the animal model differed to some extent, possibly due to protein binding of the screened compounds. In all three BBB models, piperine and SCT-64 displayed the highest BBB permeation potential. This was corroborated by data from in silico prediction. For the other piperine analogs (SCT-66, SCT-29, LAU397, and LAU399), BBB permeability was low to moderate in the two human BBB models, and moderate to high in the animal BBB model. Efflux ratios (ER) calculated from bidirectional permeability experiments indicated that the compounds were likely not substrates of active efflux transporters. PMID:27018328

  4. Blood-brain barrier permeability of bioactive withanamides present in Withania somnifera fruit extract.

    PubMed

    Vareed, Shaiju K; Bauer, Alison K; Nair, Kavitha M; Liu, Yunbao; Jayaprakasam, Bolleddula; Nair, Muraleedharan G

    2014-08-01

    The neuroprotective effect of Withania somnifera L. Dunal fruit extract, in rodent models, is known. Withanamides, the primary active constituents in W.somnifera fruit extract exhibited neuroprotective effects against β-amyloid-induced cytotoxicity in neuronal cell culture studies. Therefore, we investigated the blood-brain barrier permeability of withanamides in W.somnifera fruit extract in mice using HPLC coupled with high resolution quadrupole time of flight mass spectrometer (Q-TOF/MS) detection. Mice were administered with 250 mg/kg of W.somnifera extract by intraperitoneal injection, and the blood and brain samples analyzed by Q-TOF/MS detection. Four major withanamides were detected in brain and blood of mice administered with W.somnifera extract. The results suggested that the withanamides crossed the blood-brain barrier. These results may help to develop W.somnifera fruit extract as a preventive or therapeutic botanical drug for stress-induced neurological disorders. PMID:24458838

  5. A procedure to design a Permeable Adsorptive Barrier (PAB) for contaminated groundwater remediation.

    PubMed

    Erto, A; Lancia, A; Bortone, I; Di Nardo, A; Di Natale, M; Musmarra, D

    2011-01-01

    A procedure to optimize the design of a Permeable Adsorptive Barrier (PAB) for the remediation of a contaminated aquifer is presented in this paper. A computer code, including different routines that describe the groundwater contaminant transport and the pollutant capture by adsorption in unsteady conditions over the barrier solid surface, has been developed. The complete characterization of the chemical-physical interactions between adsorbing solids and the contaminated water, required by the computer code, has been obtained by experimental measurements. A case study in which the procedure developed has been applied to a tetrachloroethylene (PCE)-contaminated aquifer near a solid waste landfill, in the district of Napoli (Italy), is also presented and the main dimensions of the barrier (length and width) have been evaluated. Model results show that PAB is effective for the remediation of a PCE-contaminated aquifer, since the concentration of PCE flowing out of the barrier is everywhere always lower than the concentration limit provided for in the Italian regulations on groundwater quality. PMID:20846781

  6. Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

    PubMed

    Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

    2016-01-01

    Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier. PMID:27459643

  7. Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability

    PubMed Central

    Mooney, Skyler J.; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

    2016-01-01

    Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier. PMID:27459643

  8. iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

    PubMed

    Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

    2014-08-01

    iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. PMID:24643277

  9. Aging and sex influence the permeability of the blood-brain barrier in the rat

    SciTech Connect

    Saija, A.; Princi, P.; D'Amico, N.; De Pasquale, R.; Costa, G.

    1990-01-01

    The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer ({sup 14}C)-{alpha}-aminoisobutyric acid. The authors observed that: (a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; (b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; (c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging and sex-related alterations in thee permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.

  10. Development of permeable reactive barriers to prevent radionuclide migration from the nuclear waste repositories

    SciTech Connect

    Zakharova, E.; Kalmykov, S.; Batuk, O.; Kazakovskaya, T.; Shapovalov, V.; Haire, M.J.

    2007-07-01

    This paper is focused on three possible materials for permeable reactive barriers (PRB): 1) depleted uranium oxide that is accumulated as a residual product of the natural uranium enrichment process, 2) zero-valent iron and, 3) the composite material based on montmorillonite clay modified with different anion exchangers. The main aim of permeable reactive barriers is to prevent release of radionuclides emerging from a repository waste package containing spent nuclear fuel to outside the control area of the nuclear waste repository sites. The most experimentally developed material is depleted uranium oxide. It can be used both as a component of radiation shielding and as an absorbent for migrating long-lived radionuclides (especially {sup 237}Np and {sup 99}Tc). Experiments demonstrate the high sorption properties of depleted uranium oxide towards Np and Tc both from deionized water and from solution that simulates Yucca Mountain. Zero-valent iron, and the composite based on montmorillonite clay, also seem to be very promising to use in a PRB. Nano-particles of zero-valent iron with high surface will reduce high valency Np and Tc to the tetravalent state and thus immobilize them due to the extremely low solubility of corresponding hydroxides. The composite based on montmorillonite clay modified with different anion exchangers will possess high sorption affinity towards anionic and cationic species. (authors)

  11. An overview of permeable reactive barriers for in situ sustainable groundwater remediation.

    PubMed

    Obiri-Nyarko, Franklin; Grajales-Mesa, S Johana; Malina, Grzegorz

    2014-09-01

    Permeable reactive barriers (PRBs) are one of the innovative technologies widely accepted as an alternative to the 'pump and treat' (P&T) for sustainable in situ remediation of contaminated groundwater. The concept of the technology involves the emplacement of a permeable barrier containing reactive materials across the flow path of the contaminated groundwater to intercept and treat the contaminants as the plume flows through it under the influence of the natural hydraulic gradient. Since the invention of PRBs in the early 1990s, a variety of materials has been employed to remove contaminants including heavy metals, chlorinated solvents, aromatic hydrocarbons, and pesticides. Contaminant removal is usually accomplished via processes such as adsorption, precipitation, denitrification and biodegradation. Despite wide acknowledgment, there are still unresolved issues about long term-performance of PRBs, which have somewhat affected their acceptability and full-scale implementation. The current paper presents an overview of the PRB technology, which includes the state of art, the merits and limitations, the reactive media used so far, and the mechanisms employed to transform or immobilize contaminants. The paper also looks at the design, construction and the long-term performance of PRBs. PMID:24997925

  12. Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and Impairs Barrier Function in Mice.

    PubMed

    Guan, Guiping; Wang, Hongbing; Peng, Hanhui; Li, Guanya

    2016-01-01

    The purpose of this study was to explore relationships between low dose dietary supplementation with chitosan (COS) and body weight, feed intake, intestinal barrier function, and permeability in mice. Twenty mice were randomly assigned to receive an unadulterated control diet (control group) or a dietary supplementation with 30 mg/kg dose of chitosan (COS group) for two weeks. Whilst no significant differences were found between the conditions for body weight or food and water intake, mice in the COS group had an increased serum D-lactate content (P < 0.05) and a decreased jejunal diamine oxidase (DAO) activity (P < 0.05). Furthermore, mice in COS group displayed a reduced expression of occludin and ZO-1 (P < 0.05) and a reduced expression of occludin in the ileum (P < 0.05). The conclusion drawn from these findings showed that although 30 mg/kg COS-supplemented diet had no effect on body weight or feed intake in mice, this dosage may compromise intestinal barrier function and permeability. This research will contribute to the guidance on COS supplements. PMID:27610376

  13. Fungal permeable reactive barrier to remediate groundwater in an artificial aquifer.

    PubMed

    Folch, Albert; Vilaplana, Marcel; Amado, Leila; Vicent, Teresa; Caminal, Glòria

    2013-11-15

    Biobarriers, as permeable reactive barriers (PRBs), are a common technology that mainly uses bacteria to remediate groundwater in polluted aquifers. In this study, we propose to use Trametes versicolor, a white-rot fungus, as the reactive element because of its capacity to degrade a wide variety of highly recalcitrant and xenobiotic compounds. A laboratory-scale artificial aquifer was constructed to simulate groundwater flow under real conditions in shallow aquifers. Orange G dye was chosen as a contaminant to visually monitor the hydrodynamic behaviour of the system and any degradation of the dye by the fungus. Batch experiments at different pH values (6 and 7) and several temperatures (15 °C, 18 °C, 20 °C and 25 °C) were performed to select the appropriate residence time and glucose consumption rate required for continuous treatment. The maximum Orange G degradation was 97%. Continuous degradation over 85% was achieved for more than 8 days. Experimental results indicate for the first time that this fungus can potentially be used as a permeable reactive barrier in real aquifers. PMID:24095995

  14. A2A adenosine receptor regulates the human blood brain barrier permeability

    PubMed Central

    Kim, Do-Geun; Bynoe, Margaret S.

    2015-01-01

    The blood brain barrier (BBB) symbolically represents the gateway to the central nervous system. It is a single layer of specialized endothelial cells that coats the central nervous system (CNS) vasculature and physically separates the brain environment from the blood constituents, to maintain the homeostasis of the CNS. However, this protective measure is a hindrance to the delivery of therapeutics to treat neurological diseases. Here, we show that activation of A2A adenosine receptor (AR) with an FDA-approved agonist potently permeabilizes an in vitro primary human brain endothelial barrier (hBBB) to the passage of chemotherapeutic drugs and T cells. T cell migration under AR signaling occurs primarily by paracellular transendothelial route. Permeabilization of the hBBB is rapid, time-dependent and reversible and is mediated by morphological changes in actin-cytoskeletal reorganization induced by RhoA signaling and a potent down-regulation of Claudin-5 and VE-Cadherin. Moreover, the kinetics of BBB permeability in mice closely overlaps with the permeability kinetics of the hBBB. These data suggest that activation of A2A AR is an endogenous mechanism that may be used for CNS drug delivery in human. PMID:25262373

  15. Low Dosage of Chitosan Supplementation Improves Intestinal Permeability and Impairs Barrier Function in Mice

    PubMed Central

    Peng, Hanhui; Li, Guanya

    2016-01-01

    The purpose of this study was to explore relationships between low dose dietary supplementation with chitosan (COS) and body weight, feed intake, intestinal barrier function, and permeability in mice. Twenty mice were randomly assigned to receive an unadulterated control diet (control group) or a dietary supplementation with 30 mg/kg dose of chitosan (COS group) for two weeks. Whilst no significant differences were found between the conditions for body weight or food and water intake, mice in the COS group had an increased serum D-lactate content (P < 0.05) and a decreased jejunal diamine oxidase (DAO) activity (P < 0.05). Furthermore, mice in COS group displayed a reduced expression of occludin and ZO-1 (P < 0.05) and a reduced expression of occludin in the ileum (P < 0.05). The conclusion drawn from these findings showed that although 30 mg/kg COS-supplemented diet had no effect on body weight or feed intake in mice, this dosage may compromise intestinal barrier function and permeability. This research will contribute to the guidance on COS supplements. PMID:27610376

  16. a Study of Blood-Brain Barrier Permeability Variations in Vivo Using Magnetic Resonance Imaging.

    NASA Astrophysics Data System (ADS)

    Neuder, Michelle Sandy

    We have measured non-invasively the transcapillary transport of water and an extracellular marker, gadolinium diethylenetriamine pentaacetate (Gd-DTPA) in the living brain using conventional and rapid NMR imaging strategies. Detection of water exchange post-contrast and of Gd-DTPA leakage across an intact and hyperosmotically-disrupted blood-brain barrier (BBB) were investigated in animal models. The development of high speed magnetic resonance imaging methods provides a tool for measuring short-term variations in BBB permeability in vivo over relatively short experimental time periods, and for determining the influence of these permeability changes on other physiologic parameters. The overall aims of this thesis have been to exploit the high temporal resolution available with a fast scanning technique, echo-planar imaging, to (1) quantitate the permeability of the BBB to water before and after altering the exchange capacity of the capillary bed, (2) use these measurements to model small, reversible changes in permeability to Gd-DTPA in terms of the post -contrast relaxation characteristics of the blood and tissue spaces during the first- and multiple-pass phases of transport, and (3) explore the influence of an increased permeability on the first-pass kinetic behavior. We initially present the theory of two-site water exchange, a modification of the Bloch equations used to examine time-dependent changes in the nuclear spin magnetization with time. The solutions of these equations for our particular imaging experiment were initially validated in a well-characterized dialysis chamber in order to demonstrate the sensitivity of the experiment to detecting biexponential signal decay. Upon validating the theory, we measured water exchange times in vivo in rodent and canine brain. A biexponential model of NMR signal decay was used to determine both the intravascular blood volume and intravascular water lifetime. Mannitol, a hyperosmotic solution, which can increase BBB

  17. Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2016-02-01

    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB. PMID:26048259

  18. An immortalized human blood-nerve barrier endothelial cell line for in vitro permeability studies

    PubMed Central

    Yosef, Nejla; Ubogu, Eroboghene E.

    2012-01-01

    Solute and macromolecular transport studies may elucidate nutritional requirements and drug effects in healthy and diseased peripheral nerves. Endoneurial endothelial cells are specialized microvascular cells that form the restrictive blood-nerve barrier (BNB). Primary human endoneurial endothelial cells (pHEndECs) are difficult to isolate, limiting their widespread availability for biomedical research. We developed a simian virus-40 large T-antigen (SV40-LTA) immortalized human BNB cell line via stable transfection of low passage pHEndECs and observed continuous growth in culture for >45 population doublings. As observed with pHEndECs, the immortalized BNB endothelial cells were Ulex Europaeus agglutinin-1 (UEA-1)-positive and endocytosed low density lipoprotein, but lost von Willebrand factor (vWF) expression. Glucose transporter-1 (GLUT-1), P-glycoprotein (P-gp), γ-glutamyl transpeptidase (γ-GT), large neutral amino acid transporter-1 (LAT-1), creatine transporter (CRT) and monocarboxylate transporter-1 (MCT-1) mRNA expression were retained at all passages with loss of alkaline phosphatase (AP) expression after passages 16-20. Compared with an SV40-LTA immortalized human blood-brain barrier (BBB) endothelial cell line, there was increased γ-GT protein expression, equivalent expression of organic anion transporting polypeptide-C (OATP-C), organic anion transporter 3 (OAT-3), MCT-1 and LAT-1, and reduced expression of AP, CRT and P-gp by the BNB cell line at passage 20. Further studies demonstrated lower transendothelial electrical resistance (TEER: ~181 Ω.cm2 vs. 191 Ω.cm2), equivalent permeability to fluoresceinated sodium (4.84% vs. 4.39%) and lower permeability to fluoresceinated high molecular weight (70 kDa) dextran (0.39% vs. 0.52%) by the BNB cell line. This cell line retained essential molecular and biophysical properties suitable for in vitro peripheral nerve permeability studies. PMID:23104242

  19. Effects of radiofrequency radiation exposure on blood-brain barrier permeability in male and female rats.

    PubMed

    Sirav, Bahriye; Seyhan, Nesrin

    2011-12-01

    During the last several decades, numerous studies have been performed aiming at the question of whether or not exposure to radiofrequency radiation (RFR) influences the permeability of the blood-brain barrier (BBB). The objective of this study was to investigate the effect of RFR on the permeability of BBB in male and female Wistar albino rats. Right brain, left brain, cerebellum, and total brain were analyzed separately in the study. Rats were exposed to 0.9 and 1.8 GHz continuous-wave (CW) RFR for 20 min (at SARs of 4.26 mW/kg and 1.46 mW/kg, respectively) while under anesthesia. Control rats were sham-exposed. Disruption of BBB integrity was detected spectrophotometrically using the Evans-blue dye, which has been used as a BBB tracer and is known to be bound to serum albumin. Right brain, left brain, cerebellum, and total brain were evaluated for BBB permeability. In female rats, no albumin extravasation was found in in the brain after RFR exposure. A significant increase in albumin was found in the brains of the RF-exposed male rats when compared to sham-exposed male brains. These results suggest that exposure to 0.9 and 1.8 GHz CW RFR at levels below the international limits can affect the vascular permeability in the brain of male rats. The possible risk of RFR exposure in humans is a major concern for the society. Thus, this topic should be investigated more thoroughly in the future. PMID:22047463

  20. Effects of Soybean Agglutinin on Intestinal Barrier Permeability and Tight Junction Protein Expression in Weaned Piglets

    PubMed Central

    Zhao, Yuan; Qin, Guixin; Sun, Zewei; Che, Dongsheng; Bao, Nan; Zhang, Xiaodong

    2011-01-01

    This study was developed to provide further information on the intestinal barrier permeability and the tight junction protein expression in weaned piglets fed with different levels of soybean agglutinin (SBA). Twenty-five weaned crossbred barrows (Duroc × Landrace × Yorkshire) were selected and randomly allotted to five groups, each group with five replicates. The piglets in the control group were not fed with leguminous products. 0.05, 0.1, 0.15 and 0.2% SBA was added to the control diet to form four experimental diets, respectively. After the experimental period of 7 days (for each group), all the piglets were anesthetized with excess procaine and slaughtered. The d-lactic acid in plasma and the Ileal mucosa diamine oxidase (DAO) was analyzed to observe the change in the intestinal permeability. The tight junction proteins occludin and ZO-1 in the jejunum tissue distribution and relative expression were detected by immunohistochemistry and Western Blot. The results illustrated that a high dose of SBA (0.1–0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no significant affects. The contents of DAO, d-lactic acid, occludin or ZO-1, had a linear relationship with the SBA levels (0–0.2%) in diets. The high dose SBA (0.1–0.2%) could increase the intestinal permeability and reduce piglet intestinal epithelial tight junction protein occludin or ZO-1 expression, while low dose of SBA (0.05% of total diet) had no affects. PMID:22272087

  1. Tracer kinetic modelling for DCE-MRI quantification of subtle blood–brain barrier permeability

    PubMed Central

    Heye, Anna K.; Thrippleton, Michael J.; Armitage, Paul A.; Valdés Hernández, Maria del C.; Makin, Stephen D.; Glatz, Andreas; Sakka, Eleni; Wardlaw, Joanna M.

    2016-01-01

    There is evidence that subtle breakdown of the blood–brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n = 201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a “sham” DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and KTrans estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model

  2. Biogeochemical dynamics in zero-valent iron columns: Implications for permeable reactive barriers

    SciTech Connect

    Gu, B.; Phelps, T.J.; Liang, L.; Palumbo, A.V.; Jacobs, G.K.; Dickey, M.J.; Roh, Y.; Kinsall, B.L.

    1999-07-01

    The impact of microbiological and geochemical processes has been a major concern for the long-term performance of permeable reactive barriers containing zero-valent iron (Fe{sup 0}). To evaluate potential biogeochemical impacts, laboratory studies were performed over a 5-month period using columns containing a diverse microbial community. The conditions chosen for these experiments were designed to simulate high concentrations of bicarbonate and sulfate containing groundwater regimes. Groundwater chemistry was found to significantly affect corrosion rates of Fe{sup 0} filings and resulted in the formation of a suite of mineral precipitates. HCO{sub 3}{sup {minus}} ions in SO{sub 4}{sup 2{minus}}-containing water were particularly corrosive to Fe{sup 0}, resulting in the formation of ferrous carbonate and enhanced H{sub 2} gas generation that stimulated the growth of microbial populations and increased SO{sub 4}{sup 2{minus}} reduction. Major mineral precipitates identified included lepidocrocite, akaganeite, mackinawite, magnetite/maghemite, goethite, siderite, and amorphous ferrous sulfide. Sulfide was formed as a result of microbial reduction of SO{sub 4}{sup 2{minus}} that became significant after about 2 months of column operations. This study demonstrates that biogeochemical influences on the performance and reaction of Fe{sup 0} may be minimal in the short term, necessitating longer-term operations to observe the effects of biogeochemical reactions on the performance of Fe{sup 0} barriers. Although major failures of in-ground treatment barriers have not been problematic to date, the accumulation of iron oxyhydroxides, carbonates, and sulfides from biogeochemical processes could reduce the reactivity and permeability of Fe{sup 0} beds, thereby decreasing treatment efficiency.

  3. An Injectable Apatite Permeable Reactive Barrier for In Situ 90Sr Immobilization

    SciTech Connect

    Vermeul, Vincent R.; Szecsody, James E.; Fritz, Brad G.; Williams, Mark D.; Moore, Robert C.; Fruchter, Jonathan S.

    2014-04-16

    An injectable permeable reactive barrier (PRB) technology was developed to sequester 90Sr in groundwater through the in situ formation of calcium-phosphate mineral phases, specifically apatite that incorporates 90Sr into the chemical structure. An integrated, multi-scale development and testing approach was used that included laboratory bench-scale experiments, an initial pilot-scale field test, and the emplacement and evaluation of a 300-ft-long treatability-test-scale PRB. Standard groundwater wells were used for emplacement of the treatment zone, allowing treatment of contaminants too deep below ground surface for trench-and-fill type PRB technologies. The apatite amendment formulation uses two separate precursor solutions, one containing a Ca-citrate complex and the other a Na-phosphate solution, to form apatite precipitate in situ. Citrate is needed to keep calcium in solution long enough to achieve a more uniform and areally extensive distribution of precipitate formation. In the summer of 2008, the apatite PRB technology was applied as a 91-m (300-ft) -long permeable reactive barrier on the downgradient edge of a 90Sr plume beneath the Hanford Site in Washington State. The technology was deployed to reduce 90Sr flux discharging to the Columbia River. Performance assessment monitoring data collected to date indicate the barrier is meeting performance objectives. The average reduction in 90Sr concentrations at four downgradient compliance monitoring locations was 95% relative to the high end of the baseline range approximately 1 year after treatment, and continues to meet remedial objectives more than 4 years after treatment.

  4. Clinoptilolite as an in-situ permeable barrier to strontium migration in ground water

    SciTech Connect

    Cantrell, K.J.; Martin, P.F.; Szecsody, J.E.

    1994-12-31

    Batch adsorption experiments were conducted with three zeolites (clinoptilolite, chabazite, and A-51) to determine their potential applicability as in-situ permeable barriers to ground water strontium migration in the 100-N Area of the Hanford Site. Each of the zeolites was an effective adsorbent for strontium, even in competition with calcium at concentrations typical of Hanford ground water, and the authors determined that clinoptilolite would be the most cost-effective. The strontium adsorption data for calcium-saturated clinoptilolite were fitted to a Langmuir isotherm, which is linear at solution concentrations of less than 10{sup {minus}5} mol/L. In this region, the adsorption coefficient (K{sub d}) was 956 L/kg. Because strontium concentrations in hanford ground water are typically 3 x 10{sup {minus}6} mol/L, assuming linear adsorption (K{sub d} = 956 L/kg) for modeling purposes is appropriate. These data were used to design an effective barrier and were incorporated into a transport model to assess its performance. Calculations indicated that a barrier 1.3 m thick would prevent strontium-90 migration to the Columbia river at 100-N Area for over 50 yr. Because of radioactive decay and adsorption, the maximum breakthrough of strontium-90, approximately 5% of the initial input, would occur at 100 yr. Preliminary experimental work was conducted to determine the adsorption kinetics of strontium on clinoptilolite. A comparison of the adsorption rate of strontium with its residence time (within the barrier) indicates that adsorption kinetics are sufficiently fast that the barrier performance will not be significantly affected.

  5. Amniotic Fluid Activates the Nrf2/Keap1 Pathway to Repair an Epidermal Barrier Defect In Utero

    PubMed Central

    Huebner, Aaron J.; Dai, Daisy; Morasso, Maria; Schmidt, Edward E.; Schäfer, Matthias; Werner, Sabine; Roop, Dennis R.

    2013-01-01

    SUMMARY The loss of loricrin, a major component of the cornified envelope, results in a delay of epidermal barrier formation. Therefore, the living layers of the epidermis are aberrantly exposed to late-stage amniotic fluid, which may serve as the signal to upregulate genes that functionally compensate for the loss of loricrin. Consistent with this hypothesis, metabolomic studies revealed marked changes in amniotic fluid between E14.5 and E16.5 days postcoitum. In addition, we discovered that the Nrf2/Keap1 pathway detects these compositional changes and directly upregulates the expression of genes involved in the compensatory response, thus ensuring postnatal survival. In support of this finding, we demonstrate that genetically blocking the Nrf2 pathway abolishes the compensatory response and that preemptively activating Nrf2 pharmacologically rescues the delay in barrier formation in utero. Our findings reveal that the functions of Nrf2 and the composition of amniotic fluid have coevolved to ensure the formation of a functional barrier. PMID:23237955

  6. Polymer/Silicate composites – New Materials for Subsurface Permeable Reactive Barriers

    SciTech Connect

    Mason K. Harrup; Michael G. Jones; Linda Polson; Byron White

    2008-09-01

    Investigations were performed into the suitability of novel nanocomposites to serve as materials for subsurface permeable reactive barriers (PRBs). These new materials are Type I nanocomposites – they are preformed organic polymers embedded in an inorganic matrix without significant covalent bonding between the components. The required properties for these materials to function efficiently are: 1) a tunable water passing rate to approximate the hydraulic conductivity of the subsurface environment where the PRB will be placed, 2) sufficient mechanical strength (both wet and dry) to maintain barrier integrity, 3) the ability to incorporate selective metal sequestration agents so that they remain active – yet do not leach from the barrier, and 4) to be deployable through direct injection methods such that trenching is not needed. Additionally, there is a need to keep the technology as low cost as possible, while remaining reliable. Results recently obtained in our laboratory show that our materials, remarkably, exhibit all of these properties and show great promise as vadose zone deployable PRBs.

  7. Effects of ambient air particulate exposure on blood-gas barrier permeability and lung function.

    PubMed

    Bräuner, Elvira Vaclavik; Mortensen, Jann; Møller, Peter; Bernard, Alfred; Vinzents, Peter; Wåhlin, Peter; Glasius, Marianne; Loft, Steffen

    2009-01-01

    Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm(3); 7.0-11.6 microg/m(3) PM(2.5); 7.5-15.8 microg/m(3) PM(10-2.5)) or filtered (91-542 particles/cm(3)) air collected above a busy street. The clearance rate of aerosolized (99m)Tc-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of (99m)Tc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function. PMID:18752169

  8. AN IN-SITU PERMEABLE REACTIVE BARRIER FOR THE TREATMENT OF HEXAVALENT CHROMIUM AND TRICHLOROETHYLENE IN GROUNDWATER: VOLUME 3 MULTICOMPONENT REACTIVE TRANSPORT MODELING

    EPA Science Inventory

    Reactive transport modeling has been conducted to describe the performance of the permeable reactive barrier at the Coast Guard Support Center near Elizabeth City, NC. The reactive barrier was installed to treat groundwater contaminated by hexavalent chromium and chlorinated org...

  9. Ground water remediation of chromium using zero-valent iron in a permeable reactive barrier

    SciTech Connect

    Puls, R.W.; Powell, R.M.; Paul, C.J.; Blowes, D.

    1998-09-01

    A series of laboratory experiments were performed to elucidate the chromium transformation and precipitation reactions caused by the corrosion of zero-valent iron in water-based systems. Reaction rates were determined for chromate reduction in the presence of different types of iron and in systems with iron mixed with aquifer materials. Various geochemical parameters were measured to confirm the proposed reactions. Laboratory experiments were scaled up to pilot and full-scale field demonstrations. Intensive geochemical sampling in the field tests corroborate laboratory results and successfully demonstrate the effectiveness of this innovative in situ approach to remediate chromate-contaminated ground water using a permeable reactive barrier composed of zero-valent iron.

  10. An application of permeable reactive barrier technology to petroleum hydrocarbon contaminated groundwater.

    PubMed

    Guerin, Turlough F; Horner, Stuart; McGovern, Terry; Davey, Brent

    2002-01-01

    A funnel and gate permeable reactive barrier was designed and built to treat groundwater contaminated with dissolved phase toluene. ethyl benzene. and xylene and n-alkanes in the C6-C36 fraction range. Removal efficienicies for the funnel and gate system varied from 63% to 96% for the monocyclic aromatic hydrocarbons. Average removal efficiencies for C6-C9, C10-C14, and C15-C28 fraction ranges were 69.2%, 77.6% and 79.5%. respectively. The lowest average removal efficiencies were 54% for the C29-C36 n-alkane fraction. The overall average removal efficiency for the funnel and gate system towards petroleum hydrocarbons present in the groundwater was 72% during the 10 month period over which the data were collected, and has allowed relevant water quality objectives to be met. PMID:11766790

  11. Organic/inorganic nanocomposites, methods of making, and uses as a permeable reactive barrier

    DOEpatents

    Harrup, Mason K.; Stewart, Frederick F.

    2007-05-15

    Nanocomposite materials having a composition including an inorganic constituent, a preformed organic polymer constituent, and a metal ion sequestration constituent are disclosed. The nanocomposites are characterized by being single phase, substantially homogeneous materials wherein the preformed polymer constituent and the inorganic constituent form an interpenetrating network with each other. The inorganic constituent may be an inorganic oxide, such as silicon dioxide, formed by the in situ catalyzed condensation of an inorganic precursor in the presence of the solvated polymer and metal ion sequestration constituent. The polymer constituent may be any hydrophilic polymer capable of forming a type I nanocomposite such as, polyacrylonitrile (PAN), polyethyleneoxide (PEO), polyethylene glycol (PEG), polyvinyl acetate (PVAc), polyvinyl alcohol (PVA), and combinations thereof. Nanocomposite materials of the present invention may be used as permeable reactive barriers (PRBs) to remediate contaminated groundwater. Methods for making nanocomposite materials, PRB systems, and methods of treating groundwater are also disclosed.

  12. Outer Membrane Permeability Barrier Disruption by Polymyxin in Polymyxin-Susceptible and -Resistant Salmonella typhimurium

    PubMed Central

    Vaara, Martti; Vaara, Timo

    1981-01-01

    In contrast to their polymyxin-susceptible parent strains, polymyxin-resistant Salmonella typhimurium mutants (pmrA strains) did not lose their outer membrane permeability barrier to macromolecules such as lysozyme and periplasmic proteins upon polymyxin treatment. The sensitization of pmrA strains to deoxycholate-induced lysis required 10-times-higher polymyxin concentrations than did the sensitization of the parent strains. These findings indicate that the pmrA mutation affects the outer membrane and decreases its susceptibility to polymyxin. By contrast, the pmrA mutants did not differ from their parents in the uptake of gentian violet after treatment with polymyxin, suggesting a degree of specificity in the pmrA effect in the outer membrane. Images PMID:6264852

  13. Creation of a Subsurface Permeable Reactive Barrier Using In Situ Redox Manipulation

    SciTech Connect

    Vermeul, Vincent R.; Williams, Mark D.; Szecsody, James E.; Fruchter, Jonathan S.; Cole, Charles R.; Amonette, James E.

    2002-10-01

    An In Situ Redox Manipulation (ISRM) method for creating a permeable reactive barrier in the subsurface has been developed and a field-scale demonstration has been conducted at a chromate-contaminated site on the U. S. Department of Energy's Hanford site in southeastern Washington State. The ISRM treatment zone is created by reducing the ferric iron [Fe(III)] phases naturally present in the aquifer sediments to ferrous iron phases [mainly adsorbed Fe(II)] with a chemical reducing agent using an injection/withdrawal (i.e., push/pull) emplacement strategy. Sodium dithionite (Na2S2O4) is injected into the aquifer, provided a residence time sufficient to react the sediment, and any remaining unreacted reagent and reaction products are withdrawn from the aquifer. Standard groundwater wells are used, allowing treatment of contaminants too deep below the ground surface for conventional trench-and-fill technologies. Once in place, redox-sensitive contaminants migrating through this manipulated zone are destroyed (organic solvents) or immobilized (metals). In the spring of 1997, an ISRM treatability test was initiated at a chromate-contaminated site located within Hanford's 100-D Area. Analysis of groundwater samples collected from the reduced zone following emplacement of the barrier indicate that concentrations of hexavalent chromium in groundwater have decreased from a pre-emplacement concentration of approximately 1,000 ?g/L to below analytical detection limits (<8 ?g/L). Hexavalent chromium concentrations have also significantly decreased below baseline values in downgradient monitoring wells. Laboratory analysis of iron in the soil indicates the barrier should remain in place for approximately 23 years. If additional reductive capacity is needed, the barrier can be regenerated at a reduced cost using the original injection well network.

  14. Permeability of the blood-brain barrier depends on brain temperature

    PubMed Central

    Kiyatkin, Eugene A.; Sharma, Hari S.

    2009-01-01

    Increased permeability of the blood-brain barrier (BBB) has been reported in different conditions accompanied by hyperthermia, but the role of brain temperature per se in modulating brain barrier functions has not been directly examined. To delineate the contribution of this factor, we examined albumin immunoreactivity in several brain structures (cortex, hippocampus, thalamus and hypothalamus) of pentobarbital-anesthetized rats (50 mg/kg, ip), which were passively warmed to different levels of brain temperature (32–42°C). Similar brain structures were also examined for the expression of glial fibrillary acidic protein (GFAP), an index of astrocytic activation, water and ion content, and morphological cell abnormalities. Data were compared with those obtained from drug-free awake rats with normal brain temperatures (36–37°C). The numbers of albumin- and GFAP-positive cells strongly correlates with brain temperature, gradually increasing from ~38.5°C and plateauing at 41–42°C. Brains maintained at hyperthermia also showed larger content of brain water and Na+, K+ and Cl− as well as structural abnormalities of brain cells, all suggesting acute brain edema. The latter alterations were seen at ~39°C, gradually progressed with temperature increase, and peaked at maximum hyperthermia. Temperature-dependent changes in albumin immunoreactivity tightly correlated with GFAP immunoreactivity, brain water, and numbers of abnormal cells; they were found in each tested area, but showed some structural specificity. Notably, a mild BBB leakage, selective glial activation, and specific cellular abnormalities were also found in the hypothalamus and piriform cortex during extreme hypothermia (32–33°C); in contrast to hyperthermia these changes were associated with decreased levels of brain water, Na+ and K+, suggesting acute brain dehydration. Therefore, brain temperature per se is an important factor in regulating BBB permeability, alterations in brain water

  15. Microfluidic devices with permeable polymer barriers for capture and transport of biomolecules and cells

    PubMed Central

    Lee, Ho Suk; Chu, Wai Keung; Zhang, Kun

    2013-01-01

    We report a method for fabricating permeable polymer microstructure barriers in polydimethylsiloxane (PDMS) microfluidic devices and the use of the devices to capture and transport DNA and cells. The polymer microstructure in a desired location in a fluidic channel is formed in situ by the polymerization of acrylamide and polyethylene diacrylate cross-linker (PEG-DA) monomer in a solution which is trapped in the location using a pair of PDMS valves. The porous polymer microstructure provides a mechanical barrier to convective fluid flow in the channel or between two microfluidic chambers while it still conducts ions or small charged species under an electric field, allowing for the rapid capture and transport of biomolecules and cells by electrophoresis. We have demonstrated the application of the devices for the rapid capture and efficient release of bacteriophage λ genomic DNA, solution exchange and for the transport and capture of HeLa cells. Our devices will enable the multi-step processing of biomolecules and cells or individual cells within a single microfluidic chamber. PMID:23828542

  16. Asef controls vascular endothelial permeability and barrier recovery in the lung

    PubMed Central

    Tian, Xinyong; Tian, Yufeng; Gawlak, Grzegorz; Meng, Fanyong; Kawasaki, Yoshihiro; Akiyama, Tetsu; Birukova, Anna A.

    2015-01-01

    Increased levels of hepatocyte growth factor (HGF) in injured lungs may reflect a compensatory response to diminish acute lung injury (ALI). HGF-induced activation of Rac1 GTPase stimulates endothelial barrier protective mechanisms. This study tested the involvement of Rac-specific guanine nucleotide exchange factor Asef in HGF-induced endothelial cell (EC) cytoskeletal dynamics and barrier protection in vitro and in a two-hit model of ALI. HGF induced membrane translocation of Asef and stimulated Asef Rac1-specific nucleotide exchange activity. Expression of constitutively activated Asef mutant mimicked HGF-induced peripheral actin cytoskeleton enhancement. In contrast, siRNA-induced Asef knockdown or expression of dominant-negative Asef attenuated HGF-induced Rac1 activation evaluated by Rac-GTP pull down and FRET assay with Rac1 biosensor. Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, and enhancement of VE-cadherin adherens junctions and compromised HGF-protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling, and EC permeability. Intravenous HGF injection attenuated lung inflammation and vascular leak in the two-hit model of ALI induced by excessive mechanical ventilation and thrombin signaling peptide TRAP6. This effect was lost in Asef−/− mice. This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury. PMID:25518936

  17. Removal of chromium from groundwater using permeable barriers: An aquifer simulation study

    SciTech Connect

    Schmidt, M.D.; Shelton, S.P.

    1994-12-31

    Previous efforts to remediate groundwater contaminated by chromium-bearing industrial wastes have involved post-extraction methods, whereby groundwater is pumped to the surface treated and returned to the aquifer. This practice has proven effective for removing soluble pollutants. However, it is often costly and labor intensive and requires treating large volumes of water. Also, institutional obstacles such as ground and surface water discharge permits and groundwater rights must be considered. An alternative to conventional remediation methods is the in situ permeable barrier process, which intercepts soluble contaminants from solution but allows groundwater to flow through. Trench-based barriers, backfilled with reactive media, result in the direct adsorption of chemical species or the oxidation reduction of chemical species followed by precipitation. Laboratory studies were conducted to determine the technical feasibility of using trench-based media to remove chromium from groundwater. Removal of soluble hexavalent chromium (Cr(VI)) to concentrations less than the maximum contaminant level (MCL) for total chromium in drinking water (0.05 mg/l) was demonstrated with all candidate media in the aquifer simulation model. Adsorption appeared to be the principle mechanism of removal for all candidate media considered. Information gained from experience with the physical model was used in developing a computer generated, 1-D solute transport model to predict the movement of hexavalent chromium in an aquifer system.

  18. Iron hydroxy carbonate formation in zerovalent iron permeable reactive barriers: Characterization and evaluation of phase stability

    SciTech Connect

    Wilkin, Richard T.; Lee, T.R.

    2010-10-22

    Predicting the long-term potential of permeable reactive barriers for treating contaminated groundwater relies on understanding the endpoints of biogeochemical reactions between influent groundwater and the reactive medium. Iron hydroxy carbonate (chukanovite) is frequently observed as a secondary mineral precipitate in granular iron PRBs. Mineralogical characterization was carried out using X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and X-ray absorption spectroscopy on materials collected from three field-based PRBs in the US (East Helena, MT; Elizabeth City, NC; Denver Federal Center, CO). These PRBs were installed to treat a range of contaminants, including chlorinated organics, hexavalent chromium, and arsenic. Results obtained indicate that chukanovite is a prevalent secondary precipitate in the PRBs. Laboratory experiments on high-purity chukanovite separates were carried out to constrain the room-temperature solubility for this mineral. An estimated Gibbs energy of formation ({Delta}{sub f}G{sup o}) for chukanovite is - 1174.4 {+-} 6 kJ/mol. A mineral stability diagram is consistent with observations from the field. Water chemistry from the three reactive barriers falls inside the predicted stability field for chukanovite, at inorganic carbon concentrations intermediate to the stability fields of siderite and ferrous hydroxide. These new data will aid in developing better predictive models of mineral accumulation in zerovalent iron PRBs.

  19. Iron hydroxy carbonate formation in zerovalent iron permeable reactive barriers: characterization and evaluation of phase stability.

    PubMed

    Lee, Tony R; Wilkin, Richard T

    2010-07-30

    Predicting the long-term potential of permeable reactive barriers for treating contaminated groundwater relies on understanding the endpoints of biogeochemical reactions between influent groundwater and the reactive medium. Iron hydroxy carbonate (chukanovite) is frequently observed as a secondary mineral precipitate in granular iron PRBs. Mineralogical characterization was carried out using X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and X-ray absorption spectroscopy on materials collected from three field-based PRBs in the US (East Helena, MT; Elizabeth City, NC; Denver Federal Center, CO). These PRBs were installed to treat a range of contaminants, including chlorinated organics, hexavalent chromium, and arsenic. Results obtained indicate that chukanovite is a prevalent secondary precipitate in the PRBs. Laboratory experiments on high-purity chukanovite separates were carried out to constrain the room-temperature solubility for this mineral. An estimated Gibbs energy of formation (Delta(f)G degrees) for chukanovite is -1174.4 +/- 6 kJ/mol. A mineral stability diagram is consistent with observations from the field. Water chemistry from the three reactive barriers falls inside the predicted stability field for chukanovite, at inorganic carbon concentrations intermediate to the stability fields of siderite and ferrous hydroxide. These new data will aid in developing better predictive models of mineral accumulation in zerovalent iron PRBs. PMID:20554346

  20. A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

    PubMed

    Kumar, Vinod; Bouameur, Jamal-Eddine; Bär, Janina; Rice, Robert H; Hornig-Do, Hue-Tran; Roop, Dennis R; Schwarz, Nicole; Brodesser, Susanne; Thiering, Sören; Leube, Rudolf E; Wiesner, Rudolf J; Vijayaraj, Preethi; Brazel, Christina B; Heller, Sandra; Binder, Hans; Löffler-Wirth, Henry; Seibel, Peter; Magin, Thomas M

    2015-12-01

    Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation. PMID:26644517

  1. A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

    PubMed Central

    Kumar, Vinod; Bouameur, Jamal-Eddine; Bär, Janina; Rice, Robert H.; Hornig-Do, Hue-Tran; Roop, Dennis R.; Schwarz, Nicole; Brodesser, Susanne; Thiering, Sören; Leube, Rudolf E.; Wiesner, Rudolf J.; Vijayaraj, Preethi; Brazel, Christina B.; Heller, Sandra; Binder, Hans; Löffler-Wirth, Henry; Seibel, Peter

    2015-01-01

    Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI−/− and KtyII−/−K8 mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation. PMID:26644517

  2. Tight junction regulates epidermal calcium ion gradient and differentiation

    SciTech Connect

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-03-25

    Research highlights: {yields} We disrupted epidermal tight junction barrier in reconstructed epidermis. {yields} It altered Ca{sup 2+} distribution and consequentially differentiation state as well. {yields} Tight junction should affect epidermal homeostasis by maintaining Ca{sup 2+} gradient. -- Abstract: It is well known that calcium ions (Ca{sup 2+}) induce keratinocyte differentiation. Ca{sup 2+} distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca{sup 2+} gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca{sup 2+} gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca{sup 2+} flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca{sup 2+} gradient.

  3. Transformation of Reactive Iron Minerals in a Permeable Reactive Barrier (Biowall) Used to Treat TCE in Groundwater

    EPA Science Inventory

    Abstract: Iron and sulfur reducing conditions are generally created in permeable reactive barrier (PRB) systems constructed for groundwater treatment, which usually leads to formation of iron sulfide phases. Iron sulfides have been shown to play an important role in degrading ch...

  4. PERMEABLE REACTIVE SUBSURFACE BARRIERS FOR THE INTERCEPTION AND REMEDIATION OF CHLORINATED HYDROCARBON AND CHROMIUM (VI) PLUMES IN GROUND WATER

    EPA Science Inventory

    This document concerns the use of permeable reactive subsurface barriers for the remediation of plumes of chlorinated hydrocarbons and Cr(VI) species in ground water, using zero-valent iron (Fe0) as the reactive substrate. Such systems have undergone thorough laboratory research,...

  5. TREATMENT OF METALS IN GROUND WATER USING AN ORGANIC-BASED SULFATE-REDUCING PERMEABLE REACTIVE BARRIER

    EPA Science Inventory

    A pilot permeable reactive barrier (PRB) consisting of a mixture of leaf compost, zero-valent iron (ZVI) filings, limestone and pea gravel was evaluated at a former phosphate fertilizer manufacturing facility in Charleston, S.C. The PRB is designed to treat arsenic and heavy met...

  6. DESIGN, CONSTRUCTION, AND MONITORING OF THE PERMEABLE REACTIVE BARRIER IN AREA 5 AT DOVER AIR FORCE BASE

    EPA Science Inventory

    The primary objective of this project was to test the performance of two different reactive media in the same aquifer. To satisfy this objective, Battelle designed, constructed, and monitored a pilot-scale permeable reactive barrier (PRB) in Area 5 at Dover Air Force Base, DE. Th...

  7. LONG-TERM PERFORMANCE OF PERMEABLE REACTIVE BARRIERS USING ZERO-VALENT IRON: GEOCHEMICAL AND MICROBIOLOGICAL EFFECTS

    EPA Science Inventory

    Geochemical and microbiological factors that control long-term performance of subsurface permeable reactive barriers were evaluated at the Elizabeth City, NC and the Denver Federal Center, CO sites. These ground water treatment systems use zero-valent iron filings (Peerless Meta...

  8. Fifteen-year Assessment of a Permeable Reactive Barrier for Treatment of Chromate and Trichloroethylene in Groundwater

    EPA Science Inventory

    The fifteen-year performance of a granular iron, permeable reactive barrier (PRB; Elizabeth City, North Carolina) is reviewed with respect to contaminant treatment (hexavalent chromium and trichloroethylene) and hydraulic performance. Due to in-situ treatment of the chromium sou...

  9. SCANNING ELECTRON ANALYSIS OF IRON FILINGS FROM A ZERO-VALENT IRON PERMEABLE BARRIER USED FOR GROUND WATER RESTORATION

    EPA Science Inventory

    Permeable iron reactive barriers have become a popular way to remediate contaminated ground water. Although this technology has been in use for about a decade, there is still little knowledge about long-term performance issues (l). One of the biggest concerns is the corrosion of ...

  10. Evaluation of blood-brain barrier permeability changes in rhesus monkeys and man using 82Rb and positron emission tomography

    SciTech Connect

    Yen, C.K.; Budinger, T.F.

    1981-12-01

    Dynamic positron tomography of the brain with /sup 82/Rb, obtained from a portable generator (/sup 82/Sr (25 days) - /sup 82/Rb (76 sec)), provides a means of studying blood-brain barrier (BBB) permeability in physiological and clinical investigations. The BBB in rhesus monkeys was opened unilaterally be intracarotid infusion of 3 M urea. This osmotic barrier opening allowed entry into the brain of intravenously administered rubidium chloride. The BBB opening was demonstrated noninvasively using /sup 82/Rb and positron emission tomography and corroborated by the accumulation of /sup 86/Rb in tissue samples. Positron emission tomography studies can be repeated every 5 min and indicate that dynamic tomography or static imaging can be used to study BBB permeability changes induced by a wide variety of noxious stimuli. Brain tumors in human subjects are readily detected because of the usual BBB permeability disruption in and around the tumors.

  11. Calcium carbonate-based permeable reactive barriers for iron and manganese groundwater remediation at landfills.

    PubMed

    Wang, Yu; Pleasant, Saraya; Jain, Pradeep; Powell, Jon; Townsend, Timothy

    2016-07-01

    High concentrations of iron (Fe(II)) and manganese (Mn(II)) reductively dissolved from soil minerals have been detected in groundwater monitoring wells near many municipal solid waste landfills. Two in situ permeable reactive barriers (PRBs), comprised of limestone and crushed concrete, were installed downgradient of a closed, unlined landfill in Florida, USA, to remediate groundwater containing high concentrations of these metals. Influent groundwater to the PRBs contained mean Fe and Mn concentrations of approximately 30mg/L and 1.62mg/L, respectively. PRBs were constructed in the shallow aquifer (maximum depth 4.6m below land surface) and groundwater was sampled from a network of nearby monitoring wells to evaluate barrier performance in removing these metals. PRBs significantly (p<0.05) removed dissolved Fe and Mn from influent groundwater; Fe was removed from influent water at average rates of 91% and 95% (by mass) for the limestone and crushed concrete PRBs, respectively, during the first year of the study. The performance of the PRBs declined after 3years of operation, with Fe removal efficiency decreasing to 64% and 61% for limestone and concrete PRBs, respectively. A comparison of water quality in shallow and deep monitoring wells showed a more dramatic performance reduction in the deeper section of the concrete PRB, which was attributed to an influx of sediment into the barrier and settling of particulates from the upper portions of the PRBs. Although removal of Fe and Mn from redox impacts was achieved with the PRBs, the short time frame of effectiveness relative to the duration of a full-scale remediation effort may limit the applicability of these systems at some landfills because of the construction costs required. PMID:26992666

  12. Morphological evidence for a permeability barrier in the testis and spermatic duct of Gymnotus carapo (Teleostei: Gymnotidae).

    PubMed

    Meneguelli De Souza, Lara C; Retamal, Claudio A; Rocha, Gustavo M; Lopez, Maria Luisa

    2015-09-01

    Cell-cell interactions play essential roles in the regulation of gametogenesis. The involvement of junctional complexes in permeability barriers, for example, provides structural and physiological support for male germ-cell development. This study describes morphological characteristics of the reproductive system of Gymnotus carapo, a neo-tropical freshwater fish widely distributed in South and Central America, focusing on the detection of permeability barriers using morphological and biochemical approaches. Ultrastructural analysis of testes treated with the lanthanum nitrate exclusion technique showed that the tracer penetrated the interstitial compartment of the testis, surrounding and appearing within cysts containing spermatogonia and spermatocytes in early stages of meiosis, but was not detected in the spermatid cysts or inside the lumen of spermatogenic tubules. These results suggest the presence of a permeability barrier that is stabilized after meiosis is completed and serves to protect the haploid cells from the vascular system. In the spermatic-duct region, the tracer was obstructed near the lumen of the duct. Junctional complexes and focal tight junctions between adjacent cells were observed in the testis and spermatic duct. Freeze-fracture methods indeed confirmed the presence of tight junctions, which were visualized as parallel rows of individual particles between adjacent cells. More evidence supporting the existence of a permeability barrier was gathered from differences observed in the electrophoretic protein profiles of testis and spermatic-duct fluids compared to blood plasma. Together, these observations demonstrate the existence of a permeability barrier formed by tight junctions in the testis and spermatic duct of G. carapo. PMID:26073744

  13. Abnormal blood–brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI☆☆☆

    PubMed Central

    Cramer, S.P.; Simonsen, H.; Frederiksen, J.L.; Rostrup, E.; Larsson, H.B.W.

    2013-01-01

    Objectives To investigate whether blood–brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics. Methods Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls. Results Permeability measured as Ktrans was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment. Conclusions Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS. PMID:24371801

  14. Comparing the Effect of a Twice-weekly Tacrolimus and Betamethasone Valerate Dose on the Subclinical Epidermal Barrier Defect in Atopic Dermatitis.

    PubMed

    Chittock, John; Brown, Kirsty; Cork, Michael J; Danby, Simon G

    2015-07-01

    The proactive use of topical anti-inflammatory (TAI) therapy to address subclinical inflammation is an effective, contemporary clinical strategy for the management of atopic dermatitis (AD). The interaction of a proactive TAI dose with the subclinical epidermal barrier defect in AD is yet to be determined. A randomised, observer-blind, functional mechanistic study in 17 subjects with quiescent AD was performed to compare the effect of a twice-weekly dose of betamethasone valerate (0.1%) cream (BMVc), against tacrolimus (0.1%) ointment (TACo) on the biophysical and biological properties of the epidermal barrier. Application of BMVc preserved epidermal barrier function and stratum corneum (SC) integrity, but significantly elevated skin-surface pH with concomitant loss of SC cohesion. By contrast, TACo improved SC integrity, exerted an overall hydrating action, and significantly reduced caseinolytic and trypsin-like protease activity. The differential effects reported support the proactive use of TACo to promote reparation of the subclinical barrier defect in AD. PMID:25594610

  15. Raltegravir permeability across blood-tissue barriers and the potential role of drug efflux transporters.

    PubMed

    Hoque, M Tozammel; Kis, Olena; De Rosa, María F; Bendayan, Reina

    2015-05-01

    The objectives of this study were to investigate raltegravir transport across several blood-tissue barrier models and the potential interactions with drug efflux transporters. Raltegravir uptake, accumulation, and permeability were evaluated in vitro in (i) P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1), or MRP4-overexpressing MDA-MDR1 (P-gp), HEK-ABCG2, HeLa-MRP1, or HEK-MRP4 cells, respectively; (ii) cell culture systems of the human blood-brain (hCMEC/D3), mouse blood-testicular (TM4), and human blood-intestinal (Caco-2) barriers; and (iii) rat jejunum and ileum segments using an in situ single-pass intestinal perfusion model. [(3)H]Raltegravir accumulation by MDA-MDR1 (P-gp) and HEK-ABCG2-overexpressing cells was significantly enhanced in the presence of PSC833 {6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-L-valine-cyclosporine}, a P-gp inhibitor, or Ko143 [(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester], a BCRP inhibitor, suggesting the inhibition of a P-gp- or BCRP-mediated efflux process, respectively. Furthermore, [(3)H]raltegravir accumulation by human cerebral microvessel endothelial hCMEC/D3 and mouse Sertoli TM4 cells was significantly increased by PSC833 and Ko143. In human intestinal Caco-2 cells grown on Transwell filters, PSC833, but not Ko143, significantly decreased the [(3)H]raltegravir efflux ratios. In rat intestinal segments, [(3)H]raltegravir in situ permeability was significantly enhanced by the concurrent administration of PSC833 and Ko143. In contrast, in the transporter inhibition assays, raltegravir (10 to 500 μM) did not increase the accumulation of substrate for P-gp (rhodamine-6G), BCRP ([(3)H]mitoxantrone), or MRP1 [2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)] by MDA-MDR1 (P-gp)-, HEK-ABCG2-, or HeLa-MRP1-overexpressing

  16. Application Of Immobilized Sulfate Reducing Bacteria For Permeable Reactive Barriers In Abandoned Coal Mines

    NASA Astrophysics Data System (ADS)

    Kim, K.; Hur, W.; Choi, S.; Min, K.; Baek, H.

    2006-05-01

    The decline of the Korean coal industry has been drastic in production and consumption. This has been resulted mainly from the environmental concern and the collapse of commercial viability, which has eventually necessitated the government to implement the coal industry rationalization policies to reduce coal production and close down uneconomical mines. The overall drainage rates from abandoned coal mines reaches up to 80,000 ton/day. As a measure of controlling the acid mine drainage from abandoned coal mines, reactive materials in the pathways of drainage, designed to intercept and to transform the contaminants into environmentally acceptable forms can be applied at mines with small drainage rates. The main objective of this study is to design a permeable reactive barrier(PRB) to treat low flow and/or low contaminant loads of acid mine drainage. The PRB is comprised of immobilized sulfate reducing bacteria in hard beads and limestone to remove heavy metals and to raise the pH of AMD. A laboratory reactor was used to prepare a mixed culture of sulfate reducing bacteria. The microbes were separated and mixed with biodegradable matrix to form spherical beads. In order to maintain the viability of micro-organisms for a prolonged period, substrates such as saw dust, polysaccharide or glycerol was supplemented for the beads preparation. The strength of beads fortified by powered limestone to control the permeability of PRB. Different mixtures of limestone and the immobilized beads were tested to determine hydraulic conductivity and AMD treatment capacities. The characteristics of the spherical beads at various pH of AMD was investigated.

  17. Impact of mineral fouling on hydraulic behavior of permeable reactive barriers.

    PubMed

    Lin, Li; Benson, Craig H; Lawson, Elizabeth M

    2005-01-01

    This paper describes reactive transport simulations conducted to assess the impact of mineral fouling on the hydraulic behavior of continuous-wall permeable reactive barriers (PRBs) employing granular zero-valent iron (ZVI) in carbonate-rich alluvial aquifers. The reactive transport model included a geochemical algorithm for simulating corrosion and mineral precipitation reactions that have been observed in ZVI PRBs. Results of simulations show that porosity and hydraulic conductivity of the ZVI decrease over time and that flows are redistributed throughout the PRB in response to fouling of the pore space. Under typical conditions, only subtle changes occur within the first 10 years (i.e., duration of the current field experience record with PRBs), and the most significant changes do not occur until the PRB has operated for at least 30 years. However, changes can occur sooner (or later) if the rate at which mineral-forming ions are delivered to the PRB is higher (or lower) than that expected under typical conditions (i.e., due to higher/lower flow rate or inflowing ground water that has higher/lower ionic strength). When the PRB is more permeable than the aquifer, the median Darcy flux in the PRB does not change appreciably over time because the aquifer controls the rate of flow through the PRB. However, seepage velocities in the PRB increase, and residence times decrease, due to porosity reductions caused by accumulation of minerals in the pore space. When fouling becomes extensive, bypassing and reductions in flow rate in the PRB occur. PMID:16029183

  18. Mosquito repellent (pyrethroid-based) induced dysfunction of blood-brain barrier permeability in developing brain.

    PubMed

    Sinha, C; Agrawal, A K; Islam, F; Seth, K; Chaturvedi, R K; Shukla, S; Seth, P K

    2004-02-01

    Pyrethroid-based mosquito repellents (MR) are commonly used to protect humans against mosquito vector. New born babies and children are often exposed to pyrethroids for long periods by the use of liquid vaporizers. Occupational and experimental studies indicate that pyrethroids can cause clinical, biochemical and neurological changes, and that exposure to pyrethroids during organogenesis and early developmental period is especially harmful. The neurotoxicity caused by MR has aroused concern among public regarding their use. In the present study, the effect of exposure of rat pups during early developmental stages to a pyrethroid-based MR (allethrin, 3.6% w/v, 8h per day through inhalation) on blood-brain barrier (BBB) permeability was investigated. Sodium fluororescein (SF) and Evan's blue (EB) were used as micromolecular and macromolecular tracers, respectively. Exposure during prenatal (gestation days 1-20), postnatal (PND1-30) and perinatal (gestation days 1-20 + PND1-30) periods showed significant increase in the brain uptake index (BUI) of SF by 54% (P < 0.01), 70% (P < 0.01), 79% (P < 0.01), respectively. This increase persisted (68%, P < 0.01) even 1 week after withdrawal of exposure (as assessed on PND37). EB did not exhibit significant change in BBB permeability in any of the group. The results suggest that MR inhalation during early prenatal/postnatal/perinatal life may have adverse effects on infants leading to central nervous system (CNS) abnormalities, if a mechanism operates in humans similar to that in rat pups. PMID:15013076

  19. Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

    NASA Astrophysics Data System (ADS)

    Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

    2016-03-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

  20. Evaluation of a permeable reactive barrier technology for use at Rocky Flats Environmental Technology Site (RFETS)

    SciTech Connect

    DWYER,BRIAN P.

    2000-01-01

    Three reactive materials were evaluated at laboratory scale to identify the optimum treatment reagent for use in a Permeable Reactive Barrier Treatment System at Rocky Flats Environmental Technology Site (RFETS). The contaminants of concern (COCS) are uranium, TCE, PCE, carbon tetrachloride, americium, and vinyl chloride. The three reactive media evaluated included high carbon steel iron filings, an iron-silica alloy in the form of a foam aggregate, and a peculiar humic acid based sorbent (Humasorb from Arctech) mixed with sand. Each material was tested in the laboratory at column scale using simulated site water. All three materials showed promise for the 903 Mound Site however, the iron filings were determined to be the least expensive media. In order to validate the laboratory results, the iron filings were further tested at a pilot scale (field columns) using actual site water. Pilot test results were similar to laboratory results; consequently, the iron filings were chosen for the fill-scale demonstration of the reactive barrier technology. Additional design parameters including saturated hydraulic conductivity, treatment residence time, and head loss across the media were also determined and provided to the design team in support of the final design. The final design was completed by the Corps of Engineers in 1997 and the system was constructed in the summer of 1998. The treatment system began fill operation in December, 1998 and despite a few problems has been operational since. Results to date are consistent with the lab and pilot scale findings, i.e., complete removal of the contaminants of concern (COCs) prior to discharge to meet RFETS cleanup requirements. Furthermore, it is fair to say at this point in time that laboratory developed design parameters for the reactive barrier technology are sufficient for fuel scale design; however,the treatment system longevity and the long-term fate of the contaminants are questions that remain unanswered. This

  1. Mixed-species Biofilm Compromises Wound Healing by Disrupting Epidermal Barrier Function

    PubMed Central

    Sinha, Mithun; Ganesh, Kasturi; Chaney, Sarah; Mann, Ethan; Miller, Christina; Khanna, Savita; Bergdall, Valerie K.; Powell, Heather M.; Cook, Charles H.; Gordillo, Gayle M.; Wozniak, Daniel J.; Sen, Chandan K.

    2015-01-01

    In chronic wounds, biofilm infects host tissue for extended periods of time. This work establishes the first chronic pre-clinical model of wound biofilm infection aimed at addressing long-term host response. Although biofilm infected wounds did not show marked differences in wound closure, the repaired skin demonstrated compromised barrier function. This observation is clinically significant because it leads to the notion that even if a biofilm infected wound is closed as observed visually, it may be complicated by the presence of failed skin which is likely to be infected and or further complicated post-closure. Study of underlying mechanisms recognized for the first time biofilm-inducible miR-146a and miR-106b in the host skin wound-edge tissue. These miRs silenced ZO-1 and ZO-2 to compromise tight junction function resulting in leaky skin as measured by transepidermal water loss. Intervention strategies aimed at inhibiting biofilm-inducible miRNAs may be productive in restoring barrier function of host skin. PMID:24771509

  2. The role of the skin barrier in modulating the effects of common skin microbial species on the inflammation, differentiation and proliferation status of epidermal keratinocytes

    PubMed Central

    2013-01-01

    Background Skin resident microbial species are often thought of either as pathogenic or commensal. However, little is known about the role of the skin barrier in modulating their potential for causing disease. To investigate this question we measured the effects of three microbial species commonly found on the skin (Staphylococcus epidermidis, Staphylococcus aureus, and Propionibacterium acnes) on a reconstructed human epidermal model by either applying the bacteria on the model surface (intact barrier) or adding them to the culture medium (simulating barrier breach). Results When added to the medium, all of the tested species induced inflammatory responses and keratinocyte cell death with species-specific potency. P. acnes and S. epidermidis induced specific alterations in the expression of keratinocyte differentiation and proliferation markers, suggesting a barrier reparation response. S. aureus induced complete keratinocyte cell death. On the contrary, topically applied S. epidermidis and P. acnes caused no inflammatory response even when tested at high concentrations, while topical S. aureus induced a weak reaction. None of the tested species were able to alter the expression of keratinocyte differentiation or expression markers, when applied topically. Conclusions We show that the skin barrier prevents the effects of common skin bacteria on epidermal keratinocyte inflammation, differentiation and proliferation and highlight the importance of skin barrier in defending against the pathogenic effects of common skin bacteria. PMID:24245826

  3. Amyloid Triggers Extensive Cerebral Angiogenesis Causing Blood Brain Barrier Permeability and Hypervascularity in Alzheimer's Disease

    PubMed Central

    Biron, Kaan E.; Dickstein, Dara L.; Gopaul, Rayshad; Jefferies, Wilfred A.

    2011-01-01

    Evidence of reduced blood-brain barrier (BBB) integrity preceding other Alzheimer's disease (AD) pathology provides a strong link between cerebrovascular angiopathy and AD. However, the “Vascular hypothesis”, holds that BBB leakiness in AD is likely due to hypoxia and neuroinflammation leading to vascular deterioration and apoptosis. We propose an alternative hypothesis: amyloidogenesis promotes extensive neoangiogenesis leading to increased vascular permeability and subsequent hypervascularization in AD. Cerebrovascular integrity was characterized in Tg2576 AD model mice that overexpress the human amyloid precursor protein (APP) containing the double missense mutations, APPsw, found in a Swedish family, that causes early-onset AD. The expression of tight junction (TJ) proteins, occludin and ZO-1, were examined in conjunction with markers of apoptosis and angiogenesis. In aged Tg2576 AD mice, a significant increase in the incidence of disrupted TJs, compared to age matched wild-type littermates and young mice of both genotypes, was directly linked to an increased microvascular density but not apoptosis, which strongly supports amyloidogenic triggered hypervascularity as the basis for BBB disruption. Hypervascularity in human patients was corroborated in a comparison of postmortem brain tissues from AD and controls. Our results demonstrate that amylodogenesis mediates BBB disruption and leakiness through promoting neoangiogenesis and hypervascularity, resulting in the redistribution of TJs that maintain the barrier and thus, provides a new paradigm for integrating vascular remodeling with the pathophysiology observed in AD. Thus the extensive angiogenesis identified in AD brain, exhibits parallels to the neovascularity evident in the pathophysiology of other diseases such as age-related macular degeneration. PMID:21909359

  4. Permeable Reactive Barriers Designed To Mitigate Eutrophication Alter Bacterial Community Composition and Aquifer Redox Conditions.

    PubMed

    Hiller, Kenly A; Foreman, Kenneth H; Weisman, David; Bowen, Jennifer L

    2015-10-01

    Permeable reactive barriers (PRBs) consist of a labile carbon source that is positioned to intercept nitrate-laden groundwater to prevent eutrophication. Decomposition of carbon in the PRB drives groundwater anoxic, fostering microbial denitrification. Such PRBs are an ideal habitat to examine microbial community structure under high-nitrate, carbon-replete conditions in coastal aquifers. We examined a PRB installed at the Waquoit Bay National Estuarine Research Reserve in Falmouth, MA. Groundwater within and below the PRB was depleted in oxygen compared to groundwater at sites upgradient and at adjacent reference sites. Nitrate concentrations declined from a high of 25 μM upgradient and adjacent to the barrier to <0.1 μM within the PRB. We analyzed the total and active bacterial communities filtered from groundwater flowing through the PRB using amplicons of 16S rRNA and of the 16S rRNA genes. Analysis of the 16S rRNA genes collected from the PRB showed that the total bacterial community had high relative abundances of bacteria thought to have alternative metabolisms, such as fermentation, including candidate phyla OD1, OP3, TM7, and GN02. In contrast, the active bacteria had lower abundances of many of these bacteria, suggesting that the bacterial taxa that differentiate the PRB groundwater community were not actively growing. Among the environmental variables analyzed, dissolved oxygen concentration explained the largest proportion of total community structure. There was, however, no significant correlation between measured environmental parameters and the active microbial community, suggesting that controls on the active portion may differ from the community as a whole. PMID:26231655

  5. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances

    SciTech Connect

    Trnovec, T.; Kallay, Z.; Bezek, S. )

    1990-12-01

    Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultrastructural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. 68 references.

  6. Permeable Reactive Barriers Designed To Mitigate Eutrophication Alter Bacterial Community Composition and Aquifer Redox Conditions

    PubMed Central

    Hiller, Kenly A.; Foreman, Kenneth H.; Weisman, David

    2015-01-01

    Permeable reactive barriers (PRBs) consist of a labile carbon source that is positioned to intercept nitrate-laden groundwater to prevent eutrophication. Decomposition of carbon in the PRB drives groundwater anoxic, fostering microbial denitrification. Such PRBs are an ideal habitat to examine microbial community structure under high-nitrate, carbon-replete conditions in coastal aquifers. We examined a PRB installed at the Waquoit Bay National Estuarine Research Reserve in Falmouth, MA. Groundwater within and below the PRB was depleted in oxygen compared to groundwater at sites upgradient and at adjacent reference sites. Nitrate concentrations declined from a high of 25 μM upgradient and adjacent to the barrier to <0.1 μM within the PRB. We analyzed the total and active bacterial communities filtered from groundwater flowing through the PRB using amplicons of 16S rRNA and of the 16S rRNA genes. Analysis of the 16S rRNA genes collected from the PRB showed that the total bacterial community had high relative abundances of bacteria thought to have alternative metabolisms, such as fermentation, including candidate phyla OD1, OP3, TM7, and GN02. In contrast, the active bacteria had lower abundances of many of these bacteria, suggesting that the bacterial taxa that differentiate the PRB groundwater community were not actively growing. Among the environmental variables analyzed, dissolved oxygen concentration explained the largest proportion of total community structure. There was, however, no significant correlation between measured environmental parameters and the active microbial community, suggesting that controls on the active portion may differ from the community as a whole. PMID:26231655

  7. Insulin increases glomerular filtration barrier permeability through PKGIα-dependent mobilization of BKCa channels in cultured rat podocytes.

    PubMed

    Piwkowska, Agnieszka; Rogacka, Dorota; Audzeyenka, Irena; Kasztan, Małgorzata; Angielski, Stefan; Jankowski, Maciej

    2015-08-01

    Podocytes are highly specialized cells that wrap around glomerular capillaries and comprise a key component of the glomerular filtration barrier. They are uniquely sensitive to insulin; like skeletal muscle and fat cells, they exhibit insulin-stimulated glucose uptake and express glucose transporters. Podocyte insulin signaling is mediated by protein kinase G type I (PKGI), and it leads to changes in glomerular permeability to albumin. Here, we investigated whether large-conductance Ca²⁺-activated K⁺ channels (BKCa) were involved in insulin-mediated, PKGIα-dependent filtration barrier permeability. Insulin-induced glomerular permeability was measured in glomeruli isolated from Wistar rats. Transepithelial albumin flux was measured in cultured rat podocyte monolayers. Expression of BKCa subunits was detected by RT-PCR. BKCa, PKGIα, and upstream protein expression were examined in podocytes with Western blotting and immunofluorescence. The BKCa-PKGIα interaction was assessed with co-immunoprecipitation. RT-PCR showed that primary cultured rat podocytes expressed mRNAs that encoded the pore-forming α subunit and four accessory β subunits of BKCa. The BKCa inhibitor, iberiotoxin (ibTX), abolished insulin-dependent glomerular albumin permeability and PKGI-dependent transepithelial albumin flux. Insulin-evoked albumin permeability across podocyte monolayers was also blocked with BKCa siRNA. Moreover, ibTX blocked insulin-induced disruption of the actin cytoskeleton and changes in the phosphorylation of PKG target proteins, MYPT1 and RhoA. These results indicated that insulin increased filtration barrier permeability through mobilization of BKCa channels via PKGI in cultured rat podocytes. This molecular mechanism may explain podocyte injury and proteinuria in diabetes. PMID:25952906

  8. Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

    PubMed

    Rusanov, Alexander L; Luzgina, Natalia G; Barreto, George E; Aliev, Gjumrakch

    2016-01-01

    In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID:26831260

  9. Mineral Precipitation Upgradient from a Zero-Valent Iron Permeable Reactive Barrier

    SciTech Connect

    Johnson, R. L.; Thoms, R. B.; Johnson, R. O.; Nurmi, J. T.; Tratnyek, Paul G.

    2008-07-01

    Core samples taken from a zero-valent iron permeable reactive barrier (ZVI PRB) at Cornhusker Army Ammunition Plant, Nebraska, were analyzed for physical and chemical characteristics. Precipitates containing iron and sulfide were present at much higher concentrations in native aquifer materials just upgradient of the PRB than in the PRB itself. Sulfur mass balance on core solids coupled with trends in ground water sulfate concentrations indicates that the average ground water flow after 20 months of PRB operation was approximately twenty fold less than the regional ground water velocity. Transport and reaction modeling of the aquifer PRB interface suggests that, at the calculated velocity, both iron and hydrogen could diffuse upgradient against ground water flow and thereby contribute to precipitation in the native aquifer materials. The initial hydraulic conductivity (K) of the native materials is less than that of the PRB and, given the observed precipitation in the upgradient native materials, it is likely that K reduction occurred upgradient to rather than within the PRB. Although not directly implicated, guar gum used during installation of the PRB is believed to have played a role in the precipitation and flow reduction processes by enhancing microbial activity.

  10. Microbial Sulfate Reduction Enhances Arsenic Mobility Downstream of Zerovalent-Iron-Based Permeable Reactive Barrier.

    PubMed

    Kumar, Naresh; Couture, Raoul-Marie; Millot, Romain; Battaglia-Brunet, Fabienne; Rose, Jérôme

    2016-07-19

    We assessed the potential of zerovalent-iron- (Fe(0)) based permeable reactive barrier (PRB) systems for arsenic (As) remediation in the presence or absence of microbial sulfate reduction. We conducted long-term (200 day) flow-through column experiments to investigate the mechanisms of As transformation and mobility in aquifer sediment (in particular, the PRB downstream linkage). Changes in As speciation in the aqueous phase were monitored continuously. Speciation in the solid phase was determined at the end of the experiment using X-ray absorption near-edge structure (XANES) spectroscopy analysis. We identified thio-As species in solution and AsS in solid phase, which suggests that the As(V) was reduced to As(III) and precipitated as AsS under sulfate-reducing conditions and remained as As(V) under abiotic conditions, even with low redox potential and high Fe(II) content (4.5 mM). Our results suggest that the microbial sulfate reduction plays a key role in the mobilization of As from Fe-rich aquifer sediment under anoxic conditions. Furthermore, they illustrate that the upstream-downstream linkage of PRB affects the speciation and mobility of As in downstream aquifer sediment, where up to 47% of total As initially present in the sediment was leached out in the form of mobile thio-As species. PMID:27309856