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A Novel Tool to Characterize Paracellular Transport: The APTS–Dextran Ladder

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Purpose

The aim of this work was to develop an easy, manageable, and precise analytic tool to describe the tightness of cell layers by a molecular weight ladder.

Methods

Dextrans were labeled by reductive amination with fluorescent 8-aminopyrene-1,3,6-trisulfonate (APTS). This mixture, including the internal standard diazepam, was used for transport studies in Transwell models using Caco-2, ECV304, and PBMEC/C1–2 cell lines. Samples were analyzed by fluorimetry, capillary electrophoresis, and reverse-phase high-performance liquid chromatography.

Results

Following this approach, a logarithm correlation of R 2 = 0.8958 between transepithelial electrical resistance (TEER) and APTS–dextran permeability was shown. In addition, a TEER-dependent permeability pattern could be observed including each single fraction from free APTS, APTS–glucose up to APTS–dextran consisting of 35 glucose units. The TEER-independent permeability coefficients of diazepam and confocal laser scanning microscopy images confirmed the paracellular transport of APTS–dextran.

Conclusions

All in all, the developed APTS–dextran ladder is a useful tool to characterize cell layer tightness and especially to describe paracellular transport ways and the extent of leakiness of cell layers (for blood–brain barrier or intestinal studies) over time—applying a wide array from smaller to larger molecules at the same time to refine TEER, sucrose, or Evans blue measurements.

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Abbreviations

ACM:

astrocyte conditioned medium

APTS:

8-aminopyrene-1,3,6-trisulfonate

BBB:

blood–brain barrier

BMECs:

brain microvascular endothelial cells

CLSM:

confocal laser scanning microscopy

FD:

FITC dextran

FITC:

fluorescein isothiocyanate

LIF detector:

laser-induced fluorescence detector

P-gP:

P-glycoprotein

TEER:

transendothelial electrical resistance for studies with cell lines ECV304 and PBMEC/C1–2, transepithelial electrical resistance in case of Caco-2

vWF:

von Willebrand factor

γ-GT:

γ-glutamyltransferase

References

  1. W. M. Partridge (1998) Introduction to the Blood–Brain Barrier Cambridge University Press Cambridge

    Google Scholar 

  2. I. J. Hidalgo T. J. Raub R. T. Borchardt (1989) ArticleTitleCharacterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability Gastroenterology 96 736–749 Occurrence Handle2914637 Occurrence Handle1:STN:280:BiaC387jvFQ%3D

    PubMed  CAS  Google Scholar 

  3. Y. Liu C. Anthony Hunt (2005) ArticleTitleStudies of intestinal drug transport using an in silico epithelio-mimetic device Biosystems 82 154–167 Occurrence Handle16135397 Occurrence Handle1:CAS:528:DC%2BD2MXhtFKnurnE Occurrence Handle10.1016/j.biosystems.2005.06.008

    Article  PubMed  CAS  Google Scholar 

  4. J. B. Bree ParticleVan A. G. Boer Particlede M. Danhof L. A. Ginsel D. D. Breimer (1988) ArticleTitleCharacterization of an “in vitro” blood–brain barrier: effects of molecular size and lipophilicity on cerebrovascular endothelial transport rates of drugs J. Pharmacol. Exp. Ther. 247 1233–1239 Occurrence Handle3204515

    PubMed  Google Scholar 

  5. M. Boveri V. Berezowski A. Price S. Slupek A. M. Lenfant C. Benaud T. Hartung R. Cecchelli P. Prieto M. P. Dehouck (2005) ArticleTitleInduction of blood–brain barrier properties in cultured brain capillary endothelial cells: comparison between primary glial cells and C6 cell line Glia 51 187–198 Occurrence Handle15800928 Occurrence Handle10.1002/glia.20189

    Article  PubMed  Google Scholar 

  6. LK. Hayashi S. Nakao R. Nakaoke S. Nakagawa N. Kitagawa M. Niwa (2004) ArticleTitleEffects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier Regul. Pept. 123 77–83 Occurrence Handle15518896 Occurrence Handle1:CAS:528:DC%2BD2cXptFOlt7c%3D Occurrence Handle10.1016/j.regpep.2004.05.023

    Article  PubMed  CAS  Google Scholar 

  7. Y. Ban L. J. Rizollo (1997) ArticleTitleA culture model of development reveals multiple properties of RPE tight junctions Mol. Vis. 3 18 Occurrence Handle9479009 Occurrence Handle1:STN:280:DyaK1c7kvVWhtw%3D%3D

    PubMed  CAS  Google Scholar 

  8. P. G. Bannon M. J. Kim R. T. Dean J. Dawes (1995) ArticleTitleAugmentation of vascular endothelial barrier function by heparin and low molecular weight heparin Thromb. Haemost. 73 706–712 Occurrence Handle7495083 Occurrence Handle1:CAS:528:DyaK2MXltFOntr0%3D

    PubMed  CAS  Google Scholar 

  9. A. R. Hilgers R. A. Conradi P. S. Burton (1990) ArticleTitleCaco-2 cell monolayers as a model for drug transport across the intestinal mucosa Pharm. Res. 7 902–910 Occurrence Handle2235888 Occurrence Handle1:CAS:528:DyaK3cXlvVCitr4%3D Occurrence Handle10.1023/A:1015937605100

    Article  PubMed  CAS  Google Scholar 

  10. Center for Drug Evaluation and Research. Food and Drug Administration. Guidance for Industry: Waiver of in Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. http://www.fda.gov/cder/guidance/3618fnl.pdf. (accessed 08/15/05).

  11. D. A. Volpe A. B. Ciavarella E. B. Asafu-Adjaye C. D. Ellison P. J. Faustino L. X. Yu (2001) ArticleTitleMethod suitability of a Caco-2 cell model for drug permeability classification AAPS Pharm. Sci. 3 S1 Occurrence Handle10.1208/ps030101

    Article  Google Scholar 

  12. D. A. Volpe (2004) ArticleTitlePermeability classification of representative fluoroquinolones by a cell culture method AAPS Pharm. Sci. 6 E13 Occurrence Handle10.1208/ps060213

    Article  Google Scholar 

  13. G. Wilson I. F. Hassan C. J. Dix I. Williamson R. Shah M. Mackay P. Artursson (1990) ArticleTitleTransport and permeability properties of human Caco-2 cells: an in vitro model of the intestinal epithelial cell barrier J. Control. Release 11 25–40 Occurrence Handle1:CAS:528:DyaK3cXit12hu78%3D Occurrence Handle10.1016/0168-3659(90)90118-D

    Article  CAS  Google Scholar 

  14. F. Delie W. Rubas (1997) ArticleTitleA human colonic cell line sharing similarities with enterocytes as a model to examine oral absorption: advantages and limitations of the Caco-2 model Crit. Rev. Ther. Drug Carrier Syst. 14 221–286 Occurrence Handle9282267 Occurrence Handle1:CAS:528:DyaK2sXlvFeru7c%3D

    PubMed  CAS  Google Scholar 

  15. F. Joo (1996) ArticleTitleEndothelial cells of the brain and other organ systems: some similarities and differences Prog. Neurobiol. 48 255–273 Occurrence Handle8735879 Occurrence Handle1:CAS:528:DyaK28Xjs1Sgu7Y%3D Occurrence Handle10.1016/0301-0082(95)00046-1

    Article  PubMed  CAS  Google Scholar 

  16. A. M. Butt H. C. Jones N. J. Abbott (1990) ArticleTitleElectrical resistance across the blood–brain barrier in anaesthetized rats: a developmental study J. Physiol. 429 47–62 Occurrence Handle2277354 Occurrence Handle1:STN:280:By6C3MnlsFc%3D

    PubMed  CAS  Google Scholar 

  17. C. Crone O. Christensen (1981) ArticleTitleElectrical resistance of a capillary endothelium J. Gen. Physiol. 77 349–371 Occurrence Handle7241087 Occurrence Handle1:CAS:528:DyaL3MXitVGrt78%3D Occurrence Handle10.1085/jgp.77.4.349

    Article  PubMed  CAS  Google Scholar 

  18. K. Takahashi Y. Sawasaki J. J. Hata K. Mukai T. Goto (1990) ArticleTitleSpontaneous transformation and immortalization of human endothelial cells In Vitro Cell. Dev. Biol. 25 265–274

    Google Scholar 

  19. R. D. Hurst I. B. Fritz (1996) ArticleTitleProperties of an immortalized vascular endothelial/glioma cell co-culture model of the blood–brain barrier J. Cell. Physiol. 167 81–88 Occurrence Handle8698844 Occurrence Handle1:CAS:528:DyaK28XhvVSntLY%3D Occurrence Handle10.1002/(SICI)1097-4652(199604)167:1<81::AID-JCP9>3.0.CO;2-8

    Article  PubMed  CAS  Google Scholar 

  20. A. S. Easton N. J. Abbott (2002) ArticleTitleBradykinin increases permeability by calcium and 5-lipoxygenase in ECV304/C6 cell culture model of the blood–brain barrier Brain Res. 953 157–169 Occurrence Handle12384249 Occurrence Handle1:CAS:528:DC%2BD38XnvVOlu7k%3D Occurrence Handle10.1016/S0006-8993(02)03281-X

    Article  PubMed  CAS  Google Scholar 

  21. R. C. Janzer M. C. Raff (1987) ArticleTitleAstrocytes induce blood–brain barrier properties in endothelial cells Nature 325 253–257 Occurrence Handle3543687 Occurrence Handle1:STN:280:BiiC3MrnslQ%3D Occurrence Handle10.1038/325253a0

    Article  PubMed  CAS  Google Scholar 

  22. S. Kuchler-Bopp J. P. Delaunoy J. C. Artault M. Zaepfel J. B. Dietrich (1999) ArticleTitleAstrocytes induce several blood–brain barrier properties in non-neural endothelial cells NeuroReport 10 1347–1353 Occurrence Handle10363951 Occurrence Handle1:STN:280:DyaK1M3ptVKiuw%3D%3D

    PubMed  CAS  Google Scholar 

  23. D. E. M. Dolman P. Anderson C. Rollison N. J. Abbott (1998) ArticleTitleCharacterisation of a new in vitro model of the blood–brain barrier (BBB) J. Physiol. 505 56–57

    Google Scholar 

  24. R. Lauer R. Bauer B. Linz F. Pittner G. A. Peschek G. Ecker P. Friedl C. R. Noe (2004) ArticleTitleDevelopment of an in vitro blood–brain barrier model based on immortalized porcine brain microvascular endothelial cells Farmaco 59 133–137 Occurrence Handle14871505 Occurrence Handle1:CAS:528:DC%2BD2cXhtFWlsLY%3D Occurrence Handle10.1016/j.farmac.2003.11.007

    Article  PubMed  CAS  Google Scholar 

  25. M. Teifel P. Friedl (1996) ArticleTitleEstablishment of the permanent microvascular endothelial cell line PBMEC/C1–2 from porcine brains Exp. Cell Res. 228 50–57 Occurrence Handle8892970 Occurrence Handle1:CAS:528:DyaK28XntlKmsb0%3D Occurrence Handle10.1006/excr.1996.0298

    Article  PubMed  CAS  Google Scholar 

  26. K. Suda B. Rothen-Rutishauser M. Günthert H. Wunderli-Allenspach (2001) ArticleTitlePhenotypic characterization of human umbilical vein endothelial (ECV304) and urinary carcinoma (T24) cells: endothelial versus epithelial features In Vitro Cell. Dev. Biol. Anim. 37 505–514 Occurrence Handle11669284 Occurrence Handle1:STN:280:DC%2BD3Mrms1Wqsg%3D%3D Occurrence Handle10.1290/1071-2690(2001)037<0505:PCOHUV>2.0.CO;2

    Article  PubMed  CAS  Google Scholar 

  27. G. Vanier M. Segura P. Friedl S. Lacouture M. Gottschalk (2004) ArticleTitleInvasion of porcine brain microvascular endothelial cells by Streptococcus suis serotype 2 Infect. Immun. 72 1441–1449 Occurrence Handle14977949 Occurrence Handle1:CAS:528:DC%2BD2cXhvVChur8%3D Occurrence Handle10.1128/IAI.72.3.1441-1449.2004

    Article  PubMed  CAS  Google Scholar 

  28. G. Vanier A. Szczotka P. Friedl S. Lacouture M. Jacques M. Gottschalk (2006) ArticleTitle Haemophilus parasuis invades porcine brain microvascular endothelial cells Microbiology 152 135–142 Occurrence Handle16385123 Occurrence Handle1:CAS:528:DC%2BD28XntVyksg%3D%3D Occurrence Handle10.1099/mic.0.28312-0

    Article  PubMed  CAS  Google Scholar 

  29. P. Benda J. Lightbody G. Sato L. Levine W. Sweet (1968) ArticleTitleDifferential rat glial cell strain in tissue culture Science 161 370–371 Occurrence Handle4873531 Occurrence Handle1:STN:280:CCeA383lvFM%3D

    PubMed  CAS  Google Scholar 

  30. F.-T. A. Chen R. A. Evangelista (1995) ArticleTitleAnalysis of mono- and oligosaccharide isomers derivatized with 9-aminopyrene-1,4,6-trisulfonate by capillary electrophoresis with laser-induced fluorescence Anal. Biochem. 230 273–280 Occurrence Handle7503418 Occurrence Handle1:CAS:528:DyaK2MXot1Oitr4%3D Occurrence Handle10.1006/abio.1995.1474

    Article  PubMed  CAS  Google Scholar 

  31. A. Guttman F.-T. A. Chen R. A. Evangelista N. Cooke (1996) ArticleTitleHigh-resolution capillary gel electrophoresis of reducing oligosaccharides labeled with 1-aminopyrene-3,6,8,-trisulfonate Anal. Biochem. 233 234–242 Occurrence Handle8789724 Occurrence Handle1:CAS:528:DyaK28XmtVWrsA%3D%3D Occurrence Handle10.1006/abio.1996.0034

    Article  PubMed  CAS  Google Scholar 

  32. F.-T. A. Chen (2003) Characterization of oligosaccharides from starch, dextran, cellulose and glycoproteins by capillary electrophoresis P. Thibault S. Honda (Eds) Methods in Molecular Biology, Vol. 213 Humana Press Inc. Totowa, NJ 105–120

    Google Scholar 

  33. W. Neuhaus J. Trzeciak R. Lauer B. Lachmann C. R. Noe (2006) ArticleTitleAPTS-labeled dextran ladder: a novel tool to characterize cell layer tightness J. Pharm. Biomed. Anal. 40 1035–1039 Occurrence Handle16242879 Occurrence Handle1:CAS:528:DC%2BD28Xhs1Sgtrs%3D Occurrence Handle10.1016/j.jpba.2005.08.023

    Article  PubMed  CAS  Google Scholar 

  34. R. M. Arendt D. J. Greenblatt D. C. Liebisch M. D. Luu S. M. Paul (1987) ArticleTitleDeterminants of benzodiazepine brain uptake: lipophilicity versus binding affinity Psychopharmacology 93 72–76 Occurrence Handle2888155 Occurrence Handle1:CAS:528:DyaL2sXlt1KntLg%3D

    PubMed  CAS  Google Scholar 

  35. R. K. Dubey C. B. McAllister M. Inoue G. R. Wilkinson (1989) ArticleTitlePlasma binding and transport of diazepam across the blood–brain barrier. No evidence for in vivo enhanced dissociation J. Clin. Invest. 84 1155–1159 Occurrence Handle2794052 Occurrence Handle1:CAS:528:DyaL1MXmtVyltL4%3D

    PubMed  CAS  Google Scholar 

  36. J. N. Cogburn M. G. Donovan C. S. Schasteen (1991) ArticleTitleA model of human small intestinal absorptive cells. 1. Transport barrier Pharm. Res. 8 210–216 Occurrence Handle2023869 Occurrence Handle1:CAS:528:DyaK3MXhtF2isLs%3D Occurrence Handle10.1023/A:1015844104539

    Article  PubMed  CAS  Google Scholar 

  37. C. R. Noe B. Lachmann S. Mollenbeck P. Richter (1999) ArticleTitleDetermination of reducing sugars in selected beverages by capillary electrophoresis Eur. Food Res. Technol. 208 148–152 Occurrence Handle1:CAS:528:DyaK1MXjvVClurw%3D

    CAS  Google Scholar 

  38. C. R. Noe J. Freissmuth D. Rothley B. Lachmann P. Richter (1996) ArticleTitleCapillary zone electrophoresis of carbohydrate mixtures Pharmazie 51 868–873 Occurrence Handle1:CAS:528:DyaK28Xntlektrw%3D

    CAS  Google Scholar 

  39. C. R. Noe J. Freissmuth (1995) ArticleTitleCapillary zone electrophoresis of aldose enantiomers: separation after derivatization with S-(−)-1-phenylethylamine J. Chromatogr., A 704 503–512 Occurrence Handle1:CAS:528:DyaK2MXmtVyksrc%3D Occurrence Handle10.1016/0021-9673(95)00237-H

    Article  CAS  Google Scholar 

  40. P. J. Gaillard A. G. Boer Particlede (2000) ArticleTitleRelationship between permeability status of the blood–brain barrier and in vitro permeability coefficient of a drug Eur. J. Pharm. Sci. 12 95–102 Occurrence Handle11102736 Occurrence Handle1:CAS:528:DC%2BD3cXotlGjsLs%3D Occurrence Handle10.1016/S0928-0987(00)00152-4

    Article  PubMed  CAS  Google Scholar 

  41. J. Brown S. J. Reading S. Jones C. J. Fitchett J. Howl A. Martin C. L. Longland F. Michelangeli Y. E. Dubrova C. A. Brown (2000) ArticleTitleCritical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83 Lab. Invest. 80 37–45 Occurrence Handle10653001 Occurrence Handle1:CAS:528:DC%2BD3cXhtVeqsrc%3D Occurrence Handle10.1038/labinvest.3780006

    Article  PubMed  CAS  Google Scholar 

  42. H. G. Drexler H. Quentmeier W. G. Dirks R. A. MacLeod (2002) ArticleTitleBladder carcinoma cell line ECV304 is not a model system for endothelial cells In Vitro Cell. Dev. Biol. Anim 38 185–186 Occurrence Handle12197766 Occurrence Handle10.1290/1071-2690(2002)038<0185:BCCLEI>2.0.CO;2

    Article  PubMed  Google Scholar 

  43. T. Takeda Y. Yamashita S. Shimazaki Y. Mitsui (1992) ArticleTitleHistamine decreases the permeability of an endothelial cell monolayer by stimulating cyclic AMP production through the H2-receptor J. Cell. Sci. 101 745–750 Occurrence Handle1326566 Occurrence Handle1:CAS:528:DyaK38Xkt1Wjsb8%3D

    PubMed  CAS  Google Scholar 

  44. N. Borges F. Shi I. Azevado K. L. Audus (1994) ArticleTitleChanges in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs Eur. J. Pharmacol. 269 243–248 Occurrence Handle7851500 Occurrence Handle1:CAS:528:DyaK2cXmslaku7c%3D Occurrence Handle10.1016/0922-4106(94)90092-2

    Article  PubMed  CAS  Google Scholar 

  45. S. Fischer D. Renz W. Schaper G. F. Karliczek (1996) ArticleTitleEffects of barbiturates on hypoxic cultures of brain derived microvascular endothelial cells Brain Res. 707 47–53 Occurrence Handle8866712 Occurrence Handle1:CAS:528:DyaK28XovFGgtg%3D%3D Occurrence Handle10.1016/0006-8993(95)01219-2

    Article  PubMed  CAS  Google Scholar 

  46. S. Fischer D. Renz W. Schaper G. F. Karliczek (1995) ArticleTitle In vitro effects of fentanyl, methohexital, and thiopental on brain endothelial permeability Anesthesiology 82 451–458 Occurrence Handle7856903 Occurrence Handle1:CAS:528:DyaK2MXksFant7w%3D Occurrence Handle10.1097/00000542-199502000-00015

    Article  PubMed  CAS  Google Scholar 

  47. J. L. Albert J. P. Boyle J. A. Roberts R. A. Challiss S. E. Gubby M. R. Boarder (1997) ArticleTitleRegulation of brain capillary endothelial cells by P2Y receptors coupled to Ca2+, phospholipase C and mitogen-activated protein kinase Br. J. Pharmacol. 122 935–941 Occurrence Handle9384512 Occurrence Handle1:CAS:528:DyaK2sXnt1Wmurc%3D Occurrence Handle10.1038/sj.bjp.0701453

    Article  PubMed  CAS  Google Scholar 

  48. A. G. Boer Particlede D. D. Breimer (1998) Cytokines and blood–brain barrier permeability H. S. Sharma J. Westman (Eds) Progress in Brain Research Elsevier Amsterdam 425–451

    Google Scholar 

  49. R. D. Hurst J. B. Clark (1998) ArticleTitleAlterations in transendothelial electrical resistance by vasoactive agonists and cyclic AMP in a blood–brain barrier model system Neurochem. Res. 23 149–154 Occurrence Handle9475508 Occurrence Handle1:CAS:528:DyaK1cXosVyrsA%3D%3D Occurrence Handle10.1023/A:1022420606634

    Article  PubMed  CAS  Google Scholar 

  50. J. L. Madara (1998) ArticleTitleRegulation of the movement of solutes across tight junctions Annu. Rev. Physiol. 60 143–159 Occurrence Handle9558458 Occurrence Handle1:CAS:528:DyaK1cXitVOhs7s%3D Occurrence Handle10.1146/annurev.physiol.60.1.143

    Article  PubMed  CAS  Google Scholar 

  51. B. Tewes H. Franke S. Hellwig D. Hoheisel S. Decker D. Griesche T. Tilling J. Wegener H. J. Galla (1997) Preparation of endothelial cells in primary cultures obtained from the brains of 6-month-old pigs A. G. Boer Particlede W. Sutanto (Eds) Drug Transport Across the Blood Brain Barrier: in Vitro and in Vivo Techniques Harwood Academic Publishers Amsterdam 91–97

    Google Scholar 

  52. H. Suzuki O. Müller A. Guttman B. L. Karger (1997) ArticleTitleAnalysis of 1-aminopyrene-3,6,8-trisulfonate-derivatized oligosaccharides by capillary electrophoresis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry Anal. Chem. 69 4554–4559 Occurrence Handle9375516 Occurrence Handle1:CAS:528:DyaK2sXnt1Shu7k%3D Occurrence Handle10.1021/ac970090z

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We gratefully acknowledge the financial support provided by the Austrian Science Fund FWF (project P–14582 CHE).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, University of Vienna, Pharmacy Center, Althanstrasse 14, A-1090, Vienna, Austria

    Winfried Neuhaus, Joanna Trzeciak, Bodo Lachmann & Christian R. Noe

  2. Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Pharmacy Center, Althanstrasse 14, A-1090, Vienna, Austria

    Elisabeth Bogner, Michael Wirth & Franz Gabor

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  1. Winfried Neuhaus
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  2. Elisabeth Bogner
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  7. Christian R. Noe
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Neuhaus, W., Bogner, E., Wirth, M. et al. A Novel Tool to Characterize Paracellular Transport: The APTS–Dextran Ladder. Pharm Res 23, 1491–1501 (2006). https://doi.org/10.1007/s11095-006-0256-z

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