IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen
Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration. In the treatment of uterine fibroid embolization related pain, the use of emboli...
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Veröffentlicht in: | European journal of pharmaceutical sciences 2011-04, Vol.42 (5), p.489-495 |
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creator | Verret, Valentin Bevilacqua, Claudia Schwartz-Cornil, Isabelle Pelage, Jean-Pierre Wassef, Michel Namur, Julien Bédouet, Laurent Lewis, Andrew L. Martin, Patrice Laurent, Alexandre |
description | Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration.
In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads (
Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines.
Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR).
IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC)
=
4.9,
p
=
0.0009) and ST (ST: FC
=
8.7,
p
=
0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC
=
4.4;
p
=
0.0009). TNFα expression was not significantly different between IBU-BB and BB groups.
Using qPCR
+
microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. Gradient of expression of IL6 suggests diffusion of ibuprofen across the VW into the ST. |
doi_str_mv | 10.1016/j.ejps.2011.02.001 |
format | Article |
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In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads (
Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines.
Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR).
IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC)
=
4.9,
p
=
0.0009) and ST (ST: FC
=
8.7,
p
=
0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC
=
4.4;
p
=
0.0009). TNFα expression was not significantly different between IBU-BB and BB groups.
Using qPCR
+
microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. Gradient of expression of IL6 suggests diffusion of ibuprofen across the VW into the ST.</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2011.02.001</identifier><identifier>PMID: 21329755</identifier><language>eng</language><publisher>Kindlington: Elsevier B.V</publisher><subject>Agricultural sciences ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Biological and medical sciences ; Delayed-Action Preparations ; Drug Delivery Systems - methods ; Drug-delivery ; Embolization ; Female ; Gene Expression - drug effects ; General pharmacology ; Ibuprofen ; Ibuprofen - administration & dosage ; Ibuprofen - pharmacokinetics ; Ibuprofen - therapeutic use ; IL6 ; Interleukin-6 - biosynthesis ; Interleukin-6 - genetics ; Lasers ; Leiomyoma - blood supply ; Leiomyoma - surgery ; Life Sciences ; Medical sciences ; Microdissection ; Microspheres ; Pain, Postoperative - prevention & control ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Quantitative-PCR ; Reverse Transcriptase Polymerase Chain Reaction ; Sheep ; Tissue Distribution ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - genetics ; Uterine Artery - drug effects ; Uterine Artery - immunology ; Uterine Artery - pathology ; Uterine Artery Embolization - methods ; Uterine Neoplasms - blood supply ; Uterine Neoplasms - surgery ; Uterus - drug effects ; Uterus - immunology ; Uterus - pathology</subject><ispartof>European journal of pharmaceutical sciences, 2011-04, Vol.42 (5), p.489-495</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-e099678629b9c7f9ec0e5841f48c81e507731dbc0b6c9bd7e35f524cb8484fd43</citedby><cites>FETCH-LOGICAL-c419t-e099678629b9c7f9ec0e5841f48c81e507731dbc0b6c9bd7e35f524cb8484fd43</cites><orcidid>0000-0003-0423-4624 ; 0000-0002-3485-1765</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0928098711000340$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24129234$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21329755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01000487$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Verret, Valentin</creatorcontrib><creatorcontrib>Bevilacqua, Claudia</creatorcontrib><creatorcontrib>Schwartz-Cornil, Isabelle</creatorcontrib><creatorcontrib>Pelage, Jean-Pierre</creatorcontrib><creatorcontrib>Wassef, Michel</creatorcontrib><creatorcontrib>Namur, Julien</creatorcontrib><creatorcontrib>Bédouet, Laurent</creatorcontrib><creatorcontrib>Lewis, Andrew L.</creatorcontrib><creatorcontrib>Martin, Patrice</creatorcontrib><creatorcontrib>Laurent, Alexandre</creatorcontrib><title>IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration.
In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads (
Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines.
Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR).
IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC)
=
4.9,
p
=
0.0009) and ST (ST: FC
=
8.7,
p
=
0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC
=
4.4;
p
=
0.0009). TNFα expression was not significantly different between IBU-BB and BB groups.
Using qPCR
+
microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. Gradient of expression of IL6 suggests diffusion of ibuprofen across the VW into the ST.</description><subject>Agricultural sciences</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Delayed-Action Preparations</subject><subject>Drug Delivery Systems - methods</subject><subject>Drug-delivery</subject><subject>Embolization</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>General pharmacology</subject><subject>Ibuprofen</subject><subject>Ibuprofen - administration & dosage</subject><subject>Ibuprofen - pharmacokinetics</subject><subject>Ibuprofen - therapeutic use</subject><subject>IL6</subject><subject>Interleukin-6 - biosynthesis</subject><subject>Interleukin-6 - genetics</subject><subject>Lasers</subject><subject>Leiomyoma - blood supply</subject><subject>Leiomyoma - surgery</subject><subject>Life Sciences</subject><subject>Medical sciences</subject><subject>Microdissection</subject><subject>Microspheres</subject><subject>Pain, Postoperative - prevention & control</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Quantitative-PCR</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sheep</subject><subject>Tissue Distribution</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Uterine Artery - drug effects</subject><subject>Uterine Artery - immunology</subject><subject>Uterine Artery - pathology</subject><subject>Uterine Artery Embolization - methods</subject><subject>Uterine Neoplasms - blood supply</subject><subject>Uterine Neoplasms - surgery</subject><subject>Uterus - drug effects</subject><subject>Uterus - immunology</subject><subject>Uterus - pathology</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEotPCC7BA3iDEIuHa-bEtsakq-iONYFPWlmNfU48y8WAnU-AJeGycztDuWNm697vnHvsUxRsKFQXafdxUuNmligGlFbAKgD4rVlRwWQJn8LxYgWSiBCn4SXGa0gYAOsHhZXHCaM0kb9tV8edm3RE9WnL75ZLgz13ElHwYiR_JPl9xSA_dNMcY5tH68TuZfEoz5rqbMBLc9mHwv_W0TN376Y74ft7F4HAsh6AtWtKjtomYMDoft4lY79z8sCS4J_hV8cLpIeHr43lWfLv8fHtxXa6_Xt1cnK9L01A5lQhSdlx0TPbScCfRALaioa4RRlBsgfOa2t5A3xnZW45161rWmF40onG2qc-KDwfdOz2oXfRbHX-poL26Pl-rpQY0_1Mj-J5m9v2BzRZ_5CdPauuTwWHQI4Y5qWyjg1qKRZUdSBNDShHdozQFtYSlNmoJSy1hKWAqh5WH3h7l536L9nHkXzoZeHcEdDJ6cFGPxqcnrqFMsnrZ_unA5bhw7zGqZDyOBq2PaCZlg_-fj79w_LQy</recordid><startdate>20110418</startdate><enddate>20110418</enddate><creator>Verret, Valentin</creator><creator>Bevilacqua, Claudia</creator><creator>Schwartz-Cornil, Isabelle</creator><creator>Pelage, Jean-Pierre</creator><creator>Wassef, Michel</creator><creator>Namur, Julien</creator><creator>Bédouet, Laurent</creator><creator>Lewis, Andrew L.</creator><creator>Martin, Patrice</creator><creator>Laurent, Alexandre</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-0423-4624</orcidid><orcidid>https://orcid.org/0000-0002-3485-1765</orcidid></search><sort><creationdate>20110418</creationdate><title>IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen</title><author>Verret, Valentin ; Bevilacqua, Claudia ; Schwartz-Cornil, Isabelle ; Pelage, Jean-Pierre ; Wassef, Michel ; Namur, Julien ; Bédouet, Laurent ; Lewis, Andrew L. ; Martin, Patrice ; Laurent, Alexandre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-e099678629b9c7f9ec0e5841f48c81e507731dbc0b6c9bd7e35f524cb8484fd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Agricultural sciences</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Delayed-Action Preparations</topic><topic>Drug Delivery Systems - methods</topic><topic>Drug-delivery</topic><topic>Embolization</topic><topic>Female</topic><topic>Gene Expression - drug effects</topic><topic>General pharmacology</topic><topic>Ibuprofen</topic><topic>Ibuprofen - administration & dosage</topic><topic>Ibuprofen - pharmacokinetics</topic><topic>Ibuprofen - therapeutic use</topic><topic>IL6</topic><topic>Interleukin-6 - biosynthesis</topic><topic>Interleukin-6 - genetics</topic><topic>Lasers</topic><topic>Leiomyoma - blood supply</topic><topic>Leiomyoma - surgery</topic><topic>Life Sciences</topic><topic>Medical sciences</topic><topic>Microdissection</topic><topic>Microspheres</topic><topic>Pain, Postoperative - prevention & control</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Quantitative-PCR</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Sheep</topic><topic>Tissue Distribution</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Uterine Artery - drug effects</topic><topic>Uterine Artery - immunology</topic><topic>Uterine Artery - pathology</topic><topic>Uterine Artery Embolization - methods</topic><topic>Uterine Neoplasms - blood supply</topic><topic>Uterine Neoplasms - surgery</topic><topic>Uterus - drug effects</topic><topic>Uterus - immunology</topic><topic>Uterus - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verret, Valentin</creatorcontrib><creatorcontrib>Bevilacqua, Claudia</creatorcontrib><creatorcontrib>Schwartz-Cornil, Isabelle</creatorcontrib><creatorcontrib>Pelage, Jean-Pierre</creatorcontrib><creatorcontrib>Wassef, Michel</creatorcontrib><creatorcontrib>Namur, Julien</creatorcontrib><creatorcontrib>Bédouet, Laurent</creatorcontrib><creatorcontrib>Lewis, Andrew L.</creatorcontrib><creatorcontrib>Martin, Patrice</creatorcontrib><creatorcontrib>Laurent, Alexandre</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verret, Valentin</au><au>Bevilacqua, Claudia</au><au>Schwartz-Cornil, Isabelle</au><au>Pelage, Jean-Pierre</au><au>Wassef, Michel</au><au>Namur, Julien</au><au>Bédouet, Laurent</au><au>Lewis, Andrew L.</au><au>Martin, Patrice</au><au>Laurent, Alexandre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2011-04-18</date><risdate>2011</risdate><volume>42</volume><issue>5</issue><spage>489</spage><epage>495</epage><pages>489-495</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><abstract>Ibuprofen from loaded embolization beads released in tissues and induced over-expression of IL6 beyond the vascular wall, in the surrounding tissues, which confirmed diffusion of the drug in a gradient of concentration.
In the treatment of uterine fibroid embolization related pain, the use of embolics loaded with non-steroidal anti-inflammatory drugs (NSAID) relies on an efficient delivery and impregnation of the embolized tissue. Immuno-labelling and spectroscopic techniques have demonstrated the release of ibuprofen from drug eluting beads (
Wassef et al., 2008; Namur et al., 2009) but failed to demonstrate diffusion of the drug beyond the vascular wall (VW). We investigated whether ibuprofen diffused beyond the VW in surrounding tissues (ST), by tracking its biological effects through the modulation of expression of two main inflammatory cytokines.
Uterine arteries of 6 sheep were embolized with ibuprofen loaded beads (IBU-BB) or non-loaded beads (BB) and sacrificed at one week. On frozen tissue slices, VWs of occluded arteries were isolated from ST using laser capture microdissection. RNA was extracted from VW and ST samples. Gene expression of IL6 and TNFα genes was measured by quantitative real-time PCR (qPCR).
IL6 expression was significantly increased in IBU-BB compared to BB group both in VW (VW: fold-change (FC)
=
4.9,
p
=
0.0009) and ST (ST: FC
=
8.7,
p
=
0.0003). In IBU-BB, IL6 was significantly more expressed in VW than in ST (FC
=
4.4;
p
=
0.0009). TNFα expression was not significantly different between IBU-BB and BB groups.
Using qPCR
+
microdissection was useful to evaluate the spread of the biological effects of drug-loaded systems which attest of the tissular release. This approach can be considered when other drug detection techniques are unsuccessful or difficult to achieve. IL6 can be used as a marker of ibuprofen released by drug eluting beads in uterus. Gradient of expression of IL6 suggests diffusion of ibuprofen across the VW into the ST.</abstract><cop>Kindlington</cop><pub>Elsevier B.V</pub><pmid>21329755</pmid><doi>10.1016/j.ejps.2011.02.001</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-0423-4624</orcidid><orcidid>https://orcid.org/0000-0002-3485-1765</orcidid></addata></record> |
fulltext | fulltext |
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ispartof | European journal of pharmaceutical sciences, 2011-04, Vol.42 (5), p.489-495 |
issn | 0928-0987 1879-0720 |
language | eng |
recordid | cdi_hal_primary_oai_HAL_hal_01000487v1 |
source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Agricultural sciences Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Biological and medical sciences Delayed-Action Preparations Drug Delivery Systems - methods Drug-delivery Embolization Female Gene Expression - drug effects General pharmacology Ibuprofen Ibuprofen - administration & dosage Ibuprofen - pharmacokinetics Ibuprofen - therapeutic use IL6 Interleukin-6 - biosynthesis Interleukin-6 - genetics Lasers Leiomyoma - blood supply Leiomyoma - surgery Life Sciences Medical sciences Microdissection Microspheres Pain, Postoperative - prevention & control Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Quantitative-PCR Reverse Transcriptase Polymerase Chain Reaction Sheep Tissue Distribution Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - genetics Uterine Artery - drug effects Uterine Artery - immunology Uterine Artery - pathology Uterine Artery Embolization - methods Uterine Neoplasms - blood supply Uterine Neoplasms - surgery Uterus - drug effects Uterus - immunology Uterus - pathology |
title | IL6 and TNF expression in vessels and surrounding tissues after embolization with ibuprofen-loaded beads confirms diffusion of ibuprofen |
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