Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13
Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a...
Gespeichert in:
| Veröffentlicht in: | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2012-09, Vol.64 (6), p.543-547 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 547 |
|---|---|
| container_issue | 6 |
| container_start_page | 543 |
| container_title | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie |
| container_volume | 64 |
| creator | Cao, Yi-Zhan Tu, Yan-Yang Chen, Xiang Wang, Bo-Liang Zhong, Yue-Xia Liu, Ming-Hua |
| description | Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.
Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5ml), cecal ligation and puncture (CLP) plus PBS (5ml), CLP plus UTI (5000U/kg), CLP plus UTI (10,000U/kg), CLP plus UTI (20,000U/kg) and sham-operation plus UTI (10,000U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.
The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.
Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats. |
| doi_str_mv | 10.1016/j.etp.2010.11.011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1031160775</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0940299310002022</els_id><sourcerecordid>1031160775</sourcerecordid><originalsourceid>FETCH-LOGICAL-c407t-3c3078f57e874578f167a978d36de5f1223a8fb97c0365bd5d053fe1a9ea0ef33</originalsourceid><addsrcrecordid>eNp9kcGO0zAQhi0EYsvCA3CBXJC4pMzEcZzACa1YqFQBEtuz5Trj4ipxip2sxJkn4kV4JhzShRsn__Z884_1D2NPEdYIWL06rmk8rQuY77gGxHtshRXWOZac32craErIi6bhF-xRjEeAAhqBD9lFgSiaspEr9uNzGEYyo7uljKxNKhtstuuc13HUo_OZPmjn45j1U3Cesn5oqYszFOkUXXydbfxXt3ejG_z8evPxOv_1M9O-zTbbvPoj9HToyc92C5MKCHcI8sfsgdVdpCfn85Ltrt_dXH3It5_eb67ebnNTghxzbjjI2gpJtSxFUlhJ3ci65VVLwmJRcF3bfSMN8ErsW9GC4JZQN6SBLOeX7OXiewrDt4niqHoXDXWd9jRMUSFwxAqkFAnFBTVhiDGQVafgeh2-J0jN2aujStmrOXuFqFL2qefZ2X7a99T-7bgLOwEvzoCORnc2aG9c_MdVyQ3rKnHPF87qQelDSMzuS6oJSINFCWUi3ixEWgXdOgoqGkfeUOtCWqFqB_efj_4Gg1epVg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1031160775</pqid></control><display><type>article</type><title>Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Cao, Yi-Zhan ; Tu, Yan-Yang ; Chen, Xiang ; Wang, Bo-Liang ; Zhong, Yue-Xia ; Liu, Ming-Hua</creator><creatorcontrib>Cao, Yi-Zhan ; Tu, Yan-Yang ; Chen, Xiang ; Wang, Bo-Liang ; Zhong, Yue-Xia ; Liu, Ming-Hua</creatorcontrib><description>Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.
Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5ml), cecal ligation and puncture (CLP) plus PBS (5ml), CLP plus UTI (5000U/kg), CLP plus UTI (10,000U/kg), CLP plus UTI (20,000U/kg) and sham-operation plus UTI (10,000U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.
The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.
Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.</description><identifier>ISSN: 0940-2993</identifier><identifier>EISSN: 1618-1433</identifier><identifier>DOI: 10.1016/j.etp.2010.11.011</identifier><identifier>PMID: 21159497</identifier><language>eng</language><publisher>Munich: Elsevier GmbH</publisher><subject>animal models ; Animals ; Anti-Inflammatory Agents - pharmacology ; Bacterial diseases ; Bacterial sepsis ; Biological and medical sciences ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins - pharmacology ; Human bacterial diseases ; humans ; Infectious diseases ; inflammation ; Interleukin-1 - biosynthesis ; Interleukin-10 ; Interleukin-10 - biosynthesis ; Interleukin-13 ; Interleukin-6 ; Interleukin-6 - biosynthesis ; intestines ; intraperitoneal injection ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; necrosis ; pathogenesis ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; patients ; protective effect ; proteinase inhibitors ; Rats ; Rats, Wistar ; Sepsis ; sepsis (infection) ; Sepsis - immunology ; Sepsis - prevention & control ; Trypsin Inhibitors - pharmacology ; tumor necrosis factor-alpha ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor necrosis factor-α ; Ulinastatin</subject><ispartof>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, 2012-09, Vol.64 (6), p.543-547</ispartof><rights>2010 Elsevier GmbH</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-3c3078f57e874578f167a978d36de5f1223a8fb97c0365bd5d053fe1a9ea0ef33</citedby><cites>FETCH-LOGICAL-c407t-3c3078f57e874578f167a978d36de5f1223a8fb97c0365bd5d053fe1a9ea0ef33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.etp.2010.11.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26201186$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21159497$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Yi-Zhan</creatorcontrib><creatorcontrib>Tu, Yan-Yang</creatorcontrib><creatorcontrib>Chen, Xiang</creatorcontrib><creatorcontrib>Wang, Bo-Liang</creatorcontrib><creatorcontrib>Zhong, Yue-Xia</creatorcontrib><creatorcontrib>Liu, Ming-Hua</creatorcontrib><title>Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13</title><title>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</title><addtitle>Exp Toxicol Pathol</addtitle><description>Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.
Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5ml), cecal ligation and puncture (CLP) plus PBS (5ml), CLP plus UTI (5000U/kg), CLP plus UTI (10,000U/kg), CLP plus UTI (20,000U/kg) and sham-operation plus UTI (10,000U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.
The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.
Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.</description><subject>animal models</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Bacterial diseases</subject><subject>Bacterial sepsis</subject><subject>Biological and medical sciences</subject><subject>Disease Models, Animal</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Glycoproteins - pharmacology</subject><subject>Human bacterial diseases</subject><subject>humans</subject><subject>Infectious diseases</subject><subject>inflammation</subject><subject>Interleukin-1 - biosynthesis</subject><subject>Interleukin-10</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-13</subject><subject>Interleukin-6</subject><subject>Interleukin-6 - biosynthesis</subject><subject>intestines</subject><subject>intraperitoneal injection</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>necrosis</subject><subject>pathogenesis</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>patients</subject><subject>protective effect</subject><subject>proteinase inhibitors</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sepsis</subject><subject>sepsis (infection)</subject><subject>Sepsis - immunology</subject><subject>Sepsis - prevention & control</subject><subject>Trypsin Inhibitors - pharmacology</subject><subject>tumor necrosis factor-alpha</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor necrosis factor-α</subject><subject>Ulinastatin</subject><issn>0940-2993</issn><issn>1618-1433</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO0zAQhi0EYsvCA3CBXJC4pMzEcZzACa1YqFQBEtuz5Trj4ipxip2sxJkn4kV4JhzShRsn__Z884_1D2NPEdYIWL06rmk8rQuY77gGxHtshRXWOZac32craErIi6bhF-xRjEeAAhqBD9lFgSiaspEr9uNzGEYyo7uljKxNKhtstuuc13HUo_OZPmjn45j1U3Cesn5oqYszFOkUXXydbfxXt3ejG_z8evPxOv_1M9O-zTbbvPoj9HToyc92C5MKCHcI8sfsgdVdpCfn85Ltrt_dXH3It5_eb67ebnNTghxzbjjI2gpJtSxFUlhJ3ci65VVLwmJRcF3bfSMN8ErsW9GC4JZQN6SBLOeX7OXiewrDt4niqHoXDXWd9jRMUSFwxAqkFAnFBTVhiDGQVafgeh2-J0jN2aujStmrOXuFqFL2qefZ2X7a99T-7bgLOwEvzoCORnc2aG9c_MdVyQ3rKnHPF87qQelDSMzuS6oJSINFCWUi3ixEWgXdOgoqGkfeUOtCWqFqB_efj_4Gg1epVg</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Cao, Yi-Zhan</creator><creator>Tu, Yan-Yang</creator><creator>Chen, Xiang</creator><creator>Wang, Bo-Liang</creator><creator>Zhong, Yue-Xia</creator><creator>Liu, Ming-Hua</creator><general>Elsevier GmbH</general><general>Elsevier</general><scope>FBQ</scope><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></search><sort><creationdate>20120901</creationdate><title>Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13</title><author>Cao, Yi-Zhan ; Tu, Yan-Yang ; Chen, Xiang ; Wang, Bo-Liang ; Zhong, Yue-Xia ; Liu, Ming-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-3c3078f57e874578f167a978d36de5f1223a8fb97c0365bd5d053fe1a9ea0ef33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>animal models</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Bacterial diseases</topic><topic>Bacterial sepsis</topic><topic>Biological and medical sciences</topic><topic>Disease Models, Animal</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Glycoproteins - pharmacology</topic><topic>Human bacterial diseases</topic><topic>humans</topic><topic>Infectious diseases</topic><topic>inflammation</topic><topic>Interleukin-1 - biosynthesis</topic><topic>Interleukin-10</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-13</topic><topic>Interleukin-6</topic><topic>Interleukin-6 - biosynthesis</topic><topic>intestines</topic><topic>intraperitoneal injection</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>necrosis</topic><topic>pathogenesis</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>patients</topic><topic>protective effect</topic><topic>proteinase inhibitors</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sepsis</topic><topic>sepsis (infection)</topic><topic>Sepsis - immunology</topic><topic>Sepsis - prevention & control</topic><topic>Trypsin Inhibitors - pharmacology</topic><topic>tumor necrosis factor-alpha</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor necrosis factor-α</topic><topic>Ulinastatin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Yi-Zhan</creatorcontrib><creatorcontrib>Tu, Yan-Yang</creatorcontrib><creatorcontrib>Chen, Xiang</creatorcontrib><creatorcontrib>Wang, Bo-Liang</creatorcontrib><creatorcontrib>Zhong, Yue-Xia</creatorcontrib><creatorcontrib>Liu, Ming-Hua</creatorcontrib><collection>AGRIS</collection><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><jtitle>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Yi-Zhan</au><au>Tu, Yan-Yang</au><au>Chen, Xiang</au><au>Wang, Bo-Liang</au><au>Zhong, Yue-Xia</au><au>Liu, Ming-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13</atitle><jtitle>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</jtitle><addtitle>Exp Toxicol Pathol</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>64</volume><issue>6</issue><spage>543</spage><epage>547</epage><pages>543-547</pages><issn>0940-2993</issn><eissn>1618-1433</eissn><abstract>Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats.
Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5ml), cecal ligation and puncture (CLP) plus PBS (5ml), CLP plus UTI (5000U/kg), CLP plus UTI (10,000U/kg), CLP plus UTI (20,000U/kg) and sham-operation plus UTI (10,000U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals.
The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13.
Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.</abstract><cop>Munich</cop><pub>Elsevier GmbH</pub><pmid>21159497</pmid><doi>10.1016/j.etp.2010.11.011</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0940-2993 |
| ispartof | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, 2012-09, Vol.64 (6), p.543-547 |
| issn | 0940-2993 1618-1433 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1031160775 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | animal models Animals Anti-Inflammatory Agents - pharmacology Bacterial diseases Bacterial sepsis Biological and medical sciences Disease Models, Animal Enzyme-Linked Immunosorbent Assay Glycoproteins - pharmacology Human bacterial diseases humans Infectious diseases inflammation Interleukin-1 - biosynthesis Interleukin-10 Interleukin-10 - biosynthesis Interleukin-13 Interleukin-6 Interleukin-6 - biosynthesis intestines intraperitoneal injection Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences necrosis pathogenesis Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques patients protective effect proteinase inhibitors Rats Rats, Wistar Sepsis sepsis (infection) Sepsis - immunology Sepsis - prevention & control Trypsin Inhibitors - pharmacology tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - biosynthesis Tumor necrosis factor-α Ulinastatin |
| title | Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T00%3A20%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protective%20effect%20of%20Ulinastatin%20against%20murine%20models%20of%20sepsis:%20Inhibition%20of%20TNF-%CE%B1%20and%20IL-6%20and%20augmentation%20of%20IL-10%20and%20IL-13&rft.jtitle=Experimental%20and%20toxicologic%20pathology%20:%20official%20journal%20of%20the%20Gesellschaft%20f%C3%BCr%20Toxikologische%20Pathologie&rft.au=Cao,%20Yi-Zhan&rft.date=2012-09-01&rft.volume=64&rft.issue=6&rft.spage=543&rft.epage=547&rft.pages=543-547&rft.issn=0940-2993&rft.eissn=1618-1433&rft_id=info:doi/10.1016/j.etp.2010.11.011&rft_dat=%3Cproquest_cross%3E1031160775%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1031160775&rft_id=info:pmid/21159497&rft_els_id=S0940299310002022&rfr_iscdi=true |