Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin
Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as b...
Gespeichert in:
| Veröffentlicht in: | Skin pharmacology and physiology 2007-01, Vol.20 (3), p.155-161 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 161 |
|---|---|
| container_issue | 3 |
| container_start_page | 155 |
| container_title | Skin pharmacology and physiology |
| container_volume | 20 |
| creator | Kemeny, L. Koreck, A. Kis, K. Kenderessy-Szabo, A. Bodai, L. Cimpean, A. Paunescu, V. Raica, M. Ghyczy, M. |
| description | Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. Objectives: To investigate the effect of a PEA- and organic osmolyte-containing topical product (Physiogel AI®) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. Methods: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. Results: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. Conclusions: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage. |
| doi_str_mv | 10.1159/000098702 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_karge</sourceid><recordid>TN_cdi_karger_primary_98702</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>21047041</sourcerecordid><originalsourceid>FETCH-LOGICAL-c427t-983ecc26de202a1a3bc3af0c5a0ae7710b216258d3daa7b5754abd115e5450a53</originalsourceid><addsrcrecordid>eNpd0U2LFDEQBuAgiruuHjwLEjwIHlqTdCeZOS6zXwOjLrh7bqqTmp7sdie9SVrwL_irjcwwgnVJHZ4URb2EvOXsM-dy-YWVWi40E8_IKVeKVVLW8vmxF_qEvErpgTGhNFcvyQnXomZMylPy-9Lb0KMPc6K3u5CmXRjc5Cz9ihm60mekq-AzOO98T-_C5AwM9DYGO5tM137nOpcTvR9yhJ8uDJjpxvW7XK19EWgL2Q4wjpBd8BS8pRffzukFjNAjdZ7ezCN4-uPR-dfkxRaGhG8O7xm5v7q8W91Um-_X69X5pjKN0LlaLmo0RiiLggngUHemhi0zEhig1px1gishF7a2ALqTWjbQ2XInlI1kIOsz8nE_d4rhacaU29Elg8MAHssZWsFZo1nDC_zwH3wIc_Rlt1YIKZRacFXQpz0yMaQUcdtO0Y0Qf7WctX_TaY_pFPv-MHDuRrT_5CGOAt7twSPEHuMR7L__AR3Hk4E</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>225266816</pqid></control><display><type>article</type><title>Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin</title><source>MEDLINE</source><source>Karger Journals</source><source>Alma/SFX Local Collection</source><creator>Kemeny, L. ; Koreck, A. ; Kis, K. ; Kenderessy-Szabo, A. ; Bodai, L. ; Cimpean, A. ; Paunescu, V. ; Raica, M. ; Ghyczy, M.</creator><creatorcontrib>Kemeny, L. ; Koreck, A. ; Kis, K. ; Kenderessy-Szabo, A. ; Bodai, L. ; Cimpean, A. ; Paunescu, V. ; Raica, M. ; Ghyczy, M.</creatorcontrib><description>Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. Objectives: To investigate the effect of a PEA- and organic osmolyte-containing topical product (Physiogel AI®) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. Methods: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. Results: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. Conclusions: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage.</description><identifier>ISSN: 1660-5527</identifier><identifier>EISSN: 1660-5535</identifier><identifier>DOI: 10.1159/000098702</identifier><identifier>PMID: 17230055</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject><![CDATA[Administration, Cutaneous ; Adult ; Betaine - administration & dosage ; Betaine - chemistry ; Betaine - therapeutic use ; Chemistry, Pharmaceutical ; DNA - drug effects ; DNA - radiation effects ; DNA Damage ; Dose-Response Relationship, Radiation ; Drug Combinations ; Endocannabinoids ; Erythema - etiology ; Erythema - metabolism ; Erythema - prevention & control ; Ethanolamines ; Gels ; Humans ; Original Paper ; Palmitic Acids - administration & dosage ; Palmitic Acids - chemistry ; Palmitic Acids - therapeutic use ; Pyrimidine Dimers - metabolism ; Radiodermatitis - etiology ; Radiodermatitis - metabolism ; Radiodermatitis - prevention & control ; Sarcosine - administration & dosage ; Sarcosine - chemistry ; Sarcosine - therapeutic use ; Skin - drug effects ; Skin - metabolism ; Skin - radiation effects ; Sunscreening Agents - administration & dosage ; Sunscreening Agents - chemistry ; Sunscreening Agents - therapeutic use ; Treatment Outcome ; Ultraviolet Rays - adverse effects]]></subject><ispartof>Skin pharmacology and physiology, 2007-01, Vol.20 (3), p.155-161</ispartof><rights>2007 S. Karger AG, Basel</rights><rights>Copyright (c) 2007 S. Karger AG, Basel.</rights><rights>Copyright (c) 2007 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-983ecc26de202a1a3bc3af0c5a0ae7710b216258d3daa7b5754abd115e5450a53</citedby><cites>FETCH-LOGICAL-c427t-983ecc26de202a1a3bc3af0c5a0ae7710b216258d3daa7b5754abd115e5450a53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17230055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kemeny, L.</creatorcontrib><creatorcontrib>Koreck, A.</creatorcontrib><creatorcontrib>Kis, K.</creatorcontrib><creatorcontrib>Kenderessy-Szabo, A.</creatorcontrib><creatorcontrib>Bodai, L.</creatorcontrib><creatorcontrib>Cimpean, A.</creatorcontrib><creatorcontrib>Paunescu, V.</creatorcontrib><creatorcontrib>Raica, M.</creatorcontrib><creatorcontrib>Ghyczy, M.</creatorcontrib><title>Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin</title><title>Skin pharmacology and physiology</title><addtitle>Skin Pharmacol Physiol</addtitle><description>Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. Objectives: To investigate the effect of a PEA- and organic osmolyte-containing topical product (Physiogel AI®) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. Methods: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. Results: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. Conclusions: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage.</description><subject>Administration, Cutaneous</subject><subject>Adult</subject><subject>Betaine - administration & dosage</subject><subject>Betaine - chemistry</subject><subject>Betaine - therapeutic use</subject><subject>Chemistry, Pharmaceutical</subject><subject>DNA - drug effects</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Drug Combinations</subject><subject>Endocannabinoids</subject><subject>Erythema - etiology</subject><subject>Erythema - metabolism</subject><subject>Erythema - prevention & control</subject><subject>Ethanolamines</subject><subject>Gels</subject><subject>Humans</subject><subject>Original Paper</subject><subject>Palmitic Acids - administration & dosage</subject><subject>Palmitic Acids - chemistry</subject><subject>Palmitic Acids - therapeutic use</subject><subject>Pyrimidine Dimers - metabolism</subject><subject>Radiodermatitis - etiology</subject><subject>Radiodermatitis - metabolism</subject><subject>Radiodermatitis - prevention & control</subject><subject>Sarcosine - administration & dosage</subject><subject>Sarcosine - chemistry</subject><subject>Sarcosine - therapeutic use</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Sunscreening Agents - administration & dosage</subject><subject>Sunscreening Agents - chemistry</subject><subject>Sunscreening Agents - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Ultraviolet Rays - adverse effects</subject><issn>1660-5527</issn><issn>1660-5535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0U2LFDEQBuAgiruuHjwLEjwIHlqTdCeZOS6zXwOjLrh7bqqTmp7sdie9SVrwL_irjcwwgnVJHZ4URb2EvOXsM-dy-YWVWi40E8_IKVeKVVLW8vmxF_qEvErpgTGhNFcvyQnXomZMylPy-9Lb0KMPc6K3u5CmXRjc5Cz9ihm60mekq-AzOO98T-_C5AwM9DYGO5tM137nOpcTvR9yhJ8uDJjpxvW7XK19EWgL2Q4wjpBd8BS8pRffzukFjNAjdZ7ezCN4-uPR-dfkxRaGhG8O7xm5v7q8W91Um-_X69X5pjKN0LlaLmo0RiiLggngUHemhi0zEhig1px1gishF7a2ALqTWjbQ2XInlI1kIOsz8nE_d4rhacaU29Elg8MAHssZWsFZo1nDC_zwH3wIc_Rlt1YIKZRacFXQpz0yMaQUcdtO0Y0Qf7WctX_TaY_pFPv-MHDuRrT_5CGOAt7twSPEHuMR7L__AR3Hk4E</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Kemeny, L.</creator><creator>Koreck, A.</creator><creator>Kis, K.</creator><creator>Kenderessy-Szabo, A.</creator><creator>Bodai, L.</creator><creator>Cimpean, A.</creator><creator>Paunescu, V.</creator><creator>Raica, M.</creator><creator>Ghyczy, M.</creator><general>S. Karger AG</general><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>3V.</scope><scope>7QO</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope></search><sort><creationdate>20070101</creationdate><title>Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin</title><author>Kemeny, L. ; Koreck, A. ; Kis, K. ; Kenderessy-Szabo, A. ; Bodai, L. ; Cimpean, A. ; Paunescu, V. ; Raica, M. ; Ghyczy, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-983ecc26de202a1a3bc3af0c5a0ae7710b216258d3daa7b5754abd115e5450a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Administration, Cutaneous</topic><topic>Adult</topic><topic>Betaine - administration & dosage</topic><topic>Betaine - chemistry</topic><topic>Betaine - therapeutic use</topic><topic>Chemistry, Pharmaceutical</topic><topic>DNA - drug effects</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Drug Combinations</topic><topic>Endocannabinoids</topic><topic>Erythema - etiology</topic><topic>Erythema - metabolism</topic><topic>Erythema - prevention & control</topic><topic>Ethanolamines</topic><topic>Gels</topic><topic>Humans</topic><topic>Original Paper</topic><topic>Palmitic Acids - administration & dosage</topic><topic>Palmitic Acids - chemistry</topic><topic>Palmitic Acids - therapeutic use</topic><topic>Pyrimidine Dimers - metabolism</topic><topic>Radiodermatitis - etiology</topic><topic>Radiodermatitis - metabolism</topic><topic>Radiodermatitis - prevention & control</topic><topic>Sarcosine - administration & dosage</topic><topic>Sarcosine - chemistry</topic><topic>Sarcosine - therapeutic use</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Sunscreening Agents - administration & dosage</topic><topic>Sunscreening Agents - chemistry</topic><topic>Sunscreening Agents - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Ultraviolet Rays - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kemeny, L.</creatorcontrib><creatorcontrib>Koreck, A.</creatorcontrib><creatorcontrib>Kis, K.</creatorcontrib><creatorcontrib>Kenderessy-Szabo, A.</creatorcontrib><creatorcontrib>Bodai, L.</creatorcontrib><creatorcontrib>Cimpean, A.</creatorcontrib><creatorcontrib>Paunescu, V.</creatorcontrib><creatorcontrib>Raica, M.</creatorcontrib><creatorcontrib>Ghyczy, M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Skin pharmacology and physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kemeny, L.</au><au>Koreck, A.</au><au>Kis, K.</au><au>Kenderessy-Szabo, A.</au><au>Bodai, L.</au><au>Cimpean, A.</au><au>Paunescu, V.</au><au>Raica, M.</au><au>Ghyczy, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin</atitle><jtitle>Skin pharmacology and physiology</jtitle><addtitle>Skin Pharmacol Physiol</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>20</volume><issue>3</issue><spage>155</spage><epage>161</epage><pages>155-161</pages><issn>1660-5527</issn><eissn>1660-5535</eissn><abstract>Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. Objectives: To investigate the effect of a PEA- and organic osmolyte-containing topical product (Physiogel AI®) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. Methods: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. Results: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. Conclusions: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>17230055</pmid><doi>10.1159/000098702</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1660-5527 |
| ispartof | Skin pharmacology and physiology, 2007-01, Vol.20 (3), p.155-161 |
| issn | 1660-5527 1660-5535 |
| language | eng |
| recordid | cdi_karger_primary_98702 |
| source | MEDLINE; Karger Journals; Alma/SFX Local Collection |
| subjects | Administration, Cutaneous Adult Betaine - administration & dosage Betaine - chemistry Betaine - therapeutic use Chemistry, Pharmaceutical DNA - drug effects DNA - radiation effects DNA Damage Dose-Response Relationship, Radiation Drug Combinations Endocannabinoids Erythema - etiology Erythema - metabolism Erythema - prevention & control Ethanolamines Gels Humans Original Paper Palmitic Acids - administration & dosage Palmitic Acids - chemistry Palmitic Acids - therapeutic use Pyrimidine Dimers - metabolism Radiodermatitis - etiology Radiodermatitis - metabolism Radiodermatitis - prevention & control Sarcosine - administration & dosage Sarcosine - chemistry Sarcosine - therapeutic use Skin - drug effects Skin - metabolism Skin - radiation effects Sunscreening Agents - administration & dosage Sunscreening Agents - chemistry Sunscreening Agents - therapeutic use Treatment Outcome Ultraviolet Rays - adverse effects |
| title | Endogenous Phospholipid Metabolite Containing Topical Product Inhibits Ultraviolet Light-Induced Inflammation and DNA Damage in Human Skin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T00%3A49%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_karge&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Endogenous%20Phospholipid%20Metabolite%20Containing%20Topical%20Product%20Inhibits%20Ultraviolet%20Light-Induced%20Inflammation%20and%20DNA%20Damage%20in%20Human%20Skin&rft.jtitle=Skin%20pharmacology%20and%20physiology&rft.au=Kemeny,%20L.&rft.date=2007-01-01&rft.volume=20&rft.issue=3&rft.spage=155&rft.epage=161&rft.pages=155-161&rft.issn=1660-5527&rft.eissn=1660-5535&rft_id=info:doi/10.1159/000098702&rft_dat=%3Cproquest_karge%3E21047041%3C/proquest_karge%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=225266816&rft_id=info:pmid/17230055&rfr_iscdi=true |