Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats
Prenatal testosterone (T) exposure impacts postnatal cardiovascular function, leading to increases in blood pressure with associated decreased endothelium-dependent vascular relaxation in adult females. Endothelial function in males is not known. Furthermore, which of the endothelial pathways contri...
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| Veröffentlicht in: | Biology of reproduction 2013-10, Vol.89 (4), p.97-97 |
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| creator | CHINNATHAMBI, Vijayakumar YALLAMPALLI, Chandrasekhar SATHISHKUMAR, Kunju |
| description | Prenatal testosterone (T) exposure impacts postnatal cardiovascular function, leading to increases in blood pressure with associated decreased endothelium-dependent vascular relaxation in adult females. Endothelial function in males is not known. Furthermore, which of the endothelial pathways contributes to endothelial dysfunction and if there exists sex differences are not known. The objective of this study was to characterize the relative contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired endothelium-dependent vasodilation in prenatal T-exposed adult males and females. Offspring of pregnant rats treated with T propionate or its vehicle were examined. Telemetric blood pressure levels and endothelium-dependent vascular reactivity were assessed with wire myography. Levels of nitric oxide synthase (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric arteries. Mean arterial pressure was significantly higher in T males and females than in controls. Endothelium-dependent acetylcholine relaxation was significantly lower in both T males and females. EDHF-mediated relaxation was specifically blunted in T males (Emax = 48.64% ± 3.73%) compared to that in control males (Emax = 81.71% ± 3.18%); however, NO-mediated relaxation was specifically impaired in T females (Emax = 36.01% ± 4.29%) compared with that in control females (Emax = 54.56% ± 6.37%). Relaxation to sodium nitroprusside and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in T females but not in T males. Kcnn3 expression was decreased in both T males and females compared to controls. These findings suggest that prenatal T leads to an increase in blood pressure in the adult offspring, associated with blunting of endothelial cell-associated relaxation and that the effects are sex-specific: EDHF-related in males and NO-related in females. |
| doi_str_mv | 10.1095/biolreprod.113.111542 |
| format | Article |
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Endothelial function in males is not known. Furthermore, which of the endothelial pathways contributes to endothelial dysfunction and if there exists sex differences are not known. The objective of this study was to characterize the relative contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired endothelium-dependent vasodilation in prenatal T-exposed adult males and females. Offspring of pregnant rats treated with T propionate or its vehicle were examined. Telemetric blood pressure levels and endothelium-dependent vascular reactivity were assessed with wire myography. Levels of nitric oxide synthase (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric arteries. Mean arterial pressure was significantly higher in T males and females than in controls. Endothelium-dependent acetylcholine relaxation was significantly lower in both T males and females. EDHF-mediated relaxation was specifically blunted in T males (Emax = 48.64% ± 3.73%) compared to that in control males (Emax = 81.71% ± 3.18%); however, NO-mediated relaxation was specifically impaired in T females (Emax = 36.01% ± 4.29%) compared with that in control females (Emax = 54.56% ± 6.37%). Relaxation to sodium nitroprusside and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in T females but not in T males. Kcnn3 expression was decreased in both T males and females compared to controls. These findings suggest that prenatal T leads to an increase in blood pressure in the adult offspring, associated with blunting of endothelial cell-associated relaxation and that the effects are sex-specific: EDHF-related in males and NO-related in females.</description><identifier>ISSN: 0006-3363</identifier><identifier>EISSN: 1529-7268</identifier><identifier>DOI: 10.1095/biolreprod.113.111542</identifier><identifier>PMID: 23966325</identifier><identifier>CODEN: BIREBV</identifier><language>eng</language><publisher>Madison, WI: Society for the Study of Reproduction</publisher><subject>Androgens - adverse effects ; Androgens - blood ; Animals ; Biological and medical sciences ; Biological Factors - antagonists & inhibitors ; Biological Factors - metabolism ; Down-Regulation - drug effects ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - physiopathology ; Female ; Fetal Development - drug effects ; Fundamental and applied biological sciences. Psychology ; Hypertension - chemically induced ; Hypertension - metabolism ; Hypertension - physiopathology ; Intermediate-Conductance Calcium-Activated Potassium Channels - genetics ; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism ; Male ; Mesenteric Arteries - drug effects ; Mesenteric Arteries - metabolism ; Mesenteric Arteries - physiopathology ; Nitric Oxide - antagonists & inhibitors ; Nitric Oxide - metabolism ; Nitric Oxide Synthase Type III - antagonists & inhibitors ; Nitric Oxide Synthase Type III - metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sex Characteristics ; Small-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors ; Small-Conductance Calcium-Activated Potassium Channels - genetics ; Small-Conductance Calcium-Activated Potassium Channels - metabolism ; Testosterone - adverse effects ; Testosterone - blood ; Testosterone Propionate - administration & dosage ; Vasodilation - drug effects ; Vertebrates: reproduction</subject><ispartof>Biology of reproduction, 2013-10, Vol.89 (4), p.97-97</ispartof><rights>2015 INIST-CNRS</rights><rights>2013 by the Society for the Study of Reproduction, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28032970$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23966325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHINNATHAMBI, Vijayakumar</creatorcontrib><creatorcontrib>YALLAMPALLI, Chandrasekhar</creatorcontrib><creatorcontrib>SATHISHKUMAR, Kunju</creatorcontrib><title>Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats</title><title>Biology of reproduction</title><addtitle>Biol Reprod</addtitle><description>Prenatal testosterone (T) exposure impacts postnatal cardiovascular function, leading to increases in blood pressure with associated decreased endothelium-dependent vascular relaxation in adult females. Endothelial function in males is not known. Furthermore, which of the endothelial pathways contributes to endothelial dysfunction and if there exists sex differences are not known. The objective of this study was to characterize the relative contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired endothelium-dependent vasodilation in prenatal T-exposed adult males and females. Offspring of pregnant rats treated with T propionate or its vehicle were examined. Telemetric blood pressure levels and endothelium-dependent vascular reactivity were assessed with wire myography. Levels of nitric oxide synthase (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric arteries. Mean arterial pressure was significantly higher in T males and females than in controls. Endothelium-dependent acetylcholine relaxation was significantly lower in both T males and females. EDHF-mediated relaxation was specifically blunted in T males (Emax = 48.64% ± 3.73%) compared to that in control males (Emax = 81.71% ± 3.18%); however, NO-mediated relaxation was specifically impaired in T females (Emax = 36.01% ± 4.29%) compared with that in control females (Emax = 54.56% ± 6.37%). Relaxation to sodium nitroprusside and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in T females but not in T males. Kcnn3 expression was decreased in both T males and females compared to controls. These findings suggest that prenatal T leads to an increase in blood pressure in the adult offspring, associated with blunting of endothelial cell-associated relaxation and that the effects are sex-specific: EDHF-related in males and NO-related in females.</description><subject>Androgens - adverse effects</subject><subject>Androgens - blood</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Factors - antagonists & inhibitors</subject><subject>Biological Factors - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Female</subject><subject>Fetal Development - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hypertension - chemically induced</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - physiopathology</subject><subject>Intermediate-Conductance Calcium-Activated Potassium Channels - genetics</subject><subject>Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism</subject><subject>Male</subject><subject>Mesenteric Arteries - drug effects</subject><subject>Mesenteric Arteries - metabolism</subject><subject>Mesenteric Arteries - physiopathology</subject><subject>Nitric Oxide - antagonists & inhibitors</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type III - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sex Characteristics</subject><subject>Small-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors</subject><subject>Small-Conductance Calcium-Activated Potassium Channels - genetics</subject><subject>Small-Conductance Calcium-Activated Potassium Channels - metabolism</subject><subject>Testosterone - adverse effects</subject><subject>Testosterone - blood</subject><subject>Testosterone Propionate - administration & dosage</subject><subject>Vasodilation - drug effects</subject><subject>Vertebrates: reproduction</subject><issn>0006-3363</issn><issn>1529-7268</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1P3DAQhq2qqGyhP6GVLz0GbE_ijS-VEB8tEggE9BxN7HHXldeJYqdlj_xzlhb6cRjNSO8zj0bD2HspDqQwzWEfhjjROA3uQErYlmxq9YotZKNMtVS6fc0WQghdAWjYZW9z_i6ErEHBG7arwGgNqlmwh-uJEhaM_I5yGXKhaUjEz5ObLWV-S_fV7Ug2-GD5ySb7OdkShsRD4qfJDWVFMczr6oRGSo5S4TcU8R5_MddYVj9xk5_gIzfHwi8xEsfk-Bmtn8YbLHmf7XiMmd499z329ez07vhLdXH1-fz46KIaldGlAuup7dGZ2jmDoGXb1tiK2tum17o3UjrQ1nvtqTE9ICGKXqleovMKWg177NNv7zj3a3J2e-yEsRunsMZp0w0Yuv-TFFbdt-FHV4ulBtNuBR_-FfzZfHnmFvj4DGC2GP2EyYb8l2sFKLMU8Ai_lYs5</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>CHINNATHAMBI, Vijayakumar</creator><creator>YALLAMPALLI, Chandrasekhar</creator><creator>SATHISHKUMAR, Kunju</creator><general>Society for the Study of Reproduction</general><general>Society for the Study of Reproduction, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>20131001</creationdate><title>Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats</title><author>CHINNATHAMBI, Vijayakumar ; YALLAMPALLI, Chandrasekhar ; SATHISHKUMAR, Kunju</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p296t-3cfe8bad94dd9a361884a804fc5b66b911d36cff6fe59b3aeaa0b22b1adf23863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Androgens - adverse effects</topic><topic>Androgens - blood</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Factors - antagonists & inhibitors</topic><topic>Biological Factors - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Female</topic><topic>Fetal Development - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hypertension - chemically induced</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - physiopathology</topic><topic>Intermediate-Conductance Calcium-Activated Potassium Channels - genetics</topic><topic>Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism</topic><topic>Male</topic><topic>Mesenteric Arteries - drug effects</topic><topic>Mesenteric Arteries - metabolism</topic><topic>Mesenteric Arteries - physiopathology</topic><topic>Nitric Oxide - antagonists & inhibitors</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type III - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sex Characteristics</topic><topic>Small-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors</topic><topic>Small-Conductance Calcium-Activated Potassium Channels - genetics</topic><topic>Small-Conductance Calcium-Activated Potassium Channels - metabolism</topic><topic>Testosterone - adverse effects</topic><topic>Testosterone - blood</topic><topic>Testosterone Propionate - administration & dosage</topic><topic>Vasodilation - drug effects</topic><topic>Vertebrates: reproduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHINNATHAMBI, Vijayakumar</creatorcontrib><creatorcontrib>YALLAMPALLI, Chandrasekhar</creatorcontrib><creatorcontrib>SATHISHKUMAR, Kunju</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>PubMed Central (Full Participant titles)</collection><jtitle>Biology of reproduction</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHINNATHAMBI, Vijayakumar</au><au>YALLAMPALLI, Chandrasekhar</au><au>SATHISHKUMAR, Kunju</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats</atitle><jtitle>Biology of reproduction</jtitle><addtitle>Biol Reprod</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>89</volume><issue>4</issue><spage>97</spage><epage>97</epage><pages>97-97</pages><issn>0006-3363</issn><eissn>1529-7268</eissn><coden>BIREBV</coden><abstract>Prenatal testosterone (T) exposure impacts postnatal cardiovascular function, leading to increases in blood pressure with associated decreased endothelium-dependent vascular relaxation in adult females. Endothelial function in males is not known. Furthermore, which of the endothelial pathways contributes to endothelial dysfunction and if there exists sex differences are not known. The objective of this study was to characterize the relative contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired endothelium-dependent vasodilation in prenatal T-exposed adult males and females. Offspring of pregnant rats treated with T propionate or its vehicle were examined. Telemetric blood pressure levels and endothelium-dependent vascular reactivity were assessed with wire myography. Levels of nitric oxide synthase (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric arteries. Mean arterial pressure was significantly higher in T males and females than in controls. Endothelium-dependent acetylcholine relaxation was significantly lower in both T males and females. EDHF-mediated relaxation was specifically blunted in T males (Emax = 48.64% ± 3.73%) compared to that in control males (Emax = 81.71% ± 3.18%); however, NO-mediated relaxation was specifically impaired in T females (Emax = 36.01% ± 4.29%) compared with that in control females (Emax = 54.56% ± 6.37%). Relaxation to sodium nitroprusside and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in T females but not in T males. Kcnn3 expression was decreased in both T males and females compared to controls. These findings suggest that prenatal T leads to an increase in blood pressure in the adult offspring, associated with blunting of endothelial cell-associated relaxation and that the effects are sex-specific: EDHF-related in males and NO-related in females.</abstract><cop>Madison, WI</cop><pub>Society for the Study of Reproduction</pub><pmid>23966325</pmid><doi>10.1095/biolreprod.113.111542</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Androgens - adverse effects Androgens - blood Animals Biological and medical sciences Biological Factors - antagonists & inhibitors Biological Factors - metabolism Down-Regulation - drug effects Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - physiopathology Female Fetal Development - drug effects Fundamental and applied biological sciences. Psychology Hypertension - chemically induced Hypertension - metabolism Hypertension - physiopathology Intermediate-Conductance Calcium-Activated Potassium Channels - genetics Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism Male Mesenteric Arteries - drug effects Mesenteric Arteries - metabolism Mesenteric Arteries - physiopathology Nitric Oxide - antagonists & inhibitors Nitric Oxide - metabolism Nitric Oxide Synthase Type III - antagonists & inhibitors Nitric Oxide Synthase Type III - metabolism Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Sprague-Dawley Sex Characteristics Small-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors Small-Conductance Calcium-Activated Potassium Channels - genetics Small-Conductance Calcium-Activated Potassium Channels - metabolism Testosterone - adverse effects Testosterone - blood Testosterone Propionate - administration & dosage Vasodilation - drug effects Vertebrates: reproduction |
| title | Prenatal Testosterone Induces Sex-Specific Dysfunction in Endothelium-Dependent Relaxation Pathways in Adult Male and Female Rats |
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