Loading…
Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin
Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p...
Saved in:
Published in: | Phytomedicine (Stuttgart) 2013-03, Vol.20 (5), p.436-440 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3 |
---|---|
cites | cdi_FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3 |
container_end_page | 440 |
container_issue | 5 |
container_start_page | 436 |
container_title | Phytomedicine (Stuttgart) |
container_volume | 20 |
creator | de Souza Siqueira Quintans, Jullyana Menezes, Paula Passos Santos, Márcio Roberto Viana Bonjardim, Leonardo Rigoldi Almeida, Jackson Roberto Guedes Silva Gelain, Daniel Pens Araújo, Adriano Antunes de Souza Quintans-Júnior, Lucindo José |
description | Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26–30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p |
doi_str_mv | 10.1016/j.phymed.2012.12.009 |
format | article |
fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1317857425</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A399107373</galeid><els_id>S0944711312005168</els_id><sourcerecordid>A399107373</sourcerecordid><originalsourceid>FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3</originalsourceid><addsrcrecordid>eNp9ktGK1DAUhoMo7rj6BqIFb_am9aRpk8mNsCyuLix4oQvehTQ9GTO0yZh0hp3X8kF8JlO7eyEMkgNJTr7_kJM_hLymUFGg_P222v04jthXNdC6ygEgn5AV5XRdgmy_PyUrkE1TCkrZGXmR0haANlLAc3JWM9YKxmFF8GbcxXDAEf1UBFvsSpOLeiy0n5wPxhncTe4w7_u_udJ5O-hx1FOIxwKtRTOlojsWzpthn1zweVX8_pXrmCH0eD9F51-SZ1YPCV89zOfk7vrjt6vP5e2XTzdXl7elaZmYyp7X0DW2BWoYMJTIsZOMSVrXVupubQwaCmg7YKynrEVBueiaBnhv-Lrr2Dm5WOrmnn7uMU1qdMngMGiPYZ8UZVSsW9HUbUbfLehGD6hyU2GK2sy4umRSUhBMsEyVJ6hNfqCoh-DRupz-h69O8Hn0ODpzUtAsAhNDShGt2kU36nhUFNTss9qqxWc1-6xyZJ-z7M1Do_tuPnsUPRqbgbcLYHVQehNdUndfcwWeP4HgAmbiw0JgNuTgMKpkHHqDvYvZU9UH9_87_AHGi8S_</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1317857425</pqid></control><display><type>article</type><title>Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin</title><source>ScienceDirect Journals</source><creator>de Souza Siqueira Quintans, Jullyana ; Menezes, Paula Passos ; Santos, Márcio Roberto Viana ; Bonjardim, Leonardo Rigoldi ; Almeida, Jackson Roberto Guedes Silva ; Gelain, Daniel Pens ; Araújo, Adriano Antunes de Souza ; Quintans-Júnior, Lucindo José</creator><creatorcontrib>de Souza Siqueira Quintans, Jullyana ; Menezes, Paula Passos ; Santos, Márcio Roberto Viana ; Bonjardim, Leonardo Rigoldi ; Almeida, Jackson Roberto Guedes Silva ; Gelain, Daniel Pens ; Araújo, Adriano Antunes de Souza ; Quintans-Júnior, Lucindo José</creatorcontrib><description>Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26–30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/β-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/β-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/β-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with β-CD improved analgesic and anti-inflammatory effects of p-cymene.</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2012.12.009</identifier><identifier>PMID: 23357360</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Acetic Acid - adverse effects ; Analgesics - chemistry ; Analgesics - therapeutic use ; Animals ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - therapeutic use ; Anti-inflammatory drugs ; Behavior, Animal ; beta-Cyclodextrins - administration & dosage ; beta-Cyclodextrins - therapeutic use ; Carrageenan - pharmacology ; Cyclodextrin ; Cyclodextrins ; Drug Evaluation, Preclinical ; Edema - drug therapy ; Health aspects ; Hot Temperature ; Inflammation ; Macromolecular Substances - chemistry ; Male ; Medicine, Botanic ; Medicine, Herbal ; Mice ; Monoterpene ; Monoterpenes - administration & dosage ; Monoterpenes - chemistry ; Monoterpenes - isolation & purification ; Monoterpenes - therapeutic use ; p-Cymene ; Pain ; Pain Measurement - methods ; Phytotherapy ; Time Factors</subject><ispartof>Phytomedicine (Stuttgart), 2013-03, Vol.20 (5), p.436-440</ispartof><rights>2012 Elsevier GmbH</rights><rights>Copyright © 2012 Elsevier GmbH. All rights reserved.</rights><rights>COPYRIGHT 2013 Urban & Fischer Verlag</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3</citedby><cites>FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23357360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Souza Siqueira Quintans, Jullyana</creatorcontrib><creatorcontrib>Menezes, Paula Passos</creatorcontrib><creatorcontrib>Santos, Márcio Roberto Viana</creatorcontrib><creatorcontrib>Bonjardim, Leonardo Rigoldi</creatorcontrib><creatorcontrib>Almeida, Jackson Roberto Guedes Silva</creatorcontrib><creatorcontrib>Gelain, Daniel Pens</creatorcontrib><creatorcontrib>Araújo, Adriano Antunes de Souza</creatorcontrib><creatorcontrib>Quintans-Júnior, Lucindo José</creatorcontrib><title>Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26–30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/β-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/β-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/β-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with β-CD improved analgesic and anti-inflammatory effects of p-cymene.</description><subject>Acetic Acid - adverse effects</subject><subject>Analgesics - chemistry</subject><subject>Analgesics - therapeutic use</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Anti-inflammatory drugs</subject><subject>Behavior, Animal</subject><subject>beta-Cyclodextrins - administration & dosage</subject><subject>beta-Cyclodextrins - therapeutic use</subject><subject>Carrageenan - pharmacology</subject><subject>Cyclodextrin</subject><subject>Cyclodextrins</subject><subject>Drug Evaluation, Preclinical</subject><subject>Edema - drug therapy</subject><subject>Health aspects</subject><subject>Hot Temperature</subject><subject>Inflammation</subject><subject>Macromolecular Substances - chemistry</subject><subject>Male</subject><subject>Medicine, Botanic</subject><subject>Medicine, Herbal</subject><subject>Mice</subject><subject>Monoterpene</subject><subject>Monoterpenes - administration & dosage</subject><subject>Monoterpenes - chemistry</subject><subject>Monoterpenes - isolation & purification</subject><subject>Monoterpenes - therapeutic use</subject><subject>p-Cymene</subject><subject>Pain</subject><subject>Pain Measurement - methods</subject><subject>Phytotherapy</subject><subject>Time Factors</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9ktGK1DAUhoMo7rj6BqIFb_am9aRpk8mNsCyuLix4oQvehTQ9GTO0yZh0hp3X8kF8JlO7eyEMkgNJTr7_kJM_hLymUFGg_P222v04jthXNdC6ygEgn5AV5XRdgmy_PyUrkE1TCkrZGXmR0haANlLAc3JWM9YKxmFF8GbcxXDAEf1UBFvsSpOLeiy0n5wPxhncTe4w7_u_udJ5O-hx1FOIxwKtRTOlojsWzpthn1zweVX8_pXrmCH0eD9F51-SZ1YPCV89zOfk7vrjt6vP5e2XTzdXl7elaZmYyp7X0DW2BWoYMJTIsZOMSVrXVupubQwaCmg7YKynrEVBueiaBnhv-Lrr2Dm5WOrmnn7uMU1qdMngMGiPYZ8UZVSsW9HUbUbfLehGD6hyU2GK2sy4umRSUhBMsEyVJ6hNfqCoh-DRupz-h69O8Hn0ODpzUtAsAhNDShGt2kU36nhUFNTss9qqxWc1-6xyZJ-z7M1Do_tuPnsUPRqbgbcLYHVQehNdUndfcwWeP4HgAmbiw0JgNuTgMKpkHHqDvYvZU9UH9_87_AHGi8S_</recordid><startdate>20130315</startdate><enddate>20130315</enddate><creator>de Souza Siqueira Quintans, Jullyana</creator><creator>Menezes, Paula Passos</creator><creator>Santos, Márcio Roberto Viana</creator><creator>Bonjardim, Leonardo Rigoldi</creator><creator>Almeida, Jackson Roberto Guedes Silva</creator><creator>Gelain, Daniel Pens</creator><creator>Araújo, Adriano Antunes de Souza</creator><creator>Quintans-Júnior, Lucindo José</creator><general>Elsevier GmbH</general><general>Urban & Fischer Verlag</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>20130315</creationdate><title>Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin</title><author>de Souza Siqueira Quintans, Jullyana ; Menezes, Paula Passos ; Santos, Márcio Roberto Viana ; Bonjardim, Leonardo Rigoldi ; Almeida, Jackson Roberto Guedes Silva ; Gelain, Daniel Pens ; Araújo, Adriano Antunes de Souza ; Quintans-Júnior, Lucindo José</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetic Acid - adverse effects</topic><topic>Analgesics - chemistry</topic><topic>Analgesics - therapeutic use</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Anti-inflammatory drugs</topic><topic>Behavior, Animal</topic><topic>beta-Cyclodextrins - administration & dosage</topic><topic>beta-Cyclodextrins - therapeutic use</topic><topic>Carrageenan - pharmacology</topic><topic>Cyclodextrin</topic><topic>Cyclodextrins</topic><topic>Drug Evaluation, Preclinical</topic><topic>Edema - drug therapy</topic><topic>Health aspects</topic><topic>Hot Temperature</topic><topic>Inflammation</topic><topic>Macromolecular Substances - chemistry</topic><topic>Male</topic><topic>Medicine, Botanic</topic><topic>Medicine, Herbal</topic><topic>Mice</topic><topic>Monoterpene</topic><topic>Monoterpenes - administration & dosage</topic><topic>Monoterpenes - chemistry</topic><topic>Monoterpenes - isolation & purification</topic><topic>Monoterpenes - therapeutic use</topic><topic>p-Cymene</topic><topic>Pain</topic><topic>Pain Measurement - methods</topic><topic>Phytotherapy</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Souza Siqueira Quintans, Jullyana</creatorcontrib><creatorcontrib>Menezes, Paula Passos</creatorcontrib><creatorcontrib>Santos, Márcio Roberto Viana</creatorcontrib><creatorcontrib>Bonjardim, Leonardo Rigoldi</creatorcontrib><creatorcontrib>Almeida, Jackson Roberto Guedes Silva</creatorcontrib><creatorcontrib>Gelain, Daniel Pens</creatorcontrib><creatorcontrib>Araújo, Adriano Antunes de Souza</creatorcontrib><creatorcontrib>Quintans-Júnior, Lucindo José</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</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>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Souza Siqueira Quintans, Jullyana</au><au>Menezes, Paula Passos</au><au>Santos, Márcio Roberto Viana</au><au>Bonjardim, Leonardo Rigoldi</au><au>Almeida, Jackson Roberto Guedes Silva</au><au>Gelain, Daniel Pens</au><au>Araújo, Adriano Antunes de Souza</au><au>Quintans-Júnior, Lucindo José</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2013-03-15</date><risdate>2013</risdate><volume>20</volume><issue>5</issue><spage>436</spage><epage>440</epage><pages>436-440</pages><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26–30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/β-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/β-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/β-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with β-CD improved analgesic and anti-inflammatory effects of p-cymene.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>23357360</pmid><doi>10.1016/j.phymed.2012.12.009</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0944-7113 |
ispartof | Phytomedicine (Stuttgart), 2013-03, Vol.20 (5), p.436-440 |
issn | 0944-7113 1618-095X |
language | eng |
recordid | cdi_proquest_miscellaneous_1317857425 |
source | ScienceDirect Journals |
subjects | Acetic Acid - adverse effects Analgesics - chemistry Analgesics - therapeutic use Animals Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - therapeutic use Anti-inflammatory drugs Behavior, Animal beta-Cyclodextrins - administration & dosage beta-Cyclodextrins - therapeutic use Carrageenan - pharmacology Cyclodextrin Cyclodextrins Drug Evaluation, Preclinical Edema - drug therapy Health aspects Hot Temperature Inflammation Macromolecular Substances - chemistry Male Medicine, Botanic Medicine, Herbal Mice Monoterpene Monoterpenes - administration & dosage Monoterpenes - chemistry Monoterpenes - isolation & purification Monoterpenes - therapeutic use p-Cymene Pain Pain Measurement - methods Phytotherapy Time Factors |
title | Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T14%3A03%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Improvement%20of%20p-cymene%20antinociceptive%20and%20anti-inflammatory%20effects%20by%20inclusion%20in%20%CE%B2-cyclodextrin&rft.jtitle=Phytomedicine%20(Stuttgart)&rft.au=de%20Souza%20Siqueira%20Quintans,%20Jullyana&rft.date=2013-03-15&rft.volume=20&rft.issue=5&rft.spage=436&rft.epage=440&rft.pages=436-440&rft.issn=0944-7113&rft.eissn=1618-095X&rft_id=info:doi/10.1016/j.phymed.2012.12.009&rft_dat=%3Cgale_proqu%3EA399107373%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c537t-d620b4f501c303e9e6eb9339122f9ab8ccec10efb033d135e7167b4406dc68bb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1317857425&rft_id=info:pmid/23357360&rft_galeid=A399107373&rfr_iscdi=true |