Endogenous Opioids in Wound-Site Neutrophils of Sternotomy Patients
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{"title"=>"Endogenous Opioids in Wound-Site Neutrophils of Sternotomy Patients", "type"=>"journal", "authors"=>[{"first_name"=>"Hamdy", "last_name"=>"Awad", "scopus_author_id"=>"7006496213"}, {"first_name"=>"Motaz", "last_name"=>"Abas", "scopus_author_id"=>"55445505800"}, {"first_name"=>"Haytham", "last_name"=>"Elgharably", "scopus_author_id"=>"53984069900"}, {"first_name"=>"Ravi", "last_name"=>"Tripathi", "scopus_author_id"=>"43862015900"}, {"first_name"=>"Tykie", "last_name"=>"Theofilos", "scopus_author_id"=>"55444983400"}, {"first_name"=>"Sujatha", "last_name"=>"Bhandary", "scopus_author_id"=>"55176952100"}, {"first_name"=>"Chittoor", "last_name"=>"Sai-Sudhakar", "scopus_author_id"=>"6507285999"}, {"first_name"=>"Chandan K.", "last_name"=>"Sen", "scopus_author_id"=>"7103412896"}, {"first_name"=>"Sashwati", "last_name"=>"Roy", "scopus_author_id"=>"7404587610"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23118879", "sgr"=>"84868267196", "doi"=>"10.1371/journal.pone.0047569", "scopus"=>"2-s2.0-84868267196", "pui"=>"365972032", "isbn"=>"1932-6203 (Electronic)", "issn"=>"19326203"}, "id"=>"9f8e7c39-686e-3dcd-acaa-b0c1309a000b", "abstract"=>"BACKGROUND: Postoperative pain management is a critical aspect of patient care. The inflammatory state of the post-sternotomy surgical wound sensitizes nerve endings, causing pain. Unrelieved or improperly managed pain compromises wound healing. Peripheral opioid receptors play a major role in analgesia, particularly under inflammatory conditions where both opioid receptor expression and efficacy are increased. Leukocytic opioid peptides include β-endorphin (END), met-enkephalin (ENK), and dynorphin-A (DYN), with END and ENK being predominant.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: This work represents the first study of inflammatory cells collected from post-sternotomy wounds of patients undergoing cardiac surgery including coronary artery bypass grafting (CABG). Wound fluid (WF) and cells were collected from sternal wounds using a JP Blake drain at 24, 48, and 72 hours post sternum closure. Anti-CD15 staining and flow cytometry revealed that polymorphonuclear neutrophils (PMN) are the predominant cells present in wound fluid collected post-surgery. Compared to peripheral blood (PB) derived PMN, significant increases in CD177+/CD66b+ PMN were observed suggesting activation of wound-site PMN. Such activation was associated with higher levels of opioid peptide expression in PMN derived from WF. Indeed, increased level of opioid peptides in sternal wound environment was noted 72 h post-surgery. We demonstrate that WF contains factors that can significantly induce POMC transcription in human PMNs. IL-10 and IL-4 were abundant in WF and both cytokines significantly induced POMC gene expression suggesting that WF factors such as IL-10 and IL-4 contribute towards increased opioid peptide expression in wound-site PMN.\\n\\nCONCLUSIONS/SIGNIFICANCE: This approach provided a unique opportunity to study the cross-talk between inflammation and opioid peptides in PMN at a sternotomy wound-site. Wound-site PMN exhibited induction of END and ENK. In addition, sternal wound fluid significantly induced END expression in PMN. Taken together, these data constitute first clinical evidence that human wound-site PMNs are direct contributors of opioids at the sternal wound-site.", "link"=>"http://www.mendeley.com/research/endogenous-opioids-woundsite-neutrophils-sternotomy-patients", "reader_count"=>14, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>3, "Arts and Humanities"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Unspecified"=>{"Unspecified"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1, "France"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/550074"], "description"=>"<p>Cells from WF and PB were immunostained with CD177 followed by flow cytometry or cytospin analysis. Representative <b>A</b>, scatter plot and <b>B</b>, histogram and <b>C</b>, quantification from flow cytometry analysis showing cells with low (lo) or high (hi) expression of CD177. <b>D</b>, Representative images of cytospun cells derived from WF or PB. The cells were immunostained with CD177 (green) and DAPI (nucleus, red). Scale bar = 10 µm.</p>", "links"=>[], "tags"=>["cd177", "pmn", "derived"], "article_id"=>220557, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g005", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_CD177_expression_in_PMN_derived_from_WF_/220557", "title"=>"Increased CD177 expression in PMN derived from WF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:57:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/549878"], "description"=>"<p>PB and WF leukocytes were isolated and stained with FITC-conjugated anti-human CD15 followed by <b>A–B</b>, flow cytometry analysis or <b>C–D</b>, cytospin. <b>A</b>, representative flowcytometry plots showing increased CD15 positive cells in WF at 48 h post wounding as compared to peripheral blood at baseline (PB). <b>B</b>, CD15 expression analysis using flow cytometry. Data presented as mean±SD, n = 4. *<i>p</i><0.05 compared to PB. <b>C</b>, Representative images of cytospun cells derived from WF or PB. Cells were immunostained with CD15 (red) and DAPI (nucleus, blue). Scale bar = 10 µm; <b>D</b>, size analysis of cytospun cells derived from WF and PB. Data are mean ± SD; <i>p</i><0.05 compared to PB.</p>", "links"=>[], "tags"=>["cd15"], "article_id"=>220364, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g003", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PMN_in_wound_fluid_are_CD15_positive_/220364", "title"=>"PMN in wound fluid are CD15 positive.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:56:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/550143"], "description"=>"<p>Wound fluid (WF) was obtained from sternal wounds. Opioid peptide β-endorphin (END) and met-enkephalin (ENK) levels in WF was determined using ELISA at the indicated time points after surgery. The peptide levels were normalized to total albumin level in the fluid. Data are mean±SD (n = 5).* <i>p</i><0.05 compared to 24 h post-surgery.</p>", "links"=>[], "tags"=>["endogenous", "opioid", "peptide", "levels", "inflammatory"], "article_id"=>220629, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_endogenous_opioid_peptide_levels_in_wound_fluid_at_late_inflammatory_phase_/220629", "title"=>"Increased endogenous opioid peptide levels in wound fluid at late inflammatory phase.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:57:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/550386"], "description"=>"1<p>AA, African American; C, Caucasians.</p>2<p>Other procedures involved Maze, mitral valve repair/replacements, Aortic valve repair/replacements. CABG, coronary artery bypass graft.</p>", "links"=>[], "tags"=>["characteristics", "patients"], "article_id"=>220876, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_characteristics_of_patients_n_8202_8202_14_/220876", "title"=>"Demographic characteristics of patients (n = 14).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 20:58:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/549816"], "description"=>"<p>Wound cells isolated from WF were subjected to flow cytometry analysis. <b>A</b>, forward and sideward scatter (FS/SS) and flow cytometry analysis to sub-fraction wound and blood leukocytes. Based on FS/SS characteristics of blood leukocytes (PB, before surgery), three major cell populations were gated: <b><i>gate i</i></b>, granulocytes; <b><i>gate ii</i></b>, monocytes; <b><i>gate iii</i></b>, lymphocytes; <b>B</b>, quantification of cells in each of the three gates (i–iii). Solid bar, blood at baseline; open bars, WF cells at 48 h post-surgery. Data are mean ±SD, n = 4. <b>C</b>, Neutrophil count expressed in % of total leukocytes as determined by microscopic differential count. Data presented as mean± SD, n = 7. *<i>p</i><0.05 compared to PB.</p>", "links"=>[], "tags"=>["sternotomy", "wound-fluid", "predominantly"], "article_id"=>220303, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cells_in_sternotomy_wound_fluid_are_predominantly_PMN_/220303", "title"=>"Cells in sternotomy wound-fluid are predominantly PMN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:55:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/550304"], "description"=>"<p><b>A,</b> HL-60 cells were differentiated to PMN and then treated with varying dilutions (0–25%, v/v, 24 h) of wound fluid (WF) derived from sternal wounds. WF was sterile filtered and added directly to the PMN culture medium. POMC mRNA levels in WF treated PMN was measured using qPCR. Data are mean ± SD (n = 3).*, p<0.05 compared to 0% treated cells. <b>B</b>, HL-60 cells were differentiated to PMN and then were treated with 100 ng/ml of IL-10 or IL-4 for 48 h. The expression of POMC transcripts were measured using qPCR. Data are mean ± SD (n = 3). * p<0.05 compared to control. Both IL-4 and IL-10 that are abundantly present in WF significantly induced POMC mRNA expression. <b>C</b>, Levels of IL-4 and IL-10 in wound fluid (WF) and plasma were determined using ELISA at the indicated time points after surgery. The cytokine levels were normalized to the total albumin level in the fluid or plasma. Data are mean ± SD (n = 5). * <i>p</i><0.01 compared to plasma.</p>", "links"=>[], "tags"=>["induces", "opioid", "peptide", "inducing", "il-4", "il-10", "sternal"], "article_id"=>220780, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g008", "stats"=>{"downloads"=>4, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sternal_wound_environment_induces_opioid_peptide_expression_in_PMN_presence_of_opioid_inducing_IL_4_and_IL_10_in_sternal_wound_environment_/220780", "title"=>"Sternal wound environment induces opioid peptide expression in PMN: presence of opioid inducing IL-4 and IL-10 in sternal wound environment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:58:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/549968"], "description"=>"<p>The WF and PB cells were subjected to flow cytometry analysis following immunostaining with CD66b or CD43. <b>A&C,</b> representative flowcytometry histograms of CD66b and CD43; <b>B&D,</b> quantification of CD66b and CD43 flow cytometry analysis. Data presented as mean±SD, n = 4. *<i>p</i><0.05 compared to PB.</p>", "links"=>[], "tags"=>["wf", "activated", "pmn", "cd66b", "cd43"], "article_id"=>220453, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g004", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cells_from_WF_show_activated_PMN_phenotype_increased_CD66b_and_decreased_CD43_expression_/220453", "title"=>"Cells from WF show activated PMN phenotype: increased CD66b and decreased CD43 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:56:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/549726"], "description"=>"<p><b>A</b>, image of the sternal wound before closure where the Blake drain is yet to be placed; <b>B</b>, after closure of the sternum, the surgeon placed a Blake drain over the sternum, and then closed the wound in layers. The Blake drain was connected to a heparinized J-VAC bulb suction reservoir for wound fluid collection.</p>", "links"=>[], "tags"=>["sternal"], "article_id"=>220211, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fluid_and_cell_collection_from_sternal_wound_environment_/220211", "title"=>"Fluid and cell collection from sternal wound environment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:55:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/550211"], "description"=>"<p>WF derived cells were isolated from sternal wounds. <b>A</b>, mRNA expression of pro-opiomelanocortin (POMC) or preproenkephalin (PENK), the precursors of END and ENK, respectively, were determined in WF and peripheral blood (PB) PMN using quantitative PCR (qPCR). Data are mean±SD (n = 3).* <i>p</i><0.05 compared to PB; <b>B</b>, <b><i>Left</i></b>: Representative images of cytospun cells derived from WF or PB. Cells were immunostained with anti-β-Endorphin (β-END; red) and DAPI (nucleus, blue). Scale bar = 20 µm. <b><i>Right:</i></b> zoomed images of white box shown in corresponding left panels. Scale bar = 5 µm. <b>C</b>, Intracellular opioid peptide β-endorphin (END) and met-enkephalin (ENK) levels in WF derived PMN determined using ELISA at the indicated time points after surgery. The peptide levels were normalized to total cellar protein levels. Data are mean±SD (n = 3).* <i>p</i><0.05 compared to 24 h post-surgery.</p>", "links"=>[], "tags"=>["endogenous", "opioid", "peptide", "wound-site"], "article_id"=>220690, "categories"=>["Medicine", "Developmental Biology", "Genetics", "Neuroscience", "Immunology"], "users"=>["Hamdy Awad", "Motaz Abas", "Haytham Elgharably", "Ravi Tripathi", "Tykie Theofilos", "Sujatha Bhandary", "Chittoor Sai-Sudhakar", "Chandan K. Sen", "Sashwati Roy"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0047569.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_endogenous_opioid_peptide_expression_in_wound_site_PMN_/220690", "title"=>"Increased endogenous opioid peptide expression in wound-site PMN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 20:58:02"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"12", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"12"}
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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[322, 550, 671, 773, 864, 955, 1048, 1135, 1223, 1308, 1387, 1465, 1534, 1602, 1673, 1744, 1813, 1885, 1955, 2026, 2093, 2160, 2228, 2290, 2349]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[308, 530, 649, 751, 844, 933, 1021, 1107, 1194, 1277, 1357, 1426, 1501, 1572, 1634, 1702, 1768, 1838, 1910, 1976, 2046, 2114, 2181, 2241, 2298]}, {"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[312, 555, 680, 785, 880, 965, 1057, 1142, 1230, 1312, 1394, 1471, 1547, 1613, 1681, 1743, 1805, 1871, 1941, 2010, 2071, 2128, 2202, 2266, 2323]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[307, 529, 649, 751, 845, 936, 1025, 1113, 1197, 1284, 1360, 1432, 1501, 1570, 1632, 1697, 1765, 1834, 1904, 1972, 2041, 2107, 2170, 2231, 2292]}, {"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[300, 532, 651, 749, 842, 929, 1022, 1106, 1192, 1267, 1351, 1423, 1489, 1553, 1631, 1694, 1764, 1835, 1899, 1964, 2027, 2087, 2159, 2228, 2280]}, {"subject_area"=>"/Medicine and health sciences/Pain management", "average_usage"=>[342, 608, 752, 851, 938, 1033, 1133, 1206, 1319, 1403, 1474, 1555, 1614, 1687, 1752, 1825, 1900, 1939, 1992, 2044, 2104, 2139, 2200, 2265, 2331]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[321, 553, 683, 785, 880, 973, 1072, 1162, 1249, 1336, 1425, 1504, 1574, 1642, 1711, 1785, 1852, 1923, 1987, 2050, 2129, 2192, 2259, 2325, 2393]}]}
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Net::HTTPTooManyRequests

Source
Scopus
Time
2019-08-27 18:09:00 UTC
Target URL
https://api.elsevier.com/content/search/index:SCOPUS?query=DOI(10.1371%2Fjournal.pone.0047569)
Trace

/app/models/concerns/networkable.rb:21:in `get_result'
/app/models/source.rb:165:in `get_data'
/app/models/retrieval_status.rb:47:in `perform_get_data'
/app/jobs/source_job.rb:52:in `block (2 levels) in perform'
/app/jobs/source_job.rb:51:in `block in perform'
/app/jobs/source_job.rb:35:in `each'
/app/jobs/source_job.rb:35:in `perform'