{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T15:53:25Z","timestamp":1762271605623,"version":"build-2065373602"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Anesthesiology"],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Melanocortin peptides improve hemodynamic parameters and prevent death during severe hemorrhagic shock. In the present research we determined influences of a synthetic melanocortin 1\/4 receptor agonist on the molecular changes that occur in rat liver during hemorrhage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Controlled-volume hemorrhage was performed in adult rats under general anesthesia by a stepwise blood withdrawal until mean arterial pressure fell to 40 mmHg. Then rats received either saline or the synthetic melanocortin 1\/4 receptor agonist Butir-His-D-Phe-Arg-Trp-Sar-NH2 (Ro27-3225; n = 6-8 per group). Hemogasanalysis was performed throughout a 60-min period. Gene expression in liver samples was determined at 1 or 3 h using quantitative real-time polymerase chain reaction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>At 1 h, in saline-treated shocked rats, there were significant increases in activating transcription factor 3 (Atf3), early growth response 1 (Egr1), heme oxygenase (decycling) 1 (Hmox1), FBJ murine osteosarcoma viral oncogene homolog (Fos), and jun oncogene (Jun). These changes were prevented by Ro27-3225 (mean \u00b1 SEM: Atf3 152.83 \u00b1 58.62 vs. 579.00 \u00b1 124.13, P = 0.002; Egr1 13.21 \u00b1 1.28 vs. 26.63 \u00b1 1.02, P = 0.001; Hmox1 3.28 \u00b1 0.31 vs. 166.54 \u00b1 35.03, P = 0.002; Fos 4.36 \u00b1 1.03 vs. 14.90 \u00b1 3.44, P &lt; 0.001; Jun 6.62 \u00b1 1.93 vs. 15.07 \u00b1 2.09, P = 0.005; respectively). Increases in alpha-2-macroglobulin (A2m), heat shock 70kD protein 1A (Hspa1a), erythropoietin (Epo), and interleukin-6 (Il6) occurred at 3 h in shocked rats and were prevented by Ro27-3225 treatment (A2m 6.90 \u00b1 0.82 vs. 36.73 \u00b1 4.00, P &lt; 0.001; Hspa1a 10.34 \u00b1 3.28 vs. 25.72 \u00b1 3.64, P = 0.001; Epo 0.49 \u00b1 0.13 vs. 2.37 \u00b1 0.73, P = 0.002; Il6 1.05 \u00b1 0.15 vs. 1.88 \u00b1 0.23, P &lt; 0.001; respectively). Further, at 3 h in shocked rats treated with Ro27-3225 there were significant increases in tight junction protein 1 (Tjp1; 27.30 \u00b1 2.43 vs. 5.03 \u00b1 1.68, P &lt; 0.001) and nuclear receptor subfamily 4, group A, member 1 (Nr4a1; 91.03 \u00b1 16.20 vs. 30.43 \u00b1 11.0, P = 0.01) relative to sham animals. Treatment with Ro27-3225 rapidly restored blood pressure, hemogasanalysis parameters, and lactate blood levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Melanocortin treatment significantly prevents most of the systemic and hepatic detrimental changes induced by hemorrhage.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/aln.0b013e318246ea68","type":"journal-article","created":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T05:11:09Z","timestamp":1327036269000},"page":"692-700","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Molecular Changes Induced in Rat Liver by Hemorrhage and Effects of Melanocortin Treatment"],"prefix":"10.1097","volume":"116","author":[{"given":"Caterina","family":"Lonati","sequence":"first","affiliation":[{"name":"Postdoctoral Fellow, Center for Surgical Research."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Sordi","sequence":"additional","affiliation":[{"name":"Postdoctoral Fellow, Center for Surgical Research."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Assistant Professor of Pharmacology."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Spaccapelo","sequence":"additional","affiliation":[{"name":"Postgraduate Student."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Leonardi","sequence":"additional","affiliation":[{"name":"Research Assistant, Department of Internal Medicine, University of Milano, Milano, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Carlin","sequence":"additional","affiliation":[{"name":"Research Assistant, Department of Internal Medicine, University of Milano, Milano, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Ottani","sequence":"additional","affiliation":[{"name":"Assistant Professor of Pharmacology."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Galantucci","sequence":"additional","affiliation":[{"name":"Postdoctoral Fellow."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Grieco","sequence":"additional","affiliation":[{"name":"Associate Professor of Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry and Toxicology, University of Napoli \u201cFederico II,\u201d Napoli, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Catania","sequence":"additional","affiliation":[{"name":"Director, Center for Preclinical Investigation, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Guarini","sequence":"additional","affiliation":[{"name":"Full Professor of Pharmacology, Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Anesthesiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.asahq.org\/anesthesiology\/article-pdf\/116\/3\/692\/256762\/00000542-201203000-00030.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.lww.com\/00000542-201203000-00026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:04:00Z","timestamp":1760385840000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00000542-201203000-00026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.1097\/aln.0b013e318246ea68","relation":{},"ISSN":["0003-3022"],"issn-type":[{"type":"print","value":"0003-3022"}],"subject":[],"published":{"date-parts":[[2012,3,1]]}}}