{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:12:26Z","timestamp":1790651546196,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["(FAPESP\u20102010\/10391\u20109, 2010\/03571\u20100, 2007\/59374\u20106)"],"award-info":[{"award-number":["(FAPESP\u20102010\/10391\u20109, 2010\/03571\u20100, 2007\/59374\u20106)"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> There is evidence that histamine released during inflammation plays a role in bone metabolism via the H<jats:sub>2<\/jats:sub> receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H<jats:sub>2<\/jats:sub>\u2010receptor antagonist, interferes with the initiation and progression of induced periodontal disease in rat molars.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Forty male rats received 100 mg\/kg body weight of cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]). Periodontal disease was induced in the maxillary left first molars (PDSG and PDCimG); maxillary right molars were used as non\u2010ligature controls. After 7, 15, 30, and 50 days, maxillary fragments were embedded in paraffin. The sections were stained with Masson trichrome and hematoxylin and eosin and subjected to the tartrate\u2010resistant acid phosphatase (TRAP) method. The distances between the cemento\u2010enamel junction (CEJ) and alveolar process (AP) crest, as well as between the CEJ and junctional epithelium (JE) level, were measured; the number of inflammatory cells was computed. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out, and the RANKL\/OPG ratio was calculated.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In PDSG and PDCimG, a significant increase (<jats:italic>P<\/jats:italic> \u22640.05) was observed in CEJ\u2010AP and CEJ\u2010JE distances. However, the increases in both distances were significantly less in PDCimG compared with PDSG at 15, 30, and 50 days. Numerous TRAP\u2010positive osteoclasts were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory cells and the RANKL\/OPG ratio were significantly lower (<jats:italic>P<\/jats:italic> \u22640.05) than in PDSG.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL\/OPG ratio in gingival connective tissue and reducing alveolar bone resorption.<\/jats:p>","DOI":"10.1902\/jop.2013.130453","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T07:42:17Z","timestamp":1385624537000},"page":"1115-1125","source":"Crossref","is-referenced-by-count":31,"title":["Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars"],"prefix":"10.1002","volume":"85","author":[{"given":"Renata","family":"Longhini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Aparecida de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Sasso\u2010Cerri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo S\u00e9rgio","family":"Cerri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.11-S.2106"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2010.03.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.12.048"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2220\/biomedres.34.31"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050735"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4068\/cmj.2012.48.1.7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-010-0163-6"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02215-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90341-H"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2004.06.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.92.43"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.4.2402-2414.2006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02440-3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.32.555"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.9.1486"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.2.210"},{"key":"e_1_2_7_18_1","first-page":"1325","article-title":"Interaction between osteoblast and osteoclast: Impact in bone disease","volume":"19","author":"Phan TC","year":"2004","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0568"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-010-9153-1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.070073"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03280130071025"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00629-9"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.08.007"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2006.033217"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199710)173:1<10::AID-JCP2>3.0.CO;2-M"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0765.2003.02006.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2006.00932.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2011.01449.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.2964"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096564"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01965080"},{"key":"e_1_2_7_34_1","first-page":"249","article-title":"Increase of histidine decarboxylase activity in murine myelomonocytic leukemia cells (WEHI\u20103B) in parallel to their differentiation into macrophages","volume":"972","author":"Kawaguchi\u2010Nagata K","year":"1988","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.58.1918"},{"key":"e_1_2_7_36_1","first-page":"219","article-title":"Histamine synthesis by mouse T lymphocytes through induced histidine decarboxylase","volume":"66","author":"Aoi R","year":"1989","journal-title":"Immunology"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00986.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061232"},{"key":"e_1_2_7_39_1","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.4049\/jimmunol.130.4.1902","article-title":"Histamine modulation of human neutrophil oxidative metabolism, locomotion, degranulation, and membrane potential changes","volume":"130","author":"Seligmann BE","year":"1983","journal-title":"J Immunol"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00917506"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1994.1174"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2004.00516.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.11.122"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.110540"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000187"},{"key":"e_1_2_7_46_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0026-895X(25)13622-5","article-title":"Histamine\u2010induced production of interleukin\u20101 alpha from murine bone marrow stromal cells and its inhibition by H2 blockers","volume":"43","author":"Tasaka K","year":"1993","journal-title":"Mol Pharmacol"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36975-2"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2002.01990.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052053"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2012.42.6.185"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2011.01810.x"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2013.130453","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1902\/jop.2013.130453","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2013.130453","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T11:55:49Z","timestamp":1760874949000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2013.130453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1902\/jop.2013.130453"],"URL":"https:\/\/doi.org\/10.1902\/jop.2013.130453","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}