Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200121
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dc.contributor.CRUESPUNIVERSIDADE DE ESTADUAL DE CAMPINASpt_BR
dc.typeArtigo de periódicopt_BR
dc.titleHydroxyurea And A Cgmp-amplifying Agent Have Immediate Benefits On Acute Vaso-occlusive Events In Sickle Cell Disease Mice.pt_BR
dc.contributor.authorAlmeida, Camila Bononipt_BR
dc.contributor.authorScheiermann, Christophpt_BR
dc.contributor.authorJang, Jung-Eunpt_BR
dc.contributor.authorProphete, Colettept_BR
dc.contributor.authorCosta, Fernando Ferreirapt_BR
dc.contributor.authorConran, Nicolapt_BR
dc.contributor.authorFrenette, Paul Spt_BR
unicamp.authorCamila Bononi Almeida, Hematology and Hemotherapy Center, Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), UNICAMP, Campinas, São Paulo, Brazil.pt_BR
unicamp.author.externalChristoph Scheiermann,pt
unicamp.author.externalJung-Eun Jang,pt
unicamp.author.externalColette Prophete,pt
unicamp.author.externalFernando Ferreira Costa,pt
unicamp.author.externalNicola Conran,pt
unicamp.author.externalPaul S Frenette,pt
dc.subject3',5'-cyclic-amp Phosphodiesterasespt_BR
dc.subjectAcute Diseasept_BR
dc.subjectAnemia, Sickle Cellpt_BR
dc.subjectAnimalspt_BR
dc.subjectAntisickling Agentspt_BR
dc.subjectCell Adhesionpt_BR
dc.subjectCell Communicationpt_BR
dc.subjectCyclic Gmppt_BR
dc.subjectDisease Models, Animalpt_BR
dc.subjectEndothelium, Vascularpt_BR
dc.subjectErythrocytespt_BR
dc.subjectFemalept_BR
dc.subjectHumanspt_BR
dc.subjectHydroxyureapt_BR
dc.subjectLeukocyte Rollingpt_BR
dc.subjectLeukocytespt_BR
dc.subjectMalept_BR
dc.subjectMicept_BR
dc.subjectMice, Inbred C57blpt_BR
dc.subjectPyrazolespt_BR
dc.subjectPyrimidinespt_BR
dc.subjectTumor Necrosis Factor-alphapt_BR
dc.subjectVascular Diseasespt_BR
dc.description.abstractInhibition of leukocyte adhesion to the vascular endothelium represents a novel and important approach for decreasing sickle cell disease (SCD) vaso-occlusion. Using a humanized SCD-mouse-model of tumor necrosis factor-α-induced acute vaso-occlusion, we herein present data demonstrating that short-term administration of either hydroxyurea or the phosphodiesterase 9 (PDE9) inhibitor, BAY73-6691, significantly altered leukocyte recruitment to the microvasculature. Notably, the administration of both agents led to marked improvements in leukocyte rolling and adhesion and decreased heterotypic red blood cell-leukocyte interactions, coupled with prolonged animal survival. Mechanistically, these rheologic benefits were associated with decreased endothelial adhesion molecule expression, as well as diminished leukocyte Mac-1-integrin activation and cyclic guanosine monophosphate (cGMP)-signaling, leading to reduced leukocyte recruitment. Our findings indicate that hydroxyurea has immediate beneficial effects on the microvasculature in acute sickle-cell crises that are independent of the drug's fetal hemoglobin-elevating properties and probably involve the formation of intravascular nitric oxide. In addition, inhibition of PDE9, an enzyme highly expressed in hematopoietic cells, amplified the cGMP-elevating effects of hydroxyurea and may represent a promising and more tissue-specific adjuvant therapy for this disease.en
dc.relation.ispartofBloodpt_BR
dc.relation.ispartofabbreviationBloodpt_BR
dc.date.issued2012-Octpt_BR
dc.identifier.citationBlood. v. 120, n. 14, p. 2879-88, 2012-Oct.pt_BR
dc.language.isoengpt_BR
dc.description.volume120pt_BR
dc.description.firstpage2879-88pt_BR
dc.rightsfechadopt_BR
dc.rights.holderpt_BR
dc.sourcePubMedpt_BR
dc.identifier.issn1528-0020pt_BR
dc.identifier.doi10.1182/blood-2012-02-409524pt_BR
dc.identifier.urlhttp://www.ncbi.nlm.nih.gov/pubmed/22833547pt_BR
dc.date.available2015-11-27T13:28:45Z-
dc.date.accessioned2015-11-27T13:28:45Z-
dc.description.provenanceMade available in DSpace on 2015-11-27T13:28:45Z (GMT). No. of bitstreams: 1 pmed_22833547.pdf: 605435 bytes, checksum: 232b96084589db730139714875cc04a2 (MD5) Previous issue date: 2012en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/200121-
dc.identifier.idPubmed22833547pt_BR
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