Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
dARK ID: | ark:/26339/001300000pz7w |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18107 |
Resumo: | Multiple myeloma (MM) is characterized as a tumor of plasma cells which corresponds to approximately 10 % of haematological malignancies. Nowadays it is considered as an incurable disease, which can present complications such as bleeding or thrombosis. Hemostasis is the balance between procoagulant and anticoagulant systems aiming to prevent blood loss. The enzymes ectonucleotidases present on platelet surface are responsible for the regulation of extracellular levels of adenine nucleotides. ADP and ATP, as well as the nucleoside adenosine have been involved in a large number of physiological functions: ADP is the main platelets recruitment factor, while ATP is a competitive inhibitor of ADP-induced aggregation. Adenosine is a molecule able to induce vasodilation and inhibit platelet aggregation. Platelet activation process is accompanied by the secretion of platelet proteins such as platelet factor 4 (PF4) and increased formation of thromboxane (TXA2). Considering these concepts the aim of this study was to evaluate the activity of ecto-enzymes (E- NTPDase, 5'- nucleotidase and E -ADA) in platelets and measuring concentration of PF4 and TXA2 in patients with MM. The results showed a reduction in the E-NTPDase activity for ATP hydrolysis in both treated (p<0,001) patients and in those who were not receiving treatment (p<0,05) for MM in the period of blood samples collection. This reduction can result in a decrease in extracellular levels of ADP, as this enzyme is responsible for conversion of ATP into ADP, which would reduce platelet aggregation in patients with MM. When we evaluated the enzyme E- 5'- nucleotidase, no statistical difference was observed concerning its activity in these patients. An increase in E- ADA activity (p<0,001) was observed in patients with MM performing treatment, this may have occurred as a physiological response to increase of adenosine in these patients. Adenosine has vasoprotective and antiplatelet property and its increase can be related to the medicines used for these patients. Dosages of PF4 and TXB2 (stable metabolite of TXA2) showed lower values of these substances in MM untreated (p< 0,05; p< 0,001) and MM treated patients (p< 0,01; p< 0,001) in the control group. These data reveal a lower capacity aggregation and platelet activation in patients with MM, and highlight the participation of purinergic signaling in hemostasis in these patients. |
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Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiploActivity of the purinergic system enzyme in platelets of multiple mieloma patientsMieloma múltiploSistema purinérgicoPlaquetasADPATPAdenosinaMultiple myelomaPurinergic systemPlateletsAdenosineCNPQ::CIENCIAS DA SAUDE::FARMACIAMultiple myeloma (MM) is characterized as a tumor of plasma cells which corresponds to approximately 10 % of haematological malignancies. Nowadays it is considered as an incurable disease, which can present complications such as bleeding or thrombosis. Hemostasis is the balance between procoagulant and anticoagulant systems aiming to prevent blood loss. The enzymes ectonucleotidases present on platelet surface are responsible for the regulation of extracellular levels of adenine nucleotides. ADP and ATP, as well as the nucleoside adenosine have been involved in a large number of physiological functions: ADP is the main platelets recruitment factor, while ATP is a competitive inhibitor of ADP-induced aggregation. Adenosine is a molecule able to induce vasodilation and inhibit platelet aggregation. Platelet activation process is accompanied by the secretion of platelet proteins such as platelet factor 4 (PF4) and increased formation of thromboxane (TXA2). Considering these concepts the aim of this study was to evaluate the activity of ecto-enzymes (E- NTPDase, 5'- nucleotidase and E -ADA) in platelets and measuring concentration of PF4 and TXA2 in patients with MM. The results showed a reduction in the E-NTPDase activity for ATP hydrolysis in both treated (p<0,001) patients and in those who were not receiving treatment (p<0,05) for MM in the period of blood samples collection. This reduction can result in a decrease in extracellular levels of ADP, as this enzyme is responsible for conversion of ATP into ADP, which would reduce platelet aggregation in patients with MM. When we evaluated the enzyme E- 5'- nucleotidase, no statistical difference was observed concerning its activity in these patients. An increase in E- ADA activity (p<0,001) was observed in patients with MM performing treatment, this may have occurred as a physiological response to increase of adenosine in these patients. Adenosine has vasoprotective and antiplatelet property and its increase can be related to the medicines used for these patients. Dosages of PF4 and TXB2 (stable metabolite of TXA2) showed lower values of these substances in MM untreated (p< 0,05; p< 0,001) and MM treated patients (p< 0,01; p< 0,001) in the control group. These data reveal a lower capacity aggregation and platelet activation in patients with MM, and highlight the participation of purinergic signaling in hemostasis in these patients.O mieloma múltiplo (MM) caracteriza-se como um tumor de células plasmocitárias que corresponde a aproximadamente 10% das neoplasias hematológicas. Até os dias de hoje é considerada como uma doença incurável, que pode durante o seu percurso, apresentar complicações como sangramentos ou trombose. A hemostasia é o equilíbrio entre pró-coagulantes e anticoagulantes, com o objetivo de prevenir a perda de sangue. As ectonucleotidases, presentes na superfície plaquetária, são responsáveis pela regulação dos níveis extracelulares de nucleotídeos de adenina. ATP e ADP, bem como o nucleosídeo adenosina, têm sido implicados em um grande número de funções fisiológicas: o ADP é o principal fator recrutador de plaquetas, enquanto que o ATP é um inibidor competitivo da agregação induzida por ADP. A adenosina é uma molécula capaz de induzir vasodilatação e inibir a agregação plaquetária. O processo de ativação plaquetária é acompanhado pela secreção de proteínas plaquetárias, como o fator 4 plaquetário (PF4) e o aumento da formação de tromboxano (TXA2). Sendo assim, o objetivo deste trabalho foi avaliar a atividade das ecto-enzimas (E-NTPDase, E-5’-nucleotidase e E-ADA) nas plaquetas e mensurar as concentrações de PF4 e TXA2 em pacientes com MM. Os resultados demonstraram uma redução significativa na atividade da E-NTPDase para hidrólise de ATP tanto nos pacientes tratados (p<0,001) como naqueles que estavam sem receber tratamento (p<0,05) para MM. Essa redução pode acarretar em uma diminuição dos níveis extracelulares de ADP, já que essa enzima é responsável pela conversão de ATP em ADP, o que estaria reduzindo a agregação plaquetária nos pacientes com MM. Quando avaliou-se a atividade da enzima E-5’-nucleotidase, nenhuma diferença estatística foi observada nesses pacientes. Um aumento significativo (p<0,001) na atividade da E-ADA foi observado nos pacientes com MM realizando tratamento, podendo esse ter ocorrido como uma resposta fisiológica ao aumento de adenosina nesses pacientes. A adenosina tem propriedade antiagregante e vasoprotetora e o seu aumento pode estar relacionado com os medicamentos utilizados por esses pacientes. As dosagens de PF4 e TXB2 (metabólito estável do TXA2) revelaram valores séricos menores dessas substâncias nos pacientes com MM não tratados (p<0,05; p<0,001) e MM tratados (p< 0,01; p< 0,001) em relação ao grupo controle. Esses dados revelam uma menor capacidade de agregação e ativação de plaquetas nos pacientes com MM, e evidenciam a participação da sinalização purinérgica na hemostasia desses pacientes.Universidade Federal de Santa MariaBrasilAnálises Clínicas e ToxicológicasUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeSilva, José Edson Paz dahttp://lattes.cnpq.br/1177504021154172Leal, Daniela Bitencourt Rosahttp://lattes.cnpq.br/3639683273462361Fleck, Julianahttp://lattes.cnpq.br/1497762896019410Paniz, Clóvishttp://lattes.cnpq.br/3269590432120855Andrade, Sabrina Fontana de2019-09-02T14:08:56Z2019-09-02T14:08:56Z2016-08-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18107ark:/26339/001300000pz7wporAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-10T15:23:01Zoai:repositorio.ufsm.br:1/18107Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-10T15:23:01Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo Activity of the purinergic system enzyme in platelets of multiple mieloma patients |
title |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
spellingShingle |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo Andrade, Sabrina Fontana de Mieloma múltiplo Sistema purinérgico Plaquetas ADP ATP Adenosina Multiple myeloma Purinergic system Platelets Adenosine CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
title_full |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
title_fullStr |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
title_full_unstemmed |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
title_sort |
Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo |
author |
Andrade, Sabrina Fontana de |
author_facet |
Andrade, Sabrina Fontana de |
author_role |
author |
dc.contributor.none.fl_str_mv |
Silva, José Edson Paz da http://lattes.cnpq.br/1177504021154172 Leal, Daniela Bitencourt Rosa http://lattes.cnpq.br/3639683273462361 Fleck, Juliana http://lattes.cnpq.br/1497762896019410 Paniz, Clóvis http://lattes.cnpq.br/3269590432120855 |
dc.contributor.author.fl_str_mv |
Andrade, Sabrina Fontana de |
dc.subject.por.fl_str_mv |
Mieloma múltiplo Sistema purinérgico Plaquetas ADP ATP Adenosina Multiple myeloma Purinergic system Platelets Adenosine CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Mieloma múltiplo Sistema purinérgico Plaquetas ADP ATP Adenosina Multiple myeloma Purinergic system Platelets Adenosine CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Multiple myeloma (MM) is characterized as a tumor of plasma cells which corresponds to approximately 10 % of haematological malignancies. Nowadays it is considered as an incurable disease, which can present complications such as bleeding or thrombosis. Hemostasis is the balance between procoagulant and anticoagulant systems aiming to prevent blood loss. The enzymes ectonucleotidases present on platelet surface are responsible for the regulation of extracellular levels of adenine nucleotides. ADP and ATP, as well as the nucleoside adenosine have been involved in a large number of physiological functions: ADP is the main platelets recruitment factor, while ATP is a competitive inhibitor of ADP-induced aggregation. Adenosine is a molecule able to induce vasodilation and inhibit platelet aggregation. Platelet activation process is accompanied by the secretion of platelet proteins such as platelet factor 4 (PF4) and increased formation of thromboxane (TXA2). Considering these concepts the aim of this study was to evaluate the activity of ecto-enzymes (E- NTPDase, 5'- nucleotidase and E -ADA) in platelets and measuring concentration of PF4 and TXA2 in patients with MM. The results showed a reduction in the E-NTPDase activity for ATP hydrolysis in both treated (p<0,001) patients and in those who were not receiving treatment (p<0,05) for MM in the period of blood samples collection. This reduction can result in a decrease in extracellular levels of ADP, as this enzyme is responsible for conversion of ATP into ADP, which would reduce platelet aggregation in patients with MM. When we evaluated the enzyme E- 5'- nucleotidase, no statistical difference was observed concerning its activity in these patients. An increase in E- ADA activity (p<0,001) was observed in patients with MM performing treatment, this may have occurred as a physiological response to increase of adenosine in these patients. Adenosine has vasoprotective and antiplatelet property and its increase can be related to the medicines used for these patients. Dosages of PF4 and TXB2 (stable metabolite of TXA2) showed lower values of these substances in MM untreated (p< 0,05; p< 0,001) and MM treated patients (p< 0,01; p< 0,001) in the control group. These data reveal a lower capacity aggregation and platelet activation in patients with MM, and highlight the participation of purinergic signaling in hemostasis in these patients. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-08-02 2019-09-02T14:08:56Z 2019-09-02T14:08:56Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18107 |
dc.identifier.dark.fl_str_mv |
ark:/26339/001300000pz7w |
url |
http://repositorio.ufsm.br/handle/1/18107 |
identifier_str_mv |
ark:/26339/001300000pz7w |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Análises Clínicas e Toxicológicas UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1815172376249237504 |