Atividade das enzimas do sistema purinérgico em plaquetas de pacientes com mieloma múltiplo

Detalhes bibliográficos
Autor(a) principal: Andrade, Sabrina Fontana de
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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spelling 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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