Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato

Detalhes bibliográficos
Ano de defesa: 2014
Autor(a) principal: Soccal, Renata Mezomo lattes
Orientador(a): Silva, José Edson Paz da lattes
Banca de defesa: Araújo, Maria do Carmo dos Santos, Beck, Sandra Trevisan
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Centro de Ciências da Saúde
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Farmacêuticas
Departamento: Farmácia
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/28277
Resumo: The Acquired Immunodeficiency Syndrome (AIDS) is a disease of infectious origin, caused by the human immunodeficiency virus (HIV). The virus infects primarily helper T CD4+ lymphocytes, generating a severe immunosuppression and increased susceptibility to infections. Highly active antiretroviral therapy (HAART) significantly reduces viral load and restores the immune system. The infection requires monitoring throughout life and compliance failures and adverse effects of the medication are factors limiting treatment. The reasons for these effects appear to be multifactorial and between them are metabolic disorders, toxicity of antiretroviral drugs and the impact of viral replication, resulting in an increase of non-AIDS-related diseases, subclinical atherosclerosis and endothelial dysfunction. It is known that the endothelium plays a central role in maintaining vascular health. HIV-positive patients have impaired endothelial function and one of the major causes of morbidity and premature mortality are cardiovascular complications. In this context it was demonstrated that the loss of endothelial cells in vivo and in vitro, may involve the formation of reactive nitrogen species (RNS) and alter the bioavailability of nitric oxide (NO). Many regulatory mechanisms of the cardiovascular system have the involvement of NO, including vascular tone, vascular structure and cell-cell interactions in blood vessels. Studies have been conducted to elucidate the role of NO in vascular diseases. But there are few reports on the levels of this marker in HIV positive patients. Thus, the main objective of this study was to investigated the levels of nitrite/nitrate (NOx) in HIV-infected patients and verified whether the levels of this marker would alter with HAART. One hundred forty-seven volunteers were included in this case-control study. The subjects were divided into two groups: HIV-infected patients (n=101) and healthy subjects (n=46).Then, the HIV-infected patients were divided into two groups: HIV-infected patients on highly active antiretroviral therapy (HAART) (n=83) and HIV-infected patients without HAART (n=18). It was demonstrated that HIV-infected patients had significantly lower NOx levels [62.4 (28.4-116.0) μmol/L] than healthy individuals [86.8 (56.1-137.5) μmol/L]. Additionally, it was also found significantly lower NOx levels among treated [60.8 (27.9-105.4) μmol/L] compared to untreated patients [127.0 (36.2-277.1) μmol/L]. The findings suggest that these changes may be an important mechanism that predisposes patients to have a cardiovascular outcome and thus, the maintenance of these levels within the normal range may be a therapeutic strategy to reduce cardiovascular disease.
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spelling 2023-03-20T13:50:15Z2023-03-20T13:50:15Z2014-07-09http://repositorio.ufsm.br/handle/1/28277The Acquired Immunodeficiency Syndrome (AIDS) is a disease of infectious origin, caused by the human immunodeficiency virus (HIV). The virus infects primarily helper T CD4+ lymphocytes, generating a severe immunosuppression and increased susceptibility to infections. Highly active antiretroviral therapy (HAART) significantly reduces viral load and restores the immune system. The infection requires monitoring throughout life and compliance failures and adverse effects of the medication are factors limiting treatment. The reasons for these effects appear to be multifactorial and between them are metabolic disorders, toxicity of antiretroviral drugs and the impact of viral replication, resulting in an increase of non-AIDS-related diseases, subclinical atherosclerosis and endothelial dysfunction. It is known that the endothelium plays a central role in maintaining vascular health. HIV-positive patients have impaired endothelial function and one of the major causes of morbidity and premature mortality are cardiovascular complications. In this context it was demonstrated that the loss of endothelial cells in vivo and in vitro, may involve the formation of reactive nitrogen species (RNS) and alter the bioavailability of nitric oxide (NO). Many regulatory mechanisms of the cardiovascular system have the involvement of NO, including vascular tone, vascular structure and cell-cell interactions in blood vessels. Studies have been conducted to elucidate the role of NO in vascular diseases. But there are few reports on the levels of this marker in HIV positive patients. Thus, the main objective of this study was to investigated the levels of nitrite/nitrate (NOx) in HIV-infected patients and verified whether the levels of this marker would alter with HAART. One hundred forty-seven volunteers were included in this case-control study. The subjects were divided into two groups: HIV-infected patients (n=101) and healthy subjects (n=46).Then, the HIV-infected patients were divided into two groups: HIV-infected patients on highly active antiretroviral therapy (HAART) (n=83) and HIV-infected patients without HAART (n=18). It was demonstrated that HIV-infected patients had significantly lower NOx levels [62.4 (28.4-116.0) μmol/L] than healthy individuals [86.8 (56.1-137.5) μmol/L]. Additionally, it was also found significantly lower NOx levels among treated [60.8 (27.9-105.4) μmol/L] compared to untreated patients [127.0 (36.2-277.1) μmol/L]. The findings suggest that these changes may be an important mechanism that predisposes patients to have a cardiovascular outcome and thus, the maintenance of these levels within the normal range may be a therapeutic strategy to reduce cardiovascular disease.A Síndrome da Imunodeficiência Adquirida (AIDS) é uma doença de origem infecciosa, causada pelo vírus da Imunodeficiência Humana (HIV). O vírus infecta principalmente linfócitos T auxiliares CD4+, gerando uma severa imunodepressão e maior susceptibilidade a infecções. A terapia antirretroviral de alta eficácia (HAART) reduz significativamente a carga viral e restabelece o sistema imune. A infecção requer acompanhamento do paciente ao longo de toda a vida, e a falha na adesão e os efeitos adversos provocados pela medicação são fatores limitantes do tratamento. As razões para estes efeitos parecem ser multifatoriais e entre ela temos os distúrbios metabólicos, a toxicidade dos antirretrovirais (ARV) e o impacto da replicação viral, resultando em aumento de doenças não relacionadas à AIDS, aterosclerose subclínica e disfunção endotelial. Sabe-se que o endotélio desempenha um papel fundamental na saúde vascular. Pacientes HIV positivos possuem a função endotelial prejudicada, e uma das importantes causas de morbidade e mortalidade prematuras são as complicações cardiovasculares. Nesse contexto, já foi demonstrado que o prejuízo das células endoteliais, in vivo e in vitro, pode envolver a formação de espécies reativas de nitrogênio (ERNs) e alterar a biodisponibilidade do óxido nítrico (NO). Muitos mecanismos regulatórios do sistema cardiovascular têm o envolvimento do NO, incluindo o tônus vascular, a estrutura vascular e as interações célula-célula nos vasos sanguíneos. Estudos têm sido realizados a fim de elucidar o papel do NO nas doenças vasculares. Porém, existem poucos relatos sobre os níveis deste marcador em pacientes HIV positivos. Assim, o principal objetivo deste trabalho foi avaliar os níveis de nitrito/nitrato (NOX), metabólitos do NO, em pacientes HIV positivos e verificar sua possível alteração com o uso da HAART. Para isso, foram dosados os níveis séricos de NOx em 101 pacientes HIV positivos, dos quais 18 não faziam uso da medicação, e em 46 pacientes HIV negativos. Os pacientes HIV positivos apresentaram níveis de NOx [62.4 (28.4-116.0) μmol/L] inferiores aos do gupo controle [86.8 (56.1-137.5) μmol/L]. Quando comparados conforme o uso ou não do tratamento, pacientes em HAART tiveram concentrações dos metabólitos ainda menores [60.8(27.9-105.4) μmol/L] em relação aos não tratados [127.0(36.2-277.1) μmol/L]. Os achados sugerem que estas diminuições podem ser um importante mecanismo que predispõe os pacientes a terem um desfecho cardiovascular. Sendo assim, a manutenção destes níveis dentro dos limites normais pode ser uma estratégia terapêutica para reduzir as doenças cardiovasculares.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmáciaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessVírus da Imunodeficiência HumanaSíndrome da Imunodeficiência AdquiridaTerapia antiretroviral de alta eficáciaÓxido nítiricoDoença CardiovascularHuman immunodeficiency virusAcquired Immunodeficiency SyndromeHighly active antiretroviral therapyNitric oxideCardiovascular diseaseCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitratoEvaluation of nitric oxide metabolites in HIV infection and the impact of antiretroviral therapy on serum levels of nitrite/nitrateinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSilva, José Edson Paz dahttp://lattes.cnpq.br/1177504021154172Araújo, Maria do Carmo dos SantosBeck, Sandra Trevisanhttp://lattes.cnpq.br/4399153513460201Soccal, Renata Mezomo400300000005600600600600600f31cbb2c-a6b3-42b5-99ec-4f7ceeff6149c3818930-6e7f-4814-a13c-b59d0e46656aa1aecbf7-12b6-4e17-932d-5d1c71f20541ff109cf6-4409-4de1-964c-747a898bcd42reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/28277/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD52ORIGINALDIS_PPGCF_2014_SOCCAL_RENATA.pdfDIS_PPGCF_2014_SOCCAL_RENATA.pdfDissertação de mestradoapplication/pdf1208543http://repositorio.ufsm.br/bitstream/1/28277/1/DIS_PPGCF_2014_SOCCAL_RENATA.pdfb60319566b3f277e933df6ba771a3338MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/28277/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD531/282772023-03-20 10:50:15.984oai:repositorio.ufsm.br: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ório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132023-03-20T13:50:15Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
dc.title.alternative.eng.fl_str_mv Evaluation of nitric oxide metabolites in HIV infection and the impact of antiretroviral therapy on serum levels of nitrite/nitrate
title Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
spellingShingle Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
Soccal, Renata Mezomo
Vírus da Imunodeficiência Humana
Síndrome da Imunodeficiência Adquirida
Terapia antiretroviral de alta eficácia
Óxido nítirico
Doença Cardiovascular
Human immunodeficiency virus
Acquired Immunodeficiency Syndrome
Highly active antiretroviral therapy
Nitric oxide
Cardiovascular disease
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
title_full Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
title_fullStr Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
title_full_unstemmed Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
title_sort Avaliação dos metabólitos do óxido nítrico na infecção pelo HIV e impacto da terapia antirretroviral sobre as concentrações séricas de nitrito/nitrato
author Soccal, Renata Mezomo
author_facet Soccal, Renata Mezomo
author_role author
dc.contributor.advisor1.fl_str_mv Silva, José Edson Paz da
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1177504021154172
dc.contributor.referee1.fl_str_mv Araújo, Maria do Carmo dos Santos
dc.contributor.referee2.fl_str_mv Beck, Sandra Trevisan
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4399153513460201
dc.contributor.author.fl_str_mv Soccal, Renata Mezomo
contributor_str_mv Silva, José Edson Paz da
Araújo, Maria do Carmo dos Santos
Beck, Sandra Trevisan
dc.subject.por.fl_str_mv Vírus da Imunodeficiência Humana
Síndrome da Imunodeficiência Adquirida
Terapia antiretroviral de alta eficácia
Óxido nítirico
Doença Cardiovascular
topic Vírus da Imunodeficiência Humana
Síndrome da Imunodeficiência Adquirida
Terapia antiretroviral de alta eficácia
Óxido nítirico
Doença Cardiovascular
Human immunodeficiency virus
Acquired Immunodeficiency Syndrome
Highly active antiretroviral therapy
Nitric oxide
Cardiovascular disease
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Human immunodeficiency virus
Acquired Immunodeficiency Syndrome
Highly active antiretroviral therapy
Nitric oxide
Cardiovascular disease
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description The Acquired Immunodeficiency Syndrome (AIDS) is a disease of infectious origin, caused by the human immunodeficiency virus (HIV). The virus infects primarily helper T CD4+ lymphocytes, generating a severe immunosuppression and increased susceptibility to infections. Highly active antiretroviral therapy (HAART) significantly reduces viral load and restores the immune system. The infection requires monitoring throughout life and compliance failures and adverse effects of the medication are factors limiting treatment. The reasons for these effects appear to be multifactorial and between them are metabolic disorders, toxicity of antiretroviral drugs and the impact of viral replication, resulting in an increase of non-AIDS-related diseases, subclinical atherosclerosis and endothelial dysfunction. It is known that the endothelium plays a central role in maintaining vascular health. HIV-positive patients have impaired endothelial function and one of the major causes of morbidity and premature mortality are cardiovascular complications. In this context it was demonstrated that the loss of endothelial cells in vivo and in vitro, may involve the formation of reactive nitrogen species (RNS) and alter the bioavailability of nitric oxide (NO). Many regulatory mechanisms of the cardiovascular system have the involvement of NO, including vascular tone, vascular structure and cell-cell interactions in blood vessels. Studies have been conducted to elucidate the role of NO in vascular diseases. But there are few reports on the levels of this marker in HIV positive patients. Thus, the main objective of this study was to investigated the levels of nitrite/nitrate (NOx) in HIV-infected patients and verified whether the levels of this marker would alter with HAART. One hundred forty-seven volunteers were included in this case-control study. The subjects were divided into two groups: HIV-infected patients (n=101) and healthy subjects (n=46).Then, the HIV-infected patients were divided into two groups: HIV-infected patients on highly active antiretroviral therapy (HAART) (n=83) and HIV-infected patients without HAART (n=18). It was demonstrated that HIV-infected patients had significantly lower NOx levels [62.4 (28.4-116.0) μmol/L] than healthy individuals [86.8 (56.1-137.5) μmol/L]. Additionally, it was also found significantly lower NOx levels among treated [60.8 (27.9-105.4) μmol/L] compared to untreated patients [127.0 (36.2-277.1) μmol/L]. The findings suggest that these changes may be an important mechanism that predisposes patients to have a cardiovascular outcome and thus, the maintenance of these levels within the normal range may be a therapeutic strategy to reduce cardiovascular disease.
publishDate 2014
dc.date.issued.fl_str_mv 2014-07-09
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Centro de Ciências da Saúde
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Centro de Ciências da Saúde
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