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Pesquisa : D02.033.455.706.690 [Categoria DeCS]
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[PMID]:28337251
[Au] Autor:Steven S; Oelze M; Brandt M; Ullmann E; Kröller-Schön S; Heeren T; Tran LP; Daub S; Dib M; Stalleicken D; Wenzel P; Münzel T; Daiber A
[Ad] Endereço:Center for Cardiology, Department of Cardiology, Mainz, Germany; Center of Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
[Ti] Título:Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension.
[So] Source:Oxid Med Cell Longev;2017:4353462, 2017.
[Is] ISSN:1942-0994
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. . PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. . MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.
[Mh] Termos MeSH primário: Endotelina-1/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Tetranitrato de Pentaeritritol/farmacologia
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Pressão Sanguínea/efeitos dos fármacos
Peso Corporal/efeitos dos fármacos
Linhagem Celular
Ecocardiografia
Endotelina-1/genética
Endotélio Vascular/citologia
Endotélio Vascular/efeitos dos fármacos
Endotélio Vascular/metabolismo
Coração/diagnóstico por imagem
Heme Oxigenase-1/genética
Heme Oxigenase-1/metabolismo
Seres Humanos
Hipertensão Pulmonar/induzido quimicamente
Hipertensão Pulmonar/tratamento farmacológico
Molécula 1 de Adesão Intercelular/genética
Molécula 1 de Adesão Intercelular/metabolismo
Masculino
Monocrotalina/toxicidade
Tetranitrato de Pentaeritritol/uso terapêutico
Ratos
Ratos Wistar
Transdução de Sinais/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endothelin-1); 0 (Vasodilator Agents); 10L39TRG1Z (Pentaerythritol Tetranitrate); 126547-89-5 (Intercellular Adhesion Molecule-1); 73077K8HYV (Monocrotaline); EC 1.14.14.18 (Heme Oxygenase-1); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1155/2017/4353462


  2 / 374 MEDLINE  
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[PMID]:27711976
[Au] Autor:Kubas G; Rees W; Caguiat J; Asch D; Fagan D; Cortes P
[Ad] Endereço:Material Science & Engineering Program, Youngstown State University, Youngstown, Ohio.
[Ti] Título:Identification of peptide sequences that selectively bind to pentaerythritol trinitrate hemisuccinate-a surrogate of PETN, via phage display technology.
[So] Source:Biopolymers;108(2), 2017 Mar.
[Is] ISSN:1097-0282
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The present research investigates the identification of amino acid sequences that selectively bind to a pentaerythritol tetranitrate (PETN) explosive surrogate. Through the use of a phage display technique and enzyme-linked immunosorbent assays (ELISA), a peptide library was tested against pentaerythritol trinitrate hemisuccinate (PETNH), a surrogate of PETN, to screen for those with amino acids having affinity toward the explosive. The results suggest that the library contains peptides selective to PETNH. Following three rounds of panning, clones were picked and tested for specificity toward PETNH. ELISA results from these samples show that each phage clone has some level of selectivity for binding to PETNH. The peptides from these clones have been sequenced and shown to contain certain common amino acid segments among them. This work represents a technological platform for identifying amino-acid sequences selective toward any bio-chem analyte of interest.
[Mh] Termos MeSH primário: Tetranitrato de Pentaeritritol/análogos & derivados
Tetranitrato de Pentaeritritol/química
Biblioteca de Peptídeos
Peptídeos/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Sequência de Bases
Ensaio de Imunoadsorção Enzimática/métodos
Substâncias Explosivas/química
Estrutura Molecular
Tetranitrato de Pentaeritritol/metabolismo
Peptídeos/metabolismo
Análise de Sequência de Proteína/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Explosive Agents); 0 (Peptide Library); 0 (Peptides); 10L39TRG1Z (Pentaerythritol Tetranitrate); 4SL9HWA66P (pentrinitrol)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170424
[Lr] Data última revisão:
170424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161007
[St] Status:MEDLINE
[do] DOI:10.1002/bip.22997


  3 / 374 MEDLINE  
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[PMID]:26971624
[Au] Autor:Giordano BC; Field CR; Andrews B; Lubrano A; Woytowitz M; Rogers D; Collins GE
[Ad] Endereço:Chemistry Division, U.S. Naval Research Laboratory , Washington, D.C. 20375, United States.
[Ti] Título:Trace Explosives Vapor Generation and Quantitation at Parts per Quadrillion Concentrations.
[So] Source:Anal Chem;88(7):3747-53, 2016 Apr 05.
[Is] ISSN:1520-6882
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The generation of trace 2,4,6-trinitrotoluene (TNT), cyclotrimethylenetrinitramine (RDX), and pentaerythritol tetranitrate (PETN) vapors using a pneumatically modulated liquid delivery system (PMLDS) coupled to a polytetrafluoroethylene (PTFE) total-consumption micronebulizer is presented. The vapor generator operates in a continuous manner with final vapor concentrations proportional to the explosive concentration in aqueous solution delivered through the nebulizer and the diluent air flow rate. For quantitation of concentrations in the parts per billionvolume (ppbv) to parts per trillionvolume (pptrv) range, Tenax-TA thermal desorption tubes were used for vapor collection with subsequent analysis on a thermal-desorption system programmable-temperature vaporization gas chromatograph (TDS-PTV-GC) with a µ-ECD detector. With 30 min sample times and an average sampling rate of 100 mL min(-1), vapor concentrations of 38 pptrv for TNT, 25 pptrv for RDX, and 26 pptrv for PETN were determined. For parts per quadrillionvolume (ppqv) vapor quantitation of TNT and RDX, an online PTV-GC system with a negative-ion chemical ionization mass spectrometer (methane reagent gas) was used for direct sampling and capture of the vapor on the PTV inlet. Vapor concentrations as low as 160 ppqv and 710 ppqv for TNT and RDX were quantified, respectively, with an instrument duty cycle as low as 4 min.
[Mh] Termos MeSH primário: Substâncias Explosivas/análise
Tetranitrato de Pentaeritritol/análise
Triazinas/análise
Trinitrotolueno/análise
[Mh] Termos MeSH secundário: Cromatografia Gasosa-Espectrometria de Massas
Nebulizadores e Vaporizadores
Politetrafluoretileno
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Explosive Agents); 0 (Triazines); 10L39TRG1Z (Pentaerythritol Tetranitrate); 118-96-7 (Trinitrotoluene); 9002-84-0 (Polytetrafluoroethylene); W91SSV5831 (cyclonite)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160315
[St] Status:MEDLINE
[do] DOI:10.1021/acs.analchem.5b04581


  4 / 374 MEDLINE  
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[PMID]:26938517
[Au] Autor:Tsyshevsky RV; Zverev A; Mitrofanov A; Rashkeev SN; Kuklja MM
[Ad] Endereço:Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA. rtsyshev@umd.edu.
[Ti] Título:Photochemistry of the α-Al2O3-PETN Interface.
[So] Source:Molecules;21(3):289, 2016 Feb 29.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Optical absorption measurements are combined with electronic structure calculations to explore photochemistry of an α-Al2O3-PETN interface formed by a nitroester (pentaerythritol tetranitrate, PETN, C5H8N4O12) and a wide band gap aluminum oxide (α-Al2O3) substrate. The first principles modeling is used to deconstruct and interpret the α-Al2O3-PETN absorption spectrum that has distinct peaks attributed to surface F°-centers and surface-PETN transitions. We predict the low energy α-Al2O3 F°-center-PETN transition, producing the excited triplet state, and α-Al2O3 F°-center-PETN charge transfer, generating the PETN anion radical. This implies that irradiation by commonly used lasers can easily initiate photodecomposition of both excited and charged PETN at the interface. The feasible mechanism of the photodecomposition is proposed.
[Mh] Termos MeSH primário: Óxido de Alumínio/química
Tetranitrato de Pentaeritritol/química
Processos Fotoquímicos
[Mh] Termos MeSH secundário: Modelos Moleculares
Fotoquímica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
10L39TRG1Z (Pentaerythritol Tetranitrate); LMI26O6933 (Aluminum Oxide)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160304
[St] Status:MEDLINE


  5 / 374 MEDLINE  
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[PMID]:26865581
[Au] Autor:Oztekin EK; Burton DJ; Hahn DW
[Ad] Endereço:Department of Mechanical & Aerospace Engineering, University of Florida, Gainesville, FL, USA.
[Ti] Título:Detection of Explosives Using Differential Laser-Induced Perturbation Spectroscopy with a Raman-based Probe.
[So] Source:Appl Spectrosc;70(4):676-87, 2016 Apr.
[Is] ISSN:1943-3530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Explosives detection is carried out with a novel spectral analysis technique referred to as differential laser-induced perturbation spectroscopy (DLIPS) on thin films of TNT, RDX, HMX, and PETN. The utility of Raman spectroscopy for detection of explosives is enhanced by inducing deep ultraviolet laser perturbation on molecular structures in combination with a differential Raman sensing scheme. Principal components analysis (PCA) is used to quantify the DLIPS method as benchmarked against a traditional Raman scattering probe, and the related photo-induced effects on the molecular structure of the targeted explosives are discussed in detail. Finally, unique detection is observed with TNT samples deposited on commonly available background substrates of nylon and polyester. Overall, the data support DLIPS as a noninvasive method that is promising for screening explosives in real-world environments and backgrounds.
[Mh] Termos MeSH primário: Substâncias Explosivas/análise
Análise Espectral Raman/métodos
[Mh] Termos MeSH secundário: Azocinas/análise
Tetranitrato de Pentaeritritol/análise
Análise de Componente Principal
Triazinas/análise
Trinitrotolueno/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azocines); 0 (Explosive Agents); 0 (Triazines); 10L39TRG1Z (Pentaerythritol Tetranitrate); 118-96-7 (Trinitrotoluene); LLW94W5BSJ (octogen); W91SSV5831 (cyclonite)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170112
[Lr] Data última revisão:
170112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160212
[St] Status:MEDLINE
[do] DOI:10.1177/0003702816629686


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[PMID]:26832872
[Au] Autor:Arbeli Z; Garcia-Bonilla E; Pardo C; Hidalgo K; Velásquez T; Peña L; C ER; Avila-Arias H; Molano-Gonzalez N; Brandão PF; Roldan F
[Ad] Endereço:Unidad de Saneamiento y Biotecnología Ambiental (USBA), Departamento de Biología, Facultad de Ciencias, Pontificia Universidad Javeriana, Cra. 7 N. 43-82, Bogotá, Colombia. zarbeli@javeriana.edu.co.
[Ti] Título:Persistence of pentolite (PETN and TNT) in soil microcosms and microbial enrichment cultures.
[So] Source:Environ Sci Pollut Res Int;23(9):9144-55, 2016 May.
[Is] ISSN:1614-7499
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Pentolite is a mixture (1:1) of 2,4,6-trinitrotoluene (TNT) and pentaerythritol tetranitrate (PETN), and little is known about its fate in the environment. This study was aimed to determine the dissipation of pentolite in soils under laboratory conditions. Microcosm experiments conducted with two soils demonstrated that dissipation rate of PETN was significantly slower than that of TNT. Interestingly, the dissipation of PETN was enhanced by the presence of TNT, while PETN did not enhanced the dissipation of TNT. Pentolite dissipation rate was significantly faster under biostimulation treatment (addition of carbon source) in soil from the artificial wetland, while no such stimulation was observed in soil from detonation field. In addition, the dissipation rate of TNT and PETN in soil from artificial wetland under biostimulation was significantly faster than the equivalent abiotic control, although it seems that non-biological processes might also be important for the dissipation of TNT and PETN. Transformation of PETN was also slower during establishment of enrichment culture using pentolite as the sole nitrogen source. In addition, transformation of these explosives was gradually reduced and practically stopped after the forth cultures transfer (80 days). DGGE analysis of bacterial communities from these cultures indicates that all consortia were dominated by bacteria from the order Burkholderiales and Rhodanobacter. In conclusion, our results suggest that PETN might be more persistent than TNT.
[Mh] Termos MeSH primário: Tetranitrato de Pentaeritritol/análise
Microbiologia do Solo
Poluentes do Solo/análise
Solo/química
Trinitrotolueno/análise
[Mh] Termos MeSH secundário: Bactérias
Betaproteobacteria
Biodegradação Ambiental
Carbono
Substâncias Explosivas/análise
Nitrogênio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Explosive Agents); 0 (Soil); 0 (Soil Pollutants); 10L39TRG1Z (Pentaerythritol Tetranitrate); 118-96-7 (Trinitrotoluene); 7440-44-0 (Carbon); N762921K75 (Nitrogen)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160203
[St] Status:MEDLINE
[do] DOI:10.1007/s11356-016-6133-3


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[PMID]:26777676
[Au] Autor:Kauppila TJ; Flink A; Pukkila J; Ketola RA
[Ad] Endereço:Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland.
[Ti] Título:Analysis of nitrogen-based explosives with desorption atmospheric pressure photoionization mass spectrometry.
[So] Source:Rapid Commun Mass Spectrom;30(4):467-75, 2016 Feb 28.
[Is] ISSN:1097-0231
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Fast methods that allow the in situ analysis of explosives from a variety of surfaces are needed in crime scene investigations and home-land security. Here, the feasibility of the ambient mass spectrometry technique desorption atmospheric pressure photoionization (DAPPI) in the analysis of the most common nitrogen-based explosives is studied. METHODS: DAPPI and desorption electrospray ionization (DESI) were compared in the direct analysis of trinitrotoluene (TNT), trinitrophenol (picric acid), octogen (HMX), cyclonite (RDX), pentaerythritol tetranitrate (PETN), and nitroglycerin (NG). The effect of different additives in DAPPI dopant and in DESI spray solvent on the ionization efficiency was tested, as well as the suitability of DAPPI to detect explosives from a variety of surfaces. RESULTS: The analytes showed ions only in negative ion mode. With negative DAPPI, TNT and picric acid formed deprotonated molecules with all dopant systems, while RDX, HMX, PETN and NG were ionized by adduct formation. The formation of adducts was enhanced by addition of chloroform, formic acid, acetic acid or nitric acid to the DAPPI dopant. DAPPI was more sensitive than DESI for TNT, while DESI was more sensitive for HMX and picric acid. CONCLUSIONS: DAPPI could become an important method for the direct analysis of nitroaromatics from a variety of surfaces. For compounds that are thermally labile, or that have very low vapor pressure, however, DESI is better suited.
[Mh] Termos MeSH primário: Substâncias Explosivas/química
Espectrometria de Massas/métodos
[Mh] Termos MeSH secundário: Espectrometria de Massas/instrumentação
Tetranitrato de Pentaeritritol/análise
Triazinas/análise
Trinitrotolueno/análise
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Explosive Agents); 0 (Triazines); 10L39TRG1Z (Pentaerythritol Tetranitrate); 118-96-7 (Trinitrotoluene); W91SSV5831 (cyclonite)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160119
[St] Status:MEDLINE
[do] DOI:10.1002/rcm.7469


  8 / 374 MEDLINE  
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[PMID]:26463875
[Au] Autor:Hesse A; Biyikal M; Rurack K; Weller MG
[Ad] Endereço:Division 1.5, Protein Analysis, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Strasse 11, 12489, Berlin, Germany.
[Ti] Título:Development of highly sensitive and selective antibodies for the detection of the explosive pentaerythritol tetranitrate (PETN) by bioisosteric replacement.
[So] Source:J Mol Recognit;29(2):88-94, 2016 Feb.
[Is] ISSN:1099-1352
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:An improved antibody against the explosive pentaerythritol tetranitrate (PETN) was developed. The immunogen was designed by the concept of bioisosteric replacement, which led to an excellent polyclonal antibody with extreme selectivity and immunoassays of very good sensitivity. Compounds such as nitroglycerine, 2,4,6-trinitrotoluene, 1,3,5-trinitrobenzene, hexogen (RDX), 2,4,6-trinitroaniline, 1,3-dinitrobenzene, octogen (HMX), triacetone triperoxide, ammonium nitrate, 2,4,6-trinitrophenol and nitrobenzene were tested for potential cross-reactivity. The detection limit of a competitive enzyme-linked immunosorbent assay was determined to be around 0.5 µg/l. The dynamic range of the assay was found to be between 1 and 1000 µg/l, covering a concentration range of three decades. This work shows the successful application of the bioisosteric concept in immunochemistry by exchange of a nitroester to a carbonate diester. The antiserum might be used for the development of quick tests, biosensors, microtitration plate immunoassays, microarrays and other analytical methods for the highly sensitive detection of PETN, an explosive frequently used by terrorists, exploiting the extreme difficulty of its detection.
[Mh] Termos MeSH primário: Anticorpos/metabolismo
Substâncias Explosivas/imunologia
Tetranitrato de Pentaeritritol/imunologia
[Mh] Termos MeSH secundário: Afinidade de Anticorpos
Especificidade de Anticorpos
Técnicas Biossensoriais
Reações Cruzadas
Ensaio de Imunoadsorção Enzimática
Limite de Detecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Explosive Agents); 10L39TRG1Z (Pentaerythritol Tetranitrate)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151015
[St] Status:MEDLINE
[do] DOI:10.1002/jmr.2511


  9 / 374 MEDLINE  
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[PMID]:26351029
[Au] Autor:Wenzel P
[Ad] Endereço:From the Department of Medicine 2, the Center for Thrombosis and Hemostasis and the German Center for Cardiovascular Research (DZHK), partner site RhineMain, University Medical Center Mainz, Mainz, Germany. wenzelp@uni-mainz.de.
[Ti] Título:Organic Nitrates in Heart Failure Revisited: Pentaerythritol Tetranitrate Induces Heme Oxygenase 1 to Protect the Myocardium.
[So] Source:Hypertension;66(5):933-4, 2015 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Insuficiência Cardíaca/tratamento farmacológico
Ventrículos do Coração/fisiopatologia
Miocárdio/metabolismo
Tetranitrato de Pentaeritritol/farmacologia
Tetranitrato de Pentaeritritol/uso terapêutico
Espécies Reativas de Oxigênio/metabolismo
Remodelação Ventricular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Masculino
[Pt] Tipo de publicação:COMMENT; EDITORIAL
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 10L39TRG1Z (Pentaerythritol Tetranitrate)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:160726
[Lr] Data última revisão:
160726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150910
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.115.06035


  10 / 374 MEDLINE  
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[PMID]:26351025
[Au] Autor:Fraccarollo D; Galuppo P; Neuser J; Bauersachs J; Widder JD
[Ad] Endereço:From the Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hanover, Germany.
[Ti] Título:Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure.
[So] Source:Hypertension;66(5):978-87, 2015 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reduced nitric oxide bioavailability contributes to progression of cardiac dysfunction and remodeling in ischemic heart failure. Clinical use of organic nitrates as nitric oxide donors is limited by development of nitrate tolerance and reactive oxygen species formation. We investigated the effects of long-term therapy with pentaerythritol tetranitrate (PETN), an organic nitrate devoid of tolerance, in rats with congestive heart failure after extensive myocardial infarction. Seven days after coronary artery ligation, rats were randomly allocated to treatment with PETN (80 mg/kg BID) or placebo for 9 weeks. Long-term PETN therapy prevented the progressive left ventricular dilatation and improved left ventricular contractile function and relaxation in rats with congestive heart failure. Mitochondrial superoxide anion production was markedly increased in the failing left ventricular myocardium and nearly normalized by PETN treatment. Gene set enrichment analysis revealed that PETN beneficially modulated the dysregulation of mitochondrial genes involved in energy metabolism, paralleled by prevention of uncoupling protein-3, thioredoxin-2, and superoxide dismutase-2 downregulation. Moreover, PETN provided a remarkable protective effect against reactive fibrosis in chronically failing hearts. Mechanistically, induction of heme oxygenase-1 by PETN prevented mitochondrial superoxide generation, NOX4 upregulation, and ensuing formation of extracellular matrix proteins in fibroblasts from failing hearts. In summary, PETN targeting reactive oxygen species generation prevented the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance. Therefore, PETN might be a promising therapeutic option in the treatment of ischemic heart diseases involving oxidative stress and impairment in nitric oxide bioactivity.
[Mh] Termos MeSH primário: Insuficiência Cardíaca/tratamento farmacológico
Ventrículos do Coração/fisiopatologia
Miocárdio/metabolismo
Tetranitrato de Pentaeritritol/farmacologia
Tetranitrato de Pentaeritritol/uso terapêutico
Espécies Reativas de Oxigênio/metabolismo
Remodelação Ventricular/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Disponibilidade Biológica
Modelos Animais de Doenças
Insuficiência Cardíaca/fisiopatologia
Ventrículos do Coração/efeitos dos fármacos
Masculino
Óxido Nítrico/metabolismo
Óxido Nítrico Sintase Tipo III/metabolismo
Ratos
Superóxido Dismutase/metabolismo
Superóxidos/metabolismo
Resultado do Tratamento
Vasodilatadores/farmacologia
Vasodilatadores/uso terapêutico
Remodelação Ventricular/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 0 (Vasodilator Agents); 10L39TRG1Z (Pentaerythritol Tetranitrate); 11062-77-4 (Superoxides); 31C4KY9ESH (Nitric Oxide); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 1.15.1.1 (Superoxide Dismutase); EC 1.15.1.1 (superoxide dismutase 2)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:160726
[Lr] Data última revisão:
160726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150910
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.115.05931



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