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[PMID]: 29325311 [Ti] Título: [Effects of trimetazidine, a myocardial metabolism agent, on regulating 5-hydroxytrytamine system of rats with myocardial infarction and/or depression]. [So] Source: Zhonghua Nei Ke Za Zhi;57(1):48-53, 2018 Jan 01. [Is] ISSN: 0578-1426 [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: 5-Hydroxytrytamine (5-HT) system was reported to be associated with myocardial infarction (MI) and depression. The aim of the present study was to study the effect of trimetazidine on 5-HT in MI and/or depression rats. Ninety rats were divided into three groups: trimetazidine, sertraline and saline groups ( 30 in each group), and pretreated with trimetazidine, sertarline, or saline, respectively, by gavage once a day for 4 weeks. Thereafter, each group was further divided into three subgroups: MI subgroup, depression subgroup, and MI+ depression subgroup. Serum 5-HT, platelet 5-HT, 5-HT(2A) receptor (5-HT(2A)R), and serotonin transporter (SERT) were detected by enzyme linked immunosorbent assay. Similar to sertarline, comparing to saline, trimetazidine treatment increased serum 5-HT [(221±23) pg/ml vs. (176±11) pg/ml; (395±31) pg/ml vs. (195±5) pg/ml; (348±28) pg/ml vs. (183±10) pg/ml], platelet 5-HT [(305±22) pg/ml vs. (130±27) pg/ml; (252±18) pg/ml vs. (175±5) pg/ml; (241±26) pg/ml vs. (181±11) pg/ml], and platelet 5-HT(2A)R levels [(247±13) pg/ml vs. (197±12) pg/ml; (320±13) pg/ml vs. (193±18)pg/ml; (334±17) pg/ml vs. (206±15) pg/ml]), and lowered platelet SERT levels [(248±11) pg/ml vs. (323±36) pg/ml; (188±7) pg/ml vs. (278±20) pg/ml; (170±23) pg/ml vs. (282±22) pg/ml] in MI, depression and MI+ depression subgroups, respectively (all 0.05). When compared the effect of trimetazidine and sertarline treatment, serum 5-HT and platelet 5-HT(2A)R in MI group were significantly lower in trimetazidine than in sertraline group ( 0.05), while serum 5-HT and platelet 5-HT, 5-HT(2A)R in depression group rats were significantly higher in trimetazidine than in sertraline group ( 0.05).Interestingly, platelet 5-HT(2A)R in MI+ depression rats was much higher in trimetazidine than in sertraline group ( 0.05). Trimetazidine, a kind of myocardial metabolism agent, could play a role on the regulation of 5-HT, 5-HT(2A)R, and SERT levels in rats with MI and/or depression. [Mh] Termos MeSH primário: Depressão/metabolismo Infarto do Miocárdio/metabolismo Receptor 5-HT2A de Serotonina/metabolismo Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo Trimetazidina/farmacologia Vasodilatadores/farmacologia [Mh] Termos MeSH secundário: Animais Transtorno Depressivo Ensaio de Imunoadsorção Enzimática Ratos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptor, Serotonin, 5-HT2A); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (Vasodilator Agents); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180222 [Lr] Data última revisão: 180222 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180112 [St] Status: MEDLINE [do] DOI: 10.3760/cma.j.issn.0578-1426.2018.01.009

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[PMID]: 28811386 [Au] Autor: Wan P; Su W; Zhang Y; Li Z; Deng C; Zhuo Y [Ad] Endereço: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. [Ti] Título: Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway. [So] Source: Clin Sci (Lond);131(18):2363-2375, 2017 Sep 15. [Is] ISSN: 1470-8736 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs TMZ treatment also reduced the production of inflammatory cytokines Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. [Mh] Termos MeSH primário: Glaucoma/tratamento farmacológico Heme Oxigenase-1/fisiologia Proteínas de Membrana/fisiologia Fator 2 Relacionado a NF-E2/fisiologia Células Ganglionares da Retina/efeitos dos fármacos Transdução de Sinais/efeitos dos fármacos Trimetazidina/uso terapêutico [Mh] Termos MeSH secundário: Animais Apoptose/efeitos dos fármacos Citocinas/metabolismo Masculino Camundongos Camundongos Endogâmicos C57BL Espécies Reativas de Oxigênio/metabolismo Células Ganglionares da Retina/patologia Transdução de Sinais/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cytokines); 0 (Membrane Proteins); 0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, mouse); 0 (Reactive Oxygen Species); EC 1.14.14.18 (Heme Oxygenase-1); EC 1.14.14.18 (Hmox1 protein, mouse); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170912 [Lr] Data última revisão: 170912 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170817 [St] Status: MEDLINE [do] DOI: 10.1042/CS20171182

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[PMID]: 28683436 [Au] Autor: Su Q; Li L; Zhao J; Sun Y; Yang H [Ad] Endereço: Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. [Ti] Título: Effects of Trimetazidine on PDCD4/NF-κB/TNF-α Pathway in Coronary Microembolization. [So] Source: Cell Physiol Biochem;42(2):753-760, 2017. [Is] ISSN: 1421-9778 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs. METHODS: 20 Bama mini pigs were randomized into sham operation (sham), microembolization (CME), TMZ, and siRNA-PDCD4 groups (n = 5). The CME model was established by injecting polyethylene microspheres via microcatheter into the left anterior descending coronary artery. The TMZ group was injected 2.5 mg/kg drug via ear vein 30 min before CME; whereas, the siRNA-PDCD4 group was transfected with PDCD4 siRNA at the left anterior descending coronary artery via microcatheter 72h before CME. Cardiac function indexes were measured using cardiac echocardiography. The mRNA expression of PDCD4 and TNF-α in the myocardium was detected by quantitative fluorescence PCR, and the protein expression of PDCD4, NF-κB (p65), and TNF-α by Western blot. RESULTS: Echocardiographic parameters showed lower cardiac function and higher serum cTnI level in the CME group than sham, which was manifested as reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), cardiac output (CO), and increased left ventricular diastolic diameter (LVEDd). Compared to the CME group, the CME-induced cardiac function injury was reduced, and the serum cTnI level was decreased in the TMZ and siRNA-PDCD4 groups. The expressions of PDCD4, NF-κB (p65), and TNF-α were significantly increased in the CME than the sham groups (P < 0.05), and significantly decreased in the TMZ and siRNA-PDCD4 groups than the CME group (P < 0.05). CONCLUSION: TMZ pretreatment effectively reduced the myocardial damage caused by CME via inhibiting the PDCD4/NF-κB/ TNF-α pathway in cardiomyocytes. [Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/genética Traumatismos Cardíacos/tratamento farmacológico Inflamação/tratamento farmacológico Proteínas de Ligação a RNA/genética Fator de Transcrição RelA/genética Trimetazidina/administração & dosagem Fator de Necrose Tumoral alfa/genética [Mh] Termos MeSH secundário: Animais Vasos Coronários/efeitos dos fármacos Vasos Coronários/lesões Vasos Coronários/patologia Modelos Animais de Doenças Ecocardiografia Embolia/patologia Traumatismos Cardíacos/genética Traumatismos Cardíacos/patologia Seres Humanos Inflamação/genética Inflamação/patologia Masculino Miocárdio/metabolismo Miocárdio/patologia Miócitos Cardíacos/efeitos dos fármacos Miócitos Cardíacos/patologia Intervenção Coronária Percutânea/efeitos adversos Transdução de Sinais/efeitos dos fármacos Suínos Porco Miniatura [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Apoptosis Regulatory Proteins); 0 (PDCD4 protein, human); 0 (RELA protein, human); 0 (RNA-Binding Proteins); 0 (Transcription Factor RelA); 0 (Tumor Necrosis Factor-alpha); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170804 [Lr] Data última revisão: 170804 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170707 [St] Status: MEDLINE [do] DOI: 10.1159/000478067

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[PMID]: 28632748 [Au] Autor: Breedt E; Lacerda L; Essop MF [Ad] Endereço: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa. [Ti] Título: Trimetazidine therapy for diabetic mouse hearts subjected to ex vivo acute heart failure. [So] Source: PLoS One;12(6):e0179509, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid ß-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1.2 mM palmitic acid, 2.5 mM glucose) at 20 mmHg (25 min); and c) Recovery Acute Heart Failure phase (RAHF)-(1.2 mM palmitic acid, 10 mM glucose) at 100 mmHg (25 min). Treated groups received 5 µM TMZ in the perfusate during either the CAHF or RAHF stage for the full duration of each respective phase. Both lean and obese males benefited from TMZ treatment administered during the RAHF phase. Sex differences were observed only in lean groups where the phases of the estrous cycle influenced therapy; only the lean follicular female group responded to TMZ treatment during the CAHF phase. Lean luteal females rather displayed an inherent cardioprotection (without treatments) that was lost with obesity. However, TMZ treatment initiated during RAHF was beneficial for obese luteal females. TMZ treatment triggered significant recovery for male and obese female hearts when administered during RAHF. There were no differences between lean and obese male hearts, while lean females displayed a functional recovery advantage over lean males. Thus TMZ emerges as a worthy therapeutic target to consider for AHF treatment in normal and obese-diabetic individuals (for both sexes), but only when administered during the recovery phase and not during the very acute stages. [Mh] Termos MeSH primário: Cardiotônicos/farmacologia Diabetes Mellitus Experimental/patologia Insuficiência Cardíaca/patologia Coração/efeitos dos fármacos Trimetazidina/farmacologia [Mh] Termos MeSH secundário: Doença Aguda Animais Cardiotônicos/uso terapêutico Feminino Insuficiência Cardíaca/tratamento farmacológico Insuficiência Cardíaca/veterinária Frequência Cardíaca Técnicas In Vitro Masculino Camundongos Camundongos Obesos Modelos Biológicos Fatores Sexuais Trimetazidina/uso terapêutico Função Ventricular/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Cardiotonic Agents); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170919 [Lr] Data última revisão: 170919 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170621 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0179509

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[PMID]: 28587952 [Au] Autor: Li R; Tang X; Jing Q; Wang Q; Yang M; Han X; Zhao J; Yu X [Ad] Endereço: Department of Critical Care Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Department of Emergency Medicine, The First Hospital of QinHuangDao, QinHuangDao, HeBei, China. [Ti] Título: The effect of trimetazidine treatment in patients with type 2 diabetes undergoing percutaneous coronary intervention for AMI. [So] Source: Am J Emerg Med;35(11):1657-1661, 2017 Nov. [Is] ISSN: 1532-8171 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: Trimetazidine (TMZ) improves clinical outcomes in patients with chronic heart failure and stable coronary artery disease. No study has yet evaluated the efficacy of TMZ in type 2 diabetes patients with acute myocardial infarction (AMI) undergoing Percutaneous Coronary Intervention (PCI). We performed this study to evaluate the efficacy TMZ in DM patients with AMI undergoing PCI, such as the effect on reductions in myocardial enzyme, improvements in liver function, modulation of glucose levels, and improvement in cardiac function. METHODS: For this randomized study, we enrolled 173 AMI patients with type 2 diabetes undergoing PCI between January 1, 2014, and January 1, 2016. All patients received aspirin and ticagrelor upon admission and throughout their hospitalization. Patients in the experimental group were treated with a loading dose of 60mg TMZ at admission, and 20 mg TMZ three times a day thereafter. 89 patients were included in experimental group, and 84 patients were included in control group. All patients received PCI treatments. The endpoints evaluated were serum creatine kinase and its isoenzyme (CK and CK-MB), cardiac troponin I (cTNI), serum creatinine (Cr), serum urea, blood glucose, serum glutamic pyruvic transaminase (ALT), serum glutamic oxaloacetictransaminase (AST), left atrial dimension (LA), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and cardiac output (CO). FINDINGS: Compared with the control group, TMZ treatment significantly reduced CK and CK-MB on the second day in hospital ([797±582] vs. [1092±1114]; [80±60] vs. [105±100]; p=0.029, p=0.041, respectively), and cTNI after one and six days in hospital ([13.5±12.7] vs. [19.8±19.2]; [3.3±3.2] vs. [4.8±4.7]; two-tailed p=0.012). In addition, TMZ significantly lowered liver enzymes (ALT, AST) at 6days ([29.0±11.6] vs. [42.4±24.5]; [39.8±17.3] vs. [69.2±70.0]; two-tailed p=0.000), lowered glucose after 6days ([6.80±2.12] vs. [7.59±2.24]; p=0.019), and increased LVEF after ten to fourteen days ([58.4±8.6] vs. [54.9±8.4]; p=0.008). There were no significant effect on Cr and serum urea (p=0.988, p=0.569, respectively), nor on LA, LVEDD, and CO ([36.3±4.5] vs. [37.0±4.1], p=0.264; [52.0±4.9] vs. [53.1±4.6], p=0.128; [5.4±0.9] vs. [5.4±0.9], p=0.929, respectively). IMPLICATIONS: Among type 2 diabetic patients with AMI undergoing PCI, TMZ significantly reduces serum myocardial enzyme, improves liver function, adjusts blood glucose and improves cardiac function. [Mh] Termos MeSH primário: Glicemia/metabolismo Diabetes Mellitus Tipo 2/metabolismo Infarto do Miocárdio/terapia Intervenção Coronária Percutânea Trimetazidina/uso terapêutico Vasodilatadores/uso terapêutico [Mh] Termos MeSH secundário: Adenosina/análogos & derivados Adenosina/uso terapêutico Idoso Alanina Transaminase/sangue Aspartato Aminotransferases/sangue Aspirina/uso terapêutico Débito Cardíaco China Creatina Quinase/sangue Creatina Quinase Forma MB/sangue Creatinina/sangue Diabetes Mellitus Tipo 2/complicações Ecocardiografia Feminino Hemoglobina A Glicada/metabolismo Átrios do Coração/diagnóstico por imagem Seres Humanos Masculino Meia-Idade Infarto do Miocárdio/sangue Infarto do Miocárdio/complicações Infarto do Miocárdio/diagnóstico por imagem Inibidores da Agregação de Plaquetas/uso terapêutico Volume Sistólico Resultado do Tratamento Troponina I/sangue Ureia/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Platelet Aggregation Inhibitors); 0 (Troponin I); 0 (Vasodilator Agents); 0 (hemoglobin A1c protein, human); 8W8T17847W (Urea); AYI8EX34EU (Creatinine); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 2.7.3.2 (Creatine Kinase); EC 2.7.3.2 (Creatine Kinase, MB Form); GLH0314RVC (Ticagrelor); K72T3FS567 (Adenosine); N9A0A0R9S8 (Trimetazidine); R16CO5Y76E (Aspirin) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170608 [St] Status: MEDLINE

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[PMID]: 28361425 [Au] Autor: Kolik LG; Nadorova AV; Stolyaruk VN; Miroshkina IA; Tsorin IB; Kryzhanovskii SA [Ad] Endereço: V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia. lgkolik@mail.ru. [Ti] Título: Anxiolytic Properties of Trimetazidine in Experimental Models of Increased Anxiety. [So] Source: Bull Exp Biol Med;162(5):643-646, 2017 Mar. [Is] ISSN: 1573-8221 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Effect of trimetazidine (20 and 30 mg/kg) on elevated plus maze behavior of rodents was assessed in the genetic and pharmacological anxiety models. Single intraperitoneal injection of trimetazidine in a dose of 20 mg/kg prevented anxiety development in highly emotional male BALB/c mice and increased the time spent in open arms of the maze. In outbred male rats receiving 10% ethanol solution for 20 weeks, trimetazidine administered intraperitoneally in a dose of 20 mg/kg for 28 days abolished ethanol withdrawal-induced anxiogenesis developed against the background of 4-week alcohol deprivation: it increased the time spent in open arms, the number of entries into open arms, and total locomotor activity in the maze. Anxiolytic properties of trimetazidine were not inferior to those of the non-benzodiazepine anxiolytic Afobazole (fabomotizole) in acute and chronic administration. [Mh] Termos MeSH primário: Ansiolíticos/farmacologia Ansiedade/tratamento farmacológico Trimetazidina/farmacologia [Mh] Termos MeSH secundário: Alcoolismo/psicologia Animais Animais não Endogâmicos Ansiolíticos/uso terapêutico Benzimidazóis/farmacologia Benzimidazóis/uso terapêutico Avaliação Pré-Clínica de Medicamentos Etanol/efeitos adversos Masculino Camundongos Endogâmicos BALB C Morfolinas/farmacologia Morfolinas/uso terapêutico Ratos Síndrome de Abstinência a Substâncias/tratamento farmacológico Síndrome de Abstinência a Substâncias/psicologia Trimetazidina/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole); 0 (Anti-Anxiety Agents); 0 (Benzimidazoles); 0 (Morpholines); 3K9958V90M (Ethanol); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170718 [Lr] Data última revisão: 170718 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170401 [St] Status: MEDLINE [do] DOI: 10.1007/s10517-017-3677-2

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[PMID]: 28319269 [Au] Autor: Ciapponi A; Pizarro R; Harrison J [Ad] Endereço: Argentine Cochrane Centre, Institute for Clinical Effectiveness and Health Policy (IECS-CONICET), Dr. Emilio Ravignani 2024, Buenos Aires, Capital Federal, Argentina, C1414CPV. [Ti] Título: WITHDRAWN: Trimetazidine for stable angina. [So] Source: Cochrane Database Syst Rev;3:CD003614, 2017 03 20. [Is] ISSN: 1469-493X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Patients with stable angina not controlled by monotherapy with nitrates, beta blockers, or calcium channel blockers are often treated with combinations of these drugs. There may be adverse effects from, or contraindications to, the use of combinations. In low risk groups, medical treatment appears to be as good an option as percutaneous transluminal coronary angioplasty in terms of averting myocardial infarction, death, or subsequent revascularization. Revascularization procedures are too costly or inaccessible for many patients in developing countries therefore effective and safe medical treatment is needed. Trimetazidine is a less well known anti-anginal drug that controls myocardial ischaemia through intracellular metabolic changes. Trimetazidine has been reported, in some studies, to be better tolerated than combined anti-anginal therapy; however it is not considered in published guidelines. OBJECTIVES: To determine the efficacy and tolerability of trimetazidine in patients with stable angina. SEARCH METHODS: We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS and SCISEARCH, without language restriction, from inception to October 2003. Experts in the field were contacted to locate unpublished studies. SELECTION CRITERIA: Randomised studies comparing trimetazidine with placebo, or other anti-angina drug in adults with stable angina. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, assessed trial quality and extracted data. MAIN RESULTS: Twenty-three studies (1378 patients) met the inclusion criteria. There was a paucity of information about mortality, cardiovascular events and quality of life. Trimetazidine, compared with placebo, reduced the number of weekly angina attacks ( mean difference -1.44, 95% CI -2.10 to -0.79; P < 0.0001), reduced weekly nitroglycerin tablet consumption (95% CI -1.47 to -2.20, -0.73; P < 0.0001) and improved exercise time to 1 mm segment depression (P = 0.0002). Four small trials (263 patients) compared trimetazidine against other anti-anginal agents. One favoured trimetazidine over nitrates. Three tended to favour alternative regimens but with confidence intervals consistent with both major increases and decreases in frequency of angina episodes. In this subgroup, adverse events were considered in 5 trials (448 patients) and totals of 2 versus 12 drop outs due to adverse events were observed in the trimetazidine and alternative regimens respectively, but this was mostly driven by a single trial. AUTHORS' CONCLUSIONS: Trimetazidine is effective in the treatment of stable angina compared with placebo, alone or combined with conventional anti-anginal agents. Trimetazidine may result in fewer dropouts due to adverse events. Large, long term trials comparing trimetazidine with other anti-anginal drugs assessing clinically relevant important outcomes are required to establish its role in clinical management. [Mh] Termos MeSH primário: Angina Pectoris/tratamento farmacológico Trimetazidina/uso terapêutico Vasodilatadores/uso terapêutico [Mh] Termos MeSH secundário: Adulto Seres Humanos Ensaios Clínicos Controlados Aleatórios como Assunto Trimetazidina/efeitos adversos Vasodilatadores/efeitos adversos [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW [Nm] Nome de substância: 0 (Vasodilator Agents); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170628 [Lr] Data última revisão: 170628 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170321 [St] Status: MEDLINE [do] DOI: 10.1002/14651858.CD003614.pub3

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[PMID]: 28282906 [Au] Autor: Zaouali MA; Panisello A; Lopez A; Castro C; Folch E; Carbonell T; Rolo A; Palmeira CM; Garcia-Gil A; Adam R; Roselló-Catafau J [Ad] Endereço: Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), Barcelona 08036, Catalonia, Spain. daminzaouali12@yahoo.fr. [Ti] Título: GSK3ß and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation. [So] Source: Int J Mol Sci;18(3), 2017 Mar 08. [Is] ISSN: 1422-0067 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: We investigated the involvement of glycogen synthase kinase-3ß (GSK3ß) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia-reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3ß and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3ß. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3ß and VDAC, contributing to ER stress reduction and cell death prevention. [Mh] Termos MeSH primário: Apoptose Estresse do Retículo Endoplasmático Glicogênio Sintase Quinase 3 beta/metabolismo Transplante de Fígado Canais de Ânion Dependentes de Voltagem/metabolismo [Mh] Termos MeSH secundário: Animais Estresse do Retículo Endoplasmático/efeitos dos fármacos Peroxidação de Lipídeos/efeitos dos fármacos Testes de Função Hepática Transplante de Fígado/efeitos adversos Masculino Mitocôndrias/efeitos dos fármacos Mitocôndrias/metabolismo Estresse Oxidativo/efeitos dos fármacos Proteínas Proto-Oncogênicas c-akt/metabolismo Ratos Traumatismo por Reperfusão/metabolismo Traumatismo por Reperfusão/patologia Trimetazidina/farmacologia Vasodilatadores/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Vasodilator Agents); 0 (Voltage-Dependent Anion Channels); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170428 [Lr] Data última revisão: 170428 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170312 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28260320 [Au] Autor: Liu MY; Zhang LJ [Ad] Endereço: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. [Ti] Título: [Impact of trimetazidine pre-treatment on 5-hydroxytryptamine and serotonin transporter in rats with experimental myocardial infarction and depression]. [So] Source: Zhonghua Xin Xue Guan Bing Za Zhi;45(2):137-141, 2017 Feb 24. [Is] ISSN: 0253-3758 [Cp] País de publicação: China [La] Idioma: chi [Ab] Resumo: To explore the effect of trimetazidine pre-treatments on serum 5-hydroxytryptamine (5-HT) and serotonin transporter (SERT), platelet 5-HT and SERT in the Sprague Dawley rats with myocardial infarction(MI), depression, and myocardial infarction co-exist with depression (MI+ depression) and in sham operated rats. Eighty rats were divided into treatment group and placebo (saline) group by the random number table method ( =40 each group). After 4 weeks' treatment with trimetazidine, or saline, these rats were assigned to respective sham subgroup, depression subgroup, MI subgroup, MI + depression subgroup ( =10 each subgroup). All rats were sacrificed 3 days later. 5-HT in serum and platelet, and SERT in serum and platelet of the rats were tested by enzyme linked immunosorbent assay (ELISA). Data were analyzed by SPSS 17.0. In saline group, serum and platelet 5-HT levels were significantly lower in MI, depression and MI+ depression subgroup compared to sham subgroup (all <0.01). In trimetazidine pre-treatment group, serum and platelet 5-HT levels were significantly higher in the depression subgroup, MI subgroup, MI + depression subgroup than respective subgroups of saline pretreated rats (all <0.01). In saline group, SERT in serum and platelet were higher in MI, depression, MI+ depression subgroup than the sham subgroup and statistical significance was found between MI+ depression subgroup and sham subgroups. Serum SERT level was significantly lower in the treatment group compared to saline group for sham rats ( <0.01). In treatment group, serum SERT level was higher in MI, depression and MI+ depression subgroups compared to respective subgroup treated with saline while the statistical significance was found in depression subgroup between trimetazidine pre-treatment and saline control groups. Platelet SERT was higher in MI, depression and MI+ depression subgroups compared to sham subgroup post saline treatment. Platelet SERT was significantly lower in MI, depression and MI+ depression subgroups post trimetazidine pre-treatment than in respective subgroups post saline treatment (all <0.01). Our study results indicate that trimetazidine pretreatment could increase the levels of 5-HT and SERT in serum and 5-HT in platelet, and decrease the level of SERT in platelet in the rat MI and depression model. [Mh] Termos MeSH primário: Depressão Infarto do Miocárdio Trimetazidina/farmacologia Vasodilatadores/farmacologia [Mh] Termos MeSH secundário: Animais Ensaio de Imunoadsorção Enzimática Ratos Ratos Sprague-Dawley Serotonina Proteínas da Membrana Plasmática de Transporte de Serotonina [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Serotonin Plasma Membrane Transport Proteins); 0 (Vasodilator Agents); 333DO1RDJY (Serotonin); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 170727 [Lr] Data última revisão: 170727 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170306 [St] Status: MEDLINE [do] DOI: 10.3760/cma.j.issn.0253-3758.2017.02.013

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[PMID]: 28248861 [Au] Autor: Ye Z; Lu H; Su Q; Guo W; Dai W; Li H; Yang H; Li L [Ad] Endereço: aDepartment of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute bDepartment of orthodontic, the Affiliated Dental Hospital of Guangxi Medical University, Nanning, Guangxi, China. [Ti] Título: Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis. [So] Source: Medicine (Baltimore);96(9):e6059, 2017 Mar. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. METHODS: By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. RESULTS: Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] -0.30, 95% CI -0.51, -0.09, P = 0.005), Scr of postoperative 48 hours (SMD -0.66, 95% CI -1.23, -0.10, P = 0.022), and Scr of postoperative 7 days (SMD -0.74, 95% CI -1.36, -0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). CONCLUSION: Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future. [Mh] Termos MeSH primário: Meios de Contraste/efeitos adversos Insuficiência Renal/prevenção & controle Trimetazidina/uso terapêutico Vasodilatadores/uso terapêutico [Mh] Termos MeSH secundário: Creatinina/sangue Seres Humanos Incidência Insuficiência Renal/sangue Insuficiência Renal/epidemiologia Insuficiência Renal/etiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; REVIEW [Nm] Nome de substância: 0 (Contrast Media); 0 (Vasodilator Agents); AYI8EX34EU (Creatinine); N9A0A0R9S8 (Trimetazidine) [Em] Mês de entrada: 1703 [Cu] Atualização por classe: 170324 [Lr] Data última revisão: 170324 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170302 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000006059

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