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Pesquisa : D02.033.100.291.491 [Categoria DeCS]
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[PMID]:29337670
[Au] Autor:Hanif M; Khan HU; Afzal S; Mahmood A; Maheen S; Afzal K; Iqbal N; Andleeb M; Abbas N
[Ad] Endereço:1Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
[Ti] Título:Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.
[So] Source:Acta Pharm;67(4):441-461, 2017 Dec 20.
[Is] ISSN:1846-9558
[Cp] País de publicação:Croatia
[La] Idioma:eng
[Ab] Resumo:For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 µm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p < 0.05) affected by lipid concentration. The release mechanism followed Higuchi and zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.
[Mh] Termos MeSH primário: Preparações de Ação Retardada/química
Composição de Medicamentos/métodos
Glicerídeos/química
Ceras/química
[Mh] Termos MeSH secundário: Calorimetria/métodos
Portadores de Fármacos/química
Nebivolol/farmacocinética
Tamanho da Partícula
Espectroscopia de Infravermelho com Transformada de Fourier
Propriedades de Superfície
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Drug Carriers); 0 (Glycerides); 0 (Waxes); 030Y90569U (Nebivolol); 230OU9XXE4 (glyceryl monostearate); R12CBM0EIZ (carnauba wax)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:28459657
[Au] Autor:Gheldiu AM; Vlase L; Popa A; Briciu C; Muntean D; Bocsan C; Buzoianu A; Achim M; Tomuta I; Todor I; Neag M
[Ad] Endereço:University of Medicine and Pharmacy "Iuliu Hatieganu", Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Cluj-Napoca, Romania.
[Ti] Título:Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers.
[So] Source:J Pharm Pharm Sci;20:68-80, 2017.
[Is] ISSN:1482-1826
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. METHODS: This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. RESULTS: Fluvoxamine pretreatment increased Cmax and AUC0-∞  of nebivolol (Cmax: 1.67 ± 0.690  vs 2.20 ± 0.970  ng/mL; AUC0-∞: 12.1 ± 11.0  vs 19.3 ± 19.5  ng*h/mL ) and of its active metabolite (Cmax: 0.680  ± 0.220  vs 0.960 ± 0.290  ng/mL; AUC0-∞: 17.6 ±20.1  vs 25.5 ± 29.9  ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. CONCLUSIONS: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
[Mh] Termos MeSH primário: Fluvoxamina/farmacocinética
Nebivolol/farmacocinética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Relação Dose-Resposta a Droga
Feminino
Fluvoxamina/administração & dosagem
Fluvoxamina/metabolismo
Voluntários Saudáveis
Seres Humanos
Masculino
Meia-Idade
Nebivolol/administração & dosagem
Nebivolol/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
030Y90569U (Nebivolol); O4L1XPO44W (Fluvoxamine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171222
[Lr] Data última revisão:
171222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.18433/J3B61H


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[PMID]:28429695
[Au] Autor:Aslan AN; Güney MC; Akçay M; Keles T; Bozkurt E
[Ad] Endereço:Department of Cardiology, Atatürk Training and Research Hospital, Ankara, Turkey. drnabiaslan@hotmail.com.
[Ti] Título:Lichenoid type cutaneous hyperpigmentation induced by nebivolol.
[So] Source:Turk Kardiyol Dern Ars;45(3):268-270, 2017 Apr.
[Is] ISSN:1308-4488
[Cp] País de publicação:Turkey
[La] Idioma:eng
[Ab] Resumo:Cutaneous hyperpigmentation is a common and well-defined side effect of many drugs, such as non-steroidal anti-inflammatory drugs, beta-blockers, and tetracyclines, but to the best of our knowledge there is no case of skin discoloration related to nebivolol in the literature. Presently described is lichenoid type cutaneous hyperpigmentation in a 46-year-old female patient. Hyperpigmentation emerged 3 months after initiating use of nebivolol and resolved after cessation of drug use. It was concluded that effect emerged as result of therapeutic doses of nebivolol.
[Mh] Termos MeSH primário: Hiperpigmentação/induzido quimicamente
Erupções Liquenoides/induzido quimicamente
Nebivolol/efeitos adversos
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Hipertensão/tratamento farmacológico
Meia-Idade
Nebivolol/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
030Y90569U (Nebivolol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.5543/tkda.2016.02151


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[PMID]:28387384
[Au] Autor:Paton DM
[Ad] Endereço:University of Auckland School of Medical Sciences, Pharmacology & Clinical Pharmacology Auckland, New Zealand. dmpaton38@yahoo.ca.
[Ti] Título:Nebivolol/valsartan: Fixed-dose combination for treatment of hypertension.
[So] Source:Drugs Today (Barc);53(1):19-26, 2017 Jan.
[Is] ISSN:1699-3993
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:Clinical trials demonstrated that a fixed-dose combination (FDC) of the beta-blocker nebivolol (5 mg) and the angiotensin II antagonist valsartan (80 mg) produced a significant reduction of both diastolic and systolic blood pressure in patients with hypertension. Both nebivolol and valsartan contributed to this effect, partial additivity of 86.6% and 82.2% being observed for diastolic and systolic blood pressure, respectively. These values are very similar to the additivity ratios of other recently approved FDCs for hypertension. Use of the FDC nebivolol 5 mg/valsartan 80 mg formulation was associated with a low incidence of treatment-related adverse effects and of serious adverse effects. There was no evidence of adverse effects due to beta2-adrenoceptor blockade. The FDC (Byvalson) was approved and launched in 2016 in the U.S. for the treatment of hypertension.
[Mh] Termos MeSH primário: Agonistas de Receptores Adrenérgicos beta 1/administração & dosagem
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem
Anti-Hipertensivos/administração & dosagem
Pressão Sanguínea/efeitos dos fármacos
Hipertensão/tratamento farmacológico
Nebivolol/administração & dosagem
Valsartana/administração & dosagem
Vasodilatadores/administração & dosagem
[Mh] Termos MeSH secundário: Agonistas de Receptores Adrenérgicos beta 1/efeitos adversos
Agonistas de Receptores Adrenérgicos beta 1/farmacocinética
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética
Anti-Hipertensivos/efeitos adversos
Anti-Hipertensivos/farmacocinética
Aprovação de Drogas
Combinação de Medicamentos
Seres Humanos
Hipertensão/diagnóstico
Hipertensão/fisiopatologia
Nebivolol/efeitos adversos
Nebivolol/farmacocinética
Resultado do Tratamento
Estados Unidos
United States Food and Drug Administration
Valsartana/efeitos adversos
Valsartana/farmacocinética
Vasodilatadores/efeitos adversos
Vasodilatadores/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic beta-1 Receptor Agonists); 0 (Angiotensin II Type 1 Receptor Blockers); 0 (Antihypertensive Agents); 0 (Drug Combinations); 0 (Vasodilator Agents); 030Y90569U (Nebivolol); 80M03YXJ7I (Valsartan)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE
[do] DOI:10.1358/dot.2017.53.1.2560078


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[PMID]:28340419
[Au] Autor:Salma A; Lutze HV; Schmidt TC; Tuerk J
[Ad] Endereço:Institut für Energie- und Umwelttechnik e. V., (IUTA, Institute of Energy and Environmental Technology), Bliersheimer Str. 58-60, D-47229, Duisburg, Germany; University Duisburg-Essen, Faculty of Chemistry, Instrumental Analytical Chemistry, Universitätsstr. 5, D-45141, Essen, Germany.
[Ti] Título:Photolytic degradation of the ß-blocker nebivolol in aqueous solution.
[So] Source:Water Res;116:211-219, 2017 Jun 01.
[Is] ISSN:1879-2448
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nebivolol (NEB) is one of the top-sold prescription drugs belonging to the third generation of beta-blockers. However, so far, occurrence data in the environment are lacking. Within this study NEB has been found for the first time in effluent samples of wastewater treatment plants in Germany with an average concentration of 13 ng L . Its photodegradation behavior in the environment and in technical processes is largely unknown. To fill this gap, three different UV treatment procedures (UV-C at 254 nm, UV-B at 312 nm and UV-A at 365 nm) were investigated in three different matrices: pure water, pure water in presence of the hydroxyl radical (OH) scavenger tert.-butanol and real wastewater. No elimination was observed during UV-A treatment. In contrast, NEB degradation during UV-B and UV-C treatment followed pseudo first order reaction kinetics, with highest removal rate during UV-C treatment in pure water (k = 7.8 × 10 s ). The rate constant for UV-C irradiation decreased to 2.9 × 10 s in the presence of the OH scavenger and in the presence of the wastewater matrix. The rate constant for the UV-B lamp was 4.4 × 10 s , Three transformation products were identified after UV-B and UV-C photolytic degradation using high resolution mass spectrometry. The main photoreaction is the substitution of the fluorine atoms of NEB by hydroxyl groups. A photolytic cleavage of the CF bond can be excluded as the high bond dissociation energy of aromatic CF bonds (525 kJ mol ), exceeds the energy of electromagnetic radiation applied in the present study (≥254 nm, i.e., max. 471 kJ E ). The quantum yields for NEB degradation for the UV-C lamp achieved in pure water, the OH scavenged system and wastewater matrix were Φ = 0.53, 0.19 and 0.22, respectively. For UV-B Φ was 0.023 ± 0.003, noticeable differences in quantum yield were not found. The photooxidation involves reactive oxygen species such as superoxide and singlet oxygen. These oxidative species may be formed upon reaction of photo-excited NEB with oxygen.
[Mh] Termos MeSH primário: Nebivolol
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Cinética
Fotólise
Raios Ultravioleta
Purificação da Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Water Pollutants, Chemical); 030Y90569U (Nebivolol)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28302931
[Au] Autor:Gür Ö; Gurkan S; Yumun G; Turker P
[Ad] Endereço:Department of Cardiovascular Surgery, Namik Kemal University, Tekirdag, Turkey.
[Ti] Título:The Comparison of the Effects of Nebivolol and Metoprolol on Erectile Dysfunction in the Cases with Coronary Artery Bypass Surgery.
[So] Source:Ann Thorac Cardiovasc Surg;23(2):91-95, 2017 Apr 20.
[Is] ISSN:2186-1005
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Beta-blocker use is common in the cases with coronary artery bypass surgery. According to the literature, beta-blockers have positive effects but may cause erectile dysfunction (ED). The most commonly used beta-blockers in ischemic cardiac disease are nebivolol and metoprolol. In our clinic, we aimed to compare the effects of nebivolol and metoprolol succinate on ED in the sexually active cases with coronary artery bypass surgery. METHODS: In our clinic, a total of 119 patients with coronary artery bypass surgery were included in the study. International Index of Erectile Function (IIEF-5) Test was used to evaluate whether the patients had ED and to grade the cases. RESULTS: No significant difference was found in terms of anti-ischemic efficacy between metoprolol succinate and nebivolol in the postoperative period; however, the incidence of any grade ED was %85.96 in Group 1, %83.87 in Group 2. This difference was considered as statistically significant (p = 0.036). CONCLUSION: Beta-blocker use increases the risk of ED in cases with ischemic cardiac disease. We suggest that the complaints of ED could be less frequent with nebivolol use in sexually active cases with ischemic cardiac disease.
[Mh] Termos MeSH primário: Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos
Ponte de Artéria Coronária/efeitos adversos
Disfunção Erétil/induzido quimicamente
Metoprolol/efeitos adversos
Nebivolol/efeitos adversos
Ereção Peniana/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Idoso
Disfunção Erétil/fisiopatologia
Seres Humanos
Masculino
Meia-Idade
Estudos Prospectivos
Fatores de Risco
Resultado do Tratamento
Turquia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic beta-1 Receptor Antagonists); 030Y90569U (Nebivolol); GEB06NHM23 (Metoprolol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.5761/atcs.oa.16-00242


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[PMID]:28283926
[Au] Autor:Marketou M; Gupta Y; Jain S; Vardas P
[Ad] Endereço:Cardiology Department, Heraklion University Hospital, P.O. Box 1352, Stavrakia, Heraklion, Crete, Greece.
[Ti] Título:Differential Metabolic Effects of Beta-Blockers: an Updated Systematic Review of Nebivolol.
[So] Source:Curr Hypertens Rep;19(3):22, 2017 Mar.
[Is] ISSN:1534-3111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.
[Mh] Termos MeSH primário: Antagonistas Adrenérgicos beta/uso terapêutico
Anti-Hipertensivos/uso terapêutico
Pressão Sanguínea/efeitos dos fármacos
Hipertensão/tratamento farmacológico
Síndrome Metabólica/tratamento farmacológico
Nebivolol/uso terapêutico
[Mh] Termos MeSH secundário: Diabetes Mellitus/tratamento farmacológico
Etanolaminas/farmacologia
Hemodinâmica/efeitos dos fármacos
Seres Humanos
Resistência à Insulina
Óxido Nítrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Antihypertensive Agents); 0 (Ethanolamines); 030Y90569U (Nebivolol); 31C4KY9ESH (Nitric Oxide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170312
[St] Status:MEDLINE
[do] DOI:10.1007/s11906-017-0716-3


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[PMID]:28178754
[Au] Autor:Abdelkader NF; Saad MA; Abdelsalam RM
[Ad] Endereço:Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
[Ti] Título:Neuroprotective effect of nebivolol against cisplatin-associated depressive-like behavior in rats.
[So] Source:J Neurochem;141(3):449-460, 2017 May.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:One-third of cancer patients undergoing chemotherapy treatment often display symptoms of depression leading to poor adherence and decreased quality of life. Thus, this study aimed to investigate the possible protective effect of nebivolol against cisplatin-associated depressive symptoms in adult male rats. Nebivolol is a highly cardioselective ß-adrenergic receptor blocker that possesses endothelium-dependent vasodilator properties and antioxidant capacities. Animals were allocated into four groups. Group one was given aqueous solution of carboxymethyl cellulose and served as control, group two was given nebivolol (10 mg/kg p.o., daily), group three was given cisplatin (2 mg/kg i.p. once per week) for 10 consecutive weeks and group four was treated with cisplatin concomitantly with nebivolol as per above schedule. Cisplatin-treated rats showed an increase in both depressive-like behaviors in open-field and forced swimming tests. In addition, histopathological examination revealed cortical encephalomalacia along with hippocampal neuronal degeneration and kidney dysfunction. In parallel, cisplatin administration prominently reduced GABA and elevated glutamate levels in the cortical and hippocampal tissues. Furthermore, it resulted in a significant decline in cortical and hippocampal brain-derived neurotrophic factor and nitric oxide contents concomitantly with a marked decrease in endothelial- and an increase in inducible-nitric oxide synthase genes expression. On the other hand, treatment with nebivolol effectively mitigated the aforementioned cisplatin-associated behavioral, biochemical, and histopathological alterations without changing its antitumor activity as evidenced by sulforhodamine B cell survival assay. Taken together, our results suggest that nebivolol may offer a promising approach for alleviating depressive symptoms associated with the use of cisplatin.
[Mh] Termos MeSH primário: Antagonistas Adrenérgicos beta/uso terapêutico
Antineoplásicos
Cisplatino
Transtorno Depressivo/induzido quimicamente
Transtorno Depressivo/prevenção & controle
Nebivolol/uso terapêutico
Fármacos Neuroprotetores/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Química Encefálica/efeitos dos fármacos
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Transtorno Depressivo/diagnóstico por imagem
Ácido Glutâmico/metabolismo
Masculino
Atividade Motora/efeitos dos fármacos
Óxido Nítrico/metabolismo
Ratos
Ratos Wistar
Natação/psicologia
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Antineoplastic Agents); 0 (Brain-Derived Neurotrophic Factor); 0 (Neuroprotective Agents); 030Y90569U (Nebivolol); 31C4KY9ESH (Nitric Oxide); 3KX376GY7L (Glutamic Acid); 56-12-2 (gamma-Aminobutyric Acid); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170502
[Lr] Data última revisão:
170502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.13978


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[PMID]:28132913
[Au] Autor:do Vale GT; Gonzaga NA; Simplicio JA; Tirapelli CR
[Ad] Endereço:Programa de pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil; Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
[Ti] Título:Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression.
[So] Source:Eur J Pharmacol;799:33-40, 2017 Mar 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We studied whether the ß -adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O ) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H O ) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47 or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase.
[Mh] Termos MeSH primário: Etanol/toxicidade
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Córtex Renal/efeitos dos fármacos
Peroxidação de Lipídeos/efeitos dos fármacos
NADPH Oxidases/metabolismo
Nebivolol/farmacologia
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Creatinina/sangue
Citoproteção/efeitos dos fármacos
Ativação Enzimática/efeitos dos fármacos
Peróxido de Hidrogênio/metabolismo
Córtex Renal/enzimologia
Córtex Renal/lesões
Córtex Renal/metabolismo
Masculino
Óxidos de Nitrogênio/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Potássio/sangue
Ratos
Ratos Wistar
Sódio/sangue
Superóxidos/metabolismo
Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitrogen Oxides); 0 (Reactive Oxygen Species); 0 (Thiobarbituric Acid Reactive Substances); 030Y90569U (Nebivolol); 11062-77-4 (Superoxides); 3K9958V90M (Ethanol); 9NEZ333N27 (Sodium); AYI8EX34EU (Creatinine); BBX060AN9V (Hydrogen Peroxide); EC 1.6.3.- (NADPH Oxidases); RWP5GA015D (Potassium)
[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:170131
[St] Status:MEDLINE


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[PMID]:27862262
[Au] Autor:Rofaeil RR; Kamel MY; Abdelzaher WY
[Ad] Endereço:Faculty of Medicine, Minia University, Minia, El Minia, 61111, Egypt.
[Ti] Título:Different effects of selective ß1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats.
[So] Source:Fundam Clin Pharmacol;31(2):165-173, 2017 Apr.
[Is] ISSN:1472-8206
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acetaminophen (APAP) overdose is a common cause of acute liver failure, and beta-blockers are commonly used drugs in clinical practice. This study aimed to evaluate the effect of two different beta-blocker agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male Wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg/day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration. Also, nebivolol increased reduced glutathione (GSH) which was reduced with APAP administration. Moreover, immunohistochemical examination revealed that nebivolol treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced, as compared to APAP group. The protective effects of nebivolol were also verified histopathologically. On the other hand, as compared to APAP group, oral administration of atenolol (50 mg/kg) increased hepatic injury parameters but did not change hepatic NO, MDA, and GSH. In conclusion, this study revealed that nebivolol not atenolol is protective against APAP-induced hepatotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS expression.
[Mh] Termos MeSH primário: Acetaminofen/toxicidade
Atenolol/farmacologia
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Nebivolol/farmacologia
[Mh] Termos MeSH secundário: Acetaminofen/administração & dosagem
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia
Analgésicos não Entorpecentes/toxicidade
Animais
Antioxidantes/farmacologia
Pressão Sanguínea/efeitos dos fármacos
Doença Hepática Induzida por Substâncias e Drogas/etiologia
Overdose de Drogas
Glutationa/metabolismo
Frequência Cardíaca/efeitos dos fármacos
Masculino
Malondialdeído/metabolismo
Óxido Nítrico/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Óxido Nítrico Sintase Tipo III/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic beta-1 Receptor Antagonists); 0 (Analgesics, Non-Narcotic); 0 (Antioxidants); 030Y90569U (Nebivolol); 31C4KY9ESH (Nitric Oxide); 362O9ITL9D (Acetaminophen); 4Y8F71G49Q (Malondialdehyde); 50VV3VW0TI (Atenolol); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nitric Oxide Synthase Type III); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1111/fcp.12253



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