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1 / 1978

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[PMID]: 29286056 [Au] Autor: Zaid Iskandar M; Lang CC [Ad] Endereço: Ninewells Hospital and Medical School, Dundee, Scotland, UK. [Ti] Título: Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients. [So] Source: Drugs Today (Barc);53(10):545-551, 2017 Oct. [Is] ISSN: 1699-3993 [Cp] País de publicação: Spain [La] Idioma: eng [Ab] Resumo: Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest. [Mh] Termos MeSH primário: Aminobutiratos/administração & dosagem Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem Insuficiência Cardíaca/tratamento farmacológico Infarto do Miocárdio/complicações Neprilisina/antagonistas & inibidores Tetrazóis/administração & dosagem Valsartana/administração & dosagem [Mh] Termos MeSH secundário: Aminobutiratos/farmacologia Ensaios Clínicos como Assunto Seres Humanos Tetrazóis/farmacologia Valsartana/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Aminobutyrates); 0 (Angiotensin II Type 1 Receptor Blockers); 0 (LCZ 696); 0 (Tetrazoles); 80M03YXJ7I (Valsartan); EC 3.4.24.11 (Neprilysin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180306 [Lr] Data última revisão: 180306 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171230 [St] Status: MEDLINE [do] DOI: 10.1358/dot.2017.53.10.2722396

2 / 1978

MEDLINE

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[PMID]: 29269696 [Au] Autor: Yokoi K; Ando T; Kawakami O [Ad] Endereço: Department of Neurology, Anjo Kosei Hospital. [Ti] Título: [Case of posterior reversible encephalopathy syndrome caused by Fisher syndrome]. [So] Source: Rinsho Shinkeigaku;58(1):45-48, 2018 Jan 26. [Is] ISSN: 1882-0654 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: This report presents a case of a 71-year-old woman with Fisher syndrome who had posterior reversible encephalopathy syndrome (PRES) before the initiation of intravenous immunoglobulin (IVIg) treatment. She had symptoms of common cold 2 weeks before the onset of PRES. On the day of the onset, she began to stagger while walking. On day 2, she developed hypertension, vision impairment, and limb weakness and was admitted to the hospital. On day 3, she was provided steroid pulse therapy. On day 4, she developed convulsions and right imperfection single paralysis and was transferred to the our hospital. During the transfer, the patient was conscious. Her blood pressure was high at 198/107 mmHg. She had mild weakness in her limbs and face, light perception in both eyes, dilation of both pupils, total external ophthalmoplegia, no tendon reflexes, and limb and trunk ataxia. We diagnosed PRES because of the high signal intensities observed on T -weighted MRI on both sides of the parietal and occipital lobes. We also diagnosed Fisher syndrome because of a positive anti-GQ1b immunoglobulin G antibody test and albuminocytologic dissociation in the cerebrospinal fluid. PRES showed prompt improvement with antihypertensive therapy, whereas Fisher syndrome slowly improved over a course of 2 months. This case is the first report of PRES without IVIg suggesting that Fisher syndrome induces hypertension and causes PRES. [Mh] Termos MeSH primário: Síndrome de Miller Fisher/complicações Síndrome da Leucoencefalopatia Posterior/etiologia [Mh] Termos MeSH secundário: Idoso Anti-Hipertensivos/administração & dosagem Biomarcadores/sangue Biomarcadores/líquido cefalorraquidiano Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano Diltiazem/administração & dosagem Feminino Gangliosídeos/imunologia Seres Humanos Imunoglobulina G/sangue Imunoglobulinas Intravenosas Imagem por Ressonância Magnética Síndrome de Miller Fisher/diagnóstico Neuroimagem Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem Síndrome da Leucoencefalopatia Posterior/tratamento farmacológico Resultado do Tratamento Valsartana/administração & dosagem [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antihypertensive Agents); 0 (Biomarkers); 0 (Cerebrospinal Fluid Proteins); 0 (Gangliosides); 0 (Immunoglobulin G); 0 (Immunoglobulins, Intravenous); 68652-37-9 (GQ1b ganglioside); 80M03YXJ7I (Valsartan); EE92BBP03H (Diltiazem) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180227 [Lr] Data última revisão: 180227 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171223 [St] Status: MEDLINE [do] DOI: 10.5692/clinicalneurol.cn-001089

3 / 1978

MEDLINE

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[PMID]: 29337671 [Au] Autor: Stolarczyk M; Apola A; Maslanka A; Kwiecien A; Opoka W [Ad] Endereço: 1Department of Inorganic and Analytical Chemistry Jagiellonian University Medical College, Faculty of Pharmacy 30-688 Kraków, Poland. [Ti] Título: Spectrophotometric method for simultaneous determination of valsartan and substances from the group of statins in binary mixtures. [So] Source: Acta Pharm;67(4):463-478, 2017 Dec 20. [Is] ISSN: 1846-9558 [Cp] País de publicação: Croatia [La] Idioma: eng [Ab] Resumo: Applicability of derivative spectrophotometry for the determination of valsartan in the presence of a substance from the group of statins was checked. The obtained results indicate that the proposed method may be effective by using appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and D3. The method was characterized by high sensitivity and accuracy. Linearity was maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56 mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999 depending on the analyte and the order of derivative. The precision of the method was high with RSD from 0.1 to 2.5 % and recovery of individual components was within the range of 100 ± 5 %. The developed method was successfully applied to the determination of valsartan combined with fluvastatin, atorvastatin and pravastatin in laboratory prepared mixtures and in pharmaceutical preparations. [Mh] Termos MeSH primário: Inibidores de Hidroximetilglutaril-CoA Redutases/análise Espectrofotometria/métodos Valsartana/análise [Mh] Termos MeSH secundário: Atorvastatina Cálcica/análise Ácidos Graxos Monoinsaturados/análise Indóis/análise Pravastatina/análise Reprodutibilidade dos Testes Sensibilidade e Especificidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Fatty Acids, Monounsaturated); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Indoles); 48A5M73Z4Q (Atorvastatin Calcium); 4L066368AS (fluvastatin); 80M03YXJ7I (Valsartan); KXO2KT9N0G (Pravastatin) [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

4 / 1978

MEDLINE

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[PMID]: 28864378 [Au] Autor: Shamardl HA; El-Ashmony SM; Kamel HF; Fatani SH [Ad] Endereço: Department of Pharmacology (HAS), Faculty of Medicine, Fayoum University, Fayoum, Egypt; Department of Pharmacology & Clinical Pharmacy (SME), Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. Electronic address: hanan2remember@yahoo.com. [Ti] Título: Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q in l-NAME-Induced Hypertensive Rats. [So] Source: Am J Med Sci;354(2):190-198, 2017 Aug. [Is] ISSN: 1538-2990 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. MATERIALS AND METHODS: Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. RESULTS: Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. CONCLUSIONS: The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. [Mh] Termos MeSH primário: Hipertensão/tratamento farmacológico Ubiquinona/análogos & derivados Valsartana/farmacologia Vitamina D/farmacologia [Mh] Termos MeSH secundário: Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia Animais Doenças Cardiovasculares/tratamento farmacológico Hipertensão/induzido quimicamente Nefropatias/tratamento farmacológico NG-Nitroarginina Metil Éster/toxicidade Ratos Ratos Wistar Ubiquinona/farmacologia Ubiquinona/uso terapêutico Vitamina D/uso terapêutico Vitaminas/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Angiotensin II Type 1 Receptor Blockers); 0 (Vitamins); 1339-63-5 (Ubiquinone); 1406-16-2 (Vitamin D); 80M03YXJ7I (Valsartan); EJ27X76M46 (coenzyme Q10); V55S2QJN2X (NG-Nitroarginine Methyl Ester) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170908 [Lr] Data última revisão: 170908 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170903 [St] Status: MEDLINE

5 / 1978

MEDLINE

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[PMID]: 28784687 [Au] Autor: Lewis EF; Claggett BL; McMurray JJV; Packer M; Lefkowitz MP; Rouleau JL; Liu J; Shi VC; Zile MR; Desai AS; Solomon SD; Swedberg K [Ad] Endereço: From the Brigham and Women's Hospital, Boston, MA (E.F.L., B.L.C., J.L., A.S.D., S.D.S.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX (M.P.); Novartis, East Hanover, NJ (M.P.L. [Ti] Título: Health-Related Quality of Life Outcomes in PARADIGM-HF. [So] Source: Circ Heart Fail;10(8), 2017 Aug. [Is] ISSN: 1941-3297 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND: Patients with heart failure and reduced ejection fraction have impaired health-related quality of life (HRQL) with variable responses to therapies that target mortality and heart failure hospitalizations. In PARADIGM-HF trial (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure), sacubitril/valsartan reduced morbidity and mortality compared with enalapril. Another major treatment goal is to improve HRQL. Given improvements in mortality with sacubitril/valsartan, this analysis provides comprehensive assessment of impact of therapy on HRQL in survivors only. METHODS AND RESULTS: Patients (after run-in phase) completed disease-specific HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 4 month, 8 month, and annual visits. Changes in KCCQ scores were calculated using repeated measures analysis of covariance model that adjusted for treatment and baseline values (principal efficacy prespecified at 8 months). Among the 8399 patients enrolled in PARADIGM-HF, 7623 (91%) completed KCCQ scores at randomization with complete data at 8 months for 6881 patients (90% of baseline). At 8 months, sacubitril/valsartan group noted improvements in both KCCQ clinical summary score (+0.64 versus -0.29; =0.008) and KCCQ overall summary score (+1.13 versus -0.14; <0.001) in comparison to enalapril group and significantly less proportion of patients with deterioration (≥5 points decrease) of both KCCQ scores (27% versus 31%; =0.01). Adjusted change scores demonstrated consistent improvements in sacubitril/valsartan compared with enalapril through 36 months. CONCLUSIONS: Change scores in KCCQ clinical summary scores and KCCQ overall summary scores were better in patients treated with sacubitril/valsartan compared with those treated with enalapril, with consistency in most domains, and persist during follow-up beyond 8 months. These findings demonstrate that sacubitril/valsartan leads to better HRQL in surviving patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. [Mh] Termos MeSH primário: Aminobutiratos/uso terapêutico Enalapril/uso terapêutico Nível de Saúde Insuficiência Cardíaca/psicologia Qualidade de Vida Tetrazóis/uso terapêutico Valsartana/uso terapêutico [Mh] Termos MeSH secundário: Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico Antagonistas de Receptores de Angiotensina/uso terapêutico Inibidores da Enzima Conversora de Angiotensina/uso terapêutico Feminino Seguimentos Insuficiência Cardíaca/tratamento farmacológico Seres Humanos Masculino Meia-Idade Fatores de Tempo Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Aminobutyrates); 0 (Angiotensin II Type 1 Receptor Blockers); 0 (Angiotensin Receptor Antagonists); 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (LCZ 696); 0 (Tetrazoles); 69PN84IO1A (Enalapril); 80M03YXJ7I (Valsartan) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170816 [Lr] Data última revisão: 170816 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170809 [St] Status: MEDLINE

6 / 1978

MEDLINE

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[PMID]: 28737127 [Au] Autor: Kulmatycki KM; Langenickel T; Ng WH; Pal P; Zhou W; Lin TH; Rajman I; Chandra P; Sunkara G [Ti] Título: Pharmacokinetics and safety of sacubitril/valsartan (LCZ696) in patients with mild and moderate hepatic impairment
. [So] Source: Int J Clin Pharmacol Ther;55(9):728-739, 2017 Sep. [Is] ISSN: 0946-1965 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: OBJECTIVES: To assess the protein binding and pharmacokinetics of sacubitril/valsartan analytes (sacubitril, sacubitrilat, and valsartan) in an open-label, single oral dose (200 mg), parallel-group study in patients with mild and moderate hepatic impairment (Child-Pugh class A and B) and matched healthy subjects. METHODS: This study enrolled 32 subjects (n = 8 in each hepatic impairment and matched healthy subjects groups). Blood samples were collected at pre-determined time points to assess pharmacokinetics of sacubitril, sacubitrilat, and valsartan. Subjects with severe hepatic impairment were excluded as valsartan exposure is expected to be substantially increased in these patients. RESULTS: Sacubitril exposure (AUC) increased by 53% and 245% while the exposure to sacubitrilat was increased by 48% and 90% in patients with mild and moderate hepatic impairment, respectively. Sacubitril Cmax increased by 57% and 210% in mild and moderate hepatic impairment; however, for both sacubitrilat and valsartan, Cmax was unchanged. Valsartan AUC increased in patients with mild and moderate hepatic impairment by 19 - 109%, respectively. CONCLUSIONS: The increase in systemic exposures to all sacubitril/valsartan analytes correlated with the severity of liver disease. The plasma unbound fraction of sacubitrilat in patients with moderate hepatic impairment was slightly higher than in matched healthy subjects. This difference was not considered clinically significant. Safety assessments showed that sacubitril/valsartan was safe and well tolerated across all the study groups.
. [Mh] Termos MeSH primário: Aminobutiratos/efeitos adversos Aminobutiratos/farmacocinética Hepatopatias/metabolismo Fígado/efeitos dos fármacos Tetrazóis/efeitos adversos Tetrazóis/farmacocinética Valsartana/efeitos adversos Valsartana/farmacocinética [Mh] Termos MeSH secundário: Área Sob a Curva Feminino Voluntários Saudáveis Seres Humanos Fígado/metabolismo Masculino Meia-Idade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Aminobutyrates); 0 (LCZ 696); 0 (Tetrazoles); 80M03YXJ7I (Valsartan) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171026 [Lr] Data última revisão: 171026 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170725 [St] Status: MEDLINE [do] DOI: 10.5414/CP202988

7 / 1978

MEDLINE

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[PMID]: 28648033 [Ti] Título: [Update on the clinical application of valsartan/sacubitril in patients with heart failure]. [So] Source: Zhonghua Xin Xue Guan Bing Za Zhi;45(6):538-541, 2017 Jun 24. [Is] ISSN: 0253-3758 [Cp] País de publicação: China [La] Idioma: chi [Mh] Termos MeSH primário: Aminobutiratos/uso terapêutico Antagonistas de Receptores de Angiotensina/uso terapêutico Insuficiência Cardíaca/tratamento farmacológico Tetrazóis/uso terapêutico Valsartana/uso terapêutico [Mh] Termos MeSH secundário: Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Aminobutyrates); 0 (Angiotensin Receptor Antagonists); 0 (LCZ 696); 0 (Tetrazoles); 80M03YXJ7I (Valsartan) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170807 [Lr] Data última revisão: 170807 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170627 [St] Status: MEDLINE [do] DOI: 10.3760/cma.j.issn.0253-3758.2017.06.018

8 / 1978

MEDLINE

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[PMID]: 28507434 [Au] Autor: Yeom DW; Chae BR; Son HY; Kim JH; Chae JS; Song SH; Oh D; Choi YW [Ad] Endereço: College of Pharmacy, Chung-Ang University, Seoul. [Ti] Título: Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system. [So] Source: Int J Nanomedicine;12:3533-3545, 2017. [Is] ISSN: 1178-2013 [Cp] País de publicação: New Zealand [La] Idioma: eng [Ab] Resumo: A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST), a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul MCM, 45% Tween 20, and 45% Transcutol P. The amounts of SMEDDS and Poloxamer 407 were chosen as formulation variables for a 3-level factorial design. Further optimization was established by weighting different levels of importance on response variables for dissolution and total quantity, resulting in an optimal S-SMEDDS in large quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S-SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and experimental values for response variables. Consequently, compared with VST powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed excellent in vitro dissolution and in vivo oral bioavailability in rats. The magnitude of dissolution and absorption-enhancing capacities using quantity-based comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or suspension. Thus, we concluded that, in terms of developing an effective SMEDDS preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate. [Mh] Termos MeSH primário: Emulsões/administração & dosagem Valsartana/farmacocinética [Mh] Termos MeSH secundário: Administração Oral Animais Disponibilidade Biológica Caprilatos/química Sistemas de Liberação de Medicamentos/métodos Emulsões/química Emulsões/farmacocinética Etilenoglicóis/química Glicerídeos/química Masculino Polímeros Polissorbatos/química Ratos Sprague-Dawley Solubilidade Valsartana/administração & dosagem [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Caprylates); 0 (Emulsions); 0 (Ethylene Glycols); 0 (Glycerides); 0 (Polymers); 0 (Polysorbates); 80M03YXJ7I (Valsartan); A1A1I8X02B (carbitol); VFU0OU98LO (monooctanoin) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170825 [Lr] Data última revisão: 170825 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170517 [St] Status: MEDLINE [do] DOI: 10.2147/IJN.S136599

9 / 1978

MEDLINE

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[PMID]: 28492561 [Au] Autor: Senni M; Trimarco B; Emdin M; De Biase L [Ad] Endereço: Unità Complessa di Cardiologia 1, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo. [Ti] Título: [Sacubitril/valsartan, a new and effective treatment for heart failure with reduced ejection fraction]. [Ti] Título: Sacubitril/valsartan, una nuova ed efficace terapia dello scompenso cardiaco a funzione sistolica ridotta.. [So] Source: G Ital Cardiol (Rome);18(1):3-11, 2017 Jan. [Is] ISSN: 1827-6806 [Cp] País de publicação: Italy [La] Idioma: ita [Ab] Resumo: Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides. This approach can be considered a "paradigm shift" from neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF results, the European Society of Cardiology and the American Heart Association/American College of Cardiology guidelines proposed a substitution of ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on" strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are many questions that arise spontaneously from this trial, three recognized experts can help us to answer them. [Mh] Termos MeSH primário: Fármacos Cardiovasculares/administração & dosagem Insuficiência Cardíaca/tratamento farmacológico Volume Sistólico/efeitos dos fármacos Valsartana/administração & dosagem [Mh] Termos MeSH secundário: Aminobutiratos/administração & dosagem Seres Humanos Sistema Renina-Angiotensina/efeitos dos fármacos Tetrazóis/administração & dosagem Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Aminobutyrates); 0 (Cardiovascular Agents); 0 (LCZ 696); 0 (Tetrazoles); 80M03YXJ7I (Valsartan) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170619 [Lr] Data última revisão: 170619 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170512 [St] Status: MEDLINE [do] DOI: 10.1714/2654.27228

10 / 1978

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[PMID]: 28395211 [Au] Autor: Ibrahim DM; Radwan RR; Abdel Fattah SM [Ad] Endereço: Biochemistry Department, Faculty of Science, Ain Shams University, Egypt. [Ti] Título: Antioxidant and antiapoptotic effects of sea cucumber and valsartan against doxorubicin-induced cardiotoxicity in rats: The role of low dose gamma irradiation. [So] Source: J Photochem Photobiol B;170:70-78, 2017 May. [Is] ISSN: 1873-2682 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: Doxorubicin (DOX) is a highly effective antineoplastic drug; however, the clinical use of DOX is limited by its dose dependent cardiotoxicity. This study was conducted to evaluate the cardioprotective effect of sea cucumber and valsartan against DOX-induced cardiotoxicity in rats. Also, the role of exposure to low dose γ radiation (LDR) on each of them was investigated, since LDR could suppress various reactive oxygen species-related diseases. Rats received DOX (2.5mg/kg, ip) in six equal injections over a period of 2weeks, sea cucumber (14.4mg/kg, p.o) and valsartan (30mg/kg, p.o) for 8 successive weeks. Exposure to LDR (0.5Gy) was performed one day prior to DOX. Results revealed that DOX administration elevated serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK-MB) and troponin-I as well as increased cardiac lipid peroxide content and myeloperoxidase (MPO) activity. Additionally, it increased cardiac expressions of iNOS and caspase-3, accompanied by reduction in cardiac total protein and glutathione (GSH) contents. Treatment with sea cucumber or valsartan improved the cardiotoxicity of DOX. Their adjuvant therapy with LDR offers an additional benefit to the cardioprotection of the therapeutic drugs. These results confirmed by histopathological examination. In conclusion, sea cucumber and valsartan alone or combined with LDR attenuated DOX-induced cardiotoxicity via their antioxidant and anti-apoptotic activities and thus might be useful in the treatment of human patients under doxorubicin chemotherapy. [Mh] Termos MeSH primário: Antioxidantes/farmacologia Apoptose/efeitos dos fármacos Raios gama Pepinos-do-Mar/química [Mh] Termos MeSH secundário: Animais Antioxidantes/química Apoptose/efeitos da radiação Aspartato Aminotransferases/sangue Caspase 3/genética Caspase 3/metabolismo Creatina Quinase/sangue Doxorrubicina/toxicidade Glutationa/metabolismo Cardiopatias/etiologia Masculino Miocárdio/metabolismo Miocárdio/patologia Óxido Nítrico Sintase Tipo II/genética Óxido Nítrico Sintase Tipo II/metabolismo Estresse Oxidativo/efeitos dos fármacos Estresse Oxidativo/efeitos da radiação Peroxidase/metabolismo Ratos Espécies Reativas de Oxigênio/metabolismo Pepinos-do-Mar/metabolismo Troponina I/sangue Valsartana/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antioxidants); 0 (Reactive Oxygen Species); 0 (Troponin I); 80168379AG (Doxorubicin); 80M03YXJ7I (Valsartan); EC 1.11.1.7 (Peroxidase); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.7.3.2 (Creatine Kinase); EC 3.4.22.- (Caspase 3); GAN16C9B8O (Glutathione) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170920 [Lr] Data última revisão: 170920 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170411 [St] Status: MEDLINE

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