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[PMID]:29261854
[Au] Autor:Onarecker C
[Ti] Título:Clinical Question: In congestive heart failure patients with preserved ejection fraction, does spironolactone improve cardiac outcomes?
[So] Source:J Okla State Med Assoc;109(9):437-8, 2016 Sep.
[Is] ISSN:0030-1876
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Answer: No. A randomized controlled trial of patients with heart failure and an ejection fraction > 45% showed that spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. Level of Evidence for the Answer: A Limits: English, Adults, Randomized Controlled Trials, Meta-analysis, and Systematic review. Date Search Was Conducted: December 2015. Inclusion criteria: All randomized controlled trials, meta-analyses, and systematic reviews in patients with congestive heart failure with preserved ejection fractions, who were taking spironolactone, and published in the past 5 years. Exclusion criteria:; Age less than eighteen years, Eplerenone .
[Mh] Termos MeSH primário: Insuficiência Cardíaca/tratamento farmacológico
Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
Espironolactona/uso terapêutico
Volume Sistólico
[Mh] Termos MeSH secundário: Doenças Cardiovasculares/mortalidade
Parada Cardíaca/epidemiologia
Insuficiência Cardíaca/fisiopatologia
Hospitalização/estatística & dados numéricos
Seres Humanos
Avaliação de Resultados (Cuidados de Saúde)
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Nome de substância:
0 (Mineralocorticoid Receptor Antagonists); 27O7W4T232 (Spironolactone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE


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[PMID]:29310346
[Au] Autor:Korol S; Mottet F; Perreault S; Baker WL; White M; de Denus S
[Ad] Endereço:Faculty of Pharmacy, Université de Montréal.
[Ti] Título:A systematic review and meta-analysis of the impact of mineralocorticoid receptor antagonists on glucose homeostasis.
[So] Source:Medicine (Baltimore);96(48):e8719, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Spironolactone, a nonselective mineralocorticoid receptor antagonist (MRA), may have a deleterious effect on glycemia. The objective of this review was to assess current knowledge on MRAs' influence (spironolactone, eplerenone, and canrenone) on glucose homeostasis and the risk of diabetes. METHOD: A systematic review was conducted using the Medline database on articles published from 1946 to January 2017 that studied the effects of MRAs on any glucose-related endpoints, without any restrictions regarding the participants' characteristics.Study design, patient population, dose and duration of intervention, and the quantitative results on glycemic markers were extracted, interpreted for result synthesis, and evaluated for sources of bias. From the articles included in the qualitative analysis, a select number were used in a meta-analysis on studies having measured glycated hemoglobin (HbA1c) or risk of diabetes. RESULTS: Seventy-two articles were selected from the Medline database and references of articles. Results on spironolactone were heterogeneous, but seemed to be disease-specific. A potential negative effect on glucose regulation was mainly observed in heart failure and diabetes trials, while a neutral or positive effect was detected in diseases characterized by hyperandrogenism, and inconclusive for hypertension. Interpretation of data from heart failure trials was limited by the small number of studies. From a meta-analysis of 12 randomized controlled studies evaluating spironolactone's impact on HbA1c in diabetic patients, spironolactone had a nonsignificant effect in parallel-group studies (mean difference 0.03 [-0.20;0.26]), but significantly increased HbA1c in crossover studies (mean difference 0.24 [0.18;0.31]). Finally, eplerenone did not seem to influence glycemia, while limited data indicated that canrenone may exert a neutral or beneficial effect.The studies had important limitations regarding study design, sample size, duration of follow-up, and choice of glycemic markers. CONCLUSION: Spironolactone may induce disease-specific and modest alterations on glycemia. It is uncertain whether these effects are transient or not. Data from the most extensively studied population, individuals with diabetes, do not support a long-term glycemic impact in these patients. Further prospective studies are necessary to establish spironolactone's true biological effects and their clinical implications.
[Mh] Termos MeSH primário: Glicemia/efeitos dos fármacos
Homeostase/efeitos dos fármacos
Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
[Mh] Termos MeSH secundário: Canrenona/uso terapêutico
Hemoglobina A Glicada/análise
Seres Humanos
Espironolactona/análogos & derivados
Espironolactona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Mineralocorticoid Receptor Antagonists); 27O7W4T232 (Spironolactone); 6995V82D0B (eplerenone); 78O20X9J0U (Canrenone)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180115
[Lr] Data última revisão:
180115
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008719


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[PMID]:27777360
[Au] Autor:Hwang AY; Dave C; Smith SM
[Ad] Endereço:From the Department of Pharmacotherapy and Translational Research (A.Y.H., S.M.S.) and Department of Pharmaceutical Outcomes and Policy (C.D.), College of Pharmacy, and Department of Community Health and Family Medicine, College of Medicine (A.Y.H., S.M.S.), University of Florida, Gainesville.
[Ti] Título:Trends in Antihypertensive Medication Use Among US Patients With Resistant Hypertension, 2008 to 2014.
[So] Source:Hypertension;68(6):1349-1354, 2016 12.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Little is known of US trends in antihypertensive drug use for patients with treatment-resistant hypertension (TRH). We analyzed antihypertensive use among patients with TRH (treated with ≥4 antihypertensive drugs concurrently) from July 2008 through December 2014 using Marketscan administrative data. We included adults aged 18 to 65 years, with ≥6 months of continuous enrollment, a hypertension diagnosis, and ≥1 episode of overlapping use of ≥4 antihypertensive drugs; patients with heart failure were excluded. We identified 411 652 unique TRH episodes from 261 652 patients with a mean age of 55.9 years. From 2008 to 2014, we observed an increased prevalence, among TRH episodes, of ß-blockers (+6.8% [79% to 85.8%]) and dihydropyridine calcium antagonists (+8.1% [69.1% to 77.2%]), and a decreased prevalence of angiotensin-converting enzyme inhibitors (-12.5% [60.4% to 47.9%]) and nondihydropyridine calcium antagonists (-5.0% [15% to 10%]). The prevalence of most other classes changed by <5% from 2008 to 2014. Thiazide diuretic use was largely unchanged from 2008 to 2014, with hydrochlorothiazide being by far the most prevalent thiazide diuretic; chlorthalidone use increased only modestly (+2.6% [3.8% to 6.4%]). Aldosterone antagonist use increased only modestly (+2.9% [7.3% to 10.2%]). Use of optimal regimens increased steadily (+13.8% [50.8% to 64.6%]) during the study period, whereas combined angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use declined (-11.4% [17.7% to 6.3%]). Our results highlight the persistent infrequent use of recommended therapies in TRH, including spironolactone and chlorthalidone, and suggest a need for better efforts to increase the use of such approaches in light of recent evidence demonstrating their efficacy.
[Mh] Termos MeSH primário: Anti-Hipertensivos/uso terapêutico
Clortalidona/uso terapêutico
Resistência a Medicamentos
Hipertensão/diagnóstico
Hipertensão/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Anti-Hipertensivos/farmacologia
Determinação da Pressão Arterial/métodos
Bloqueadores dos Canais de Cálcio/uso terapêutico
Estudos de Coortes
Quimioterapia Combinada
Uso de Medicamentos/tendências
Feminino
Seguimentos
Seres Humanos
Hidroclorotiazida/uso terapêutico
Masculino
Meia-Idade
Segurança do Paciente
Estudos Retrospectivos
Medição de Risco
Índice de Gravidade de Doença
Espironolactona/uso terapêutico
Resultado do Tratamento
Estados Unidos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antihypertensive Agents); 0 (Calcium Channel Blockers); 0J48LPH2TH (Hydrochlorothiazide); 27O7W4T232 (Spironolactone); Q0MQD1073Q (Chlorthalidone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29216985
[Au] Autor:Takemoto Y; Ramirez RJ; Kaur K; Salvador-Montañés O; Ponce-Balbuena D; Ramos-Mondragón R; Ennis SR; Guerrero-Serna G; Berenfeld O; Jalife J
[Ad] Endereço:Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan; Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan.
[Ti] Título:Eplerenone Reduces Atrial Fibrillation Burden Without Preventing Atrial Electrical Remodeling.
[So] Source:J Am Coll Cardiol;70(23):2893-2905, 2017 Dec 12.
[Is] ISSN:1558-3597
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aldosterone inhibitor eplerenone (EPL) has been shown to reduce the incidence of atrial fibrillation (AF) in patients with systolic heart failure, but the mechanism is unknown. OBJECTIVES: This study hypothesized that by reducing atrial dilation and fibrosis in the absence of heart failure, EPL also reduces AF burden and prevents AF perpetuation. METHODS: The authors conducted a randomized controlled study in 34 sheep that were atrially tachypaced (13 ± 1 week). They compared daily oral EPL (n = 19) versus sugar pill (SP) treatment (n = 15) from the start of tachypacing. The endpoint was a continuous 7-day stretch of persistent AF (n = 29) or completion of 23 weeks tachypacing (n = 5). RESULTS: EPL significantly reduced the rate of left atrial dilation increase during AF progression. Atria from EPL-treated sheep had less smooth muscle actin protein, collagen-III expression, interstitial atrial fibrosis, and cell hypertrophy than SP-treated sheep atria did. However, EPL did not modify the AF-induced increase in the rate of dominant frequency and ion channel densities seen under SP treatment, but rather prolonged the time to persistent AF in 26% of animals. It also reduced the degree of fibrillatory conduction, AF inducibility, and AF burden. CONCLUSIONS: In the sheep model, EPL mitigates fibrosis and atrial dilation, modifies AF inducibility and AF complexity, and prolongs the transition to persistent AF in 26% of animals, but it does not prevent AF-induced electrical remodeling or AF persistence. The results highlight structural remodeling as a central upstream target to reduce AF burden, and the need to prevent electrical remodeling to avert AF perpetuation.
[Mh] Termos MeSH primário: Fibrilação Atrial/prevenção & controle
Remodelamento Atrial/efeitos dos fármacos
Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
Espironolactona/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Fibrilação Atrial/patologia
Estimulação Cardíaca Artificial
Fibrose
Masculino
Ovinos
Espironolactona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mineralocorticoid Receptor Antagonists); 27O7W4T232 (Spironolactone); 6995V82D0B (eplerenone)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:29188952
[Au] Autor:Arkkila P; Nordin A
[Ti] Título:Treatment of ascites and its complications.
[So] Source:Duodecim;132(18):1719-25, 2016.
[Is] ISSN:0012-7183
[Cp] País de publicação:Finland
[La] Idioma:eng
[Ab] Resumo:The underlying cause of ascites should always be treated if possible. Adhering to a low-salt diet is most important in the treatment of ascites. Diuretics are used in the treatment of clinically established and abundant ascites. The first-line drug in diuretic therapy is spironolactone, when necessary in combination with furosemide. The most important complications of ascites are hepatorenal syndrome and spontaneous bacterial peritonitis. The development of ascites lowers the quality of life, and is associated with significant mortality. Although new groundbreaking therapies are not available, prognosis of the patients is expected to be improved through optimization of current therapies.
[Mh] Termos MeSH primário: Ascite/complicações
Ascite/terapia
[Mh] Termos MeSH secundário: Ascite/mortalidade
Dieta Hipossódica
Diuréticos/uso terapêutico
Furosemida/uso terapêutico
Síndrome Hepatorrenal/etiologia
Seres Humanos
Peritonite/etiologia
Prognóstico
Qualidade de Vida
Espironolactona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Diuretics); 27O7W4T232 (Spironolactone); 7LXU5N7ZO5 (Furosemide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


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[PMID]:28457401
[Au] Autor:de Sousa MV; Guida JP; do Valle CF; Camargo LF; Rivelli GG; Mazzali M
[Ad] Endereço:Renal Transplant Unit, Division of Nephrology, Department of Medicine, School of Medical Sciences, University of Campinas, UNICAMP, Campinas-SP, Brazil. Electronic address: marcosnefro@gmail.com.
[Ti] Título:Spironolactone in Post-Transplant Proteinuria: A Safe Alternative Therapy.
[So] Source:Transplant Proc;49(4):813-816, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Aldosterone is involved in the process of renal allograft fibrosis, clinically manifest by proteinuria and allograft dysfunction, with increased risk for cardiovascular death. The treatment with aldosterone antagonists appears to be effective in controlling proteinuria, with a protective effect on progression of renal fibrosis. METHODS: This retrospective, cohort study included kidney transplant recipients from January 1993 to June 2015. Inclusion criteria were persistent proteinuria >0.5 g/d, longer than 6 months, and spironolactone therapy. RESULTS: One hundred forty transplant recipients fulfilled the inclusion criteria and were divided into 3 groups, according to proteinuria levels at the beginning of spironolactone therapy: low (<1 g/24 h), intermediate (1-3 g/24 h), and nephrotic (>3 g/24 h). Groups were comparable in demographic data, with a higher incidence of living related donors in the nephrotic group. In patients with proteinuria ≥1 g/d, we observed a significant reduction in proteinuria after 6 months of therapy that persisted over time. Blood pressure and glomerular filtration rate persisted stable over time. Adverse events were not severe to withdrawal therapy. CONCLUSIONS: Spironolactone can be a safe alternative to control post-transplant proteinuria, especially in patients with mild to moderate allograft dysfunction with proteinuria ≥1 g/day.
[Mh] Termos MeSH primário: Diuréticos/uso terapêutico
Transplante de Rim/efeitos adversos
Proteinúria/tratamento farmacológico
Espironolactona/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
Proteinúria/etiologia
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 27O7W4T232 (Spironolactone)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28912358
[Au] Autor:Alpañés M; Álvarez-Blasco F; Fernández-Durán E; Luque-Ramírez M; Escobar-Morreale HF
[Ad] Endereço:DiabetesObesity and Human Reproduction Research Group, Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal & Universidad de Alcalá & Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS & Centro de Investigación Biomédica en Red Diabetes y Enfermedades
[Ti] Título:Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial.
[So] Source:Eur J Endocrinol;177(5):399-408, 2017 Nov.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). DESIGN: We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 µg of ethinylestradiol and 150 µg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). METHODS: The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension). A complete anthropometric, biochemical, hormonal and metabolic evaluation was conducted every three months and data were submitted to intention-to-treat analyses. RESULTS: Twenty-four patients were assigned to COC plus spironolactone and 22 patients to metformin. Compared with metformin, COC plus spironolactone caused larger decreases in hirsutism score (mean difference 4.6 points, 95% CI: 2.6-6.7), total testosterone (1.1 nmol/L, 0.4-1.7), free testosterone (25 pmol/L, 12-39), androstenedione (5.5 nmol/L, 1.8-9.2) and dehydroepiandrosterone sulfate (2.7 µmol/L, 1.4-4.0). Menstrual dysfunction was less frequent with COC plus spironolactone (OR: 0.06, 95% CI: 0.02-0.23). No differences were found in frequencies of abnormal glucose tolerance (OR: 1.7, 95% CI: 0.7-4.4), dyslipidemia (OR: 0.6, 95% CI: 0.2-1.8) or hypertension (OR: 0.3, 95% CI: 0.5-2.0). No major adverse events occurred and biochemical markers were similarly safe with both treatments. CONCLUSIONS: COC plus spironolactone was more effective than metformin for symptoms of PCOS showing similar safety and overall neutral effects on cardiometabolic risk factors.
[Mh] Termos MeSH primário: Anticoncepcionais Orais Combinados/uso terapêutico
Metformina/uso terapêutico
Síndrome do Ovário Policístico/tratamento farmacológico
Espironolactona/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Anticoncepcionais Orais Combinados/administração & dosagem
Anticoncepcionais Orais Combinados/efeitos adversos
Esquema de Medicação
Feminino
Hirsutismo/sangue
Hirsutismo/tratamento farmacológico
Seres Humanos
Hipoglicemiantes/administração & dosagem
Hipoglicemiantes/efeitos adversos
Hipoglicemiantes/uso terapêutico
Metformina/administração & dosagem
Metformina/efeitos adversos
Síndrome do Ovário Policístico/sangue
Espironolactona/administração & dosagem
Espironolactona/efeitos adversos
Testosterona/sangue
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Contraceptives, Oral, Combined); 0 (Hypoglycemic Agents); 27O7W4T232 (Spironolactone); 3XMK78S47O (Testosterone); 9100L32L2N (Metformin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0516


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[PMID]:28888268
[Au] Autor:Hayer MK; Edwards NC; Slinn G; Moody WE; Steeds RP; Ferro CJ; Price AM; Andujar C; Dutton M; Webster R; Webb DJ; Semple S; MacIntyre I; Melville V; Wilkinson IB; Hiemstra TF; Wheeler DC; Herrey A; Grant M; Mehta S; Ives N; Townend JN
[Ad] Endereço:Birmingham Cardio-Renal Group (University of Birmingham Institute of Cardiovascular Sciences), Queen Elizabeth Hospital, Edgbaston, Birmingham.
[Ti] Título:A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial.
[So] Source:Am Heart J;191:37-46, 2017 Sep.
[Is] ISSN:1097-6744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. AIM: The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. DESIGN: This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40weeks of treatment with spironolactone 25mg once daily to chlorthalidone 25mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40weeks of randomly allocated drug therapy and at 46weeks after discontinuation of the study drug.
[Mh] Termos MeSH primário: Clortalidona/administração & dosagem
Ventrículos do Coração/diagnóstico por imagem
Hipertrofia Ventricular Esquerda/etiologia
Falência Renal Crônica/complicações
Espironolactona/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Relação Dose-Resposta a Droga
Quimioterapia Combinada
Feminino
Seguimentos
Ventrículos do Coração/fisiopatologia
Seres Humanos
Hipertrofia Ventricular Esquerda/mortalidade
Hipertrofia Ventricular Esquerda/fisiopatologia
Falência Renal Crônica/mortalidade
Falência Renal Crônica/fisiopatologia
Imagem Cinética por Ressonância Magnética
Masculino
Meia-Idade
Antagonistas de Receptores de Mineralocorticoides/administração & dosagem
Estudos Prospectivos
Análise de Onda de Pulso
Método Simples-Cego
Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem
Taxa de Sobrevida/tendências
Fatores de Tempo
Resultado do Tratamento
Estados Unidos/epidemiologia
Rigidez Vascular
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Mineralocorticoid Receptor Antagonists); 0 (Sodium Chloride Symporter Inhibitors); 27O7W4T232 (Spironolactone); Q0MQD1073Q (Chlorthalidone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171014
[Lr] Data última revisão:
171014
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170911
[St] Status:MEDLINE


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[PMID]:28874460
[Au] Autor:Martin-Lorenzo M; Martinez PJ; Baldan-Martin M; Ruiz-Hurtado G; Prado JC; Segura J; de la Cuesta F; Barderas MG; Vivanco F; Ruilope LM; Alvarez-Llamas G
[Ad] Endereço:From the Department of Immunology, IIS-Fundacion Jimenez Diaz, REDinREN, Madrid, Spain (M.M.-L., P.J.M., F.V., G.A.-L.); Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain (M.B.-M., M.G.B.); Hypertension Unit, Instituto de Investigación imas12, Hospital U
[Ti] Título:Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.
[So] Source:Hypertension;70(5):1049-1056, 2017 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered ( <0.0001). Metabolic concentrations were quantified and ranged from ng/mL malate to µg/mL citrate. Citrate and oxaloacetate increased in RH versus pseudoresistant. Together with α-ketoglutarate and malate, they were able to discriminate between responders and nonresponders, being the 4 metabolites increased in nonresponders. Combined as a prediction panel, they showed receiver operating characteristiccurve with area under the curve of 0.96. We show that citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone.
[Mh] Termos MeSH primário: Ácido Cítrico
Resistência a Medicamentos/fisiologia
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Hipertensão
Espironolactona
[Mh] Termos MeSH secundário: Idoso
Anti-Hipertensivos/administração & dosagem
Anti-Hipertensivos/efeitos adversos
Anti-Hipertensivos/farmacocinética
Cromatografia Líquida/métodos
Ácido Cítrico/análise
Ácido Cítrico/metabolismo
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/urina
Feminino
Seres Humanos
Hipertensão/tratamento farmacológico
Hipertensão/epidemiologia
Hipertensão/metabolismo
Ácidos Cetoglutáricos/análise
Ácidos Cetoglutáricos/metabolismo
Masculino
Meia-Idade
Valor Preditivo dos Testes
Prognóstico
Espanha/epidemiologia
Espironolactona/administração & dosagem
Espironolactona/efeitos adversos
Espironolactona/farmacocinética
Urinálise/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Ketoglutaric Acids); 27O7W4T232 (Spironolactone); 2968PHW8QP (Citric Acid); 8ID597Z82X (alpha-ketoglutaric acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.09819


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[PMID]:28870958
[Au] Autor:Bouhenna MM; Orlikova B; Talhi O; Schram B; Pinto DCGA; Taibi N; Bachari K; Diederich M; Silva AMS; Mameri N
[Ad] Endereço:Unité de Recherche URIE, Ecole Nationale Polytechnique, Alger, Algeria.
[Ti] Título:Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.
[So] Source:Anticancer Res;37(9):5225-5233, 2017 09.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). MATERIALS AND METHODS: The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. RESULTS: Both spiro(coumarin-cyclohexanone) and spiro(6- methyllactone-cyclohexanone) down-regulated cancer cell viability and proliferation. Compound inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. CONCLUSION: Results show that compound and compound have potential as anti-cancer agents. In addition, compound exerted NF-kB inhibition activity in leukemia cancer cells.
[Mh] Termos MeSH primário: Cicloexanonas/farmacologia
Leucemia/patologia
NF-kappa B/metabolismo
Espironolactona/farmacologia
[Mh] Termos MeSH secundário: Bioensaio
Caspase 3/metabolismo
Caspase 7/metabolismo
Morte Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Cromatografia Líquida de Alta Pressão
Cicloexanonas/síntese química
Cicloexanonas/química
Seres Humanos
Células K562
Espironolactona/síntese química
Espironolactona/química
Estereoisomerismo
Fator de Necrose Tumoral alfa/farmacologia
Células U937
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclohexanones); 0 (NF-kappa B); 0 (Tumor Necrosis Factor-alpha); 27O7W4T232 (Spironolactone); 5QOR3YM052 (cyclohexanone); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 7)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE



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