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Am J Nephrol ; 50(5): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655812


BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.

Eur J Heart Fail ; 21(11): 1426-1433, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31523892


AIMS: Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40 mg) or placebo. The primary endpoints were change from baseline to 20 weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20 weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate. CONCLUSIONS: In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function. CLINICAL TRIAL REGISTRATION: Identifier NCT02992288.

Reprod Fertil Dev ; 30(2): 359-370, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28768567


The aim of this study was to evaluate the viability, antrum formation and in vitro development of isolated secondary follicles from vitrified caprine ovarian cortex in a medium previously established for fresh isolated secondary follicles, in the absence (α-minimum essential medium (α-MEM+) alone) or presence of FSH and vascular endothelial growth factor (VEGF; α-MEM++FSH+VEGF). Ovarian fragments were distributed among five treatments (T1 to T5): fresh follicles were fixed immediately (T1), follicles from fresh tissue were cultured in vitro in α-MEM+ (T2) or α-MEM++FSH+VEGF (T3) and follicles from vitrified tissue were cultured in vitro in α-MEM+ (T4) or α-MEM++FSH+VEGF (T5). After 6 days of culture, treated follicles (T2, T3, T4 and T5) were evaluated for morphology, viability and follicular development (growth, antrum formation and proliferation of granulosa cells by Ki67 and argyrophilic nucleolar organiser region (AgNOR) staining). The levels of reactive oxygen species (ROS) in the culture media were also assessed. Overall, morphology of vitrified follicles was altered (P<0.05) compared with the fresh follicles. Follicular viability, antrum formation and ROS were similar between treatments (P>0.05). The average overall and daily follicular growth was highest (P<0.05) in T3. Granulosa cells in all treatments (T1, T2, T3, T4 and T5) stained positive for Ki67. However, fresh follicles from T3 had significantly higher AgNOR staining (P<0.05) compared with follicles of T1, T2, T4 and T5. In conclusion, secondary follicles can be isolated from vitrified and warmed ovarian cortex and survive and form an antrum when growing in an in vitro culture for 6 days.

Criopreservação/veterinária , Cabras/embriologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Folículo Ovariano/fisiologia , Ovário/citologia , Animais , Antígenos Nucleares/metabolismo , Proliferação de Células , Forma Celular , Sobrevivência Celular , Células Cultivadas , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante/farmacologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/farmacologia
Am J Nephrol ; 40(6): 572-81, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25591469


BACKGROUND/AIMS: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b study. ARTS-DN investigated whether the mineralocorticoid receptor antagonist finerenone reduces albuminuria without causing major alterations in serum potassium levels in patients with type 2 diabetes mellitus and a clinical diagnosis of DN who were receiving a renin-angiotensin-system (RAS) inhibitor. METHODS: Patients were randomized to oral finerenone 1.25-20 mg or placebo once daily. The primary objectives were to assess the ratio of the urinary albumin-to-creatinine ratio at day 90 to that at baseline in patients receiving finerenone, and to compare it with that in the placebo group. Additional exploratory analyses included evaluating changes from baseline in serum potassium levels, efficacy and safety biomarkers, and health-related quality of life. RESULTS: Of 1,501 patients screened, 821 (the sample population) received at least one dose of finerenone/placebo. Baseline characteristics included: male, 77.8%; white, 84.2%; very high albuminuria (formerly macroalbuminuria), 38.4%; high albuminuria (formerly microalbuminuria), 60.3%; median (range) estimated glomerular filtration rate, 66.3 (24.5-130.7) ml/min/1.73 m(2); and systolic blood pressure (mean ± standard deviation), 138.1 ± 14.4 mm Hg. There was a history of cardiovascular disease in 39.6%, diabetic neuropathy in 20.0%, and diabetic retinopathy in 19.9% of patients. CONCLUSION: ARTS-DN is the first phase 2b trial of finerenone in combination with a RAS inhibitor in patients with type 2 diabetes mellitus and a clinical diagnosis of DN.

Albuminúria/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Naftiridinas/administração & dosagem , Idoso , Albuminúria/urina , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Creatinina/urina , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Método Duplo-Cego , Hipertensão Pulmonar Primária Familiar/complicações , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Naftiridinas/efeitos adversos , Potássio/sangue
Ambito odontol ; 5(30): 5-12, jul.-ago. 1996. ilus
Artigo em Português | BBO - Odontologia | ID: biblio-849750


Os autores relacionam os tecidos dentais e a proteção da dentina polpa, assim como fazem uma revisão dos materiais utilizados ao longo dos anos até os tempos atuais para esse fim. Neste trabalho propõe-se a utilização de hidróxido de cálcio, adesivos dentinários e ionômero de vidro para os diversos tipos de cavidades, tanto para resina composta quanto para amálgama

Adesivos Dentinários , Cimentos de Ionômeros de Vidro , Hidróxido de Cálcio/administração & dosagem , Forramento da Cavidade Dentária , Dentina , Óleos Industriais
Rev. paul. odontol ; 18(2): 35-39, mar.-abr. 1996. ilus
Artigo em Português | LILACS, BBO - Odontologia | ID: lil-345002


Este trabalho mostra uma nova proposta de ensino de escultura e oclusäo dental. O estudante entra em contato com os princípios básicos de oclusäo já no início do curso. A escultura, além de trabalhos em cera, se desenvolve através de técnicas restauradoras atuais como: facetas, incrustaçöes em resina composta, assim como restauraçöes em amálgama, resina composta entre outras. Com isso o estudante de odontologia tem contato com a parte clínica e aplicaçäo da escultura e oclusäo dental na prática diária

Oclusão Dentária , Escultura , Ensino , Dente