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1.
Pan Afr Med J ; 35: 10, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32117525

RESUMO

Introduction: Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali). Methods: We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests. Results: Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q2cum = 0.73, attesting severe sexual dimorphism associated with arterial hypertension. This model involved eight parameters whose plasma concentration was modified (homocysteine, NT-proBNP, potassium, urea, blood glucose, sodium, chlorine and total proteins). Conclusion: We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.


Assuntos
Hiper-Homocisteinemia/epidemiologia , Hipertensão/epidemiologia , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Qualidade de Vida , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Mali , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
2.
Int Heart J ; 61(1): 77-82, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956150

RESUMO

This study aimed to evaluate whether the heart is the target organ of endogenous atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with heart failure (HF) with reduced ejection fraction (HFrEF).We measured the plasma levels of cyclic guanosine monophosphate (cGMP), which is a second messenger of ANP and BNP, in the aortic root (AO) and coronary sinus (CS) in 237 patients with HFrEF. Plasma levels of cGMP were significantly higher in the CS than those in the AO in 237 patients with HFrEF (10.0 ± 4.5 versus 10.5 ± 4.3 pmoL/mL, P < 0.0001) and were significantly higher in the CS than those in the AO (8.0 ± 3.6 versus 8.9 ± 3.8 pmoL/mL, P < 0.0001) in mild HF patients (New York Heart Association (NYHA) II, n = 114), but there was no difference in plasma cGMP between the AO and the CS (11.9 ± 4.4 versus 11.9 ± 4.3 pmoL/mL, NS) in severe HF patients (NYHA III-IV, n = 123). In mild HF patients, log (ANP + BNP) in the AO was an independent predictor of (CS-AO) cGMP among hemodynamics and nitrate therapy. There was a significant correlation between log [(CS-AO) ANP + (CS-AO) BNP] and (CS-AO) cGMP (r = 0.455, P < 0.0001) in mild HF patients.These findings indicate that cGMP is produced from the failing heart and that the heart is the target organ of endogenous ANP and BNP in patients with HFrEF. In severe HF patients, cGMP production may be attenuated because of the downregulation of biological receptors and/or increased cGMP degradation in the failing heart.


Assuntos
Fator Natriurético Atrial/metabolismo , Insuficiência Cardíaca/fisiopatologia , Peptídeo Natriurético Encefálico/metabolismo , Idoso , Cateterismo Cardíaco , GMP Cíclico/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico
3.
Forensic Sci Int ; 306: 110079, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812084

RESUMO

The utility of biochemical marker analysis in forensic autopsy cases is still uncertain due to the postmortem changes which they undergo. Thus, research is required to elucidate alternative samples and biochemical markers which are less affected by postmortem changes. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to be elevated in congestive heart failure (CHF), acute myocardial infarction (AMI), and sepsis patients. Although NT-proBNP is reportedly excreted into the urine, no study has previously evaluated the diagnostic efficacy of urinary concentrations in a forensic setting. The aim of this study was to evaluate the diagnostic efficacy of NT-proBNP concentration in urine obtained postmortem in a series of forensic autopsy cases. METHODS: Urinary NT-proBNP was measured in 36 AMI, 10 CHF, and 19 sepsis cases, and in 124 control cases (all with postmortem interval [PMI]<72h). RESULTS: Urinary NT-proBNP was significantly higher in AMI, CHF, and sepsis cases than in control cases. Cut-off values for diagnosing AMI, CHF, and sepsis-related fatalities were 98 (sensitivity, 55.6 %; specificity, 73.4 %), 1050 (sensitivity, 80.0 %; specificity, 94.4 %), and 363pg/mL (sensitivity, 84.2 %; specificity, 85.5 %), respectively. Furthermore, we subdivided the control cases according to the death process as either acute death (87 cases) or prolonged death cases (37 cases). Although urine NT-proBNP of CHF and sepsis cases were significantly higher compared with both cases, the concentration in the AMI cases were significantly high only when compared with the acute death cases. CONCLUSION: This study is the first to elucidate the diagnostic utility of NT-proBNP measurement in urine obtained postmortem in a series of causes of death. This study suggests the diagnostic efficacy for AMI, CHF, and sepsis-related fatality in cases in which the PMI was within 72h.


Assuntos
Biomarcadores/urina , Medicina Legal , Peptídeo Natriurético Encefálico/urina , Fragmentos de Peptídeos/urina , Mudanças Depois da Morte , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Causas de Morte , Criança , Creatina Quinase Forma MB/metabolismo , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Líquido Pericárdico/metabolismo , Sensibilidade e Especificidade , Sepse/metabolismo , Troponina/sangue , Adulto Jovem
4.
Int J Mol Sci ; 20(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398927

RESUMO

Atrial natriuretic peptide (ANP) is a cardiac hormone belonging to the family of natriuretic peptides (NPs). ANP exerts diuretic, natriuretic, and vasodilatory effects that contribute to maintain water-salt balance and regulate blood pressure. Besides these systemic properties, ANP displays important pleiotropic effects in the heart and in the vascular system that are independent of blood pressure regulation. These functions occur through autocrine and paracrine mechanisms. Previous works examining the cardiac phenotype of loss-of-function mouse models of ANP signaling showed that both mice with gene deletion of ANP or its receptor natriuretic peptide receptor A (NPR-A) developed cardiac hypertrophy and dysfunction in response to pressure overload and chronic ischemic remodeling. Conversely, ANP administration has been shown to improve cardiac function in response to remodeling and reduces ischemia-reperfusion (I/R) injury. ANP also acts as a pro-angiogenetic, anti-inflammatory, and anti-atherosclerotic factor in the vascular system. Pleiotropic effects regarding brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were also reported. In this review, we discuss the current evidence underlying the pleiotropic effects of NPs, underlying their importance in cardiovascular homeostasis.


Assuntos
Sistema Cardiovascular/metabolismo , Peptídeos Natriuréticos/metabolismo , Animais , Sistema Cardiovascular/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Peptídeo Natriurético Encefálico/farmacologia , Peptídeos Natriuréticos/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Remodelação Vascular/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(6): 680-683, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31315722

RESUMO

OBJECTIVE: To explore the correlation between major inflammatory factors and septic shock in intensive care unit (ICU) patients, and to provide a basis for the diagnosis and treatment of septic shock. METHODS: The patients admitted to ICU of the Third People's Hospital of Datong from March 2017 to August 2018 were selected as the research objects. According to the diagnostic criteria of septic shock, the patients were divided into septic shock group and non-septic group. The basic information and inflammatory factors levels of the two groups, including age, gender, body mass index (BMI), course of disease, acute physiology and chronic health evaluation II (APACHE II), infection site and pathogenic; and C-reactive protein (CRP), procalcitonin (PCT), neutrophil lymphocyte ratio (NLR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ), interleukins (IL-1ß, IL-2, IL-6, IL-8) at 8 hours after diagnosis, were compared. Logistic regression was used to analyze the influencing factors of septic shock in ICU patients. RESULTS: A total of 154 ICU patients were selected, of whom 74 had septic shock. The APACHE II score of septic shock group was significantly higher than that of non-sepsis group (23.42±3.64 vs. 15.67±2.26, P < 0.05). There was no significant difference in other baseline data between the two groups. The levels of CRP, NT-proBNP, TNF-α, IFN-γ, PCT, IL-6, IL-8 in the septic shock group were significantly higher than those in the non-septic group [CRP (mg/L): 164.3±22.6 vs. 52.3±16.2, NT-proBNP (ng/L): 426.3±288.9 vs. 167.3±80.6, TNF-α (ng/L): 193.4±39.3 vs. 88.1±20.3, IFN-γ (ng/L): 133.3±52.0 vs. 97.0±56.1, PCT (ng/L): 27.6±10.2 vs. 7.3±4.1, IL-6 (ng/L): 83.0±17.6 vs. 20.9±6.4, IL-8 (ng/L): 445.8±34.0 vs. 84.0±25.7, all P < 0.05]. It was shown by Logistic regression analysis that CRP, NT-proBNP, TNF-α, PCT, IL-6 were independent risk factors for septic shock [CRP: odds ratio (OR) = 1.662, 95% confidence interval (95%CI) = 1.132-2.567; NT-proBNP: OR = 14.688, 95%CI = 3.580-20.238; TNF-α: OR = 1.093, 95%CI = 1.043-1.343; PCT: OR = 6.378, 95%CI = 4.556-12.243; IL-6: OR = 9.641, 95%CI = 2.242-13.786; all P < 0.05]. CONCLUSIONS: The levels of inflammatory factors CRP, NT-proBNP, TNF-α, PCT and IL-6 were significantly increased, which were important factors for early diagnosis of septic shock.


Assuntos
Choque Séptico/diagnóstico , Choque Séptico/metabolismo , APACHE , Proteína C-Reativa/metabolismo , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-6/metabolismo , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Pró-Calcitonina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Int J Mol Sci ; 20(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336656

RESUMO

Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.


Assuntos
Coração/fisiologia , Rim/fisiologia , Peptídeo Natriurético Encefálico/metabolismo , Transdução de Sinais , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Animais , Suscetibilidade a Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/genética , Neprilisina/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico
7.
Am J Chin Med ; 47(5): 1075-1097, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311298

RESUMO

Pirarubicin (THP) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. Unfortunately, the clinical effectiveness of THP is limited by its dose-related cardiotoxicity. Apocynum leaf extract is an extract of the dried leaves of Apocynum venetum L. (a member of the Apocynaceae family, AVLE) that has many positive effects on the cardiovascular system and is widely consumed as tea in China. In this study we established a cardiactoxicity rat model, which showed that pretreatment with AVLE attenuated THP-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. AVLE also significantly reduced serum levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (CTnT), and lactate dehydrogenase (LDH); and increased serum superoxide dismutase (SOD) levels. Treatment with AVLE or dexrazoxane (DZR) resulted in an increase Cytochrome C (cytc) in the mitochondria and reduced Cytc and cleaved-caspase-3 levels (p<0.05) in cytoplasm. We also found that AVLE significantly reduced voltage-dependent anion channel 1 (VDAC1), adenosine nucleotide transporter 1 (ANT1), and cyclophilin D (CYPD) mRNA expression (p<0.05). Furthermore, AVLE appeared to exert therapeutic effects in a dose-dependent manner. Our study suggests the anti-oxidant and anti-apoptotic properties of AVLE may be responsible for the observed cardioprotective effects.


Assuntos
Antioxidantes/administração & dosagem , Apocynum/química , Cardiotoxicidade/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Cardiotoxicidade/fisiopatologia , Creatina Quinase/genética , Creatina Quinase/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Humanos , Masculino , Malondialdeído/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Folhas de Planta/química , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Troponina/genética , Troponina/metabolismo
8.
PLoS One ; 14(6): e0216285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211784

RESUMO

Stress-induced cardiac hypertrophy leads to heart failure. Our previous studies demonstrate that insulin-like growth factor-II receptor (IGF-IIR) signaling is pivotal to hypertrophy regulation. In this study, we show a novel IGF-IIR alternative spliced transcript, IGF-IIRα (150 kDa) play a key role in high-salt induced hypertrophy mechanisms. Cardiac overexpression of IGF-IIRα and high-salt diet influenced cardiac dysfunction by increasing pathophysiological changes with up-regulation of hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). We found that, cardiac hypertrophy under high-salt conditions were amplified in the presence of IGF-IIRα overexpression. Importantly, high-salt induced angiotensin II type I receptor (AT1R) up regulation mediated IGF-IIR expressions via upstream mitogen activated protein kinase (MAPK)/silent mating type information regulation 2 homolog 1 (SIRT1)/heat shock factor 1 (HSF1) pathway. Further, G-coupled receptors (Gαq) activated calcineurin/nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3)/protein kinase C (PKC) signaling was significantly up regulated under high-salt conditions. All these effects were observed to be dramatically over-regulated in IGF-IIRα transgenic rats fed with a high-salt diet. Altogether, from the findings, we demonstrate that IGF-IIRα plays a crucial role during high-salt conditions leading to synergistic cardiac hypertrophy.


Assuntos
Cardiomegalia/patologia , Receptor IGF Tipo 2/genética , Cloreto de Sódio na Dieta/efeitos adversos , Processamento Alternativo , Animais , Fator Natriurético Atrial/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Cardiomegalia/veterinária , Feminino , Sistema de Sinalização das MAP Quinases , Masculino , Peptídeo Natriurético Encefálico/metabolismo , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos
9.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1642-1647, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090329

RESUMO

This paper was aimed to investigate the inhibitory effect of aconitine(AC) on angiotensin Ⅱ(Ang Ⅱ)-induced H9 c2 cell hypertrophy and explore its mechanism of action. The model of hypertrophy was induced by Ang Ⅱ(1×10-6 mol·L-1),and cardiomyocytes were incubated with different concentrations of AC. Western blot was used to quantify the protein expression levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),ß-myosin heavy chain(ß-MHC),and α-smooth muscle actin(α-SMA). Real-time quantitative PCR(qRT-PCR) was used to quantify the mRNA expression levels of cardiac hypertrophic markers ANP,BNP and ß-MHC. In addition,the fluorescence intensity of the F-actin marker,an important component of myofibrils,was detected by using laser confocal microscope. AC could significantly reverse the increase of total protein content in H9 c2 cells induced by Ang Ⅱ; qRT-PCR results showed that AC could significantly inhibit the ANP,BNP and ß-MHC mRNA up-regulation induced by AngⅡ. Western blot results showed that AC could significantly inhibit the ANP,BNP and ß-MHC protein up-regulation induced by AngⅡ. In addition,F-actin expression induced by Ang Ⅱ could be inhibited by AC,and multiple indicators of cardiomyocyte hypertrophy induced by Ang Ⅱ could be down-regulated,indicating that AC may inhibit cardiac hypertrophy by inhibiting the expression of hypertrophic factors,providing new clues for exploring the cardiovascular protection of AC.


Assuntos
Aconitina/farmacologia , Angiotensina II , Miócitos Cardíacos/efeitos dos fármacos , Actinas/metabolismo , Fator Natriurético Atrial/metabolismo , Miosinas Cardíacas/metabolismo , Cardiomegalia , Células Cultivadas , Humanos , Hipertrofia , Cadeias Pesadas de Miosina/metabolismo , Peptídeo Natriurético Encefálico/metabolismo
10.
Arthritis Rheumatol ; 71(10): 1691-1700, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31066998

RESUMO

OBJECTIVE: A prognostic equation and risk score calculator derived from the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) are being used to predict 1-year survival in patients with pulmonary arterial hypertension (PAH), but little is known about the performance of these REVEAL survival prediction tools in systemic sclerosis (SSc)-associated PAH (SSc-PAH). METHODS: Prospectively gathered data from the Johns Hopkins Pulmonary Hypertension Program and Pulmonary Hypertension Assessment and Recognition of Outcome in Scleroderma Registries were used to evaluate the predictive accuracy of the REVEAL models for predicting the probability of 1-year survival in patients with SSc-PAH. Model discrimination was assessed by comparison of the Harrell's C-index, model fit was assessed using multivariable regression techniques, and model calibration was assessed by comparing predicted to observed survival estimates. RESULTS: The validation cohort consisted of 292 SSc-PAH patients with a 1-year survival rate of 87.4%. The C-index for predictive accuracy of the REVEAL prognostic equation (0.734, 95% confidence interval [95% CI] 0.652-0.816) and for the risk score (0.743, 95% CI 0.663-0.823) demonstrated good discrimination, comparable to that in the model development cohort. The calibration slope was 0.707 (95% CI 0.400-1.014), indicating that the overall model fit was marginal (P = 0.06). The magnitude of risk assigned to low distance on the 6-minute walk test (6MWD) and elevated serum levels of brain natriuretic peptide (BNP) was lower in the validation cohort than was originally seen in the REVEAL derivation cohort. Model calibration was poor, particularly for the highest risk groups. CONCLUSION: In predicting 1-year survival in patients newly diagnosed as having SSc-PAH, the REVEAL prognostic equation and risk score provide very good discrimination but poor calibration. REVEAL prediction scores should be interpreted with caution in newly diagnosed SSc-PAH patients, particularly those with higher predicted risk of poor 1-year survival resulting from a low 6MWD or a high BNP serum level.


Assuntos
/mortalidade , Escleroderma Sistêmico/complicações , Idoso , Pressão Atrial , Pressão Sanguínea , Comorbidade , Feminino , Frequência Cardíaca , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Prognóstico , Insuficiência Renal/epidemiologia , Reprodutibilidade dos Testes , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resistência Vascular , Teste de Caminhada
11.
Int J Mol Sci ; 20(8)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013779

RESUMO

Currently, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are widely used as diagnostic biomarkers for heart failure (HF) and cardiac dysfunction in clinical medicine. They are also used as postmortem biomarkers reflecting cardiac function of the deceased before death in forensic medicine. Several previous studies have reviewed BNP and NT-proBNP in clinical medicine, however, few articles have reviewed their application in forensic medicine. The present article reviews the biological features, the research and application status, and the future research prospects of BNP and NT-proBNP in both clinical medicine and forensic medicine, thereby providing valuable assistance for clinicians and forensic pathologists.


Assuntos
Biomarcadores , Medicina Legal , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Diagnóstico , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Testes de Função Cardíaca , Humanos , Peptídeo Natriurético Encefálico/genética , Fragmentos de Peptídeos/genética , Prognóstico , Proteólise , Índice de Gravidade de Doença , Transdução de Sinais , Pesquisa Médica Translacional
12.
Lab Chip ; 19(9): 1676-1685, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30942226

RESUMO

Although cardiovascular diseases such as heart failure (HF) affect 30 million people globally, the early detection of HF has, until recently, been difficult and prone to misdiagnoses. Monitoring the circulatory levels of a relatively new biomarker, the N-terminal prohormone of a B-type natriuretic peptide, could be used for early risk evaluation of HF. Therefore, we developed a pneumatically-driven, automatic integrated microfluidic platform equipped with micromixers, micropumps, and microvalves for the simultaneous detection of NT-proBNP in up to six clinical samples within 25 min by using a novel aptamer-based sandwich assay, and the limit of detection was only 1.53 pg mL-1; given that the chip is 64% more compact than those developed in our prior works and requires only 5 µL of sample input, it may serve as a promising tool for early diagnosis of HF.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/instrumentação , Dispositivos Lab-On-A-Chip , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Integração de Sistemas , Aptâmeros de Nucleotídeos/genética , Sequência de Bases , Calibragem , Desenho de Equipamento , Humanos , Limite de Detecção , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Fatores de Tempo
13.
Cardiovasc Diabetol ; 18(1): 45, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935417

RESUMO

BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. METHODS AND RESULTS: The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. CONCLUSIONS: Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.


Assuntos
Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hipertensão/complicações , Miocárdio/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Função do Átrio Esquerdo/efeitos dos fármacos , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Fibrose , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Recuperação de Função Fisiológica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
BMJ Case Rep ; 12(4)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975785

RESUMO

Mesalazine (5-aminosalicylic acid)-based products are a widely used treatment for inflammatory bowel disease in children and adults. Associated myopericarditis is an uncommon but recorded phenomenon related to drug hypersensitivity. Unless recognised, this important complication may culminate in the development of dilated cardiomyopathy and severe heart failure. We report the case of a boy with Crohn's disease who developed myopericarditis 14 days after starting treatment with mesalazine. Discontinuation of the drug rapidly led to normalisation of left ventricular structure and function, and a parallel improvement in the levels of plasma N-terminal pro-B-type natriuretic peptide and other markers of myocardial damage. Clinicians should be aware of this potentially life-threatening adverse effect of mesalazine therapy, which is quickly and fully reversible on cessation of the agent.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença de Crohn/tratamento farmacológico , Mesalamina/efeitos adversos , Miocardite/diagnóstico , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Adolescente , Diagnóstico Diferencial , Humanos , Masculino , Miocardite/induzido quimicamente , Miocardite/metabolismo
15.
Circ Arrhythm Electrophysiol ; 12(4): e007045, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30943765

RESUMO

BACKGROUND: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. METHODS: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKIIδ were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patch-clamp recordings in isolated cardiomyocytes. RESULTS: SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKIIδ. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKIIδ in Langendorff hearts and inhibited CaMKIIδ-dependent RyR phosphorylation. In line with CaMKIIδ and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. CONCLUSIONS: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.


Assuntos
Parada Cardíaca/metabolismo , Neuropeptídeos/metabolismo , Secretogranina II/metabolismo , Taquicardia Ventricular/metabolismo , Animais , Biomarcadores/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Parada Cardíaca/fisiopatologia , Humanos , Camundongos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Técnicas de Patch-Clamp , Fragmentos de Peptídeos/metabolismo , Fosforilação , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular/fisiopatologia , Troponina T/metabolismo , Regulação para Cima
16.
Vet J ; 244: 16-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825889

RESUMO

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival. Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Doenças das Valvas Cardíacas/veterinária , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Doenças do Cão/sangue , Cães , Proteína 3 Ligante de Ácido Graxo/sangue , Feminino , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/metabolismo , Masculino , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Valor Preditivo dos Testes , Troponina I/sangue , Troponina I/metabolismo
17.
Acta Biochim Biophys Sin (Shanghai) ; 51(4): 422-430, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877756

RESUMO

Angiotensin II (AII) has been well known to induce cardiomyocyte hypertrophy. Epigallocatechin-3-gallate (EGCG) is the main active component of green tea and it has been shown to exhibit strong cardioprotective potential, although the underlying molecular mechanisms remain unclear. In this study, we investigated the role and mechanism of EGCG in preventing AII-induced cardiomyocyte hypertrophy using rat H9c2 cardiomyocytes cells. Reactive oxygen species assay, cell size, and mRNA expression of cardiac hypertrophy markers ANP and BNP were assessed in response to AII treatment. In addition, expression of proteins involved in Hippo signaling pathway were determined by western blot analysis. We found that AII treatment resulted in significant upregulation of ANP and BNP expression levels and increase in H9c2 cell size, which were markedly attenuated by EGCG treatment. Furthermore, our results suggested that EGCG inhibited AII-induced cardiac hypertrophy via regulating the Hippo signaling pathway. Therefore, EGCG may be an effective agent for preventing cardiac hypertrophy.


Assuntos
Cardiomegalia/prevenção & controle , Catequina/análogos & derivados , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Angiotensina II , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Catequina/química , Catequina/farmacologia , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Estrutura Molecular , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Proteínas Serina-Treonina Quinases/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética
18.
Chin Med J (Engl) ; 132(7): 819-826, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30829708

RESUMO

BACKGROUND: The early identification of heart failure (HF) risk may favorably affect outcomes, and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification. This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme (CK-MB), B-type natriuretic peptide (BNP), galectin-3 (Gal-3) and soluble suppression of tumorigenicity-2 (sST2) for HF diagnosis, and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms. METHODS: A total of 193 participants (80 patients with HF and 113 age- and gender-matched healthy controls) were included from June 2017 to December 2017. The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters. The accuracy and importance of these predictor variables were assessed using random forest algorithms. RESULTS: Patients with HF exhibited significantly higher levels of CK-MB, BNP, Gal-3, and sST2. BNP exhibited a good independent predictive capacity for HF (AUC 0.956). However, CK-MB, sST2, and Gal-3 exhibited a modest diagnostic performance for HF, with an AUC of 0.709, 0.711, and 0.777, respectively. BNP was the most important variable, with a remarkably higher mean decrease accuracy and Gini. Furthermore, there was a general increase in predictive performance using the multi-marker model, and the sensitivity, specificity was 91.5% and 96.7%, respectively. CONCLUSION: The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables. The combination of CK-MB, BNP, Gal-3, and sST2 achieves improvement in prediction accuracy for HF.


Assuntos
Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Adulto , Algoritmos , Biomarcadores/sangue , Biomarcadores/metabolismo , Creatina Quinase Forma MB/sangue , Creatina Quinase Forma MB/metabolismo , Ecocardiografia , Feminino , Galectina 3/sangue , Galectina 3/metabolismo , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo
19.
J Am Coll Cardiol ; 73(11): 1288-1296, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30898204

RESUMO

BACKGROUND: Circulating natriuretic peptide (NP) levels are markedly lower in healthy men than women. A relative NP deficiency in men could contribute to their higher risk of hypertension and cardiovascular disease. Epidemiological studies suggest testosterone may contribute to sex-specific NP differences. OBJECTIVES: This study aimed to determine the effect of testosterone administration on NP levels using a randomized, placebo-controlled design. METHODS: One hundred and fifty-one healthy men (20 to 50 years of age) received goserelin acetate to suppress endogenous production of gonadal steroids, and anastrazole to suppress conversion of testosterone to estradiol. Subjects were randomized to placebo gel or 4 different doses of testosterone (1%) gel for 12 weeks. Serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and total testosterone levels were measured at baseline and follow-up. RESULTS: Men who did not receive testosterone replacement (placebo gel group) after suppression of endogenous gonadal steroid production experienced a profound decrease in serum testosterone (median 540 to 36 ng/dl; p < 0.0001). This was accompanied by an increase in median NT-proBNP (+8 pg/ml; p = 0.02). Each 1-g increase in testosterone dose was associated with a 4.3% lower NT-proBNP at follow-up (95% confidence interval: -7.9% to -0.45%; p = 0.029). An individual whose serum testosterone decreased by 500 ng/dl had a 26% higher predicted follow-up NT-proBNP than someone whose serum testosterone remained constant. CONCLUSIONS: Suppression of testosterone production in men led to increases in circulating NT-proBNP, which were attenuated by testosterone replacement. Inhibition of NP production by testosterone may partly explain the lower NP levels in men. (Dose-Response of Gonadal Steroids and Bone Turnover in Men; NCT00114114).


Assuntos
Anastrozol/farmacologia , Gosserrelina/farmacologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Testosterona , Administração Tópica , Adulto , Androgênios/administração & dosagem , Antineoplásicos Hormonais/farmacologia , Inibidores da Aromatase/farmacologia , Correlação de Dados , Monitoramento de Medicamentos/métodos , Estradiol/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/metabolismo
20.
Curr Cardiol Rev ; 15(4): 283-290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30914031

RESUMO

Natriuretic peptides, produced by cardiac myocytes, are regulators of the intravascular volume and blood pressure, and also exhibit neuroendocrine, metabolic and growth controlling effects. In heart failure, their synthesis increases exponentially as part of the neuroendocrine activation, but their beneficial effects are diminished. The paper reviews relevant data about their role as diagnosis and prognosis markers in heart failure, the hemodynamic and clinical benefits of their use as therapy in heart failure, together with the main adverse effects. Peptides non-specifically increase in extracardiac pathology and the literature reveals the mechanisms of increase, significance and threshold values to exclude cardiac dysfunction.


Assuntos
Doenças Cardiovasculares/genética , Hemodinâmica/genética , Peptídeo Natriurético Encefálico/metabolismo , Peptídeos Natriuréticos/metabolismo , Doenças Cardiovasculares/metabolismo , Humanos
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