Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 964
Filtrar
1.
Biosci Biotechnol Biochem ; 84(1): 111-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31512553

RESUMO

Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial-mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson's analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments.


Assuntos
Adenocarcinoma/patologia , Movimento Celular , Proliferação de Células , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal , Troponina T/genética , Troponina T/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Bases de Dados Genéticas , Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Invasividade Neoplásica , Prognóstico , Transfecção
2.
Food Chem ; 301: 125278, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31387033

RESUMO

Softening is always a problem in fish preservation. This study was aimed to investigate the role of myofibrillar structural proteins degradation in fish softening. The changes of myofibrillar structural proteins, muscle ultrastructure, myofibril fragmentation, and shear force were studied. The results indicated that during the superchilled preservation of grass carp (Ctenopharyngodon idella), small (low-molecular-weight) myofibrillar structural proteins like desmin and troponin-T initiated textural deterioration, leading to Z-disk weakening and actin loosening. In contrast, giant (high-molecular-weight) myofibrillar structural proteins like titin and nebulin were degraded in more amount in the later storage, contributing to Z-disk and M-band disassembly and vague of light and dark regions (I and A bands). Compared to each other, desmin and titin played more important part in softening. All these changes were involved in the increase of muscle fibril segments and the sharp decrease of shear force.


Assuntos
Carpas/metabolismo , Produtos Pesqueiros , Proteínas de Peixes/química , Miofibrilas/química , Animais , Conectina/química , Conectina/metabolismo , Desmina/química , Desmina/metabolismo , Proteínas de Peixes/metabolismo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , Proteólise , Troponina T/química , Troponina T/metabolismo
3.
Int J Mol Sci ; 20(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288395

RESUMO

BACKGROUND: Cardiac troponin I (cTn I) and cardiac troponin T (cTn T) are currently widely used as diagnostic biomarkers for myocardial injury caused by ischemic heart diseases in clinical and forensic medicine. However, no previous meta-analysis has summarized the diagnostic roles of postmortem cTn I and cTn T. The aim of the present study was to meta-analyze the diagnostic roles of postmortem cTn I and cTn T for cardiac death in forensic medicine, present a systematic review of the previous literature, and determine the postmortem cut-off values of cTn I and cTn T. METHODS: We searched multiple databases for the related literature, performed a meta-analysis to investigate the diagnostic roles of postmortem cardiac troponins, and analyzed the receiver operating characteristic (ROC) curve to determine their postmortem cut-off values. RESULTS AND CONCLUSIONS: The present meta-analysis demonstrated that postmortem cTn I and cTn T levels were increased in pericardial fluid and serum in cardiac death, especially in patients with acute myocardial infarction (AMI). We determined the postmortem cut-off value of cTn I in the pericardial fluid at 86.2 ng/mL, cTn I in serum at 9.5 ng/mL, and cTn T in serum at 8.025 ng/mL.


Assuntos
Morte , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Mudanças Depois da Morte , Troponina I/metabolismo , Troponina T/metabolismo , Autopsia , Biomarcadores , Humanos , Miocárdio/patologia , Curva ROC
4.
Clin Chim Acta ; 495: 507-511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152696

RESUMO

BACKGROUND: The pneumatic tube system (PTS) is widely established in clinical laboratories. We aimed to evaluate the impacts of PTS on high-sensitivity cardiac troponin T (hs-cTnT) assays. METHODS: The hemolysis distribution of hs-cTnT PTS specimens from emergency department (ED) were determined by hemolysis index (HI). Grouped samples from 15 healthy volunteers were delivered to the laboratory via manual delivery (MD) or PTS. Interference studies were conducted to access the influence of different hemolysis degrees on hs-cTnT assays. RESULTS: 7.26% PTS specimens from ED were hemolyzed in clinic. Compared with MD samples, we found highly elevated free plasma hemoglobin (Hb) in PTS samples. Hs-cTnT was interfered negatively with free Hb (R = -0.625, P < .001), and it was also validated in interference studies (R ≥ -0.820, all P ≤ .001). Clinically significant bias occurred in each hs-cTnT concentration at 100 mg/dl free Hb (Bias≥ - 13.85%, all P < .05). Moreover, bias of hs-cTnT assays at 50 mg/dl free Hb was approaching 10%, especially at 30 ng/l hs-cTnT concentration (Bias: -11.72%, P < .001). CONCLUSIONS: PTS could increase the frequency of specimen hemolysis which might cause false decrease in hs-cTnT assays. Hence, clinicians should be aware of the increased measurement bias in hs-cTnT from hemolyzed PTS samples with free Hb ≥50 mg/dl.


Assuntos
Análise Química do Sangue/instrumentação , Limite de Detecção , Miocárdio/metabolismo , Troponina T/sangue , Reações Falso-Negativas , Feminino , Voluntários Saudáveis , Humanos , Masculino , Troponina T/metabolismo , Adulto Jovem
5.
Anim Sci J ; 90(8): 1050-1059, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199034

RESUMO

The objective of this study was to create various pH/temp decline rates in hot-boned bull beef M. longissimus lumborum (LL) through a combination of electrical stimulation (ES) and pre-rigor holding temperature. The relationship between the pre-rigor interventions, the activities of µ-calpain and small heat shock proteins (sHSP), and the impacts on meat product quality were determined. Paired LL loins from 13 bulls were hot-boned within 40 min of slaughter, immediately ES and subjected to various holding temperatures (5, 15, 25, and 35°C) for 3 hr. The rate of muscle pH decline, sarcomere length, shear force, and proteolysis of muscle proteins were measured. ES-25°C had a longer sarcomere length compared to non-electrical stimulation samples. ES-25°C and ES-35°C samples had lower shear force values, higher µ-calpain activity and higher desmin, troponin-T, and sHSP degradation. The above findings suggest that pH/temp decline rates created in hot-boned muscle impacted muscle protein proteolysis by increasing the activity of proteases and degradation of sHSP.


Assuntos
Calpaína/análise , Estimulação Elétrica , Qualidade dos Alimentos , Proteínas de Choque Térmico/análise , Músculo Esquelético/metabolismo , Carne Vermelha/análise , Temperatura Ambiente , Animais , Bovinos , Desmina/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Peptídeo Hidrolases/metabolismo , Proteólise , Sarcômeros/patologia , Resistência ao Cisalhamento , Fatores de Tempo , Troponina T/metabolismo
6.
Anal Sci ; 35(9): 973-978, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31080197

RESUMO

In this study, a direct and label-free immunosensor was designed and constructed by modifying the screen-printed electrode with graphene nanoplatelets (GNPs) for the detection of the cardiac troponin T (cTnT). Firstly, GNPs were drop-casted onto carbon working electrode. Monoclonal cTnT antibodies were then immobilized on the GNPs via physical adsorption; finally, BSA was introduced to block non-specific binding sites. The detection of cTnT was performed using an electrochemiluminescence (ECL) technique with tris(bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2) used as a luminophore and TPrA (tripropylamine) as a co-reactant. The ECL intensity was demonstrated to be directly proportional to the cTnT concentration where a linear range from 100 pg mL-1 to 5 fg mL-1 of the cTnT detection was established. An extremely low limit of detection was achieved to be 0.05 fg mL-1 with an outstanding specificity. Additionally, this immunosensor showed excellent percentage recovery for real samples analyses in artificially spiked human serum.


Assuntos
Técnicas Biossensoriais/métodos , Grafite/química , Imunoensaio/métodos , Miocárdio/metabolismo , Nanoestruturas/química , Troponina T/análise , Adsorção , Eletroquímica , Eletrodos , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Medições Luminescentes , Sistemas Automatizados de Assistência Junto ao Leito , Impressão , Troponina T/sangue , Troponina T/metabolismo
7.
Int Heart J ; 60(3): 601-607, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105151

RESUMO

Recent studies reported that cardiac troponin elevation after percutaneous coronary intervention is related to adverse cardiac events. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are often used to assess lesion characteristics in the coronary arteries. However, little is known about the trend of cardiac troponin elevation after diagnostic invasive intracoronary examination and the prognostic influence. We assessed the relationship between myocardial injury manifested by the high-sensitivity cardiac troponin T (hs-cTnT) level after invasive intracoronary examination and future adverse cardiac outcomes. We evaluated 115 patients with stable coronary artery disease who underwent IVUS or OCT for detailed coronary assessment during coronary angiography (CAG). Baseline and post-procedural (within 24 hours after examination) hs-cTnT were measured. In consequence, post-procedural hs-cTnT level and percentage increase were higher in patients with IVUS or OCT during CAG than in those without. Periprocedural myocardial injury (PMI, defined as post-procedural hs-cTnT with upper reference limit greater than five-fold) occurred in 10 (8.6%) patients. There were no significant differences in baseline characteristics between patients with and without PMI, except for left-ventricular diastolic dimension. Only two major adverse cardiac events (MACE, defined as cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization) occurred in non-PMI during a mean observation period of 32 ± 18 months. On Kaplan-Meier analysis, MACE-free survival rate was similar between PMI and non-PMI. In conclusion, a few imperceptible PMI derived by hs-cTnT assay occurred after diagnostic invasive intracoronary examination. However, it was not associated with subsequent poor cardiac outcome.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Troponina T/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia de Coerência Óptica
8.
Biomed Pharmacother ; 115: 108883, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004989

RESUMO

Cardiotoxicity is a serious adverse reaction to cancer chemotherapy and may lead to critical heart damage. Imatinib mesylate (IMB), a selective tyrosine kinase inhibitor, is sometimes accompanied by severe cardiovascular complications. To minimize risk, early biomarkers of such complications are of utmost importance. At the present time, microRNAs (miRNAs) are intensively studied as potential biomarkers of many pathological processes. Many miRNAs appear to be specific in some tissues, including the heart. In the present study we have explored the potential of specific miRNAs to be early markers of IMB-induced cardiotoxicity. Doxorubicin (DOX), an anthracycline with well-known cardiotoxicity, was used for comparison. NMRI mice were treated with IMB or DOX for nine days in doses corresponding to the highest recommended doses in oncological patients, following which plasmatic levels of miRNAs were analyzed in miRNA microarrays and selected cardio-specific miRNAs were quantified using qPCR. The plasmatic level of miR-1a, miR-133a, miR-133b, miR-339, miR-7058, miR-6236 and miR-6240 were the most different between the IMB-treated and control mice. Interestingly, most of the miRNAs affected by DOX were also affected by IMB showing the same trends. Concerning selected microRNAs in the hearts of individual mice, only miR-34a was significantly increased after DOX treatment, and only miR-205 was significantly decreased after IMB and DOX treatment. However, no changes in any miRNA expression correlated with the level of troponin T, a classical marker of heart injury.


Assuntos
Doxorrubicina/toxicidade , Coração/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , MicroRNAs/sangue , MicroRNAs/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , MicroRNAs/genética , Troponina T/sangue , Troponina T/genética , Troponina T/metabolismo
10.
Appl Biochem Biotechnol ; 189(2): 396-410, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31025171

RESUMO

Although embryonic stem (ES) cells (ESCs) may be a promising donor source for the repair of infarcted or ischemic heart tissues, their successful application in regenerative medicine has been hampered by difficulties in enriching, identifying, and selecting cardiomyocytes from the differentiating cells. We established transgenic human ES cell lines by transcriptional control of the α-cardiac myosin heavy chain (α-MHC) promoter driving green fluorescent protein (GFP) expression. Differentiated GFP-expressing cells display the characteristics of cardiomyocytes (CMs). Apela, a recently identified short peptide, up-regulated the expression of the cardiac-restricted transcription factors Tbx5 and GATA4 as well as differentiated the cardiomyocyte markers α-MHC and ß-MHC. Flow cytometric analysis showed that apela increased the percentage of GFP-expressing cells in the beating foci of the embryoid bodies. The percentage of cardiac troponin T (TNT)-positive cells and the protein expression of TNT were increased in the ES cell-derived CMs with apela treatment. Functionally, the contractile frequency of the ES-derived CMs responded appropriately to the vasoactive drugs isoprenaline and carbachol. Our work presented a protocol for specially labelling and enriching CMs by combining transgenic human ES cell lines and exogenous growth factor treatment.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias Humanas/metabolismo , Miócitos Cardíacos/metabolismo , Hormônios Peptídicos/metabolismo , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , Linhagem Celular , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Humanos , Miócitos Cardíacos/citologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Hormônios Peptídicos/genética , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Troponina T/metabolismo , Regulação para Cima , Miosinas Ventriculares/genética , Miosinas Ventriculares/metabolismo
11.
Eur J Clin Invest ; 49(7): e13116, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30932178

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) modulates brain health and cognition, which can interfere with executive cognitive function. BDNF was implicated with microcirculatory ischaemia and may reflect cardiomyocyte injury. We aimed to determine whether prospective changes (%Δ) in BDNF and cardiac troponin T (cTnT) will be associated with executive cognitive function in a bi-ethnic cohort. DESIGN: A prospective investigation was conducted over a three-year period in a bi-ethnic sex cohort (N = 338; aged 20-65 years) from South Africa. Fasting serum samples for BDNF and cTnT were obtained. The STROOP-color-word conflict test (CWT) was applied to assess executive cognitive function at baseline. RESULTS: In Blacks, BDNF (P < 0.001) increased over the three-year period while cTnT did not change. In contrast, in Whites, BDNF and cTnT decreased over three years. In Black men, no change in cTnT was associated with increased ΔBDNF (ß = 0.25; 95% CI 0.05-0.45; P = 0.02). In the Black men, constant cTnT levels were inversely associated with executive cognitive function (ß = -0.33; 95% CI -0.53 to -0.12; P = 0.003). Three-year increases in BDNF increased the likelihood for chronic lower cTnT levels at a pre-established cut-point of <4.2 ng/L [OR = 2.35 (1.12-4.94), P = 0.02]. The above associations were not found in the White sex groups. CONCLUSIONS: Central neural control mechanisms may have upregulated BDNF in Black men as a way to protect against myocardial stress progression and to possibly improve processes related to cognitive interference control. High-sensitive cTnT levels may act as an early predictor of disturbed neural control mechanisms.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Função Executiva/fisiologia , Troponina T/metabolismo , Adulto , Grupo com Ancestrais do Continente Africano/etnologia , Idoso , Grupo com Ancestrais do Continente Europeu/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , África do Sul/etnologia , Teste de Stroop , Adulto Jovem
12.
Mol Med Rep ; 19(6): 4927-4934, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957182

RESUMO

Congenital heart disease (CHD) is the most common type of birth defect, and the leading cause of fetal mortality. The long noncoding RNA (lncRNA) uc.457 is differentially expressed in cardiac tissue from patients with a ventricular septal defect; however, its role in cardiac development and CHD remains unknown. In the present study, the role of uc.457 in the differentiation and maturation of cardiomyocytes was investigated. Bioinformatics approaches were employed to analyze putative transcription factor (TF) regulation, histone modifications and the biological functions of uc.457. Subsequently, uc.457 overexpression and small interfering RNA­mediated knockdown were performed to evaluate the functional role of the lncRNA in the dimethyl sulfoxide­induced differentiation of P19 cells into cardiomyocytes. Bioinformatics analyses predicted that uc.457 binds to TFs associated with cardiomyocyte growth and cardiac development. Cell Counting Kit­8 assays demonstrated that uc.457 overexpression inhibited cell proliferation, whereas knockdown of uc.457 enhanced the proliferation of differentiating cardiomyocytes. Additionally, reverse transcription­quantitative polymerase chain reaction and western blot analyses revealed that overexpression of uc.457 suppressed the mRNA and protein expression of histone cell cycle regulation defective homolog A, natriuretic peptide A, cardiac muscle troponin T and myocyte­specific enhancer factor 2C. Collectively, the results indicated that overexpression of uc.457 inhibited the differentiation and proliferation of cardiomyocytes, suggesting that dysregulated uc.457 expression may be associated with CHD.


Assuntos
RNA Longo não Codificante/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Chaperonas de Histonas/genética , Chaperonas de Histonas/metabolismo , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Troponina T/genética , Troponina T/metabolismo
13.
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
14.
Meat Sci ; 153: 144-151, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30946977

RESUMO

A study was conducted to elucidate the impact of pulsed electric field (PEF) on the activity of calpains, proteolytic activity of desmin and troponin-T and physicochemical properties of beef Biceps femoris during ageing. The meat samples (meat blocks) were subjected to two PEF treatments; T1 (5 kV, 90 Hz, 0.38 kV/cm) and T2 (10 kV, 20 Hz, 0.61 kV/cm) and a non-treated control was run in parallel. The samples were vacuum packaged and aged for 1, 7 and 14 days at 4 ±â€¯1 °C. This study reports for the first time the impact of PEF-processing on the calpain activity in beef. Early post-mortem activation of calpain 2 was observed in PEF-treated samples. An increase in the calpain activity and proteolysis of desmin and troponin-T was observed. No significant effect of PEF was observed on the shear force of tough muscles from culled dairy animals during the entire ageing period.


Assuntos
Calpaína/metabolismo , Eletricidade , Manipulação de Alimentos/métodos , Carne Vermelha/análise , Animais , Bovinos , Desmina/metabolismo , Músculo Esquelético/metabolismo , Proteólise , Resistência ao Cisalhamento , Troponina T/metabolismo
15.
Rev Port Cardiol ; 38(2): 129-139, 2019 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30871747

RESUMO

INTRODUCTION: Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by ventricular dilatation and impaired systolic function. Familial forms account for 30-50% of cases. Autosomal dominant inheritance is the predominant pattern of transmission. Causal genetic variants have been identified in several genes and molecular diagnosis has implications for genetic counseling and risk stratification. OBJECTIVE: We aimed to estimate the frequency of genetic variants and the molecular basis of DCM in Portugal. METHODS: We performed a multicenter study of unrelated patients, recruited between 2013 and 2014. Variants in 15 genes were screened using PCR with direct sequencing (next-generation sequencing with at least 30-fold coverage combined with Sanger sequencing). RESULTS: A total of 107 patients were included, 64 (60%) men, mean age at diagnosis 38±13 years, with 48 (45%) familial cases. In total, 31 rare variants in eight genes (mainly in MYBPC3, TNNT2 and LMNA) were identified, in 28 patients (26%). Only four variants had been previously described in association with DCM, 11 with hypertrophic cardiomyopathy, and nine variants were novel. Four variants were likely pathogenic and the remainder were of uncertain significance. We found no major differences in the main clinical and imaging characteristics between patients with or without rare variants and patients with likely pathogenic variants. CONCLUSIONS: Our results reflect the complexity and diversity of DCM genetics. For better interpretation of the pathogenicity of the variants found and their causative roles in DCM, molecular cascade screening of families is imperative. Further insight into genotype-phenotype correlations and risk stratification is desirable.


Assuntos
Cardiomiopatia Dilatada/genética , Proteínas de Transporte/genética , DNA/genética , Ventrículos do Coração/diagnóstico por imagem , Lamina Tipo A/genética , Mutação , Troponina T/genética , Adulto , Cardiomiopatia Dilatada/epidemiologia , Cardiomiopatia Dilatada/metabolismo , Proteínas de Transporte/metabolismo , Análise Mutacional de DNA , Ecocardiografia , Eletrocardiografia , Feminino , Marcadores Genéticos/genética , Variação Genética , Ventrículos do Coração/fisiopatologia , Humanos , Lamina Tipo A/metabolismo , Masculino , Fenótipo , Portugal/epidemiologia , Estudos Retrospectivos , Troponina T/metabolismo
16.
Circ Res ; 124(8): 1228-1239, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30732532

RESUMO

RATIONALE: Subcellular Ca2+ indicators have yet to be developed for the myofilament where disease mutation or small molecules may alter contractility through myofilament Ca2+ sensitivity. Here, we develop and characterize genetically encoded Ca2+ indicators restricted to the myofilament to directly visualize Ca2+ changes in the sarcomere. OBJECTIVE: To produce and validate myofilament-restricted Ca2+ imaging probes in an adenoviral transduction adult cardiomyocyte model using drugs that alter myofilament function (MYK-461, omecamtiv mecarbil, and levosimendan) or following cotransduction of 2 established hypertrophic cardiomyopathy disease-causing mutants (cTnT [Troponin T] R92Q and cTnI [Troponin I] R145G) that alter myofilament Ca2+ handling. METHODS AND RESULTS: When expressed in adult ventricular cardiomyocytes RGECO-TnT (Troponin T)/TnI (Troponin I) sensors localize correctly to the sarcomere without contractile impairment. Both sensors report cyclical changes in fluorescence in paced cardiomyocytes with reduced Ca2+ on and increased Ca2+ off rates compared with unconjugated RGECO. RGECO-TnT/TnI revealed changes to localized Ca2+ handling conferred by MYK-461 and levosimendan, including an increase in Ca2+ binding rates with both levosimendan and MYK-461 not detected by an unrestricted protein sensor. Coadenoviral transduction of RGECO-TnT/TnI with hypertrophic cardiomyopathy causing thin filament mutants showed that the mutations increase myofilament [Ca2+] in systole, lengthen time to peak systolic [Ca2+], and delay [Ca2+] release. This contrasts with the effect of the same mutations on cytoplasmic Ca2+, when measured using unrestricted RGECO where changes to peak systolic Ca2+ are inconsistent between the 2 mutations. These data contrast with previous findings using chemical dyes that show no alteration of [Ca2+] transient amplitude or time to peak Ca2+. CONCLUSIONS: RGECO-TnT/TnI are functionally equivalent. They visualize Ca2+ within the myofilament and reveal unrecognized aspects of small molecule and disease-associated mutations in living cells.


Assuntos
Cálcio/metabolismo , Cardiomiopatia Hipertrófica/genética , Mutação , Miócitos Cardíacos/metabolismo , Miofibrilas/metabolismo , Sarcômeros/metabolismo , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Adenoviridae , Animais , Benzilaminas/farmacologia , Cardiomiopatia Hipertrófica/metabolismo , Cobaias , Técnicas In Vitro , Masculino , Miofibrilas/efeitos dos fármacos , Miosinas/efeitos dos fármacos , Miosinas/metabolismo , Simendana/farmacologia , Transdução Genética/métodos , Troponina I/genética , Troponina I/metabolismo , Troponina T/genética , Troponina T/metabolismo , Uracila/análogos & derivados , Uracila/farmacologia , Ureia/análogos & derivados , Ureia/farmacologia
17.
PLoS One ; 14(2): e0212892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30811490

RESUMO

BACKGROUND: Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease. METHODS: We examined 3,348 participants (67-90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011-13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders. RESULTS: Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures. CONCLUSIONS: Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage.


Assuntos
Doenças Cardiovasculares/diagnóstico , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Troponina T/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , Rigidez Vascular
18.
Ann Emerg Med ; 73(5): 491-499, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30661856

RESUMO

STUDY OBJECTIVE: We evaluate whether a combination of a 1-hour high-sensitivity cardiac troponin algorithm and History, ECG, Age, Risk Factors, and Troponin (HEART) score reduces admission rate (primary outcome) and affects time to discharge, health care-related costs, and 30-day outcome (secondary outcomes) in patients with symptoms suggestive of an acute coronary syndrome. METHODS: This prospective observational multicenter study was conducted before (2013 to 2014) and after (2015 to 2016) implementation of a strategy including level of high-sensitivity cardiac troponin T or I at 0 and 1 hour, combined with the HEART score. Patients with a nonelevated baseline high-sensitivity cardiac troponin level, a 1-hour change in high-sensitivity cardiac troponin T level less than 3 ng/L, or high-sensitivity cardiac troponin I level less than 6 ng/L and a HEART score less than or equal to 3 were considered to be ruled out of having acute coronary syndrome. A logistic regression analysis was performed to adjust for differences in baseline characteristics. RESULTS: A total of 1,233 patients were included at 6 centers. There were no differences in regard to median age (64 versus 63 years) and proportion of men (57% versus 54%) between the periods. After introduction of the new strategy, the admission rate decreased from 59% to 33% (risk ratio 0.55 [95% confidence interval {CI} 0.48 to 0.63]; odds ratio 0.33 [95% CI 0.26 to 0.42]; adjusted odds ratio 0.33 [95% CI 0.25 to 0.42]). The median hospital stay was reduced from 23.2 to 4.7 hours (95% CI of difference -20.4 to -11.4); median health care-related costs, from $1,748 to $1,079 (95% CI of difference -$953 to -$391). The number of clinical events was very low. CONCLUSION: In this before-after study, clinical implementation of a 1-hour high-sensitivity cardiac troponin algorithm combined with the HEART score was associated with a reduction in admission rate and health care burden, with very low rates of adverse clinical events.


Assuntos
Cardiopatias/diagnóstico , Troponina T/metabolismo , Idoso , Algoritmos , Estudos Controlados Antes e Depois , Feminino , Cardiopatias/metabolismo , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Nitric Oxide ; 84: 60-68, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30633959

RESUMO

OBJECTIVE: To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. METHODS: This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. RESULTS: We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). CONCLUSIONS: In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography. CLINICAL TRIAL REGISTRATION: NCT01939301.


Assuntos
Óxido Nítrico/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagem , Embolia Pulmonar/fisiopatologia , Troponina T/metabolismo , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/fisiopatologia
20.
Eur J Appl Physiol ; 119(4): 847-855, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30627826

RESUMO

PURPOSE: Exercise induces a cardioprotective effect referred to as "preconditioning". Whether the preconditioning impacts upon the cardiac troponin T (cTnT) response to subsequent exercise bouts is unclear. This study investigated the effects of an initial exercise bout, a second exercise bout 48 h later, as well as subsequent exercise every 48 h for 4 days or a single identical exercise bout after 8 days of inactivity gap on cTnT response to acute exercise. METHODS: Twenty-eight sedentary overweight young women were randomly assigned to either six bouts of exercise each separated by 48 h or three bouts of exercise with 48 h between the first two bouts and 8 days between the second and third bouts. All exercise bouts were identical (60% [Formula: see text], 200 kJ) and the total testing period (10 days) was the same for both groups. cTnT was assessed before and after the 1st, 2nd, and final exercise bouts. RESULTS: cTnT increased (129%, P < 0.05) after the first bout of exercise in both groups (peak post-exercise cTnT, median [range], ng l-1: 3.43[< 3.00-27.26]) with no between-group differences in the response. The second exercise bout had no significant (P > 0.05) effect on post-exercise cTnT (< 3.00[< 3.00-21.96]). The final exercise bout resulted in an increase (190%, P < 0.05) in cTnT (4.35[< 3.00-13.05]) in both groups. CONCLUSIONS: A single bout exercise resulted in a temporary blunting of cTnT response to acute exercise 48 h later. The effect of exercise preconditioning was not preserved, regardless of whether followed by repeated exercise every 48 h or a cessation of exercise for 8 days.


Assuntos
Treino Aeróbico , Exercício/fisiologia , Consumo de Oxigênio/fisiologia , Resistência Física/fisiologia , Troponina T/metabolismo , Adulto , Feminino , Humanos , Masculino , Esforço Físico/fisiologia , Fatores de Tempo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA