RESUMO
In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.
Assuntos
Síndrome Coronariana Aguda , Hormônios Peptídicos , Humanos , Hormônio Adrenocorticotrópico , Peptídeo Natriurético Encefálico , Sistema Hipotálamo-Hipofisário , Síndrome Coronariana Aguda/tratamento farmacológico , Hidrocortisona , Sistema Hipófise-SuprarrenalRESUMO
Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.
Assuntos
Resistência à Insulina , Traumatismo por Reperfusão Miocárdica , Animais , Fator Natriurético Atrial , Dieta Hiperlipídica , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Obesidade/complicações , Obesidade/etiologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Recent large-scale clinical trials have shown that SGLT2-inhibitors reduce cardiovascular events in diabetic patients. However, the regulation and functional role of cardiac sodium-glucose cotransporter (SGLT1 is the dominant isoform) compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. Given that glucose is an important preferential substrate for myocardial energy metabolism under conditions of ischemia-reperfusion injury (IRI), we hypothesized that SGLT1 contributes to cardioprotection during the acute phase of IRI via enhanced glucose transport, particularly in insulin-resistant phenotypes. METHODS AND RESULTS: The hearts from mice fed a high-fat diet (HFD) for 12 weeks or a normal-fat diet (NFD) were perfused with either the non-selective SGLT-inhibitor phlorizin or selective SGLT2-inhibitors (tofogliflozin, ipragliflozin, canagliflozin) during IRI using Langendorff model. After ischemia-reperfusion, HFD impaired left ventricular developed pressure (LVDP) recovery compared with the findings in NFD. Although phlorizin-perfusion impaired LVDP recovery in NFD, a further impaired LVDP recovery and a dramatically increased infarct size were observed in HFD with phlorizin-perfusion. Meanwhile, none of the SGLT2-inhibitors significantly affected cardiac function or myocardial injury after ischemia-reperfusion under either diet condition. The plasma membrane expression of GLUT4 was significantly increased after IRI in NFD but was substantially attenuated in HFD, the latter of which was associated with a significant reduction in myocardial glucose uptake. In contrast, SGLT1 expression at the plasma membrane remained constant during IRI, regardless of the diet condition, whereas SGLT2 was not detected in the hearts of any mice. Of note, phlorizin considerably reduced myocardial glucose uptake after IRI, particularly in HFD. CONCLUSIONS: Cardiac SGLT1 but not SGLT2 plays a compensatory protective role during the acute phase of IRI via enhanced glucose uptake, particularly under insulin-resistant conditions, in which IRI-induced GLUT4 upregulation is compromised.
Assuntos
Glicemia/efeitos dos fármacos , Resistência à Insulina , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Florizina/farmacologia , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Compostos Benzidrílicos/farmacologia , Glicemia/metabolismo , Canagliflozina/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/metabolismo , Glucosídeos/farmacologia , Preparação de Coração Isolado , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Obesidade/sangue , Obesidade/fisiopatologia , Transdução de Sinais , Transportador 1 de Glucose-Sódio/metabolismo , Tiofenos/farmacologiaRESUMO
Lung oxygenation impairment often occurs in patients with type B acute aortic dissection (AAD), necessitating mechanical ventilation. Patients receiving mechanical ventilation are at risk of complications, so a low-oxygen condition requiring mechanical ventilation should be avoided. We explored the predictors of oxygenation impairment. We enrolled 46 patients with type B AAD who had been medically treated and underwent computed tomography. Blood was sampled to measure markers of inflammation, such as the C-reactive protein (CRP) levels and white blood cell count. The arterial partial pressure of oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) was calculated to quantify the severity of respiratory failure. Spearman's rank correlation analysis revealed that the minimum PaO2/FiO2 ratio was significantly correlated with gender, age, and current smoker, and the peak CRP, body temperature, and D-dimer values. A multivariate regression analysis revealed that younger age, male sex, and the peak CRP level were significant predictors of the minimum PaO2/FiO2 ratio (P = 0.01, 0.035 and 0.005, respectively). A covariance structure analysis showed that a younger age and the peak CRP level were significant predictors of oxygenation impairment in type B AAD. Oxygenation impairment in type B AAD is correlated with younger age and a higher peak CRP level. This will enable the identification of patients whose respiratory condition is susceptible to worsening and help prevent mechanical ventilation, leading to the provision of appropriate therapy.
Assuntos
Aneurisma da Aorta Torácica/sangue , Dissecção Aórtica/sangue , Proteína C-Reativa/metabolismo , Consumo de Oxigênio , Oxigênio/sangue , Respiração Artificial/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/terapia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/terapia , Biomarcadores/sangue , Permeabilidade Capilar/fisiologia , Feminino , Humanos , Masculino , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] µmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca , Corpos Cetônicos , Neprilisina , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Masculino , Feminino , Corpos Cetônicos/sangue , Corpos Cetônicos/metabolismo , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Idoso , Pessoa de Meia-Idade , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Valsartana/uso terapêutico , Ácidos Graxos não Esterificados/sangueRESUMO
AIMS: Although the haemodynamic effects of angiotensin receptor-neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. METHODS: We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). RESULTS: At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) µU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA-IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA-IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) µU/mL, P < 0.001; HOMA-IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA-IR levels at 3 months independently of the baseline fasting blood insulin and HOMA-IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). CONCLUSIONS: In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.
Assuntos
Insuficiência Cardíaca , Resistência à Insulina , Insulinas , Disfunção Ventricular Esquerda , Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos , Glucose , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Ácido ÚricoRESUMO
We recently reported that the selective inhibition of urate transporter-1 (URAT1), which is primarily expressed in the kidneys, ameliorates insulin resistance by attenuating hepatic steatosis and improving brown adipose tissue function in diet-induced obesity. In this study, we evaluated the effects of dotinurad, a URAT1-selective inhibitor, on the hearts of high-fat diet (HFD)-fed obese mice for 16-20 weeks and on neonatal rat cardiomyocytes (NRCMs) exposed to palmitic acid. Outside the kidneys, URAT1 was also expressed in cardiomyocytes and indeed worked as a uric acid transporter. Dotinurad substantially attenuated HFD-induced cardiac fibrosis, inflammatory responses, and cardiac dysfunction. Intriguingly, among various factors related to the pathophysiology of diet-induced obesity, palmitic acid significantly increased URAT1 expression in NRCMs and subsequently induced apoptosis, oxidative stress, and inflammatory responses via MAPK pathway, all of which were reduced by dotinurad. These results indicate that URAT1 is a potential therapeutic target for metabolic heart disease.
RESUMO
There is a host of research on the structure of working memory (WM) and its relationship with intelligence in adults, but only a few studies have involved children. In this paper, several different WM models were tested on 170 Japanese school children (from 7 years and 5 months to 11 years and 6 months). Results showed that a model distinguishing between modalities (i.e., verbal and spatial WM) fitted the data well and was therefore selected. Notably, a bi-factor model distinguishing between modalities, but also including a common WM factor, presented with a very good fit, but was less parsimonious. Subsequently, we tested the predictive power of the verbal and spatial WM factors on fluid and crystallized intelligence. Results indicated that the shared contribution of WM explained the largest portion of variance of fluid intelligence, with verbal and spatial WM independently explaining a residual portion of the variance. Concerning crystallized intelligence, however, verbal WM explained the largest portion of the variance, with the joint contribution of verbal and spatial WM explaining the residual part. The distinction between verbal and spatial WM could be important in clinical settings (e.g., children with atypical development might struggle selectively on some WM components) and in school settings (e.g., verbal and spatial WM might be differently implicated in mathematical achievement).
RESUMO
OBJECTIVE: Accumulating evidence indicates that high uric acid (UA) is strongly associated with obesity and metabolic syndrome and drives the development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Although urate transporter-1 (URAT1), which is primarily expressed in the kidneys, plays a critical role in the development of hyperuricemia, its pathophysiological implication in NAFLD and insulin resistance remains unclear. We herein investigated the role and functional significance of URAT1 in diet-induced obese mice. METHODS: Mice fed a high-fat diet (HFD) for 16-18 weeks or a normal-fat diet (NFD) were treated with or without a novel oral URAT1-selective inhibitor (dotinurad [50 mg/kg/day]) for another 4 weeks. RESULTS: We found that URAT1 was also expressed in the liver and brown adipose tissue (BAT) other than the kidneys. Dotinurad administration significantly ameliorated HFD-induced obesity and insulin resistance. HFD markedly induced NAFLD, which was characterized by severe hepatic steatosis as well as the elevation of serum ALT activity and tissue inflammatory cytokine genes (chemokine ligand 2 (Ccl2) and tissue necrosis factor α (TNFα)), all of which were attenuated by dotinurad. Similarly, HFD significantly increased URAT1 expression in BAT, resulting in lipid accumulation (whitening of BAT), and increased the production of tissue reactive oxygen species (ROS), which were reduced by dotinurad via UCP1 activation. CONCLUSIONS: In conclusion, a novel URAT1-selective inhibitor, dotinurad, ameliorates insulin resistance by attenuating hepatic steatosis and promoting rebrowning of lipid-rich BAT in HFD-induced obese mice. URAT1 serves as a key regulator of the pathophysiology of metabolic syndrome and may be a new therapeutic target for insulin-resistant individuals, particularly those with concomitant NAFLD.
Assuntos
Tecido Adiposo Marrom/metabolismo , Resistência à Insulina/genética , Transportadores de Ânions Orgânicos/metabolismo , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Feminino , Insulina/metabolismo , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Transportadores de Ânions Orgânicos/efeitos dos fármacos , Triglicerídeos/metabolismoRESUMO
There is growing interest in 3-iodothyronamine (T1AM), an active thyroid hormone metabolite, that induces negative inotropic and chronotropic actions in the heart and exerts systemic hypothermic action. We explored the direct impact of T1AM on cardiomyocytes with a focus on the regulation of the intracellular temperature and natriuretic peptide (NP) expression. A thermoprobe was successfully introduced into neonatal rat cardiomyocytes, and the temperature-dependent changes in the fluorescence intensity ratio were measured using a fluorescence microscope. After one-hour incubation with T1AM, the degree of change in the fluorescence intensity ratio was significantly lower in T1AM-treated cardiomyocytes than in equivalent solvent-treated controls (P < 0.01), indicating the direct hypothermic action of T1AM on cardiomyocytes. Furthermore, T1AM treatment upregulated B-type NP (BNP) gene expression comparable to treatment with endothelin-1 or phenylephrine. Of note, ERK phosphorylation was markedly increased after T1AM treatment, and inhibition of ERK phosphorylation by an MEK inhibitor completely cancelled both T1AM-induced decrease in thermoprobe-measured temperature and the increase in BNP expression. In summary, T1AM decreases fluorescent thermoprobe-measured temperatures (estimated intracellular temperatures) and increases BNP expression in cardiomyocytes by activating the MEK/ERK pathway. The present findings provide new insight into the direct myocardial cellular actions of T1AM in patients with severe heart failure.
Assuntos
Miócitos Cardíacos , Peptídeos Natriuréticos , Animais , Quinases de Proteína Quinase Ativadas por Mitógeno , Peptídeo Natriurético Encefálico/genética , Ratos , Temperatura , TironinasRESUMO
This study aimed to explore the relationships among autism spectrum disorder (ASD) traits, loneliness, and social networking services (SNS) use. We created a questionnaire to evaluate manners during LINE use, which included five factors: "low literacy," "inactive use," "low responsiveness," "lack of consideration," and "low group activity." Structural equation modeling revealed that difficulties in attention switching and low communication skills were associated with low literacy, low social skills were associated with inactive use, and low literacy and inactive use were associated with loneliness. We suggested that SNS use plays a role in maintaining and enhancing friendships, whereas college students with higher ASD traits tend to use inappropriate manners for SNS, which is associated with loneliness.
Assuntos
Transtorno do Espectro Autista/psicologia , Solidão/psicologia , Rede Social , Estudantes/psicologia , Adolescente , Amigos , Humanos , Masculino , Fenótipo , Habilidades Sociais , Inquéritos e Questionários , Adulto JovemRESUMO
Increasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.
Assuntos
Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/fisiologia , Fator Natriurético Atrial/farmacologia , Fígado Gorduroso/prevenção & controle , Intolerância à Glucose/prevenção & controle , Resistência à Insulina , Termogênese , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Thyroid hormone metabolism can be closely associated with cardiovascular disorders. We examined the relationship between low triiodothyronine (T3) levels and heart failure status, including B-type natriuretic peptide (BNP) levels, in 625 patients with cardiovascular disorders who underwent cardiac catheterization. A multiple regression analysis revealed that the left ventricular ejection fraction (LVEF), hemoglobin (Hb) levels, sex (male), free T3 (FT3) levels, and estimated glomerular filtration rate (eGFR) were significantly negatively associated with the log BNP value, while age was significantly positively associated with the log BNP value (P < 0.001 each). Furthermore, the log BNP and age were significantly negatively associated with the FT3 levels, while the Hb and body mass index (BMI) were significantly positively associated with the FT3 levels (P < 0.001 each). Theoretically constructed structure equation modeling (SEM) revealed an inverse association between FT3 and BNP (ß = -0.125, P = 0.002), and the same relationship remained in the patient group with normal-range BNP values (ß = -0.198, P = 0.008). We demonstrated a significant relationship between high BNP and low serum FT3 levels, and this relationship remained significant in patients with normal BNP levels. These results indicate that low T3 is associated with high plasma BNP levels rather than worsening of hemodynamics.
Assuntos
Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Tri-Iodotironina/sangue , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Taxa de Filtração Glomerular , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Análise de Regressão , Volume SistólicoRESUMO
Accumulating evidence suggests that high serum uric acid (UA) is associated with left ventricular (LV) dysfunction. Although xanthine oxidase (XO) activation is a critical regulatory mechanism of the terminal step in ATP and purine degradation, the pathophysiological role of cardiac tissue XO in LV dysfunction remains unclear. We herein investigated the role and functional significance of tissue XO activity in doxorubicin-induced cardiotoxicity. Either doxorubicin (10 mg/kg) or vehicle was intraperitonially administered in a single injection to mice. Mice were treated with or without oral XO-inhibitors (febuxostat 3 mg/kg/day or topiroxostat 5 mg/kg/day) for 8 days starting 24 h before doxorubicin injection. Cardiac tissue XO activity measured by a highly sensitive assay with liquid chromatography/mass spectrometry and cardiac UA content were significantly increased in doxorubicin-treated mice at day 7 and dramatically reduced by XO-inhibitors. Accordingly, XO-inhibitors substantially improved LV ejection fraction (assessed by echocardiography) and LV developed pressure (assessed by ex vivo Langendorff heart perfusion) impaired by doxorubicin administration. This was associated with an increase in XO-derived hydrogen peroxide production with concomitant upregulation of apoptotic and ferroptotic pathways, all of which were reduced by XO-inhibitors. Furthermore, metabolome analyses revealed enhanced purine metabolism in doxorubicin-treated hearts, and XO-inhibitors suppressed the serial metabolic reaction of hypoxanthine-xanthine-UA, the paths of ATP and purine degradation. In summary, doxorubicin administration induces cardiac tissue XO activation associated with impaired LV function. XO-inhibitors attenuate doxorubicin-induced cardiotoxicity through inhibition of XO-derived oxidative stress and cell death signals as well as the maintenance of cardiac energy metabolism associated with modulation of the purine metabolic pathway.
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Ácido Úrico , Xantina Oxidase , Animais , Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/toxicidade , Febuxostat , CamundongosRESUMO
In patients with cardiovascular disorders, blood total ketone body (TKB) levels increase with worsening heart failure and are consumed as an alternative fuel to fatty acid and glucose. We investigated factors contributing to the increase in the blood TKB levels in patients with cardiovascular disorders. The study population consisted of 1030 consecutive patients who underwent cardiac catheterization. Covariance structure analyses were performed to clarify the direct contribution of hemodynamic parameters, including the left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI), and B-type natriuretic peptide (BNP) levels, to TKB by excluding other confounding factors. These analyses showed that the TKB levels were significantly associated with the BNP level (P = 0.003) but not the LVEDP, LVESVI, or LVEDVI levels. This was clearly demonstrated on a two-dimensional contour line by Bayesian structure equation modeling. The TKB level was positively correlated with the BNP level, but not LVEDP, LVESVI or LVEDVI. These findings suggested that elevated blood TKB levels were more strongly stimulated by the increase in BNP than by hemodynamic deterioration. BNP might induce the elevation of TKB levels for use as an important alternative fuel in the failing heart.
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Doenças Cardiovasculares/sangue , Corpos Cetônicos/sangue , Peptídeo Natriurético Encefálico/sangue , Idoso , Pressão Sanguínea , Doenças Cardiovasculares/fisiopatologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume SistólicoRESUMO
Activity in the alpha band of the electroencephalogram (EEG) reflects functional inhibition of the cerebral cortex. The superior frontal cortex (SFC) is known to control alpha activity. Based on this relationship between SFC and alpha, we hypothesized that SFC controlled alpha mediates proactive control over interference. In this study, we examined the relationship between SFC and alpha in the flanker task by simultaneously recording EEG and near infrared spectroscopy (NIRS). Forty participants performed a flanker task with occasional (compatible 75%, incompatible 25%) and successive (incompatible 100%) conditions. In the occasional condition, larger SFC activity was related to pre-stimulus alpha enhancement under occipital electrodes. This is consistent with a model in which SFC enhances pre-stimulus alpha activity, leading to proactive control over interference. However, we could not detect a correlation between SFC activity and alpha activity in the successive condition. Active inhibition may have been reduced by a need to continuously inhibit brain regions associated with the irrelevant information. This may have reduced the role of the SFC in controlling alpha activity. Based on these findings, we postulate that there are two cerebral mechanisms of proactive control over interference.
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Ritmo alfa , Função Executiva/fisiologia , Lobo Frontal/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Espectroscopia de Luz Próxima ao Infravermelho , Adulto JovemRESUMO
OBJECTIVE: The right prefrontal cortex (PFC) plays an essential role in active processing within visuospatial working memory (VSWM). The aim of this study was to examine developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks in school-age participants. METHODS: We recruited 80 school-age children who were classified into three age groups: 7- to 8-year-old, 9- to 10-year-old, and 11- to 12-year-old children. We used near infrared spectroscopy (NIRS) to measure PFC activity during visuospatial memory task. Memory stimuli were presented either sequentially or simultaneously. RESULTS: In all three groups, right-lateralized PFC activity was observed during sequential presentation, suggesting specialization of the right PFC for VSWM. During simultaneous presentation, right-lateralized PFC activity was not observed in 7- to 8-year-old children or 9- to 10-year-old children. In contrast, PFC activity was right-lateralized in 11- to 12-year-old children. CONCLUSIONS: We suggest that specialization of the right PFC for VSWM is already present before school-age, but widely distributed activity in response to visuospatial memory tasks changes to more focal activity in VSWM-specific regions during the early school years. SIGNIFICANCE: Using NIRS, we showed developmental changes in the recruitment patterns of the PFC during visuospatial memory tasks.
Assuntos
Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/crescimento & desenvolvimento , Desempenho Psicomotor/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/tendências , Criança , Feminino , Humanos , Masculino , Córtex Pré-Frontal/metabolismo , Tempo de Reação/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Objective This study was carried out to examine the usefulness of point-of-care (POC) cardiac troponin in diagnosing acute coronary syndrome (ACS) and to understand the limitations of a POC cardiac troponin I/T-based diagnoses. Methods Patients whose cardiac troponin levels were measured in the emergency department using a POC system (AQT System; Radiometer, Tokyo, Japan) between January and December 2016 were retrospectively examined (N=1,449). Patients who were < 20 years of age or who were admitted with cardiopulmonary arrest were excluded. The sensitivity and specificity of the POC cardiac troponin levels for the diagnosis of ACS were determined. Result One hundred and twenty of 1,449 total patients had ACS (acute myocardial infarction, n=88; unstable angina n=32). On comparing the receiver operating characteristic (ROC) curves, the area under the curve (AUC) values for POC cardiac troponin I and cardiac troponin T were 0.833 and 0.786, respectively. The sensitivity and specificity of POC cardiac troponin I when using the 99th percentile (0.023 ng/mL) as the diagnostic cut-off value were 69.0% and 88.1%, respectively. The sensitivity of POC cardiac troponin I (99th percentile) was higher in the patients sampled > 3 hours after symptom onset (83.3%) than in those sampled ≤ 3 hours after symptom onset (58.8%, p < 0.01). Conclusion When sampled > 3 hours after the onset of symptoms, the POC cardiac troponin I level is considered to be suitable for use in diagnosing ACS. However, when sampled ≤ 3 hours after the onset of symptoms, careful interpretation of POC cardiac troponins is therefore required to rule out ACS.
Assuntos
Síndrome Coronariana Aguda/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Angina Instável/diagnóstico , Área Sob a Curva , Biomarcadores , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Tóquio , Troponina T/sangueRESUMO
Near-infrared spectroscopy studies in children with attention deficit hyperactivity disorder (ADHD) have shown excessive prefrontal activity responsible for coping with interference. However, it is possible that the previous results were influenced by verbal, reading, and memory developments. The flanker task is an interference task that does not require a verbal response, reading, or memorization. We examined activity in the superior frontal cortex (SFC) during the flanker task in 12 children with ADHD and 14 children with typical development using near-infrared spectroscopy. SFC activity was significantly greater in children with ADHD than in those with typical development. The results showed excessive interference coping activity in children with ADHD irrespective of verbal, reading, and memory development. Moreover, SFC activity was positively correlated with the inattention subscale score of the ADHD rating scale. We suggest that children with ADHD need greater SFC activation to cope with interference, and the inefficient mechanism is demanding and hard to sustain, which causes inattention symptoms of children with ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Lobo Frontal/irrigação sanguínea , Hemodinâmica/fisiologia , Criança , Feminino , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Humanos , Masculino , Testes Neuropsicológicos , Oxiemoglobinas/metabolismo , Estimulação Luminosa , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Spatial working memory (SWM) involves both simultaneous and sequential encoding, but the differences in their neural correlates are unclear. We investigated the differences in prefrontal cortex activity related to these SWM encoding types. We also examined the patterns of brain activity influencing individual visuospatial abilities (VSA). We conducted SWM tasks with two different conditions, sequential and simultaneous encoding, and examined hemodynamic activity in 39 healthy adults using near-infrared spectroscopy. The bilateral dorsolateral prefrontal cortex was activated more strongly in the sequential condition compared with the simultaneous condition. This suggests that prefrontal cortex activity underlying SWM is modulated by the type of encoding. We also found that individuals with high VSA showed weaker activation in the right-dorsolateral prefrontal cortex compared with those with lower VSA during the simultaneous condition. This hypoactivation is thought to reflect neural efficiency in the individuals with high ability. These findings are expected to lead to a better understanding of neural substrates for SWM.