RESUMEN
BACKGROUND: Catecholamines (CAs) are involved in a wide range of physiological and pathological processes in the body and are progressively being used as important biomarkers for a variety of diseases. It is of great significance for accurate quantification of CAs to the diagnosis and treatment of diseases. However, the separation of CAs from complex biological matrices is still a great challenge due to the trace levels of CAs and the limited selectivity of existing pretreatment methods. RESULTS: In this work, a dual-recognition imprinted membrane (BA-MIM) was developed to utilize the synergistic action of pH-responsive boron affinity and molecular imprinted cavities for highly selective capture and release of CAs. The prepared BA-MIM possessed remarkable adsorption capacity (maximum capacity, 43.3 mg g-1), desirable surface hydrophilicity (46.2°), superior selectivity (IF = 6.2, α = 14.3), as well as favorable reusability (number of cycles, 6 times). On this basis, an integrated analytical method based on BA-MIM extraction combined with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was innovatively developed to highly selective separation, enrichment, and detection of CAs in rat brain tissue. Under the optimum conditions, a low quantitation limits (0.05-0.10 ng mL-1), wide linear range (10-1000 ng mL-1), good linearity (r2 > 0.99), and satisfactory recoveries (88.5%-98.5 %) were obtained for CAs. The proven method was further applied to kidney-yang-deficiency-syndrome (KYDS) group rat model, revealed the intrinsic connection between kidney disease and catecholamine metabolism. SIGNIFICANCE: This work provides an excellent reference paradigm for the effective construction of dual-recognition functional membrane material to the high-selective analysis of trace targets in complex matrices. Additionally, this integrated analytical strategy demonstrates its efficiency, sustainability, versatility, and convenience, showing remarkable prospect in a variety of applications for biological sample analysis.
Asunto(s)
Catecolaminas , Impresión Molecular , Catecolaminas/análisis , Catecolaminas/química , Animales , Concentración de Iones de Hidrógeno , Ratas , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Adsorción , Membranas Artificiales , Límite de Detección , Ratas Sprague-DawleyRESUMEN
INTRODUÇÃO Cardiomiopatia (CMP) induzida por estresse, como a cardiomiopatia de Takotsubo, pode ter características clínicas semelhantes à isquemia miocárdica, como elevação de troponinas, alterações no Eletrocardiograma (ECG), mas sem obstrução coronariana ou lesões isquêmicas. Semelhante, a CMP induzida por Feocromocitoma possui sintomas também semelhantes a CMP hipertrófica, hipertensão e edema pulmonar devido a fatores cardiogênicos ou não cardiogênicos. Ambas supracitadas podem ter associação com excesso de catecolaminas, mas raramente estão associadas. RELATO DO CASO Paciente masculino, 46 anos, diabético, com história de estresse por situações familiares importantes, recentemente. Chega no serviço de emergência, com queixas de dispnéia, náuseas e êmese, iniciados há 1 dia, associado a retenção urinária e parestesia em mãos e paraparesia de membros inferiores. Refere também tratamento com Amoxicilina + Clavulanato há um mês por Colecistite Aguda. Na chegada, paciente se encontrava taquicárdico, taquipneico e saturando 98% em uso de óculos nasal a 2l/min, além de acidose metabólica. Realizou-se uma tomografia computadorizada de abdome, que evidenciou uma massa em Adrenal, sugestivo de Feocromocitoma, bem como metanefrinas urinárias e catecolaminas positivas. Ainda na emergência, evoluiu com insuficiência respiratória aguda por edema agudo de pulmão, necessitando de manejo com Nitroglicerina e 03 ampolas de Furosemida e uso de máscara não reinalante a 10l/min. Foi encaminhado para Unidade de Terapia Intensiva, onde foi realizado um ECG com alterações primárias da repolarização, seguido de alterações nos valores de Troponina e alterações no Ecocardiograma (ECO) de acinesia apical, hipocinesia de todos os segmentos médios e contratilidade preservada em segmentos basais. Cateterismo cardíaco com achados semelhantes ao ECO e presença de balonamento na ventriculografia, além de ausência de lesões obstrutivas em coronárias. CONCLUSÃO A excepcionalidade desse caso diz respeito ao quadro de síndrome coronariana aguda com dois motivos plausíveis e evidenciados na condução do caso, sendo eles: CMP de Takotsubo e a induzida por Feocromocitoma. Fica evidente, pela evolução do quadro, a gravidade do mesmo e a importância de considerar diagnósticos diferenciais, inclusive os menos comuns.
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Humanos , Masculino , Persona de Mediana Edad , Feocromocitoma , Cardiomiopatía de Takotsubo , Edema Pulmonar , Insuficiencia Respiratoria , Cateterismo Cardíaco , Catecolaminas , Colecistitis Aguda , Disnea , ElectrocardiografíaRESUMEN
BACKGROUND: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI. METHODS: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise. RESULTS: Among 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI. CONCLUSION: PI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload.
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Catecolaminas , Prueba de Esfuerzo , Tolerancia al Ejercicio , Humanos , Prueba de Esfuerzo/métodos , Persona de Mediana Edad , Masculino , Tolerancia al Ejercicio/fisiología , Femenino , Catecolaminas/sangre , Adulto , Norepinefrina/sangre , Hemodinámica/fisiología , Frecuencia Cardíaca/fisiología , Epinefrina/sangre , Ejercicio Físico/fisiología , Gasto Cardíaco/fisiologíaRESUMEN
BACKGROUND: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise. METHODS: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm. RESULTS: Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. CONCLUSIONS: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.
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Electroencefalografía , Metilfenidato , Humanos , Método Doble Ciego , Metilfenidato/farmacología , Masculino , Adulto , Femenino , Electroencefalografía/efectos de los fármacos , Adulto Joven , Estimulantes del Sistema Nervioso Central/farmacología , Catecolaminas/metabolismo , Ondas Encefálicas/efectos de los fármacosRESUMEN
Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 µM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (ISK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of ISK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.
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Células Endoteliales , Epinefrina , Especies Reactivas de Oxígeno , Transducción de Señal , Humanos , Transducción de Señal/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Óxido Nítrico/metabolismo , Catecolaminas/metabolismo , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , NADPH Oxidasas/metabolismo , Receptores de Dopamina D5/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores Dopaminérgicos/metabolismoRESUMEN
Detecting dopamine (DA) is critical for early diagnosis of neurological and psychiatric disorders. However, the presence of other catecholamine neurotransmitters with structural similarities to DA causes significant interference in its detection. Herein, we introduce S stripping defects via laser-induced MoS2 to functionalize MoS2 electrodes and improve their selectivity for DA electrochemical detection. The sensing results show its excellent immunity to interference from other neurotransmitters, ensuring the preservation of the DA electrochemical signal even in the mixed neurotransmitters such as acetylcholine (ACh), γ-aminobutyric acid (GABA), epinephrine (EP), norepinephrine (NP), and serotonin (5-HT). DFT calculations further reveal that the negatively charged S-stripping defects enhance DA adsorption on the surface of the functionalized MoS2 electrode, contributing to its excellent performance. Moreover, this functionalized electrodes successfully monitor DA released from living PC12 cells in the presence of other interference, highlighting its potential applicability in intercellular signaling communication.
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Dopamina , Técnicas Electroquímicas , Electrodos , Rayos Láser , Neurotransmisores , Dopamina/análisis , Células PC12 , Técnicas Electroquímicas/métodos , Animales , Neurotransmisores/análisis , Ratas , Disulfuros/química , Catecolaminas/análisis , Epinefrina/análisis , Norepinefrina/análisis , Teoría Funcional de la Densidad , MolibdenoRESUMEN
BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.
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Cardiomiopatías , Modelos Animales de Enfermedad , Epinefrina , Microcirculación , Choque Séptico , Animales , Perros , Choque Séptico/fisiopatología , Choque Séptico/complicaciones , Choque Séptico/sangre , Epinefrina/sangre , Microcirculación/efectos de los fármacos , Cardiomiopatías/fisiopatología , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Volumen Sistólico/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/complicaciones , Función Ventricular Izquierda/efectos de los fármacos , Catecolaminas/sangre , Troponina/sangre , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/fisiopatología , Factores de Tiempo , Imagen de Perfusión Miocárdica/métodos , Imagen por Resonancia MagnéticaRESUMEN
The human body synthesizes catecholamine neurotransmitters, such as dopamine and noradrenaline. Monitoring the levels of these molecules is crucial for the prevention of important diseases, such as Alzheimer's, schizophrenia, Parkinson's, Huntington's, attention-deficit hyperactivity disorder, and paragangliomas. Here, we have synthesized, characterized, and functionalized the BODIPY core with picolylamine (BDPy-pico) in order to create a sensor capable of detecting these biomarkers. The sensing properties of the BDPy-pico probe in solution were studied using fluorescence titrations and supported by DFT studies. Catecholamine sensing was also performed in the solid state by a simple strip test, using an optical fiber as the detector of emissions. In addition, the selectivity and recovery of the sensor were assessed, suggesting the possibility of using this receptor to detect dopamine and norepinephrine in human saliva.
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Compuestos de Boro , Catecolaminas , Colorantes Fluorescentes , Compuestos de Boro/química , Humanos , Catecolaminas/análisis , Colorantes Fluorescentes/química , Saliva/química , Dopamina/análisis , Norepinefrina/análisis , Espectrometría de Fluorescencia/métodos , Técnicas Biosensibles/métodosRESUMEN
BACKGROUND: Myocardial injury (MI) after acute ischemic stroke (AIS) poses a significant threat to patient prognosis. However, effective intervention strategies are currently lacking. PURPOSE: To elucidate the mechanism of MI after AIS and effects of Naoxintong capsule (NXT) therapy. METHOD: In vivo, after a rat model of middle cerebral artery occlusion (MCAO)-induced MI was established and assessed. NXT was administered prophylactically to evaluate its pharmacodynamic effects and mechanisms. In vitro, a noradrenaline (NA)-induced damage cell model was constructed. Subsequently, the NXT was applied to the cell models to examine its cardioprotective effects and potential mechanisms. RESULTS: The in vivo findings revealed that following MCAO, there was a notable upregulation of TH expression in the rat brain, which subsequently triggered an increase in serum levels of various biomarkers, including AD, NA, AST, cTnT, CK-MB, and NT-proBNP. Histological analysis employing H&E staining and TUNEL assay disclosed significant pathological alterations and an escalation in apoptotic activity within the myocardial tissue. The myocardial tissue exhibited elevated levels of MDA alongside diminished CAT activity. Additionally, a marked increase in the Bax/Bcl-2 ratio, Cytochrome C release, and Caspase-3 activation was observed, all of which are indicative of heightened apoptotic activity. Administration of the NXT intervention successfully attenuated TH expression in the brains of rats subjected to MCAO, consequently leading to a reduction in circulating levels of catecholamines (CAs). NXT also exhibited significant efficacy at ameliorating cardiac oxidative stress and reducing apoptosis. In vitro, stimulation with NA led to an increase in ROS levels and calcium ion concentration in H9c2 cardiomyocytes. However, the administration of NXT has been found to effectively alleviate these adverse effects, thereby protecting H9c2 cardiomyocytes from the deleterious consequences of oxidative stress and calcium dyshomeostasis. CONCLUSION: Overall, this study has demonstrated that increased CAs synthesis in the brain after AIS in experimental rats led to a surge in circulating CAs, ultimately leading to MI. NXT can alleviate MI due to cerebral ischemia by increasing improving brain catecholamine synthesis, cardiac oxidative stress, and apoptosis.
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Apoptosis , Catecolaminas , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Masculino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Catecolaminas/metabolismo , Apoptosis/efectos de los fármacos , Ratas , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Miocardio/metabolismo , Miocardio/patología , NorepinefrinaRESUMEN
It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/ß) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/ß was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.
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Ratas Sprague-Dawley , Caracteres Sexuales , Estrés Psicológico , Animales , Masculino , Femenino , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Ratas , Rombencéfalo/metabolismo , Motilidad Gastrointestinal/fisiología , Catecolaminas/metabolismo , Tirosina 3-Monooxigenasa/metabolismo , Sistema Nervioso Autónomo/fisiopatología , Sistema Nervioso Autónomo/metabolismo , Frecuencia Cardíaca/fisiología , Hormona Liberadora de Corticotropina/metabolismo , Vaciamiento Gástrico/fisiología , Colina O-Acetiltransferasa/metabolismoRESUMEN
OBJECTIVE: Winter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions. METHODS: Fourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale. RESULTS: HRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval. CONCLUSION: Prolonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.
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Afecto , Expediciones , Frecuencia Cardíaca , Estaciones del Año , Humanos , Regiones Antárticas , Afecto/fisiología , Masculino , Adulto , Frecuencia Cardíaca/fisiología , Nervio Vago/fisiología , Femenino , Sistema Nervioso Autónomo/fisiología , Catecolaminas/sangreAsunto(s)
Hipoglucemia , Humanos , Recién Nacido , Femenino , Catecolaminas/sangre , Embarazo , FetoAsunto(s)
Catecolaminas , Hipoglucemia , Humanos , Recién Nacido , Catecolaminas/sangre , Femenino , Embarazo , FetoRESUMEN
BACKGROUND: It is extremely essential to accurately differentiate pheochromocytoma from Adrenal incidentalomas (AIs) before operation, especially biochemical tests were inconclusive. We aimed to evaluate the value of magnetic resonance imaging (MRI) features to differentiate pheochromocytomas among adrenal tumors, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive. METHODS: With institutional review board approval, this study retrospectively compared 35 pheochromocytoma (PHEO) patients with 27 non-pheochromocytoma(non-PHEO) patients between January 2022 to September 2023, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive. T test was used for the independent continuous data and the chi-square test was used for categorical variables. Univariate and multivariate logistic regression were applied to find the independent variate of the features to differentiate PHEO from non-PHEO and ROC analysis was applied to evaluate the diagnostic value of the independent variate. RESULTS: We found that the T2-weighted (T2W) signal intensity in patients with pheochromocytoma was higher than other adrenal tumors, with greatly significant (p < 0.001). T2W signal intensity ratio (T2W nodule-to-muscle SI ratio) was an independent risk factor for the differential diagnosis of adrenal PHEOs from non-PHEOs. This feature alone had 91.4% sensitivity and 81.5% specificity to rule out pheochromocytoma based on optimal threshold, with an area under the receiver operating characteristics curve (AUCROC) of 0.910(95% C I: 0.833-0.987). CONCLUSION: Our study confirms that T2W signal intensity ratio can differentiate PHEO from non-PHEO, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive.
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Neoplasias de las Glándulas Suprarrenales , Imagen por Resonancia Magnética , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Diagnóstico Diferencial , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Adulto , Catecolaminas/metabolismo , Anciano , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Perceptual decisions are often accompanied by a feeling of decision confidence. Where the parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on the (pre)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electroencephalography was measured. Where cholinergic effects were not robust, catecholaminergic enhancement improved perceptual sensitivity, while at the same time leaving metacognitive sensitivity unaffected. Neurally, catecholaminergic elevation did not affect sensory representations of task-relevant visual stimuli but instead enhanced well-known decision signals measured over the centroparietal cortex, reflecting the accumulation of sensory evidence over time. Crucially, catecholaminergic enhancement concurrently impoverished neural markers measured over the frontal cortex linked to the formation of metacognitive evaluations. Enhanced catecholaminergic neuromodulation thus improves perceptual but not metacognitive decision-making.
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Clorhidrato de Atomoxetina , Catecolaminas , Toma de Decisiones , Electroencefalografía , Metacognición , Humanos , Masculino , Femenino , Toma de Decisiones/fisiología , Toma de Decisiones/efectos de los fármacos , Metacognición/fisiología , Adulto , Adulto Joven , Catecolaminas/metabolismo , Clorhidrato de Atomoxetina/farmacología , Percepción Visual/fisiología , Percepción Visual/efectos de los fármacos , Inhibidores de Captación Adrenérgica/farmacología , Acetilcolina/metabolismoRESUMEN
The development of nanozymes (NZ) for the simultaneous detection of multiple target chemicals is gaining paramount attention in the field of food and health sciences, and waste management industries. Nanozymes (NZ) effectively compensate for the environmental vulnerability of natural enzymes. Considering the development gap of NZ with diverse applications, we synthesized versatile Schiff's base ligands following a facile route and readily available starting reagents (glutaraldehyde, aminopyridines). DPDI, one of the synthesized ligands, readily reacted with transition metal ions (Cu+2, Ag+1, Zn+2 in specific) under ambient conditions, yielding the corresponding nanoparticles/MOF. The structures of ligands and their products were confirmed using various analytical techniques. The enzymatic efficacy of DPDI-Cu (km 0.25 mM=, Vmax = 10.75 µM/sec) surpassed Tremetese versicolor laccase efficacy (km 0. 5 mM=, Vmax = 2.15 µM/sec). Additionally, DPDI-Cu proved resilient to changing pH, temperature, ionic strength, organic solvent, and storage time compared to laccase and provided reusability. DPDI-Cu proved promising for colorimetric detection of dopamine, epinephrine, catechol, tetracycline, and quercetin. The mechanism of oxidative detection of TC was studied through LC/MS analysis. DPDI-Cu-bentonite composite efficiently adsorbed tetracycline with maximum Langmuir adsorption of 208 mg/g. Moreover, DPDI/Cu and DPDI-Ag nanoparticles possessed antifungal activity exhibiting a minimum inhibitory concentration of 400 µg/mL and 3.12 µg/mL against Aspergillus flavus. Florescent dye tracking and SEM/TEM analysis confirmed that DPDI-Ag caused disruption of the plasma membrane and triggered ROS generation and apoptosis-like death in fungal cells. The DPDI-Ag coating treatment of wheat seeds confirmed the non-phytotoxicity of Ag-NPs.
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Antibacterianos , Antifúngicos , Catecolaminas , Bases de Schiff , Tetraciclina , Bases de Schiff/química , Bases de Schiff/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antifúngicos/farmacología , Antifúngicos/química , Catecolaminas/química , Tetraciclina/química , Tetraciclina/farmacología , Tetraciclina/análisis , Ligandos , Nanoestructuras/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Nanopartículas del Metal/químicaRESUMEN
Endothelial dysfunction contributes to the pathogenesis of Takotsubo syndrome (TTS). However, the exact mechanism underlying endothelial dysfunction in the setting of TTS has not been completely clarified. This study aims to investigate the roles of angiotensin II (Ang II) and intermediate-conductance Ca2+-activated K+ (SK4) channels in catecholamine-induced endothelial dysfunction. Human cardiac microvascular endothelial cells (HCMECs) were exposed to 100⯵M epinephrine (Epi), mimicking the setting of TTS. Epi treatment increased the ET-1 concentration and reduced NO levels in HCMECs. Importantly, the effects of Epi were found to be mitigated in the presence of Ang II receptor blockers. Furthermore, Ang II mimicked Epi effects on ET-1 and NO production. Additionally, Ang II inhibited tube formation and increased cell apoptosis. The effects of Ang II could be reversed by an SK4 activator NS309 and mimicked by an SK4 channel blocker TRAM-34. Ang II also inhibited the SK4 channel current (ISK4) without affecting its expression level. Ang II could depolarize the cell membrane potential. Ang II promoted ROS release and reduced protein kinase A (PKA) expression. A ROS blocker prevented Ang II effect on ISK4. The PKA activator Sp-8-Br-cAMPS increased SK4 channel currents. Epinephrine enhanced the activity of ACE by activating the α1 receptor/Gq/PKC signal pathway, thereby promoting the secretion of Ang II. The study suggested that high-level catecholamine can increase Ang II release from endothelial cells by α1 receptors/Gq/PKC signal pathway. Ang II can inhibit SK4 channel current by increasing ROS generation and reducing PKA expression, thereby contributing to endothelial dysfunction.
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Angiotensina II , Catecolaminas , Células Endoteliales , Especies Reactivas de Oxígeno , Angiotensina II/farmacología , Humanos , Catecolaminas/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Epinefrina/farmacología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Apoptosis/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal/efectos de los fármacos , Células CultivadasRESUMEN
Catecholamines (CATs) are neurotransmitters and allostatic hormones whose plasma concentrations are physiologically modified in various species such as human, rats, mice and donkeys, with advancing age. However, currently these mechanisms are less well elucidated in horses and more specifically in mares. The hypothesis of this study was that, as in afore mentioned species, the CATs could experience physiological changes with advancing age. The objective of this study was to evaluate the concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA), and serotonin (5-HT) in mares of different ages. Blood samples were drawn from 56 non-pregnant Spanish Purebred mares belonging to four different age groups: 6 to 9 years, 10 to 12 years, 13 to 16 years and > 16 years. The concentrations of A, NA, DA, and 5-HT were determined by competition EIA-Technical 3-CAt EIA, specifically validated for horses. Mares aged > 16 years showed lower A, DA, and 5-HT but higher NA concentrations than 6-9, 10-12, and 13-16 years (p < 0.05). Mares of 13-16 years showed lower A and higher NA than 6-9 and 10-12 years (p < 0.05). A and NA (r=-0.72; p < 0.05), and NA and 5-HT (r=-0.67; p < 0.05) were negatively correlated, and A and 5-HT (r = 0.74; p < 0.05) were positively correlated. Advanced age leads to a predominance of sympathetic nervous activity and lower serotonergic activity in non-pregnant mares.
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Envejecimiento , Catecolaminas , Animales , Caballos/sangre , Caballos/fisiología , Femenino , Catecolaminas/sangre , Envejecimiento/fisiología , Serotonina/sangre , Factores de Edad , Norepinefrina/sangre , Dopamina/sangre , Epinefrina/sangreRESUMEN
ABSTRACT: Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway.