RESUMEN

To investigate the release of lipolytic hormones during various high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), and their effects on fat loss. 39 young women categorized as obese (with a body fat percentage (BFP) ≥30%) were randomly allocated to one of the following groups: all-out sprint interval training (SIT, n =10); supramaximal HIIT (HIIT120, 120%V̇O2peak, n = 10); HIIT (HIIT90, 90%V̇O2peak, n = 10), or MICT, (60%V̇O2peak, n = 9) for a twelve-week observation period consisting of 3 to 4 exercise sessions per week. Serum epinephrine (EPI) and growth hormone (GH) were measured during the 1st, 20th, and 44th training sessions. Body weight (BW), body mass index (BMI), whole-body fat mass (FM) and BFP were assessed pre- and post-intervention. Following the 1st and 20th sessions, significant increases in EPI (p < 0.05) were observed post-exercise in HIIT120 and HIIT90, but not in SIT and MICT. In the 44th session, the increased EPI was found in SIT, HIIT120, and HIIT90, but not in MICT (p < 0.05). For the GH, a significant increase was observed post-exercise in all groups in the three sessions. The increased EPI and GH returned to baselines 3 hours post-exercise. After the 12-week intervention, significant reductions in FM and BFP were found in all groups, while reductions in BW and BMI were only found in the SIT and HIIT groups. Greater reductions in FM and BFP, in comparison to MICT, were observed in the SIT and HIIT groups (p < 0.05). 12-week SIT, HIIT120, and HIIT90, in comparison to MICT, were more efficacious in fat reduction in obese women, partly benefiting from the greater release of lipolytic hormones during training sessions.

Asunto(s)

Índice de Masa Corporal , Epinefrina , Entrenamiento de Intervalos de Alta Intensidad , Obesidad , Humanos , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Epinefrina/sangre , Adulto Joven , Obesidad/terapia , Obesidad/sangre , Hormona de Crecimiento Humana/sangre , Lipólisis , Consumo de Oxígeno , Tejido Adiposo/metabolismo , Adulto , Peso Corporal

RESUMEN

In this cross-sectional, descriptive, and observational study conducted at Fundación Valle del Lili in Colombia, the clinical and sociodemographic characteristics of anaphylaxis were investigated in a cohort of 80 patients who sought medical care between January 2021 and December 2022. With a median age of 16 years and a notable prevalence among individuals aged below 18 years, the study revealed that 63.8% of patients had concomitant allergic diseases. Medications emerged as the primary triggers for anaphylaxis, followed by food. The mucocutaneous system was predominantly affected in 55% of cases, with respiratory involvement observed in 37.5%. Alarmingly, anaphylactic shock occurred in 17.5%, and 7.5% experienced biphasic anaphylaxis. Intramuscular adrenaline was administered in 88.8% of cases, with 75% of patients not receiving an allergy consultation upon discharge, and 52.5% lacking follow-up for allergy care. Considering that in Colombia epidemiological data on the clinical and sociodemographic aspects of anaphylaxis remain largely unknown, this study documents the features of anaphylaxis in both adult and pediatric populations and highlights the urgent need for improved awareness, timely evaluation by allergists, and comprehensive follow-up care for individuals experiencing anaphylaxis.

Asunto(s)

Anafilaxia , Humanos , Anafilaxia/epidemiología , Colombia/epidemiología , Masculino , Femenino , Adolescente , Adulto , Estudios Transversales , Adulto Joven , Niño , Persona de Mediana Edad , Preescolar , Prevalencia , Epinefrina/administración & dosificación , Hipersensibilidad a los Alimentos/epidemiología , Lactante , Anciano

RESUMEN

RATIONALE: Anaphylactic shock, a severe and rapid systemic allergic reaction, poses significant treatment challenges. Epinephrine, the first-line treatment, effectively reverses symptoms but can complicate the clinical picture by elevating lactate levels, blurring the distinction between shock-induced hypoperfusion and drug-induced metabolic effects. PATIENT CONCERNS: A 26-year-old female presented with anaphylactic shock following an antibiotic infusion, experiencing chest tightness, hypotension, and pulmonary edema, without significant past medical history apart from a noted allergy to fish and shrimp. DIAGNOSES: Anaphylaxis was diagnosed based on clinical presentation and supported by imaging that revealed pulmonary edema, despite normal troponin levels and electrocardiogram. INTERVENTIONS: Treatment included 0.5 mg of intramuscular epinephrine and 5 mg of intravenous dexamethasone, with subsequent intubation and mechanical ventilation in the intensive care unit. An intravenous epinephrine infusion was also administered for hemodynamic support. OUTCOMES: While epinephrine resolved the pulmonary edema and stabilized circulation, it led to a significant, albeit transient, increase in lactate levels, which normalized following discontinuation of epinephrine, indicating the metabolic effect of the drug rather than ongoing tissue hypoperfusion. LESSONS: This case illustrates the importance of recognizing epinephrine-induced lactate elevation in anaphylactic shock, necessitating a nuanced interpretation of lactate dynamics. Clinicians must differentiate between lactate elevations due to tissue hypoperfusion and those arising from epinephrine's pharmacologic effects to optimize patient care.

Asunto(s)

Anafilaxia , Epinefrina , Ácido Láctico , Humanos , Anafilaxia/tratamiento farmacológico , Anafilaxia/sangre , Femenino , Adulto , Epinefrina/administración & dosificación , Ácido Láctico/sangre , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación

RESUMEN

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.

Asunto(s)

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/fisiología

RESUMEN

The activation of stressors can disrupt the body's homeostasis, leading to the release of stress hormones such as epinephrine, noradrenaline, and glucocorticoids. Moreover, emerging evidence highlights the profound impact of stress on microglia, which are specialized macrophages residing in the brain's parenchyma. Following stress, microglia exhibit notable morphological activation and increased phagocytic activity. Microglia express various receptors that enable them to respond to stress hormones originating from both central and peripheral sources, thereby exerting pro-inflammatory or anti-inflammatory effects. In this article, we review the advancements in studying the structural and functional changes of microglia induced by exposure to stressors. Additionally, we explore the role of stress hormones in mediating the effects of these stressors on microglia.

Asunto(s)

Microglía , Microglía/fisiología , Microglía/metabolismo , Humanos , Animales , Estrés Fisiológico/fisiología , Estrés Psicológico/fisiopatología , Epinefrina/metabolismo , Epinefrina/fisiología , Norepinefrina/metabolismo , Norepinefrina/fisiología , Glucocorticoides/metabolismo , Encéfalo/fisiología , Encéfalo/metabolismo , Fagocitosis/fisiología

RESUMEN

Chronic stress-induced epinephrine (EPI) accelerates breast cancer progression and metastasis, but the molecular mechanisms remain unclear. Herein, we found a strong positive correlation between circulating EPI levels and the tumoral expression of ubiquitin-specific peptidase 22 (USP22) in patients with breast cancer. USP22 facilitated EPI-induced breast cancer progression and metastasis by enhancing adipose triglyceride lipase (ATGL)-mediated lipolysis. Targeted USP22 deletion decreased ATGL expression and lipolysis, subsequently inhibiting EPI-mediated breast cancer lung metastasis. USP22 acts as a bona fide deubiquitinase for the Atgl gene transcription factor FOXO1, and EPI architects a lipolysis signaling pathway to stabilize USP22 through AKT-mediated phosphorylation. Notably, USP22 phosphorylation levels are positively associated with EPI and with downstream pathways involving both FOXO1 and ATGL in breast cancers. Pharmacological USP22 inhibition synergized with ß-blockers in treating preclinical xenograft breast cancer models. This study reveals a molecular pathway behind EPI's tumor-promoting effects and provides a strong rationale for combining USP22 inhibition with ß-blockers to treat aggressive breast cancer.

Asunto(s)

Neoplasias de la Mama , Epinefrina , Lipólisis , Ubiquitina Tiolesterasa , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Lipólisis/efectos de los fármacos , Femenino , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Epinefrina/metabolismo , Humanos , Animales , Ratones , Línea Celular Tumoral , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Lipasa/metabolismo , Lipasa/genética , Transducción de Señal/efectos de los fármacos , Metástasis de la Neoplasia , Fosforilación , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Aciltransferasas

RESUMEN

Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.4 µM epinephrine had a higher incidence of the 30 day primary cardiovascular endpoint (37.2% vs. 15.3% in those without hyperreactivity, adjusted HR 2.76, 95% CI 1.5-5.1, p = 0.002). PRESS performs well in identifying a hyperreactive phenotype in patients with PAD (AUC [cross-validation] 0.81, 95% CI 0.68 -0.94, n = 84) and in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 -0.79, n = 35). Following multivariable adjustment, PAD individuals with a PRESS score above the median are at higher risk for a future cardiovascular event (adjusted HR 1.90, CI 1.07-3.36; p = 0.027, n = 129, NCT02106429). This study derives and validates the ability of PRESS to discriminate platelet hyperreactivity and identify those at increased cardiovascular risk. Future studies in a larger independent cohort are warranted for further validation. The development of a platelet reactivity expression score opens the possibility for a personalized approach to antithrombotic therapy for cardiovascular risk reduction.

Asunto(s)

Plaquetas , Enfermedades Cardiovasculares , Enfermedad Arterial Periférica , Agregación Plaquetaria , Humanos , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/epidemiología , Masculino , Femenino , Plaquetas/metabolismo , Persona de Mediana Edad , Anciano , Agregación Plaquetaria/efectos de los fármacos , Enfermedades Cardiovasculares/sangre , Factores de Riesgo de Enfermedad Cardiaca , Activación Plaquetaria , Epinefrina/sangre , Factores de Riesgo

RESUMEN

Single-atom nanozymes have garnered significant attention due to their exceptional atom utilization and ability to establish well-defined structure-activity relationships. However, conventional pyrolytic synthesis methods pose challenges such as high energy consumption and random local environments at the active sites, while achieving non-pyrolytic synthesis of single-atom nanozymes remains a formidable technical hurdle. The present study focuses on the synthesis of laccase-like iron-based single-atom nanozymes (Fe-SAzymes) using a non-pyrolysis method facilitated by microwave irradiation. Under low iron loading conditions, Fe-SAzymes exhibited significantly enhanced laccase activity (12.1 U/mg), surpassing that of laccase by 24-fold. Moreover, Fe-SAzymes demonstrated efficient catalytic oxidation of epinephrine (EP), enabling its colorimetric detection. Owing to the remarkable laccase activity of Fe-SAzymes, the conventional nanozymes EP detection time was reduced from 60 min to 20 min, with an impressive low detection limit as low as 2.95 µM. In addition, an ultra-sensitive fluorescence method for EP detection was developed using the internal filter effect of EP oxidation products and CDs combined with carbon dots probe. The detection limit of fluorescence method was only 0.39 µM. Therefore, an visual, fast, and highly sensitive dual-mode EP detection strategy has great potential in the clinical diagnostic industry.

Asunto(s)

Colorimetría , Epinefrina , Hierro , Lacasa , Lacasa/química , Lacasa/metabolismo , Colorimetría/métodos , Epinefrina/análisis , Hierro/química , Espectrometría de Fluorescencia , Límite de Detección , Nanoestructuras/química , Oxidación-Reducción , Fluorescencia , Microondas

RESUMEN

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.

Asunto(s)

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/metabolismo

RESUMEN

Fascia iliaca compartment block (FICB) reduces opioid consumption and pain scores after total hip arthroplasty (THA), and has recently been widely applied. We investigated whether FICB could also reduce postoperative bleeding. One hundred and fifteen consecutive patients who underwent elective THA under general anesthesia over 5 months were retrospectively analyzed. They were divided into 2 groups: the FICB group received an epinephrine-mixed FICB procedure and the control group did not receive any block. Using the hematocrit measured at 4 different time points (preoperative and 1, 24, and 48 hours after surgery), the estimated blood loss (EBL) was calculated for 3 different time periods (0-1, 1-24, 24-48 hours after surgery). EBL at 1 to 24 hours (226 vs 398 mL, P = .008) was significantly lower in the FICB group than in the control group. Additionally, the number of packed red cell (PRC) units transfused per patient over 48 hours was 0.38 units in the FICB group, which was significantly lower than the 0.70 units used in the control group (P = .040). Epinephrine-mixed FICB in THA has the potential to reduce postoperative bleeding in the first 24 hours after surgery as well as reduce PRC transfusion requirements.

Asunto(s)

Artroplastia de Reemplazo de Cadera , Epinefrina , Bloqueo Nervioso , Hemorragia Posoperatoria , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Epinefrina/administración & dosificación , Estudios Retrospectivos , Masculino , Femenino , Anciano , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/etiología , Persona de Mediana Edad , Bloqueo Nervioso/métodos , Fascia/inervación , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Vasoconstrictores/uso terapéutico , Vasoconstrictores/administración & dosificación , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología

RESUMEN

High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1°C for 3 h) or chronic (30 vs. 40 ± 1°C for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1°C), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1°C). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggest that Y4 receptor may play physiological roles in response to HT in male chicks.

Asunto(s)

Pollos , Neuropéptido Y , ARN Mensajero , Receptores de Neuropéptido Y , Bazo , Regulación hacia Arriba , Animales , Receptores de Neuropéptido Y/metabolismo , Receptores de Neuropéptido Y/genética , Bazo/metabolismo , Masculino , Neuropéptido Y/metabolismo , Neuropéptido Y/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Calor , Epinefrina/metabolismo

RESUMEN

BACKGROUND: Estimates for the prevalence of food allergy vary widely, with a paucity of data for adults. The aim of this analysis was to report trends in the incidence and prevalence of food allergy in England, using a national primary care dataset. METHODS: We analysed data from Clinical Practice Research Datalink between 1998 and 2018, with linked data to relevant hospital encounters in England. The main outcomes were incidence and prevalence of food allergy, according to three definitions of food allergy: possible food allergy, probable food allergy, and probable food allergy with adrenaline autoinjectors prescription. We also evaluated the difference in proportion of patients prescribed adrenaline autoinjectors by English Index of Multiple Deprivation (IMD), age, and by previous food anaphylaxis, and explored differences in patient encounters (general practice vs emergency department setting). FINDINGS: 7 627 607 individuals in the dataset were eligible for inclusion, of whom 150 018 (median age 19 years [IQR 4-34]; 82 614 [55·1%] female and 67 404 [44·9%] male) had a possible food allergy. 121 706 met diagnostic criteria for probable food allergy, of whom 38 288 were prescribed adrenaline autoinjectors. Estimated incidence of probable food allergy doubled between 2008 and 2018, from 75·8 individuals per 100 000 person-years (95% CI 73·7-77·9) in 2008 to 159·5 (156·6-162·3) individuals per 100 000 person-years in 2018. Prevalence increased from 0·4% (23 399 of 6 432 383) to 1·1% (82 262 of 7 627 607) over the same period and was highest in children under 5 years (11 951 [4·0%] of 296 406 in 2018) with lower prevalence in school-aged children (from 11 353 [2·4%] of 473 597 in 2018 for children aged 5-9 years to 6896 [1·7%] of 404 525 for those aged 15-19 years) and adults (42 848 [0·7%] of 5 992 454 in 2018). In those with previous food anaphylaxis, only 2321 (58·3%) of 3980 (975 [64·0%] of 1524 children and young people and 1346 [54·8%] of 2456 adults) had a prescription for adrenaline autoinjector. Adrenaline autoinjectors prescription was less common in those resident in more deprived areas (according to IMD). In the analysis of health-care encounters, 488 604 (97·1%) of 503 198 visits recorded for food allergy occurred in primary care, with 115 655 (88·4%) of 130 832 patients managed exclusively in primary care. INTERPRETATION: These estimates indicate an important and increasing burden of food allergy in England. Our findings that most patients with food allergy are managed outside the hospital system, with low rates of adrenaline autoinjector prescription in those with previous anaphylaxis, highlight a need to better support those working in primary care to ensure optimal management of patients with food allergy. FUNDING: UK Food Standards Agency and UK Medical Research Council.

Asunto(s)

Epinefrina , Hipersensibilidad a los Alimentos , Humanos , Femenino , Hipersensibilidad a los Alimentos/epidemiología , Masculino , Inglaterra/epidemiología , Adolescente , Niño , Adulto , Preescolar , Adulto Joven , Incidencia , Epinefrina/administración & dosificación , Prevalencia , Anafilaxia/epidemiología

RESUMEN

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.

Asunto(s)

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 , Molibdeno

RESUMEN

Upper gastrointestinal bleeding (UGIB) is a major cause of morbidity and mortality. Clinical symptoms that patients may present with include: hematemesis, coffee-ground emesis, melena, and hematochezia. Clinical signs can range from tachycardia to shock. The anatomical landmark that differentiates upper gastrointestinal (GI) bleeds from lower bleeds is the ligament of Treitz. The first steps of treating a patient who presents with signs of UGIB are resuscitation with appropriate fluids and blood products as necessary. The consideration of endoscopy and the urgency at which it should be performed is also vital during initial resuscitation. Endoscopic therapy should ideally be performed within 24 hours of presentation after initial stabilization with crystalloids and blood products. Intravenous proton pump inhibitors are the mainstay in the initial management of upper GI bleeding from a non-variceal etiology, and they should be administered in the acute setting to decrease the probability of high-risk stigmata seen during endoscopy. Pro-kinetic agents can be given 30 minutes to an hour before endoscopy and may aid in the diagnosis of UGIB. There are 3 broad categories of endoscopic management for UGIB: injection, thermal, and mechanical. Each endoscopic method can be used alone or in combination with others; however, the injection technique with epinephrine should always be used in conjunction with another method to increase the success of achieving hemostasis. In this review article, we will review the steps of triage and initial resuscitation in UGIB, causes of UGIB and their respective management, several endoscopic techniques and their effectiveness, and prognosis with a primary focus limited to non-variceal bleeding.

Asunto(s)

Endoscopía Gastrointestinal , Hemorragia Gastrointestinal , Hemostasis Endoscópica , Humanos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica/métodos , Endoscopía Gastrointestinal/métodos , Inhibidores de la Bomba de Protones/uso terapéutico , Tracto Gastrointestinal Superior , Epinefrina/administración & dosificación , Epinefrina/uso terapéutico , Resucitación/métodos

RESUMEN

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.

Asunto(s)

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 Magnética

RESUMEN

RATIONALE: At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. PATIENT CONCERNS: A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. DIAGNOSIS: The patient was diagnosed with persistent severe allergic reaction (grade I). INTERVENTIONS: Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. OUTCOMES: During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. LESSONS: For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.

Asunto(s)

Epinefrina , Humanos , Masculino , Epinefrina/administración & dosificación , Adulto Joven , Inyecciones Intramusculares , Infusiones Intravenosas , Dolor Abdominal/tratamiento farmacológico , Dolor Abdominal/etiología , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/tratamiento farmacológico , Hipersensibilidad a las Drogas/diagnóstico , Índice de Severidad de la Enfermedad

RESUMEN

6-Cyanodopamine is a novel catecholamine released from rabbit isolated heart. However, it is not known whether this catecholamine presents any biological activity. Here, it was evaluated whether 6-cyanodopamine (6-CYD) is released from rat vas deferens and its effect on this tissue contractility. Basal release of 6-CYD, 6-nitrodopamine (6-ND), 6-bromodopamine, 6-nitrodopa, and 6-nitroadrenaline from vas deferens were quantified by LC-MS/MS. Electric-field stimulation (EFS) and concentration-response curves to noradrenaline, adrenaline, and dopamine of the rat isolated epididymal vas deferens (RIEVD) were performed in the absence and presence of 6-CYD and /or 6-ND. Expression of tyrosine hydroxylase was assessed by immunohistochemistry. The rat isolated vas deferens released significant amounts of both 6-CYD and 6-ND. The voltage-gated sodium channel blocker tetrodotoxin had no effect on the release of 6-CYD, but it virtually abolished 6-ND release. 6-CYD alone exhibited a negligible RIEVD contractile activity; however, at 10 nM, 6-CYD significantly potentiated the noradrenaline- and EFS-induced RIEVD contractions, whereas at 10 and 100 nM, it also significantly potentiated the adrenaline- and dopamine-induced contractions. The potentiation of noradrenaline- and adrenaline-induced contractions by 6-CYD was unaffected by tetrodotoxin. Co-incubation of 6-CYD (100 pM) with 6-ND (10 pM) caused a significant leftward shift and increased the maximal contractile responses to noradrenaline, even in the presence of tetrodotoxin. Immunohistochemistry revealed the presence of tyrosine hydroxylase in both epithelial cell cytoplasm of the mucosae and nerve fibers of RIEVD. The identification of epithelium-derived 6-CYD and its remarkable synergism with catecholamines indicate that epithelial cells may regulate vas deferens smooth muscle contractility.

Asunto(s)

Dopamina , Contracción Muscular , Conducto Deferente , Masculino , Animales , Conducto Deferente/efectos de los fármacos , Conducto Deferente/metabolismo , Conducto Deferente/fisiología , Contracción Muscular/efectos de los fármacos , Ratas , Dopamina/metabolismo , Dopamina/farmacología , Ratas Wistar , Norepinefrina/farmacología , Norepinefrina/metabolismo , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiología , Estimulación Eléctrica , Epinefrina/farmacología , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

Asunto(s)

Abdomen , Vasoconstrictores , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Abdomen/cirugía , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéutico , Unidades de Cuidados Intensivos , Cardiotónicos/administración & dosificación , Norepinefrina , Epinefrina/administración & dosificación , Dobutamina/administración & dosificación , Dopamina , Vasopresinas , Milrinona/administración & dosificación

RESUMEN

PURPOSE OF REVIEW: Epinephrine is the first line treatment for anaphylaxis, however, there are limited data to support this. This review examines data surrounding evidence for the use of epinephrine in anaphylaxis, data on prescription for and use of epinephrine autoinjectors, and data examining newer routes of delivery of epinephrine; with a focus on recent publications over the past few years. RECENT FINDINGS: With recent epidemiologic studies of anaphylaxis and new forms of epinephrine being studied, new data on the effects of epinephrine are aiding in the understanding of epinephrine's effects and the shortcomings of epinephrine both in its effect and utility in the real world. SUMMARY: Epinephrine is still considered the first line therapy for anaphylaxis, and we are starting to have a better understanding of its effects in both healthy patients and those with anaphylaxis.

Asunto(s)

Anafilaxia , Epinefrina , Anafilaxia/tratamiento farmacológico , Anafilaxia/epidemiología , Epinefrina/administración & dosificación , Epinefrina/uso terapéutico , Humanos , Medicina Basada en la Evidencia

RESUMEN

PURPOSE OF REVIEW: Anaphylaxis is a severe, potentially life-threatening allergic reaction that requires rapid identification and intervention. Current management includes early recognition, prompt administration of epinephrine, and immediate medical attention. However, challenges remain in accurate diagnosis, timely treatment, and personalized care. This article reviews the integration of artificial intelligence and machine learning in enhancing anaphylaxis management. RECENT FINDINGS: Artificial intelligence and machine learning can analyze vast datasets to identify patterns and predict anaphylactic episodes, improve diagnostic accuracy through image and biomarker analysis, and personalize treatment plans. Artificial intelligence-powered wearable devices and decision support systems can facilitate real-time monitoring and early intervention. The ethical considerations of artificial intelligence use, including data privacy, transparency, and bias mitigation, are also discussed. SUMMARY: Future directions include the development of predictive models, enhanced diagnostic tools, and artificial intelligence-driven educational resources. By leveraging artificial intelligence and machine learning, healthcare providers can improve the management of anaphylaxis, ensuring better patient outcomes and advancing personalized medicine.

Asunto(s)

Algoritmos , Anafilaxia , Inteligencia Artificial , Aprendizaje Automático , Humanos , Anafilaxia/diagnóstico , Medicina de Precisión/métodos , Epinefrina/uso terapéutico , Epinefrina/administración & dosificación