Efecto de la privación de sueño MOR sobre marcadores metabólicos e inflamatorios en ratas

El sueño es una condición biológica imprescindible, se caracteriza por una conducta de pasividad y disminución de la respuesta a estímulos externos. El sueño se ha dividido en dos fases: la fase de sueño de ondas lentas (SOL) y la fase de sueño de movimientos oculares rápidos (SMOR), la que se presenta una pérdida del tono muscular, acompañada de la mayoría de las ensoñaciones que se presentan a lo largo del sueño. La privación de esta fase de sueño es el objeto de estudio del presente trabajo. La modernidad de los medios de comunicación, las jornadas laborales excesivas, la rotación de turnos laborales, etc. han favorecido a la disminución en las horas de sueño, esto tiene efecto no solo en el desempeño laboral y social, sino también en la salud de la personas, pues cada vez existen más evidencias de que la privación de sueño (PS) contribuye al incremento en la incidencia de enfermedades metabólicas. El objetivo de este trabajo fue determinar las alteraciones que pueden provocar diferentes periodos de privación de sueño de movimientos oculares rápidos (PSMOR), así como un periodo de recuperación de 20 días posterior a 8 días de PSMOR sobre los niveles de glucosa y su comportamiento en la prueba de tolerancia a la glucosa oral (PTGO), niveles de insulina, IL-6 y hormonas relacionadas con la ingesta de alimento (grelina y leptina), así como las concentraciones de corticosterona como marcador general de inducción a estrés fisiológico. Para el desarrollo del proyecto se utilizó como modelo rata macho Wistar de 3 meses de edad, en 4 grupos experimentales con n=5 por experimento independiente: 1 día de PSMOR, 4 días de PSMOR, 8 días de PSMOR y 8 días de PSMOR con 20 días de recuperación, para cada experimento de realizó la PTGO en 5 tiempos de observación, posteriores a la administración de dextrosa anhidra y el perfil de lípidos en sangre total. Las citocinas y hormonas se analizaron por la técnica de ELISA, también se evaluó el peso corporal durante y después de la PSMOR. Los animales del grupo control fueron mantenidos durante los mismos periodos en la caja de privación de sueño pero solo con aserrín.Para el análisis estadístico, los resultados se presentan como M ± EEM. En todos los casos se utilizó un análisis de varianza, y para encontrar diferencias entre grupos se utilizaron pruebas de comparaciones múltiples (Tukey y Newman-Keuls), la totalidad de las pruebas estadísticas se efectuaron en el programa GB-STAT. Los resultados reflejan una disminución progresiva del peso corporal dependiente del tiempo de PSMOR, dicho efecto no puede ser reversible a pesar de transcurrir 20 días de recuperación. La PSMOR induce hipoglucemia en todos los tiempos, sin embargo la recuperación provoca un incremento en las concentraciones de glucosa. En cuanto a la insulina se observa una disminución en la concentración desde el día 1 de PSMOR, misma que se restablece posterior al periodo de recuperación. La PSMOR causa disminución en los niveles de triglicéridos, lipoproteínas de alta densidad (HDL), lipoproteínas de muy baja densidad (VLDL) e incrementos en la concentración de lipoproteínas de baja densidad (LDL). La PSMOR induce un incremento en los niveles de corticosterona a los 8 días de PSMOR, condición que se mantiene luego de 20 días de recuperación. La PSMOR por 8 días también induce un incremento en los niveles de grelina y una disminución progresiva en los niveles de leptina. Las concentraciones de IL-6 se incrementan por efecto de la PSMOR, sin embargo, después de 20 días de recuperación estos niveles no se restablecen. Concluimos que los efectos metabólicos inducidos por la PSMOR son dependientes de su duración, algunas alteraciones fisiológicas inducidas por la PSMOR como el peso corporal, IL-6, corticosterona y glucosa, no se restablecen después de un periodo de recuperación de 20 días

Cytokine and microRNA levels during different periods of paradoxical sleep deprivation and sleep recovery in rats

Background Sleep has a fundamental role in the regulation of homeostasis. The aim of this study was to assess the effect of different periods of paradoxical sleep deprivation (PSD) and recovery on serum levels of cytokines and miRNAs related to inflammatory responses. Methods Male Wistar rats were submitted to a PSD of 24, 96, or 192 h, or of 192 h followed by 20 days of recovery (192 h PSD+R). The concentrations of corticosterone, cytokines (IL-6, TNF, IL-10, Adiponectin) and miRNAs (miR-146a, miR-155, miR-223, miR-16, miR-126, miR-21) in serum were evaluated. Results At PSD 24 h a significant increase of IL-6 and decrease of IL-10 were observed. At PSD 96h adiponectin increased. At 192 h of PSD IL-6 increased significantly again, accompanied by a threefold increase of IL-10 and an increase of serum corticosterone. After 20 days of recovery (192 h PSD+R) corticosterone, IL-6 and TNF levels increased significantly, while IL-10 decreased also significantly. Regarding the miRNAs at 24 h of PSD serum miR-146a, miR-155, miR-223, and miR-16 levels all increased. At 96 h of PSD miR-223 decreased. At 192 h of PSD decreases in miR-16 and miR-126 were observed. After recovery serum miR-21 increased and miR-16 decreased. Conclusion PSD induces a dynamic response likely reflecting the induced cellular stress and manifested as variating hormonal and inflammatory responses. Sleep deprivation disturbed corticosterone, cytokine and miRNA levels in serum related to the duration of sleep deprivation, as short-term PSD produced effects similar to those of an acute inflammatory response and long-term PSD induced long-lasting disturbances of biological mediators

Efecto de la privación de sueño MOR sobre la expresión de moléculas reguladoreas del metabolismo y citocinas en ratas

Sleep is an indispensable physiological activity, it is considered that the human being spends a third of his life sleeping, which indicates that the functions of sleep are of vital importance. Although the function of sleep is not fully described, several theories are considered, among them, it deters the regulation of metabolism and the immune response. It has been observed that sleep deprivation induces important alterations in glucose metabolism, and believes that there is a relation between obesity and lack of sleep, besides it has been shown that sleep deprivation induces alterations in the immune response , this alterations also are related with some alterations as the insulin resistance, however little has been described about the response of the organism to different periods of sleep deprivation and its recovery, therefore the effect of the MOR sleep deprivation was evaluated in different periods (1 day, 4 days and 8 days) and 20 days of recovery after 8 days of MOR sleep deprivation, on the concentration and expression of metabolic regulatory molecules and cytokines in rats, the first day it´s found a decrease of concentration of leptin, insulin, IL-10 and IL-1β and increase the miRNAs 155, 146a and 223 as well as the concentration of IL-6. At day 4, the increase in food consumption, in the expression of mRNA resistine, TNF, ACSL1 and PPARγ in liver were observed. It decreases leptin, expression of GLUT4 and miRNA 223. On day 8 of MOR sleep deprivation, the increase in food consumption is maintained, ghrelin, corticosterone, IL-10, IL-6 and Leptin, insulin and miRNAs 16 and 126. Passing the recovery period the expression of adiponectin increases, FATP, ACSL 1, PPARγ, IL-6, as well as TNF and IL-6 concentration and decreased expression of GLUT4 and the concentration of IL-10. The results demonstrate that the response of the organism subjected to the different periods of MOR sleep deprivation, the increase in food consumption is maintained, ghrelin, corticosterone, IL-10, IL-6 and Leptin, insulin and miRNAs 16 and 126. Passing the recovery period the expression of adiponectin increases, FATP, ACSL 1, PPARγ, IL-6, as well as TNF and IL-6 concentration and decreased expression of GLUT4 and the concentration of IL-10. The results demonstrate that the response of the organism subjected to the different periods of MOR sleep deprivation depends on time of the same and that a prolonged recovery time is insufficient to reverse the alterations caused by MOR sleep deprivation.El sueño es una actividad fisiológica indispensable, se considera que el ser humano pasa una tercera parte de su vida durmiendo, lo que indica que las funciones del sueño son de vital relevancia. A pesar de que la función del sueño no está descrita en su totalidad se consideran varias teorías, entre ellas destaca la regulación del metabolismo y de la respuesta inmune. Se ha observado que la privación de sueño induce importantes alteraciones en el metabolismo de la glucosa, y se cree que existe una relación entre la obesidad y la falta de sueño, además de ello se ha demostrado que la privación de sueño induce alteraciones en la respuesta inmune. Dichas alteraciones también se relación con algunas alteraciones como la resitencia a la insulina, sin embargo poco se ha descrito sobre la respuesta del organismo ante diferentes periodos de privación de sueño y su recuperación. Por lo anterior se evaluó el efecto de la privación de sueño MOR a diferentes periodos (1 día, 4 días y 8 días) y 20 días de recuperación posterior a 8 días de privación de sueño MOR, sobre la concentración y expresión de moléculas reguladoras del metabolismo y citocinas en ratas, al primer día se encuentra una disminución en la concentración de leptina, insulina, IL-10 e IL-1β e incrementan los miRNAs 155, 146a y 223 así como la concentración de IL-6. Al día 4 se observa incremento en el consumo de alimento, en la expresión del RNAm de resistina, TNF, ACSL1 y PPARγ en hígado. Así mismo disminuye la leptina, la expresión de GLUT4 y el miRNA 223. En el día 8 de privación de sueño MOR se mantiene el aumento en el consumo de alimento, se incrementa la grelina, la corticosterone, IL-10, IL-6 y diminuyen la leptina, insulina y los miRNAs 16 y 126. Pasando el periodo de recuperación se incrementa la expresión de adiponectina, FATP, ACSL 1, PPARγ, IL-6, así como la concentración de TNF e IL-6 y disminuye la expresión de GLUT4 y la concentración eño MOR es dependiente al tiempo de la misma y que es insuficiente un periodo prolongado de recuperación para revertir las alteraciones provocadas por la privación de sueño MOR

Inflammation Related MicroRNAs Are Modulated in Total Plasma and in Extracellular Vesicles from Rats with Chronic Ingestion of Sucrose

Circulating microRNAs (miRNAs) and the functional implications of miRNAs contained in extracellular vesicles (EVs) have gained attention in the last decade. Little is known about the regulation of the abundance of plasma miRNAs in response to chronic ingestion of carbohydrates. Therefore, we explored the circulating levels of miR-21, miR-146a, miR-155, and miR-223 in rats consuming sucrose in drinking water. Weanling Wistar rats were 25 weeks with 30% sucrose in drinking water, and miRNAs expression was determined in total plasma and in microvesicles, by RT-qPCR with TaqMan probe based assays for miR-21, miR-146a, miR-155, and miR-223, using cel-miR-39 (as spike in control and reference). Endotoxemia was also measured. Sucrose-fed animals showed higher body weight and retroperitoneal adipose tissue as well as higher glucose and triglyceride plasma levels than controls. Plasma endotoxin levels were low and not different among groups. Plasma miR-21 and miR-223 were higher in the sucrose group (p<0.05), whereas miR-155 tended to be lower (p=0.0661), and miR-146a did not show significant differences. In the plasma EVs the same trend was found except for miR-146a that showed significantly higher levels (p<0.05). Overall, our results show that high carbohydrate ingestion modulates circulating miRNAs levels related to an inflammatory response

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients

Background: Several easy-to-use risk scoring systems have been built to identify patients at risk of developing complications associated with COVID-19. However, information about the ability of each score to early predict major adverse outcomes during hospitalization of severe COVID-19 patients is still scarce. Methods: Eight risk scoring systems were rated upon arrival at the Emergency Department, and the occurrence of thrombosis, need for mechanical ventilation, death, and a composite that included all major adverse outcomes were assessed during the hospital stay. The clinical performance of each risk scoring system was evaluated to predict each major outcome. Finally, the diagnostic characteristics of the risk scoring system that showed the best performance for each major outcome were obtained. Results: One hundred and fifty-seven adult patients (55 ± 12 years, 66% men) were assessed at admission to the Emergency Department and included in the study. A total of 96 patients (61%) had at least one major outcome during hospitalization; 32 had thrombosis (20%), 80 required mechanical ventilation (50%), and 52 eventually died (33%). Of all the scores, Obesity and Diabetes (based on a history of comorbid conditions) showed the best performance for predicting mechanical ventilation (area under the ROC curve (AUC), 0.96; positive likelihood ratio (LR+), 23.7), death (AUC, 0.86; LR+, 4.6), and the composite outcome (AUC, 0.89; LR+, 15.6). Meanwhile, the inflammation-based risk scoring system (including leukocyte count, albumin, and C-reactive protein levels) was the best at predicting thrombosis (AUC, 0.63; LR+, 2.0). Conclusions: Both the Obesity and Diabetes score and the inflammation-based risk scoring system appeared to be efficient enough to be integrated into the evaluation of COVID-19 patients upon arrival at the Emergency Department

Diagnostic Performance of Serum MicroRNAs for ST-Segment Elevation Myocardial Infarction in the Emergency Department

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department

The prognostic importance of the angiotensin II/angiotensin-(1–7) ratio in patients with SARS-CoV-2 infection

Background: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1–7) levels in patients with COVID-19 is scarce. Objective: To characterize the Ang II–ACE2–Ang-(1–7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. Methods: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1–7), and Ang-(1–9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). Results: Serum from 74 patients [age: 58 (48–67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10–21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1–7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1–7) concentration was lower in patients who died. The Ang II/Ang-(1–7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1–7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 10 3 /µl (OR = 8.43) were independent predictors of mortality from COVID-19. Conclusion: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II–ACE2–Ang-(1–7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome