Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by (1)H-NMR ...spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a (1)H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA.
Hibiscus sabdariffa
L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, ...we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of
H. sabdariffa
L. calyx extract (HSCE)
.
Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 μM trolox/g of sample). HSCE significantly inhibited (100–1000 μg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca
2+
-activated K
+
channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of
H. sabdariffa
L. calyx extract.
Resumen Introducción La ventilación no invasiva (VNI) se ha convertido en un tratamiento habitual de la insuficiencia respiratoria aguda (IRA). Nuestro objetivo ha sido identificar factores ...predictores de fracaso de VNI para detectar precozmente a los pacientes en los que no tendrá éxito. Pacientes y métodos Estudio de cohortes prospectivo que incluyó a todos los pacientes con IRA que recibieron VNI como tratamiento inicial entre 2005 y 2009, en una unidad de cuidados intensivos pediátricos de 14 camas de un hospital universitario de tercer nivel. Se recogieron datos clínicos e información sobre la VNI, previamente a su inicio, a las 2, 8, 12 y 24 horas. La razón entre saturación de hemoglobina y fracción de oxígeno inspirada (S/F) se calculó retrospectivamente. Se definió fallo de VNI como necesidad de intubación o necesidad de rescate con presión binivel (BLPAP). Se realizaron análisis estadísticos univariable y multivariable. Resultados Un total de n = 282 pacientes recibieron soporte no invasivo, presión continua = 71, BLPAP = 211. El porcentaje de éxito de la muestra global fue 71%. Los pacientes tratados con BLPAP vs. presión continua, aquellos con S/F más elevados a las 2 horas ( odds ratio 0,991, IC 95%: 0,986-0,996, p = 0,001) y los mayores de 6 meses ( hazard ratio 0,375, IC 95% 0,171-0,820, p = 0,014), presentaron menor riesgo de fracaso. Los pacientes con frecuencias cardíacas más altas y mayor presión positiva inspiratoria en vía aérea a las 2 horas ( odds ratio 1,021, IC 95%: 1,008-1,034, p = 0,001; hazard ratio 1,214, IC 95%: 1,046-1,408, p = 0,011) presentaron mayor riesgo de fracaso. Conclusiones La edad < 6 meses, S/F, frecuencia cardíaca y presión positiva inspiratoria en la vía aérea a las 2 horas son factores predictores independientes de fracaso de VNI inicial en pacientes con IRA admitidos en una unidad de cuidados intensivos pediátricos.
Agomelatine (AGO) is an antidepressant drug with agonistic activity at melatonin receptor 1 (MT1) and MT2 and with neutral antagonistic activity at serotonin receptor 5-HT2C. Although experimental ...studies show that melatonin reduces hypertriglyceridemia and hepatic steatosis induced by excessive fructose intake, no studies have tested if AGO exerts similar actions. To address this issue we have treated male Wistar rats with fructose (15% in the drinking water) and/or AGO (40 mg/kg/day) for two weeks. AGO reduced body weight gain, feeding efficiency and hepatic lipid levels without affecting caloric intake in fructose-treated rats. AGO has also decreased very low-density lipoprotein (VLDL) production and circulating TAG levels after an oral load with olive oil. Accordingly, treatment with AGO reduced the hepatic expression of fatty acid synthase (Fasn), a limiting step for hepatic de novo lipogenesis (DNLG). The expression of apolipoprotein B (Apob) and microsomal triglyceride transfer protein (Mttp) in the ileum, two crucial proteins for intestinal lipoprotein production, were also downregulated by treatment with AGO. Altogether, the present data show that AGO mimics the metabolic benefits of melatonin when used in fructose-treated rats. This study also suggests that it is relevant to evaluate the potential of AGO to treat metabolic disorders in future clinical trials.
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•Agomelatine reduces circulating triacylglycerides in fructose-treated rats.•Agomelatine reduces hepatic lipids in fructose-treated rats.•Agomelatine reduces ileal Mttp and Apob expression in fructose-treated rats.•Agomelatine reduces triglycerides after olive oil gavage in fructose-treated rats.
Objectives To analyze in a retrospective cohort if sodium concentration in the rehydration fluids influence natremia in children with diabetic ketoacidosis (DKA). Study design Consecutive episodes of ...diabetic ketoacidosis admitted in a tertiary care referral center from 2000 to 2005. Rehydration was programmed for 48 hours with a 2-bag system. Initial rehydration was performed with isotonic fluids and thereafter with variable tonicity. Analysis of the influence of the different factors on natremia was performed with a multivariate linear regression analysis. Results Forty-two episodes of DKA were reviewed. Increased sodium content in rehydration fluids behaved as an independent variable, causing a positive tendency of natremia ( P < .008). Conclusions Sodium concentration in the rehydration fluids behaves as an independent factor that influences positively the trend of the serum concentration of sodium during DKA rehydration. We propose the use of isotonic solutions for rehydration in diabetic ketoacidosis.
Purpose Observational studies show that longer breastfeeding periods reduce maternal risk of type 2 diabetes mellitus. However, it is currently unknown if the long-term benefits of breastfeeding for ...maternal glucose homeostasis are linked to changes in the endocrine pancreas. Methods We presently evaluated functional, morphological and molecular aspects of the endocrine pancreas of mice subjected to two sequential cycles of pregnancy and lactation (L21). Age-matched mice not allowed to breastfeed (L0) and virgin mice were used as controls. Results L21 mice exhibited increased tolerance and increased glucose-stimulated insulin secretion (GSIS) by isolated islets. Pancreatic islets of L21 mice did not present evident morphological changes to justify the increased GSIS. On the other hand, islets of L21 mice exhibited a reduction in Cavb3 and Kir6.2 expression with concordant increased intracellular Ca2+ levels after challenge with glucose. Conclusion Altogether, the present findings show the breastfeeding exerts long-term benefits for maternal endocrine pancreas by increasing intracellular Ca2+ levels and GSIS.
ResumenIntroducciónLos fluidos isotónicos, en la mayoría de los casos, constituyen la forma más segura de administración de líquidos por vía intravenosa. Los objetivos de nuestro trabajo han sido ...describir las prácticas de prescripción de los fluidos intravenosos de mantenimiento y estudiar los posibles factores asociados. Material y métodoEstudio transversal, descriptivo, multicéntrico de ámbito nacional, mediante encuesta on-line, difundida a través de sociedades científicas médicas y la Organización Médica Colegial, entre diciembre de 2016 y diciembre de 2017. ResultadosUn total de 487 encuestas fueron recibidas, 456 de pediatras. El 28,95% (IC 95%: 24,77-33,13) de ellos prescribían habitualmente fluidos hipotónicos y el 81,14% (IC 95%: 77,54-84,74) se basaba en la regla de Holliday y Segar para calcular el volumen total a infundir. El perfil del pediatra en España que utiliza fluidos hipotónicos intravenosos es el de médico residente de pediatría, pediatra que trabaja en áreas diferentes a las unidades de cuidados intensivos pediátricos, en hospitales privados, y aquellos que reconocen que no existe un consenso al respecto en su grupo de trabajo. ConclusionesMás de una cuarta parte de los pediatras en nuestro país sigue utilizando los fluidos hipotónicos como fluidoterapia intravenosa de mantenimiento. Diferentes factores podrían estar asociados a este hecho. Estos estudios son prueba de las grandes dificultades existentes para trasladar el conocimiento a la práctica.
Aim: To compare diagnostic accuracy in cord blood of interleukin‐6 (IL‐6) with C‐reactive protein (CRP) as predictors of early‐onset neonatal sepsis (EOS) in newborns with prenatal risk factors for ...infection.
Methods: During 12 months, cord blood IL‐6 and CRP were measured immediately after birth in neonates with prenatal risk factors of infection. The odds of developing sepsis based on IL‐6 and CRP values were calculated using likelihood ratios (LR), and their accuracy as predictors was compared by binary logistic regression. Multivariable logistic regression analyses were performed to identify independent risk factors for sepsis.
Results: Ten of 128 neonates (7.8%) were diagnosed with EOS confirmed with positive blood culture in five cases (3.9%). Cord blood IL‐6 was a greater predictor of sepsis than CRP ROC for IL‐6 (0.88) vs. CRP (0.70). IL‐6‐positive and IL‐6‐negative LR 7.14 vs. −0.11 were superior to those calculated for CRP 2.86 vs. −0.51. Chorioamnionitis and Apgar at 1 min were identified as independent risk factors for EOS.
Conclusions: Cord blood IL‐6 showed superior LR than CRP; therefore, it is a better predictor to initiate treatment in neonates with prenatal infectious risk factors immediately after birth.
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