The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events.
Early IV metoprolol ...during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI).
The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up.
Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval CI: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046).
In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions. (Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The METOCARD-CNIC Trial; NCT01311700).
In veterinary field, drug exposure during milk production in dairy cattle is considered a major health problem which concerns dairy consumers. The induced expression of the ABC transporter G2 (ABCG2) ...in the mammary gland during lactation plays a significant role in the active secretion of many compounds into milk. The main objective of this study was to determine the involvement of ABCG2 in the secretion into milk of the antiparasitic clorsulon in sheep as well as the possible effect of the coadministration of model ABCG2 inhibitors such as macrocyclic lactones on this process. Cells transduced with the ovine variant of ABCG2 were used to carry out
in vitro
transepithelial transport assays in which we showed that clorsulon is a substrate of the ovine transporter. In addition, ivermectin and abamectin significantly inhibited clorsulon transport mediated by ovine ABCG2.
In vivo
interactions were studied in Assaf sheep after coadministration of clorsulon (in DMSO, 2 mg/kg, s.c.) with ivermectin (Ivomec
®
, 0.2 mg/kg, s.c.) or abamectin (in DMSO, 0.2 mg/kg, s.c.). After ivermectin and abamectin treatment, no relevant statistically significant differences in plasma levels of clorsulon were reported between the experimental groups since there were no differences in the area under the plasma concentration-curve (AUC) between clorsulon treatment alone and coadministration with macrocyclic lactones. With regard to milk, total amount of clorsulon, as percentage of dose excreted, did not show statistically significant differences when macrocyclic lactones were coadministered. However, the AUC for clorsulon significantly decreased (
p
< 0.05) after coadministration with ivermectin (15.15 ± 3.17 μg h/mL) and abamectin (15.30 ± 3.25 μg h/mL) compared to control group (20.73 ± 4.97 μg h/mL). Moreover, milk parameters such as half-life (
T
1/2
) and mean residence time (MRT) were significantly lower (
p
< 0.05) after coadministration of macrocyclic lactones. This research shows that the milk pharmacokinetics of clorsulon is affected by the coadministration of ABCG2 inhibitors, reducing drug persistence in milk.
•Higher heating value is an important parameter to characterize biomass as a fuel.•Higher heating value of 20 samples was experimentally determined.•Structural analysis of 20 samples was ...experimentally determined.•Equations to correlate structural analysis data and HHV were developed.
The importance of waste biomass as an energy source is likely to increase during the coming years as a result of European energy policy objectives, and because of the wide range of possibilities that it offers: it is a cheap fuel, widespread, and available in large quantities. In addition to crops and forestry operations, the Spanish fruit, olive and wine industries generate large amounts of currently undervalued solid wastes such as stones, branches, pulps or pomaces. The use of these by-products offers environmental benefits like removing waste and preventing fires at the same time as providing an energy yield. A proper energy valorization will require a complete physicochemical characterization. In this article, a structural and thermal characterization is developed from twenty samples from the olive and wine industries, as well as from forest and agro wastes. In addition, predictive equations are proposed to determine higher heating value (HHV) from chemical composition. For this purpose, the chemical extraction method (also called the ‘classic’ method) was used, and results were obtained in accordance with the data shown in the bibliography. Two predictive equations were developed: one based on lignin and hemicellulose content, and the other based on lignin quantity. Both present an absolute average error (AAE) of 0.87% and 1.13%, respectively.
University teachers have adapted to different situations during the development of distance learning due to the pandemic caused by the COVID-19 virus. This study was conducted by assigning a data ...collection instrument to 993 teachers who are part of 15 technological universities (TUs) and 7 polytechnic universities (PUs) to determine how they were affected by COVID-19. The questions asked were related to the social, economic, academic, emotional, and health effects experienced. The results show that 63% of the teachers working online complained that online teaching invaded their family privacy; 56% pointed out that working from home and the virtual classes affected their performance as teachers; 90% of the teachers thought that they dedicated too much extra to preparing for their classes; 15% were stressed; 4% felt negative under the new teaching scheme of virtual classes; finally, 38% of the teachers stated that repeated interaction with electronic devices had a lot of negative impacts on their emotional wellbeing. By means of a G-test, it was determined that gender was independent from the studied effects. Through a multiple correspondence analysis (MCA), it was determined that, of the total number of teachers who responded to the questionnaire, half were comfortable with the online teaching model and the other half were not. The most impacted effects were the economic, training and connectivity independently from the gender.
Aims
Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells ...and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We aimed to determine the effects of dapagliflozin alone and in combination with sacubitril/valsartan (LCZ696) or spironolactone on the function of myocardial fibroblasts of patients with heart failure and reduced ejection fraction (HFrEF).
Methods and results
Myocardial fibroblasts isolated from HFrEF patients (n = 5) were treated with dapagliflozin alone (1 nM–1 μM) or combined with LCZ696 (100 nM) or spironolactone (100 nM). The migratory rate was determined by wound‐healing scratch assay. Expression of heart failure (HF) markers and signalling pathways activation were analysed with multiplexed protein array. Commercially available cardiac fibroblasts from healthy donors were used as Control (n = 4). Fibroblasts from HFrEF show higher migratory rate compared with control (P = 0.0036), and increased expression of HF markers fold‐change (Log2): COL1A1–1.3; IL‐1b–1.9; IL‐6–1.7; FN1–2.9 (P < 0.05). Dapagliflozin slowed the migration rate of HFrEF fibroblasts in a dose‐dependent manner and markedly decreased the expression of IL‐1β, IL‐6, MMP3, MMP9, GAL3, and FN1. SGLT2i had no effect on control fibroblasts. These effects were associated with decreased phosphorylation of AKT/GSK3 and PYK2 kinases and the signal transducer and activator of transcription (STAT). A combination of dapagliflozin + LCZ696 further decreased fibroblast migration, although it did not have a significant effect on the regulation of signalling pathways and the expression of biomarkers induced by SGLT2 inhibition alone. In contrast, the combination of dapagliflozin + spironolactone did not change the migration rate of fibroblast but significantly altered SGLT2i responses on MMP9, GAL3, and IL‐1b expression, in association with increased phosphorylation of the kinases AKT/GSK3 and ERK1/2.
Conclusions
SGLT2i, LCZ696, and spironolactone modulate the function of isolated myocardial fibroblasts from HFrEF patients through the activation of different signalling pathways. The combination of SGLT2i + LCZ696 shows an additive effect on migration, while spironolactone modifies the signalling pathways activated by SGLT2i and its beneficial effects of biomarkers of heart failure.
•The sample solvent for HILIC analysis can cause distorted and double peaks.•Different extraction solvents, sample treatments, and injection types are evaluated to overcome the drawback.•Two HILIC-MS ...methods were evaluated.•The methods were applied to plasma samples of pigs with pulmonary hypertension.
HILIC is a separation technique increasingly used for the study of polar metabolites. However, HILIC suffers of a drawback related to the solvents used for these analyses: acetonitrile as sample solvent leads to the best chromatographic peaks, but it is not capable to extract/dissolve the most polar compounds. In this work we evaluated the use of several strategies for the extraction of polar compounds from plasma samples and, although methanol was the ideal solvent for analyte extraction, distorted peaks were obtained in the chromatography. Different strategies were tested included changing the solvent after extraction or modifying the injection volume and type. Finally, the best solution was using the lowest injection volume possible and to employ a simple sandwich injection including acetonitrile during the injection of the sample. This remarkably improves the peak shape when methanol is used in the sample. We evaluated and applied two HILIC-MS methods, in positive and negative ionization modes, on plasma samples from pigs with pulmonary hypertension produced by aorto-pulmonary shunting to identify metabolic signatures underlying damage to the right heart. Our analyses revealed altered relevant metabolic pathways, suggestive of oxidative stress and reduced energy demands.
Abstract Early detection of right ventricular (RV) involvement in chronic pulmonary hypertension (PH) is essential due to prognostic implications. T1 mapping by cardiac magnetic resonance (CMR) has ...emerged as a noninvasive technique for extracellular volume fraction (ECV) quantification. We assessed the association of myocardial native T1 time and equilibrium contrast ECV (Eq-ECV) at the RV insertion points with pulmonary hemodynamics and RV performance in an experimental model of chronic PH. Right heart catheterization followed by immediate CMR was performed on 38 pigs with chronic PH (generated by surgical pulmonary vein banding) and 6 sham-operated controls. Native T1 and Eq-ECV values at the RV insertion points were both significantly higher in banded animals than in controls and showed significant correlation with pulmonary hemodynamics, RV arterial coupling, and RV performance. Eq-ECV values also increased before overt RV systolic dysfunction, offering potential for the early detection of myocardial involvement in chronic PH.
Iron homeostasis is an important process for flower development and plant fertility. The role of plastids in these processes has been shown to be essential. To document the relationships between ...plastid iron homeostasis and flower biology further, a global study (transcriptome, proteome, metabolome, and hormone analysis) was performed of Arabidopsis flowers from wild-type and triple atfer1-3-4 ferritin mutant plants grown under iron-sufficient or excess conditions. Some major modifications in specific functional categories were consistently observed at these three omic levels, although no significant overlaps of specific transcripts and proteins were detected. These modifications concerned redox reactions and oxidative stress, as well as amino acid and protein catabolism, this latter point being exemplified by an almost 10-fold increase in urea concentration of atfer1-3-4 flowers from plants grown under iron excess conditions. The mutant background caused alterations in Fe–haem redox proteins located in membranes and in hormone-responsive proteins. Specific effects of excess Fe in the mutant included further changes in these categories, supporting the idea that the mutant is facing a more intense Fe/redox stress than the wild type. The mutation and/or excess Fe had a strong impact at the membrane level, as denoted by the changes in the transporter and lipid metabolism categories. In spite of the large number of genes and proteins responsive to hormones found to be regulated in this study, changes in the hormonal balance were restricted to cytokinins, especially in the mutant plants grown under Fe excess conditions.
The global aquaculture has shown an impressive growth in the last decades contributing with a major part of total food fish supply. However, it also helps in the spread of diseases that in turn, ...causes great economic losses. The White Spot Syndrome Virus (WSSV) is one of the major viral pathogen for the shrimp aquaculture industry. Several attempts to eliminate the virus in the shrimp have been addressed without achieving a long-term effectiveness. In this work, we determine the capacity of the commercial non-toxic PVP-coated silver nanoparticles to promote the response of the immune system of WSSV-infected shrimps with or without an excess of iron ions. Our results showed that a single dose of metallic silver in the nanomolar range (111 nmol/shrimp), which is equivalent to 12 ng/mL of silver nanoparticles, produces 20% survival of treated infected shrimps. The same concentration administered in healthy shrimps do not show histological evidence of damage. The observed survival rate could be associated with the increase of almost 2-fold of LGBP expression levels compared with non-treated infected shrimps. LGBP is a key gene of shrimp immunological response and its up-regulation is most probably induced by the recognition of silver nanoparticles coating by specific pathogen-associated molecular pattern recognition proteins (PAMPs) of shrimp. Increased LGBP expression levels was observed even with a 10-fold lower dose of silver nanoparticles (1.2 ng/shrimp, 0.011 nmol of metallic silver/shrimp). The increase in LGBP expression levels was also observed even in the presence of iron ion excess, a condition that favors virus proliferation. Those results showed that a single dose of a slight amount of silver nanoparticles were capable to enhance the response of shrimp immune system without toxic effects in healthy shrimps. This response could be enhanced by administration of other doses and might represent an important alternative for the treatment of a disease that has still no cure, white spot syndrome virus.
The simplicity and low cost of rapid point-of-care tests greatly facilitate large-scale population testing, which can contribute to controlling the spread of the COVID-19 virus. We evaluated the ...applicability of a self-testing strategy for SARS-CoV2 in a population-based, cross-sectional study in Cantabria, Spain, between April and May 2020. For the self-testing strategy, participants received the necessary material for the self-collection of blood and performance of a rapid antibody test using lateral flow immunoassay at home without the supervision of healthcare personnel. A total of 1,022 participants were enrolled. Most participants correctly performed the COVID-19 self-test the first time (91.3% 95% CI 89.4-92.9). Only a minority of the participants (0.7%) needed the help of healthcare personnel, while 6.9% required a second kit delivery, for a total valid test result in 96.9% of the participants. Incorrect use of the self-test was not associated with the educational level, age over 65, or housing area. Prevalence of IgG antibodies against SARS-CoV2 for subjects with a valid rapid test result was 3.1% (95% CI 2.2-4.4), similar to the seroprevalence result obtained using a conventional approach carried out by healthcare professionals. In conclusion, COVID-19 self-testing should be considered as a screening tool.
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