Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats.

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

Correction to: Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

Following publication of the original article [1], we have been notified of the below corrections to the 5th paragraph in the Discussion section.

Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

BACKGROUND: A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature. METHODS: This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum. RESULTS: UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO. CONCLUSION: UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.

Diagnostic performance of the measurement of nitric oxide in exhaled air in the diagnosis of COPD phenotypes.

INTRODUCTION: COPD is a highly heterogeneous disease that has a serious impact on affected populations. Patients share some of the features of bronchial asthma, often summarized under the term ACOS (asthma-COPD overlap syndrome). The objective of this study is to evaluate the utility of the measurement of nitric oxide in exhaled air (FENO50) in the diagnosis of COPD phenotypes. MATERIAL AND METHODS: The study comprised cross-sectional observation of patients receiving assistance during a respiratory outpatient visit. Patient data was collected on lung function, FENO, questionnaires scoring CAT®(COPD Assessment Test), and COPD clinical phenotype. RESULTS: 192 patients were studied: 103 with COPD; 16 healthy non-smokers; 30 healthy smokers; and 43 asthmatics. COPD patients were grouped by phenotype: 34 non exacerbators (33.0%); 22 ACOS (21.3%); 13 frequent exacerbators with emphysema (12.6%); and 34 frequent exacerbators with chronic bronchitis (33.0%). ACOS patients showed significantly higher FENO50 values compared to the others after adjustments for confounding factors. FENO50 demonstrated greater diagnostic accuracy than the bronchodilator test (BT) in the diagnosis of ACOS and COPD phenotypes (AUC 0.79 vs 0.74), with an optimal cut-off value of 19 ppb (sensitivity 0.68, specificity 0.75). CONCLUSIONS: Patients with COPD have different levels of FENO50 depending on the COPD phenotype. FENO50 measurement provides better diagnostic accuracy than BT, with an optimal cut-off value of 19 ppb.

[Bronchiectasis following colectomy in a patient with ulcerative colitis and factor V Leiden mutation]. / Bronquiectasias tras colectomía en paciente con colitis ulcerosa y mutación del factor V Leiden.

For some years it has been known that lung disease may be present in patients with inflammatory bowel disease (IBD). Diseases of the central airway, bronchi, and lung parenchyma are among the most common forms of lung involvement in IBD patients. Bronchiectasis is frequent and almost always appears after the onset of disease and in close association with inflammatory activity. However, reports of the appearance of bronchiectasis following colectomy for an exacerbation of IBD have been rare. We present the case of a 36-year-old man with severe ulcerative colitis who, following a total colectomy, developed bilateral bronchiectasis 12 months after surgery and for whom both preoperative and postoperative computed tomography scans were available.

[Chronic thromboembolic pulmonary hypertension associated with endomyocardial fibrosis of the right ventricle]. / Hipertensión pulmonar tromboembólica crónica asociada a fribrosis endomiocárdica del ventrículo derecho.

Chronic thromboembolic pulmonary hypertension is a rare sequela to an acute untreated or recurrent pulmonary embolism. The mechanisms that underlie the failure to resolve the thrombus are still uncertain. As most patients are not diagnosed until a relatively late stage, little is known about the course of their illness. We report the case of a 51-year-old woman who had previously been diagnosed with and operated on for endomyocardial fibrosis of the right ventricle and who developed chronic thromboembolic pulmonary hypertension several years later.