Low-Density Lipoprotein Has an Enormous Capacity To Bind (E)-4-Hydroxynon-2-enal (HNE): Detection and Characterization of Lysyl and Histidyl Adducts Containing Multiple Molecules of HNE

(E)-4-Hydroxynon-2-enal (HNE), an electrophilic bifunctional cytotoxic lipid peroxidation product, forms covalent adducts with nucleophilic side chains of amino acid residues. HNE-derived adducts have been implicated in many pathophysiological processes including atherosclerosis, diabetes, and Alzheimer’s disease. Tritium- and deuterium-labeled HNE (d4-HNE) were used orthogonally to study adduction with proteins and individual nucleophilic groups of histidyl, lysyl, and cysteine residues. Using tritium-labeled HNE, we detected the binding of 486 molecules of HNE per low-density lipoprotein (LDL) particle, significantly more than the total number of all reactive nucleophiles in the LDL particle. This suggests the formation of adducts that incorporate multiple molecules of HNE with some nucleophilic amino acid side chains. We also found that the reaction of a 1:1 mixture of d4-HNE and d0-HNE with N-acetylhistidine, N-acetyl-Gly-Lys-OMe, or N-acetyl cysteine generates 1:1, 2:1, and 3:1 adducts, which exhibit unique mass spectral signatures that aid in structural characterization. A domino-like reaction of initial 1:1 HNE Michael adducts of histidyl or lysyl nucleophiles with multiple additional HNE molecules forms 2:1 and 3:1 adducts that were structurally characterized by tandem mass spectrometry

Simulating the pollutant dispersion during persistent Wintertime thermal Inversions over urban areas. The case of Madrid

A correct simulation of the dispersion during wintertime thermal inversions is important not only to improve the physical understanding of the phenomena but also to design and evaluate strategies to improve air quality. In this study WRF with the multilayer urban canopy scheme BEP-BEM is used to simulate the dispersion during one of those episodes over Madrid, Spain, using a passive tracer representing NOx. The results are compared against NOx measurements obtained at 24 ground stations, grouped in 5 zones. The results show a strong spatial variability of dispersive conditions, with a tendency of the pollutants to accumulate in the topographical depressions. Furthermore, a simple methodology is proposed to derive NO2 from NOx concentrations based on an empirical fitting of two months of observations. The statistical indicators for NO2 computed in this way are similar to those obtained with photochemical models, making this approach a valid, and computationally efficient, alternative, in particular for forecasting purposes. In the last part of this contribution, the model is used to derive information that can be useful for air pollution abatement strategies. In particular, it has been found that: 1) there is no pollutant accumulation from one day to the following one, so the air quality of one day is entirely determined by the emissions and meteorological conditions of that day, 2) displacing part of the emissions of the rush hours to the central hours of the day, when the dispersive conditions are more favorable, can significantly reduce the peaks, and to a lesser extent the daily mean, without changing the total amount of pollutants emitted. So, reducing the total amount of pollutants emitted is not the only way to improve air quality. Benefits can be achieved also by redistributing the emissions in a more optimal way during the whole diurnal cycle

A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study

BACKGROUND AND STUDY AIMS: A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the efficacy and safety of this stent in a large cohort. PATIENTS AND METHODS: Patients with a PFC undergoing EUS-guided drainage with this novel stent were prospectively enrolled in this multicenter cohort study. RESULTS: There were 61 patients: 46 patients (75 %) with walled-off necrosis (WON) and 15 (25 %) with a pancreatic pseudocyst. Stent placement was technically successful in 60 patients (98 %, 95 %CI 95 % - 100 %). Clinical success, defined as resolution of clinical symptoms in combination with a decrease in the PFC size to </= 2 cm on imaging, was achieved in 93 % of patients with a pancreatic pseudocyst (95 %CI 77 % - 100 %) and in 81 % of patients with WON (95 %CI 69 % - 94 %). Treatment failure occurred in nine patients (16 %, 95 %CI 6 % - 26 %), including four patients who required surgical intervention. Stent removal was performed in 82 % of patients after a median of 32 days (range 2 - 178) and was rated as easy in all but one patient. In 10 patients, endoscopic stent removal was not performed because of stent migration (n = 3), stent dislodgement during necrosectomy (n = 3), stent removal during surgery (n = 2), or refusal by the patient (n = 2). In total, five major complications were reported (9 %, 95 %CI 2 % - 16 %), including PFC infection (n = 4) and perforation (n = 1). CONCLUSION: EUS-guided drainage using this novel stent is feasible and the clinical results obtained are promising with a low major complication rate