Lipotoxic stress alters the membrane lipid profile of extracellular vesicles released by Huh-7 hepatocarcinoma cells.

Extracellular vesicles (EVs) are well-known mediators in intercellular communication playing pivotal roles in promoting liver inflammation and fibrosis, events associated to hepatic lipotoxicity caused by saturated free fatty acid overloading. However, despite the importance of lipids in EV membrane architecture which, in turn, affects EV biophysical and biological properties, little is known about the lipid asset of EVs released under these conditions. Here, we analyzed phospholipid profile alterations of EVs released by hepatocarcinoma Huh-7 cells under increased membrane lipid saturation induced by supplementation with saturated fatty acid palmitate or Δ9 desaturase inhibition, using oleate, a nontoxic monounsaturated fatty acid, as control. As an increase of membrane lipid saturation induces endoplasmic reticulum (ER) stress, we also analyzed phospholipid rearrangements in EVs released by Huh-7 cells treated with thapsigargin, a conventional ER stress inducer. Results demonstrate that lipotoxic and/or ER stress conditions induced rearrangements not only into cell membrane phospholipids but also into the released EVs. Thus, cell membrane saturation level and/or ER stress are crucial to determine which lipids are discarded via EVs and EV lipid cargos might be useful to discriminate hepatic lipid overloading and ER stress.

[Surgical management for atrial septal defect secundum in aged patients].

Between 1989 and 1992, atrial septal defect secundum (ASD) were closed in 8 patients aged 51 to 77 years with the use of cardiopulmonary bypass. The notable characteristics in our cases were; 1) All but one had slight or moderate left to right shunt ratios. Although pulmonary hypertension was present, the obstructive pulmonary vascular change had not progressed so far. 2) Atrial fibrillation was present in 6 patients (75%) and some other cardiac lesions (atrioventricular insufficiency, ischemic heart disease, intracardiac anomaly) coexisted with ASD in a high frequency. And surgical procedures other than ASD closure were required in 5 patients. 3) We must take care to prevent cardiac complications (i.e., arrhythmia) as well as extracardiac malfunctions in postoperative care, because aged patients had some organic dysfunctions of respiratory, renal and hepatic systems. 4) Post-operative courses were satisfactory and there was no operative mortality. All patients obtained improvements in their quality of life. Consequently, we concluded that surgical closure is recommended even for aged patients with ASD, except for Eisenmenger's syndrome.