Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae.

Glycosphingolipids (GSLs) are products of lipid glycosylation that have been implicated in the development of cardiovascular diseases. In diabetes, the adipocyte microenvironment is characterized by hyperglycemia and inflammation, resulting in high levels of GSLs. Therefore, we sought to assess the GSL content in extracellular vesicles derived from the adipose tissues (adiposomes) of obese-diabetic (OB-T2D) subjects and their impact on endothelial cell function. To this end, endothelial cells were exposed to adiposomes isolated from OB-T2D versus healthy subjects. Cells were assessed for caveolar integrity and related signaling, such as Src-kinase and caveolin-1 (cav-1) phosphorylation, and functional pathways, such as endothelial nitric oxide synthase (eNOS) activity. Compared with adiposomes from healthy subjects, OB-T2D adiposomes had higher levels of GSLs, especially LacCer and GM3; they promoted cav-1 phosphorylation coupled to an obvious loss of endothelial surface caveolae and induced eNOS-uncoupling, peroxynitrite generation, and cav-1 nitrosylation. These effects were abolished by Src kinase inhibition and were not observed in GSL-depleted adiposomes. At the functional levels, OB-T2D adiposomes reduced nitric oxide production, shear response, and albumin intake in endothelial cells and impaired flow-induced dilation in healthy arterioles. In conclusion, OB-T2D adiposomes carried a detrimental GSL cargo that disturbed endothelial caveolae and the associated signaling.

One-Shot Dilatation vs Metal Dilator During Percutaneous Nephrolithotomy in Flank-Free Supine Position: A Randomized Controlled Study.

Background: The creation and dilatation of the nephrostomy tract is a fundamental step in percutaneous nephrolithotomy (PCNL). In one-shot dilatation (OSD), we used a single Amplatz dilator over a central Alken rod. PCNL in the supine position is as effective and safe as in the prone position. The Barts flank-free modified supine position sums several advantages of the different supine positions. We evaluated the efficacy and safety of OSD compared with metal telescopic dilator (MTD) during PCNL while the patient was in Barts flank-free modified supine position. Materials and Methods: Within 2.5 years, 150 patients with kidney stone candidates for PCNL were randomized into two equal groups according to the dilatation technique. In the OSD group, dilatation was performed using a single Amplatz dilator (30F) and in the MTD group dilatation was performed by sequential MTD (9-30F). All PCNL procedures were done with patients in Barts flank-free modified supine position. Patient characteristics, operative data, and results were collected for statistical analysis. Results: There are no statistically significant differences between both groups regarding patients' characters. The tracts were effectively dilated in all patients. Statistical analyses show a significant difference (p ˂ 0.05) between both groups regarding the time of dilatation (seconds; 68 ± 15 vs 147 ± 18), time of X-ray exposure (seconds; during dilatation; 36 ± 10 vs 61 ± 15 and the total; 157 ± 16 vs 181 ± 20), hemoglobin loss (mg/dL; 0.7 ± 0.2 vs 1.2 ± 0.3), and hospital stay (days; 3 ± 0.6 vs 3.7 ± 0.7) with favorable results to OSD. Complication rates were comparable between the two groups. Conclusions: OSD is efficient as MTD during PCNL while patients are in Barts flank-free modified supine position, with less dilatation time, X-ray exposure, blood loss, and hospital stay than MTD.