Re‐endothelialization of rat lung scaffolds through passive,gravity‐driven seeding of segment‐specific pulmonary endothelial cells

Effective re‐endothelialization is critical for the use of decellularized scaffolds for ex vivo lung engineering. Current approaches yield insufficiently re‐endothelialized scaffolds that haemorrhage and become thrombogenic upon implantation. Herein, gravity‐driven seeding coupled with bioreactor culture facilitated widespread distribution and engraftment of endothelial cells throughout rat lung scaffolds. Initially, human umbilical vein endothelial cells were seeded into the pulmonary artery by either gravity‐driven, variable flow perfusion seeding or pump‐driven, pulsatile flow perfusion seeding. Gravity seeding evenly distributed cells and supported cell survival and re‐lining of the vascular walls while perfusion pump‐driven seeding led to increased cell fragmentation and death. Using gravity seeding, rat pulmonary artery endothelial cells and rat pulmonary vein endothelial cells attached in intermediate and large vessels, while rat pulmonary microvascular endothelial cells deposited mostly in microvessels. Combination seeding of these cells led to positive vascular endothelial cadherin staining. In addition, combination seeding improved barrier function as assessed by serum albumin extravasation; however, leakage was observed in the distal portions of the re‐endothelialized tissue suggesting that recellularization of the alveoli is necessary to complete barrier function of the capillary–alveolar network. Overall, these data indicate that vascular recellularization of rat lung scaffolds is achieved through gravity seeding. Copyright © 2016 John Wiley & Sons, Ltd.     

Estimating bone mineral content based on different types of muscle strength tests

The aims of this pilot study were to verify which muscle strength tests better explain bone mineral content (BMC) of the femoral neck and lumbar spine and to develop predictive equations to estimate femoral neck and lumbar spine BMC. Twenty-nine subjects aged 56–76 years old (12 women and 17 men) participated in the study. Femoral neck and lumbar spine BMC was evaluated by Dual X-ray absorptiometry (DXA). Muscle strength measurements included maximal isometric voluntary contractions of knee extensors and flexors, vertical jump, 5-repetition maximum of the leg press (5-RM_LP) and seated leg curl (5-RM_LC), and handgrip strength. Women presented a moderate to strong correlation between femoral neck BMC and 5-RM_LP (r = 0.819), 5-RM_LC (r = 0.879), knee extensors peak torque (r = 0.699), and handgrip strength (r = 0.663), as well as between lumbar spine BMC and the 5-RM_LP test (r = 0.845) and manual grip strength (r = 0.699). For females, the 5-RM_LP and 5-RM_LC tests most fully explained femoral neck BMC (R² = 0.859) and the 5-RM_LP test and body mass explained lumbar spine density (R² = 0.757) for females. Men did not present correlations between BMC and strength variables. For females, the 5-RM_LP and 5-RM_LC variables explained the variations of femoral neck BMC, while 5-RM_LP and body mass explained lumbar spine BMC. Future studies should evaluate a larger sample size and prioritize the strength tests with a greater predictive capacity.     

Subcutaneous implantable cardioverter defibrillator in children and adolescents: results from the S-ICD “Monaldi care” registry

Journal of Interventional Cardiac Electrophysiology - Implantable cardioverter defibrillators (ICD) are widely accepted therapy in children and adolescents who are survivors of cardiac arrest or...     

Management of atrial fibrillation: two decades of progress — a scientific statement from the European Cardiac Arrhythmia Society

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The aim of this review was to evaluate the...     

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner alpha3beta1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming alpha3beta1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin alpha3beta1. These data provide evidence for a novel regulatory role of tetraspanin microdomains on the collagenolytic activity of MT1-MMP and indicate that CD151 is a key regulator of MT1-MMP in endothelial homeostasis.     

Folding of a donor-acceptor polyrotaxane by using noncovalent bonding interactions

Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain pi electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT(4+)), a pi electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined "folded" secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT(4+). This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures.