Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats

We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats

Anomalous Dielectric Behavior of a Pb/Sn Perovskite: Effect of Trapped Charges on Complex Photoconductivity

Organic–inorganic metal halide perovskites (MHPs) exhibit prominent electronic and optical properties benefiting the performance of solar cells and light-emitting diodes. However, the dielectric properties of these materials have remained poorly understood, despite probably influencing delayed charge recombination and device capacitance. Herein, we characterize the unprecedented dielectric behavior of MHPs comprising methylammonium cations, Pb/Sn as metals, and Br/I as halides using time-resolved microwave conductivity (TRMC) measurements. At specific compositions, the above MHPs exhibit negative real and positive imaginary photoconductivities, the polarities of which are opposite those observed for conventional photogenerated charge carriers. Comparing the observed TRMC kinetics with that of inorganic perovskites (SrTiO₃ and BaTiO₃) and characterizing its dependence on temperature, frequency, and near-infrared second push pulse, we conclude that the above behavior is due to the trapping of polaronic holes/electrons by oriented dipoles of organic cations, which opens a hitherto unexplored route to the dynamical control of dielectric permittivity by photoirradiation

First-in-human trial of Stabilizer device in neuroendovascular therapy.

ObjectivesFlow diverter or stent implantation to intracranial target lesion requires large inner diameter microcatheter navigation. The exchange method using stiff long wire is often necessary if it is difficult to navigate over the regular guidewire. However, this method has an intrinsic risk of vessel damage and may cause severe complications. We investigated the safety and efficacy of a new device, the Stabilizer device for navigation in a first-in-human clinical trial under the Certified Review Board agreement.Materials and methodsThe Stabilizer is a 320 cm length exchange wire with a stent for anchoring and is compatible with a 0.0165" microcatheter. The trial design is a prospective single-arm open-label registry. Inclusion criteria are elective flow diverter treatment or stent-assisted coiling, expected to be difficult to navigate a microcatheter with a regular micro guidewire, and obtained documented consent. The primary endpoint of the study was a hemorrhagic complication.ResultsFive patients were enrolled in this trial. The median age is 52 years, ranges from 41 to 70, and all patients were female. Three aneurysms were located on the internal carotid artery, one on the vertebral artery, and one on the basilar artery. Basilar artery aneurysm was treated by stent-assisted coiling and others were treated by flow diverter deployment. All cases successfully navigate microcatheter for the treatment by the trial method using Stabilizer device without any adverse event.ConclusionsThe results from this first-in-human consecutive five cases show the safety of the Stabilizer device in neuro-endovascular therapy for navigation of devices to the intracranial target lesion