Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries

<p><b>Objective:</b> We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.</p> <p><b>Methods and Results:</b> One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 micromol/L) reduced tumor necrosis factor-alpha (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.</p> <p><b>Conclusion:</b> Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.</p&gt

The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.<br></br> Methods and Results—In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-kB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 micromol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E-/-, mice in which the NBD peptide (150 microg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).<br></br> Conclusion—The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kB activation

LIBS experiments for quantitative detection of retained fuel

Abstract Laser Induced Breakdown Spectroscopy (LIBS) provides chemical information from atomic and ionic plasma emissions generated by laser vaporization of a sample. At the ENEA research center, in collaboration with IPPLM, an equipment has been set up to qualitatively and quantitatively determine the chemical composition of impurities deposited on Plasma Facing Components (PFC). The strength of the LIBS, for its capability of light elements detection, is fully exploited to determine the deuterium content since this element can be considered as the best choice proxy for tritium; the latter being is of great importance in assessing safe conditions to assure the continuous operation in nuclear fusion tokamak. Here we present the results of the Double Pulse LIBS (DP-LIBS) probing of deuterated samples with the simultaneous optical detection by medium-resolution and high-resolution spectrometer. Deuterium emission at 656.1 nm has been detected then the elemental composition has been quantified by applying the Calibration Free (CF) approach. The obtained results demonstrate that the DP-LIBS technique combined with CF analysis is suitable for the quantitative determination of tritium content inside the PFCs of next fusion devices like ITER

Detection by LIBS of the deuterium retained in the FTU toroidal limiter

In this paper the Laser Induced Breakdown Spectroscopy (LIBS) measurement of the deuterium (used as a proxy for tritium) retained in and the surface elemental composition of the FTU Mo (TZM) toroidal limiter tiles, carried out from remote (∼2.5 m) during short breaks of the operations or during machine maintenance, are reported. Single pulse technique has been used with the FTU vessel under high vacuum or in Nitrogen or Argon atmosphere. In vacuum experiments Dα and Hα lines have been detected with good resolution, while in Ar atmosphere (5 × 104 Pa) the two lines were partially overlapped due to Stark broadening. First results of measurements in N2 atmosphere (105 Pa) showed no presence of Dα and Hα lines. These measurements were also carried out for supporting the foreseen use of a robotic arm for an extended LIBS analysis of retained deuterium in the FTU vessel components. Keywords: LIBS, FTU tokamak, Toroidal limiter, Deuterium retentio

High-density mapping to guide ablation of a right bundle branch morphology premature ventricular contraction from the right outflow tract

The Rhythmia ultrahigh-density mapping system with a specific algorithm seems to be helpful in identifying the target area to successfully treat multiple morphologies by catheter ablation in the right ventricular outflow tract RVOT. Interestingly, the acquisition process seemed to be extremely faster than a standard manual point-by-point premature ventricular contraction (PVC) mapping

Deuterium retention and erosion in liquid Sn samples exposed to D2 and Ar plasmas in GyM device

The use of tin (Sn) as a liquid metal for plasma facing components has been recently proposed as a solution to the high heat load issue on the divertor target plates in nuclear fusion reactors. Due to its low vapor pressure, low reactivity with hydrogen and good resilience to neutron impact, tin is a good candidate as plasma facing component. However its high atomic number poses concerns about plasma contamination.In this paper two fundamental aspects have been investigated: deuterium retention and erosion fluxes from the Sn surface towards the plasma. The samples were exposed to plasma inside the linear machine GyM in magnetic cusp configuration. This setup permits to expose free liquid specimens without the need for the Capillary Porous System. Moreover it permits to lower the magnetic field in order to increase Sn Larmor radius and consequently limit Sn re-deposition in erosion experiments.Ex-situ analyses by ion beam diagnostics on solid samples exposed to deuterium plasma have proved that the amount of retained atomic deuterium is very low, approximately 0.18 at% estimated by Nuclear Reaction Analysis and 0.25 at% estimated by Elastic Recoil Detection Analysis.In the framework of erosion studies, the spectroscopic parameter S/XB was evaluated in Ar plasma for the SnI line at 380.1 nm by Optical Emission Spectroscopy and mass loss measurements in the 5–11 eV Te range, at a density ne ∼ 1.5 × 1011 cm−3. An average value of 150 ± 23 was obtained. Keywords: Liquid metals, Deuterium retention, Erosion, Double-cusp magnetic configuration, Ion beam diagnostics, S/XB spectroscopic paramete

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors

Cross machine investigation of magnetic tokamak dust : Morphological and elemental analysis

The presence of magnetic dust can be an important issue for future fusion reactors where plasma breakdown is critical. Magnetic dust has been collected from contemporary fusion devices (FTU, Alcator C-Mod, COMPASS and DIII-D) that feature different plasma facing components. The results of morphological and elemental analysis are presented. Magnetic dust is based on steel or nickel alloys and its magnetism is generated by intense plasma-material interactions. In spite of the strong similarities in terms of morphology and composition, X-ray diffraction analysis revealed differences in the structural evolution that leads to non-trivial magnetic responses