Salt-Sensitive Hypertension in GR+/− Rats Is Accompanied with Dysregulation in Adrenal Soluble Epoxide Hydrolase and Polyunsaturated Fatty Acid Pathways

Mutations within the glucocorticoid receptor (GR) gene locus lead to glucocorticoid resistance which is characterized by several clinical symptoms such as adrenal gland hyperplasia and salt-sensitive hypertension, although the underlying mechanisms are still unknown. We studied GR haploinsufficient (GR^+/−) Sprague Dawley rats which, on a standard diet, showed significantly increased plasma aldosterone and corticosterone levels and an adrenocortex hyperplasia accompanied by a normal systolic blood pressure. Following a high salt diet, these rats developed salt-sensitive hypertension and maintained elevated enzyme-soluble epoxide hydrolase (sEH) in adrenal glands, while sEH was significantly decreased in wild-type rats. Furthermore, GR^+/− rats showed dysregulation of the equilibrated linoleic and arachidonic acid pathways, with a significant increase of less active metabolites such as 8,9-DiHETrE. In Sprague Dawley rats, GR haploinsufficiency induced steroid disturbances, which provoked hypertension only in combination with high salt intake, which was accompanied by disturbances in sEH and fatty acid metabolism. Our results suggest that sEH inhibition could be a potential target to treat hypertension in patients with GR haploinsufficiency.     

A structural investigation relating to the pozzolanic activity of rice husk ashes

Various factors determine the applicability of rice husk ash (RHA) as a pozzolanic material. The amount and accessibility of reactive sites is thought to be a key factor. A structural study of RHA samples in relation to their reactivity has been performed; Silica in RHA formed by burning rice husk in a laboratory furnace under continuous supply of air have been characterized as a function of incineration temperature, time and cooling regime. The characterization methods included chemical analyses, conductivity measurements, microscopic analysis, X-ray diffraction (XRD) and ²⁹Si magic-angle spinning (MAS) nuclear magnetic resonance (NMR). In line with earlier observations, the analyses show that the highest amounts of amorphous silica occur in samples burnt in the range of 500 °C–700 °C. The ²⁹Si NMR data allow direct identification of the reactive silanol sites in the RHA samples. De-convolution of the NMR spectra clearly shows that the quickly cooled RHA resulting from burning rice husk for 12 h at 500 °C has the highest amount of silanol groups. This sample also induced the largest drop in conductivity when added to a saturated calcium hydroxide solution giving an indication of its reactivity towards lime. Therefore, this RHA is the favorable sample to be used as pozzolanic cement additive.     

Effect of the molecular architecture of graft copolymers on the phase morphology and tensile properties of PS/EVA blends

Graft copolymers of poly(ethylene‐co‐vinyl acetate) (EVA) grafted with polystyrene (PS) with different molecular weight and different EVA/PS ratio were prepared by coupling reaction between acyl chloride functionalized PS (PS‐COCl) and hydrolyzed EVA. PS‐COCl with controlled molecular weight was prepared by anionic polymerization of styrene, followed by end capping with phosgene. The effect of the molecular architecture of the graft copolymer on the compatibilization of PS/EVA blends was investigated. Substantial improvement in the elongation at break and ductility was observed using the graft copolymer with PS segments with molecular weight as high as 66,000 g/mol and with a PS proportion equal or higher than EVA. The effect of the compatibilization on the morphology was also investigated by scanning electron microscopy and atomic force microscopy. The blend that presented the highest value of elongation at break also displayed dispersed phase constituted by inclusions of the PS phase inside the EVA particle forming a cocontinuous structure, as observed by AFM. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Quantum Model of Hysteresis in a Single-Domain Magnetically Soft Ferromagnet

A quantum model of a magnetically soft ferromagnet constructed based on a single domain of an α-Fe crystal magnetized to saturation and placed in an alternating magnetic field is suggested. Based on the method of an effective Hamiltonian, the model takes into account the Zeeman energy, the spin-orbital interaction, and the interaction with the crystal field. In order to take into account the magnetic anisotropy, an expansion of a trial single-electron wave function into a series in terms of a small parameter of the spin-orbital interaction is suggested. The nonlinear equations of motion for the magnetization and orbital moment of the domain have been determined within the Heisenberg representation. The parameters of the nonlinear equations have been determined by comparing with the experimental data on the magnetic anisotropy of iron. The equations were solved numerically using the Runge–Kutta method with taking into account the magnetic friction introduced phenomenologically. The dependence of the magnetization of a single domain on the strength of the applied magnetic field has been characterized by hysteresis. The main parameters of the hysteresis loop are in quantitative agreement with the experimentally measured magnetic properties of nanoparticles of iron and iron oxide. A method of simulating the magnetization dynamics of a multidomain ferromagnet in the approximation of a strong crystal field has been suggested.     

Corrosion behaviour of sol–gel treated and painted AA2024 aluminium alloy

Design, development and scale-up of environmentally friendly coatings are very important in order to replace chromate based coatings for aluminium alloys. Barrier properties, paint adhesion and possibly self-healing ability are relevant aspects for replacement of chromate-based pre-treatments. Sol–gel materials are candidates for use in protective coating applications, as it is possible to form highly adherent and chemically inert oxide films on metal substrates.     

Advanced Postirradiation Characterization of Nuclear Fuels Using Pulsed Neutrons

Methods for postirradiation characterization of bulk (cm³) irradiated materials or even spent nuclear fuels are sparse due to their extremely radioactive nature. While several methods exist to characterize smaller volumes (<?1 mm³) of such samples, selecting these volumes from larger samples is challenging. X-ray-based methods are prohibitive due to the strong γ-radiation from the sample flooding the detectors. Neutron-based methods available in the proximity of irradiation reactors allow for thermal neutron radiography or computed tomography using a small reactor source, but one cannot assess isotope distributions or microstructural features such as phases, texture, or strain from diffraction measurements due to flux limitations. We present herein a pathway to provide pulsed neutron characterization of bulk irradiated samples using time-of-flight neutron diffraction for microstructural characterization and energy-resolved neutron imaging for assessment of isotopic densities and distributions. Ultimately, laser-driven pulsed neutron sources may allow deployment of these techniques pool-side at irradiation reactors.

     

Highly-efficient fabrication of nanoscrolls from functionalized graphene oxide by Langmuir–Blodgett method

We report a Langmuir–Blodgett (LB) approach for highly-efficient fabrication of nanoscrolls from functionalized graphene oxide single sheets. Transmission electron microscope study reveals that the scroll has a tubular structure without caps at its ends. The scrolls align parallel to the moving barriers of the LB equipment and exhibit a loose-dense pattern during the LB compression process. We find that specific solvents can unwind the scrolled structures. Electrical characterization of the well-aligned scrolls was also performed. The method demonstrated here opens up a new avenue for high-yield fabrication of carbon nanoscrolls using functionalized graphene oxide as the building blocks.     

Comparison of Repeated Doses of C-kit-Positive Cardiac Cells versus a Single Equivalent Combined Dose in a Murine Model of Chronic Ischemic Cardiomyopathy

Using a murine model of chronic ischemic cardiomyopathy caused by an old myocardial infarction (MI), we have previously found that three doses of 1 × 10⁶ c-kit positive cardiac cells (CPCs) are more effective than a single dose of 1 × 10⁶ cells. The goal of this study was to determine whether the beneficial effects of three doses of CPCs (1 × 10⁶ cells each) can be fully replicated by a single combined dose of 3 × 10⁶ CPCs. Mice underwent a 60-min coronary occlusion; after 90 days of reperfusion, they received three echo-guided intraventricular infusions at 5-week intervals: (1) vehicle × 3; (2) one combined dose of CPCs (3 × 10⁶) and vehicle × 2; or (3) three doses of CPCs (1 × 10⁶ each). In the combined-dose group, left ventricular ejection fraction (LVEF) improved after the 1st CPC infusion, but not after the 2nd and 3rd (vehicle) infusions. In contrast, in the multiple-dose group, LVEF increased after each CPC infusion; at the final echo, LVEF averaged 35.2 ± 0.6% (p < 0.001 vs. the vehicle group, 27.3 ± 0.2%). At the end of the study, the total cumulative change in EF from pretreatment values was numerically greater in the multiple-dose group (6.6 ± 0.6%) than in the combined-dose group (4.8 ± 0.8%), although the difference was not statistically significant (p = 0.08). Hemodynamic studies showed that several parameters of LV function in the multiple-dose group were numerically greater than in the combined-dose group (p = 0.08 for the difference in LVEF). Compared with vehicle, cardiomyocyte cross-sectional area was reduced only in the multiple-dose group (−32.7%, 182.6 ± 15.1 µm² vs. 271.5 ± 27.2 µm², p < 0.05, in the risk region and −28.5%, 148.5 ± 12.1 µm² vs. 207.6 ± 20.5 µm², p < 0.05, in the noninfarcted region). LV weight/body weight ratio and LV weight/tibia length ratios were significantly reduced in both cell treated groups vs. the vehicle group, indicating the attenuation of LV hypertrophy; however, the lung weight/body weight ratio was significantly reduced only in the multiple-dose group, suggesting decreased pulmonary congestion. Taken together, these results indicate that in mice with chronic ischemic cardiomyopathy, the beneficial effects of three doses of CPCs on LV function and hypertrophy cannot be fully replicated with a single dose, notwithstanding the fact that the total number of cells delivered with one or three doses is the same. Thus, it is the multiplicity of doses, and not the total number of cells, that accounts for the superiority of the repeated-dose paradigm. This study supports the idea that the efficacy of cell therapy in heart failure can be augmented by repeated administrations.     

The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe⁻/H₂Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O₂ consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H₂O₂), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.     

Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.