Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan,Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.     

High‐pressure synthesis of a 12CaO·7Al2O3–12SrO·7Al2O3 solid solution

Solid solutions of 12CaO·7Al₂O₃ (C12A7) and 12SrO·7Al₂O₃ (S12A7) crystals were synthesized under high pressure. X‐ray diffraction patterns revealed that the lattice constants of the synthesized samples depend linearly on the compositional ratio of C12A7 and S12A7. Electron‐probe X‐ray microanalyses show that the chemical compositions of the crystals are represented by xC12A7·(1?x)S12A7 (0<x<1). These results indicate that the variation in the lattice constants is originated from a difference in the ionic radii of Ca²⁺ and Sr²⁺ ions. From impedance measurements, it was found that S12A7 has the highest conductivity (~1 × 10^?3 Scm^?1 at 550°C) among the solid solutions in the C12A7–S12A7 system.     

Inward Migration of Glass‐Modifier Cations During Heat Treatment Under an N2 Atmosphere

An Na⁺/Ca²⁺‐deficient layer is observed to form on the glass surface region up to a depth of hundreds of nanometers when a soda‐lime‐silicate glass is heat treated under an N₂ atmosphere near its glass‐transition temperature. The measurements were performed using X‐ray photoelectron spectroscopy with C₆₀‐ion sputtering (C₆₀‐XPS) and dynamic secondary‐ion mass spectrometry (D‐SIMS) with consideration of the mass and charge balances. The increase in the amount of hydrogen is substantially less than the decrease in the total charge due to the loss of modifier cations in the Na⁺/Ca²⁺‐deficient layer; furthermore, the oxygen concentration in this layer is lower than the bulk value, suggesting that the silanol groups in the surface layer of the glass are dehydrated. A high‐concentration layer of Ca²⁺ is also confirmed in the dehydration layer of the glass heat treated under an N₂ atmosphere, suggesting that Na⁺ and Ca²⁺ ions migrate inward into the glass via an ion‐exchange reaction with protons, which migrate toward the surface from the bulk. We also confirmed that a thicker Na⁺/Ca²⁺‐deficient layer is formed on glass surfaces with higher water content. Our results suggest that the dehydration of the silanol groups is the driving force of the inward migration of Na⁺ and Ca²⁺ ions.     

The low-temperature performance of NOx storage and reduction catalyst

The catalytic performance and the behavior of NO_x storage and reduction (NSR) over a model catalyst for lean-burn gasoline engines have been mainly investigated and be discussed based on the temperature and reducing agents use in this study. The experimental results have shown that the NO_x storage amount in the lean atmosphere was the same as the NO_x reduction amount from the subsequent rich spike (RS) above the temperature of 400 °C, while the former was greater than the latter below the temperature of 400 °C. This indicated that when the temperature was below 400 °C compared with the NO_x storage stage, the reduction of the stored NO_x is somehow restricted. We found that the reduction efficiencies with the reducing agents decrease in the order H₂ > CO > C₃H₆ below 400 °C, thus not all of the NO_x storage sites could be fully regenerated even using an excessive reducing agent of CO or C₃H₆, which was supplied to the NSR catalyst, while all the NO_x storage sites could be fully regenerated if an adequate amount of H₂ was supplied. We also verified that the H₂ generation more favorably occurred through the water gas shift reaction than through the steam reforming reaction. This difference in the H₂ generation could reasonably explain why CO was more efficient for the reduction of the stored NO_x than C₃H₆, and hinted as a promising approach to enhance the low-temperature performance of the current NSR catalysts though promoting the H₂ generation reaction.     

Formation of microcapsules of medicines by the rapid expansion of a supercritical solution with a nonsolvent

The rapid expansion from a supercritical solution with a nonsolvent (RESS‐N) was applied to the formation of polymeric microcapsules containing medicines such as p‐acetamidophenol, acetylsalicylic acid, 1,3‐dimethylxanthine, flavone, and 3‐hydroxyflavone. A suspension of medicine in carbon dioxide (CO₂) containing a cosolvent and dissolved polymer was sprayed through a nozzle to atmospheric pressure. The pre‐expansion pressure was 10–25 MPa, and the temperature was 308–333 K. The polymers were poly(L ‐lactic acid) (molecular weight = 5000), poly(ethylene glycol) (PEG; PEG4000, molecular weight = 3000; PEG6000, molecular weight = 7500; and PEG20000, molecular weight = 20,000), poly(methyl methacrylate) (molecular weight = 15,000), ethyl cellulose (molecular weight = 5000), and PEG–poly(propylene glycol)–PEG triblock copolymer (molecular weight = 13,000). The solubilities of the polymers as coating materials and these medicines as core substance were very low in CO₂. However, the solubilities of these polymers in CO₂ significantly increased with the addition of low molecular weight alcohols as cosolvents. After RESS‐N, polymeric microcapsules were formed according to the precipitation of the polymer caused by a decrease in the solvent power of CO₂. This method offered three advantages: (1) enough of the coating polymers, which were insoluble in pure CO₂, dissolved; (2) the microparticles of the medicine were encapsulated without adhesion between the particles because a nonsolvent was used as a cosolvent and the cosolvent remaining in the mixture was removed by the gasification of CO₂; and (3) the polymer‐coating thickness was controlled with changes in the feed composition of the polymer for drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 742–752, 2003     

Chemical Shifts of Silicon X-ray Photoelectron Spectra by Polymerization Structures of Silicates

The binding energy of Si 2 p electrons and the kinetic energy of the Si(KLL) X-ray-excited state were measured by using X-ray photoelectron spectroscopy (XPS) and X-ray Auger electron spectroscopy (XAES), respectively, for silicates with SiO₄ tetrahedra of various polymerization types. The resulting Si 2 p XPS binding energies varied from 101.3 eV in merwinite (monomeric structure) to 103.4 eV in quartz and cristobalite (three-dimensional framework structure). A clear chemical-shift relation was observed, relating the polymerization structures of SiO₄ tetrahedra to the plots of their Si 2 p XPS binding energy versus the kinetic energy of their Si(KLL) XAES spectra. Thus, the structural state of the surface silicates in various substances can be deduced from this chemical-shift relationship.     

Do Aphid Carcasses on the Backs of Larvae of Green Lacewing Work as Chemical Mimicry against Aphid-Tending Ants?

Ants attack and exclude natural enemies of aphids in ant–aphid mutualisms. However, larvae of the green lacewing, Mallada desjardinsi, prey on the cowpea aphid, Aphis craccivora, without exclusion by aphid-tending ants. Lacewing larvae are protected from ants by carrying aphid carcasses on their backs. Here, we tested whether cuticular hydrocarbons (CHCs) of aphid carcasses affected the aggressiveness of aphid-tending ants. Aphid carcasses were washed with n-hexane to remove lipids. Lacewing larvae with washed aphid carcasses were attacked by aphid-tending ants more frequently than those with untreated aphid carcasses. We measured the aggressiveness of aphid-tending ants to lacewing larvae that were either carrying a piece of cotton wool (a dummy aphid carcass) treated with CHCs from aphids or lacewing larvae, or carrying aphid carcasses. The rates of attack by ants on lacewing larvae carrying CHCs of aphids or aphid carcasses were lower than that of attack on lacewing larvae with conspecific CHCs. Chemical analysis by gas chromatography/mass spectrometry showed similarity of CHCs between aphids and aphid carcasses. These results suggest that aphid carcasses on the backs of lacewing larvae function via chemical camouflage to limit attacks by aphid-tending ants.