Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)     

In Situ Observation of Zirconia Particles at 1200°C by High-Resolution Electron Microscopy

Zirconia (ZrO₂) particles (average diameter, 30 nm) were observed in an in situ heating experiment up to 1200°C using a 400-kV high-resolution electron microscope. Thermal vibration of atoms on a (001) surface plane was observed at 1100°C. At 1200°C, grain growth and sintering phenomena were recorded on a videotape, showing (100) lattice planes migrating on a surface of a particle. Direct observation of the sintering process on a lattice level was accomplished for the first time.     

Bromine addition and successive amine substitution of mesoporous ethylenesilica: Reaction, characterizations and arsenate adsorption

Bromination and subsequent ethylenediamine substitution of the CC double bond in mesoporous ethylenesilica were carried out to explore the characteristics of this periodic mesoporous organosilica. The structures of the products (BrPMO and EDA–BrPMO, respectively) were analysed by IR, Br K-edge EXAFS and NMR spectroscopies, as well as X-ray diffraction and nitrogen adsorption. We showed (1) that the formulae of the two products that formed were [CHBrSiO_1.5]_0.45[CHSiO_1.5]_0.55 and [NH₂CH₂CH₂NHCHSiO_1.5]_0.05 [CHBrSiO_1.5]_0.40[CHSiO_1.5]_0.55, respectively, (2) that the addition of Br₂ at room temperature occurred on the CC double bonds with disturbing the framework structure, (3) that IR absorption band of CC bonds that reacted with Br₂ is significantly different from that of inactive CC bond, (4) that the length of the C–Br bond was considerably longer than in conventional alkyl bromides, and (5) that a large proportion of the ν(C–Br) band remained at the same position in the IR absorption spectrum after the ethylenediamine (EDA) substitution, while a new ν(C–Br) absorption also appeared. The mechanisms of these reactions are discussed at both the micro and mesoscopic levels.

Arsenate adsorption on EDA–BrPMO, in which the EDA is directly bound to the “surface” of the mesopores, was compared with adsorption on EDA–Pr–PMO, which was prepared by the direct synthesis of 3-chloropropyl-functionalized mesoporous ethanesilica followed by the substitution of Cl with EDA. The strength of the adsorption, as measured with the distribution coefficient, was greater for the former adsorbent than the latter. The origin of this difference was attributed to the distance between amino group and the surface.     

Effective renaturation of reduced lysozyme by gentle removal of urea

To increase the folding yield of concentrated reduced lysozyme,we developed a renaturation method by means of dialysis fromconcentrated urea with redox agents. After lysozyme was incubatedin the reducing buffer (8 M urea solution) with oxidized glutathione,renaturation of reduced lysozyme was started by dialysis againstthe dialyzing buffer containing 8 M urea with redox agents.The urea concentration of the dialyzing bottle was graduallydiluted with dialyzing buffer without urea at a flow rate of0.1 ml/min by high pressure pump. Using this systematic dialysis,a concentration as high as 5 mg/ml of reduced lysozyme couldbe renaturated in 80% yield, while the folding yield was <5%even at a concentration of 1 mg/ml using a conventional rapiddilution method [Goldberg et al. (1991) Biochemistry, 30, 2790–2797].Therefore, it was concluded that gentle removal of urea fromdenatured proteins, dissolved in concentrated urea solution,by means of dialysis should be useful to renature denaturedproteins effectively.     

Photo-regulated metal coordination of azobenzene polymer having sterically controlled ion binding sites

Summary 2,2-Dimethylazobenzenes having metal chelating ligands at meta-positions were synthesized, and the interaction with metal ions were estimated for syn- and anti-ligands on thermal isomerization. The azobenzenes with the metal-interaction were transformed to vinyl azobenzenes and copolymerized with styrene. The metal extracting ability was found in photo-isomerized polymer having syn-bis(iminodiacetic acid) groups; the selectivity was high for Cu(II) ion.     

Discharge properties and chemical stability of SrZrO films

Abstract— MgO thin film is currently used as a surface protective layer for dielectric materials because MgO has a high resistance during ion sputtering and exhibits effective secondary electron emission. The secondary‐electron‐emission coefficient γ of MgO is high for Ne ions; however, it is low for Xe ions. The Xe content of the discharge gas of PDPs needs to be raised in order to increase the luminous efficiency. Thus, the development of high‐γ materials replacing MgO is required. The discharge properties and chemical surface stability of SrO containing Zr (SrZrO) as the candidate high‐γ protective layer for noble PDPs have been characterized. SrZrO films have superior chemical stability, especially the resistance to carbonation because of the existence of a few adsorption sites due to their amorphous structure. The firing voltage is 60 V lower than that of MgO films for a discharge gas of Ne/Xe = 85/15 at 60 kPa.     

Surface modification of biodegradable plastics by ion beams

Biodegradable plastics can be used as conventional plastics, while on disposal they decompose to water and carbon dioxide by microorganisms existing in natural environment. Products using biodegradable plastics have recently been developed in many companies pursuing ecology. In this study, surface modification of biodegradable plastics was carried out by inert ion beams for improvement of photo deterioration under an ultraviolet ray. The hardness of biodegradable plastics tended generally to decrease with irradiation of an ultraviolet ray. In this method, the hardness of ion-bombarded biodegradable plastics was kept at an initial value under an ultraviolet ray, because the modified layer by ion bombardment intercepted an ultraviolet ray. The hardness of He⁺ ion-bombarded biodegradable plastics showed larger value than that of Ar⁺ ion bombardment. He⁺ ion bombardment at ion energy of 10 keV produced the suitable property with both of high transmittance of a visible ray and high interception of an ultraviolet ray in a surface layer of biodegradable plastics.     

Catalyst‐Free GaN Nanorods Synthesized by Selective Area Growth

GaN nanorod formation on Ga‐polar GaN by continuous mode metalorganic chemical vapor deposition selective area growth (MOCVD SAG) is achieved under a relatively Ga‐rich condition. The Ga‐rich condition, provided by applying a very low V/III ratio, alters the growth rates of various planes of the defined nanostructure by increasing relative growth rate of the semi‐polar tilted m‐plane {1–101} that usually is the slowest growing plane under continuous growth conditions. This increased growth rate relative to the non‐polar m‐plane {1–100} and even the c‐plane (0001), permits the formation of GaN nanorods with nonpolar sidewalls. In addition, a new growth mode, called the NH₃‐pulsed mode, is introduced, utilizing the advantages of both the continuous mode and the lower growth rate pulsed mode to form nanorods. Finally, nanorods grown under the different growth modes are compared and discussed.     

Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products

The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na⁺ excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.