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The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan.Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro.The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P.001), and ρ = 0.502 (P = .029), respectively].This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.

In previous works, we developed a self-healing organic coating with dispersed spherical capsules for corrosion protection. The capsule consisted of a polyurethane shell and healing agent as the inner. When the coating was damaged physically, the capsules were broken, and the healing agent was released from the broken capsules to the damaged area. The healing agent could react with moisture in the air to form the self-healing structure and cover the damaged area of coating. In the present investigation, a self-healing organic coating with spherical and fibrous capsules was formed on aluminum alloys. The corrosion behavior of the specimen coated with the self-healing coating was examined in a Cu2+/Cl− solution after physical damage, and it was found that no corrosion occurred during the corrosion test. This is discussed in terms of the high healing ability of fibrous capsules as a result of the high projected area.

It is well known that corrosion protection of pure Al is enormously improved by the formation of porous anodic oxide films and by pore sealing treatment. However, the effects of anodizing and pore sealing on corrosion protection for Al alloys are unclear, because the alloying elements included in Al alloys affect the structure of anodic oxide films. In the present study, porous anodic oxide films are formed on pure Al, 1050-, 3003- and 5052-Al alloys, and pore sealing was carried out in boiling water. Changes in the structure and corrosion protection ability of porous anodic oxide films on pure Al and the Al alloys by pore sealing, were examined by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). SEM observation showed that anodic oxide films formed on pure Al have a smooth surface after pore sealing, and that cracks are formed in anodic oxide films on 1050-, 3003- and 5052-aluminum alloys, after pore sealing. Corrosion protection after pore sealing increased with anodizing time on pure Al, but only slightly increased with anodizing time on the Al alloys.

Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.

Background Vestibular hair cell loss and its role in balance disorders are not yet completely understood due largely to the lack of precise hair cell damage protocols. New method Our damage protocol aims to selectively remove type I hair cells in a way that produces consistent and predictable lesions that can be used for reliable inter-animal and inter-group comparison in balance research. This objective is achieved by transtympanic injection of gentamicin on both the round window membrane and oval window over a fixed time period followed by thorough washing. Results We achieved nearly total and consistent loss of type I hair cells at 94 % for the crista ampullaris of the lateral semicircular canal (LSC) and 86 % for the utricular macula with negligible loss of type II hair cells at 4% for the crista ampullaris of the LSC and 6% for the utricular macula. While the vestibular function was compromised in the relevant study group, this group had a zero mortality rate with no significant suppression of body weight gain. Comparison with existing methods Gentamicin is typically administered via intraperitoneal systemic injection or, more recently, transtympanic injection. The intraperitoneal method is simple, but mortality rate is high. The transtympanic injection method produces ototoxic damage but with inconsistent lesion size. This inconsistency prevents reliable comparisons among animals. Conclusions This protocol employs a transtympanic injection method which selectively targets type I hair cells for removal in the vestibular epithelia in a time-dependent manner, uniformly damages vestibular function, and causes uniform hair cell loss.

A strain (Hime 5-1T) of lactic acid bacterium was isolated from the gut of the grasshopper Metrioptera engelhardti from a mountainous area of Nagano Prefecture, Japan. Strain Hime 5-1T had a low 16S rRNA gene sequence similarity to known lactic acid bacteria, with the closest recognized relatives being Lactobacillus tucceti (96.7 %), Lactobacillus furfuricola (96.5 %), Lactobacillus versmoldensis (96.3 %) and Lactobacillus nodensis (96.1 %). Comparative analyses of the rpoA and pheS gene sequences indicated that Hime 5-1T is not closely related to other Lactobacillus species. Strain Hime 5-1T is a Gram-stain-positive, catalase-negative and homofermentative bacterium with yellowish colonies, which contrasts with the whitish colonies of its closest recognized relatives. Based on phenotypic and genotypic properties, we conclude that the isolated bacterium represents a novel species of the genus Lactobacillus , for which the name Lactobacillus metriopterae sp. nov. is proposed. The type strain is Hime 5-1T (=JCM 31635T=DSM 103730T). 16S rRNA gene based high-throughput sequencing revealed that L. metriopterae is the dominant microbiota in the gut of Metrioptera engelhardti.

Anodic oxide films on aluminum are classified into two groups: porous-type anodic oxide films (PAOF) and barrier-type anodic oxide films (BAOF). The present paper is a review of the corrosion of pure aluminum (Al) and Al alloys covered with PAOF and BAOF, focusing on the role of anodic oxide films in the process of corrosion. Several topics are discussed in detail, including (a) changes in the dissolution mode of PAOF in acidic media by pore sealing, (b) hydration and dissolution of BAOF in pure water and neutral solutions containing organic and inorganic electrolytes, (c) pitting corrosion during the cathodic polarization of Al covered with PAOF and BAOF, (d) corrosion of PAOF-covered Al/Bi/Sn alloys in alcohols at 142°C, and (e) synergistic effects of Cl− and Cu2+ ions in the corrosion of PAOF-covered Al alloys in aqueous solutions.

Two types of self-repairing coatings for the protection of Al and its alloys are reviewed: (1) organic coatings with capsules containing repairing agent and (2) porous anodic oxide films with inhibitor solution stored in the pores of the oxide film. First, polyurethane microcapsules containing liquid surface-repairing agents were synthesized and polyurethane coating with the capsules was painted on Al alloy specimens. After mechanical damage to the coating, self-repairing occurred by the reaction of water vapor in the air with the repairing agents released from the capsules. Second, porous-type anodic oxide films were formed on Al alloys, and the pores of the anodic oxide films were filled with inhibitor solutions, followed by application of a covering polyurethane layer. Inhibitors released from the pores efficiently protected the Al alloy substrate from corrosion arising from induced mechanical damage.

Introduction: One of metal fine particles’ applications is Surface Enhanced Raman Scattering; SERS) with their surface plasmon resonance. It is usually performed on the substrates which have gold or silver clusters on their surface. It can be enhanced at the gap between two clusters much more than at the surface of a cluster. However, this enhancement at the gap of clusters was limited because these clusters were usually placed on the plate substrate. Placed these nanoparticles on the surface of the larger particles, the enhanced point can be moved on any place. In this study, we tried to prepare polystyrene (PS) particles which have smaller metal particles deposited by the electroplating on their surface. Experimental: PS beads ( The flash electroplating was performed with DC power supply with 1 – 10 V in aqueous solutions containing silver ions. After rinsed with distilled water, the particles were observed by scanning electron microscopy. Photoabsorption spectrum of Ag deposited samples were measured for evaluation of LSPR. Results and Discussions: SEM images of Ag electroplated with 3 V for 5 s in 0.001 M AgNO3 aqueous solution on the template by 1.0 μm PS beads were shown in Fig. 1. With lower voltage, 1 V, less Ag clusters were generated. With higher voltage, the clusters were rapidly grown and covered the PS beads’ surface so that it is not found the gap between the clusters. Same tendency was found the results with more concentrated silver solution. It is suggested that the optimal condition for placing Ag clusters on the PS beads was the electroplating with 3 or 5 V. It is also indicated that the Ag particles’ size can be controlled by the applied DC voltage and applied period of electrodeposition. In addition, the Ag cluster induced photoabsorption with surface plasmon resonance (SPR) around 480 nm region. The photoabsorption was observed particularly strongly in the brushy structure (using 1.0 μm PS beads and 5 V applied), and it was shown that it was due to the strong electromagnetic field derived from the nanogap structure in the Ag clusters. This also shows that SPR is localized. We have succeeded in preparing the localized surface plasmon resonance (LSPR) active structure and found that its optical properties can be controlled using a very simple method with an electroplating process. These results suggest that one of the possibilities of the helpful to high sensitivity the sensor using the surface enhanced method (Raman, IR, photoluminescence (PL) and more). Acknowledgement: This work was supported by JSPS KAKENHI Grant Number JP19K05191. Figure 1

Coating is one of the most useful techniques for corrosion protection of metallic materials, however, if coating is damaged, local corrosion will occur. It is important to repair the damaged area of coating soon, however it needs much cost. From these, our research group develop the coating with self-healing property, called by self-healing coating. In this coating capsules containing healing-agent of coating are dispersed. If the coating is damaged, capsules will be broken at the same time. The healing-agent containing in capsules will flow out. The healing-agent reacts with the water vapor in the air to form a healing-structure and cover the damaged area of coating. The capsules contained healing-agent are produced as follows. First, the prepolymer, this is precursor of shell of capsules, drip into the aqueous solution dissolved glycerol, it hardly dissolves in the aqueous solution since the prepolymer is the oil phase. A mixture of oil droplets dispersed in the aqueous solution is formed. When this mixture is agitated with high speed, the oil droplets become micro spheres and emulsion forms. Furthermore, the reaction between prepolymer and glycerol occurs only at this interface between oil phase and water phase, spherical shaped capsules contained a healing-agent in a polyurethane shell can be produced. From our previous study, the coating with these spherical capsules has a self-healing property, because healing-structure could be observed at the damaged area of coating, but this structure covered damaged area, incompletely. It is necessary to improve self-healing property of coating. From the self-healing mechanism of the coating, the self-healing property of the coating will be strongly depended on the amount of healing-agent flowing to the damaged area. Therefore, we start the development of the coating with capsules with other shape such as fiber shape are dispersed in order to develop an advanced self-healing coating with higher healing property. Considering the procedure of capsule formation, the shape of capsules can be controlled by the agitation speed and viscosity of prepolymer solution. The shape of capsules will be related to the amount of healing-agent flow from capsules to the damaged area of coating, when coating is damaged. e.g. more amount of healing-agent will flow from fiber shaped capsules than that from spherical shaped capsules, because fiber capsules will be arranged horizontally to the metal substrate due to the flow during the formation of coating, and the more capsules will be broken, when vertical damage was formed in the coating. In this paper, the shape of capsules produced from prepolymer solution with high viscosity and self-healing property of coating dispersed with these capsules were discussed. The procedure synthesizing capsules is follows. The prepolymer prepared by reaction between TDI and glycerol in cyclohexanone as a solvent under 75 ℃, 600 rpm. In order to increase the prepolymer concentration and viscosity of solution, the heat treatment of prepolymer solution were performed under 140 ℃, 8 min. After heat treatment, IPDI as a healing-agent, and xylene as inhibiter solidification inside of capsules were added. First, this prepolymer solution drip into the sodium dodecyl sulfate and glycerol aqueous solution with low agitation speed (200 rpm). The prepolymer solution was not dissolved in the aqueous solution and small oil droplets were dispersed in the aqueous solution. The shape of some of droplets will be changed from spherical to long spheroidal or fiber by agitation of solution. Furthermore, the shell formation reaction take place only at the interface between oil and water phases, the spherical, spheroidal and fiber shaped capsules could be formed. For comparison, the capsules produced under high agitation speed (600 rpm) and those from prepolymer solution without heat treatment were also prepared. These capsules were observed by a scanning electron microscope SEM. Fig. 1-a show the shape of capsules prepared from prepolymer solution without heat treatment under high agitation speed, 600 rpm. From this image, only spherical with 20 - 60 µm of diameter can be observed. The shape of capsules from same prepolymer under low agitation speed, 200 rpm, also only spherical however the size of capsules is bit larger, the maximum diameter is about 80 µm, as shown in Fig. 1-b. The shape of the capsule the produced from prepolymer with heat treatment with high agitation speed, shown in Fig. 1-c, are similar to that without heat treatment. In contrast to these, the capsules produced from prepolymer with heat treatment under low agitation speed have some kinds of shape, such as spherical, spheroidal and long fiber. The coating dispersed with these shaped capsules will be also discussed. Figure 1

Al and Al alloys are used for many purposes, e.g. automobiles, heat exchanger, electronics, because of their good properties such as lightness, high heat conductivity, good processability, hardness, and so on. However, corrosion protection of these materials are not so high, corrosion of Al, such as pitting corrosion and atmospheric corrosion, will occur during operation. From this, some kinds of surface treatments are needed for improvement of corrosion protection of Al used for long-term. A polymeric coating is one of popular technique to improve the corrosion protection of substrate metal. However, corrosion protection of substrate covered by polymeric coating will easily lose by mechanical damage of the coating, leading to exposure of substrate metal to surroundings and to the local corrosion of substrate under damaged area of coating. From above, new surface treatment techniques for Al substrate to keep high corrosion protection, even the surface was damaged, are developed in our research group. This is a coating, with self-healing property by dispersion of micro-capsules containing the healing agent of coating. When the coating is damaged, the healing agent flow out to the damaged area of coating and react with water vapor to form the self-healing structure and this can be covered to the damaged area of coating. However, the procedure of synthesis of micro-capsule containing healing agent is too complex and yield of this is too low to synthesize the capsules with low cost. From above, we start to develop the new type of self-healing coating. This coating can be formed on Al alloy anodized. As you know by anodic oxidation of Al alloy, electrochemically in some kind of acidic solution, porous type of anodic oxide film can be formed on Al alloy, which have many small pores arranged regularity. Pores of porous film are used as a container of healing agent of coating. Firstly, the pores in porous film formed on Al alloy were filled by healing agent. And then, this sample was covered by polyurethane coating. If this coating was damaged, mechanically, healing agent contained in pores of porous film, flow out to the damaged area and reaction with water to form polyurea as a self-healing structure and cover to the exposed Al substrate. In this study, healing property of this type of self-healing coating is investigated by observation of the surface of specimen with scratchin. #1050 Al alloy (size : 20 mm × 20 mm × 1.5 mmt) were electro-polished in CH3COOH / HClO4solution. And then anodic oxide films were formed on pretreated specimens by anodizing in (COOH)2 solution with a constant current density of 200 Am-2 for 1 hr. The anodized specimens immersed in IPDI for 100 min with ultrasonic bath, in order to promote that IPDI soln. to penetrate to pores of the porous film. After wiping the surface of the specimen by soft tissue, then a mixed solution of ethylene glycol and prepolymer of polyurethane coating was purged to specimen surface and leave for 24 h to form the polyurethane coating on anodized Al alloy surface. The prepolymer was synthesized by using the mixture of TDI, glycerol and cyclohexanone. Mixture was agitated under 600 rpm of stirring rate for 24 h. In order to remove the water dissolved in this mixture, the first 1 h of agitation, the mixture was bubbled by passing pure N2 gas. During the agitation, TDI reacts with glycerol to form the precursor of polyurethane. After specimen damaged by scratching with 7 N of load and ageing, corrosion protection of damaged Al alloy specimens with polyurethane coating were evaluated by immersion tests. The coated specimens were immersed to CuSO4 / KCl solution kept at room temperature for 1 day. After the immersion tests, to remove the coating, the specimens were immersed to the coating remover solution. And then, specimens were immersed to H3PO4 / K2CrO4 solution. Surfaces after immersion tests and removing of surface layer were observed by scanning electron microscopy (SEM). From the SEM observation for damaged specimen covered with porous film and normal coating, as shown in Fig. 1-a, sharp and deep scar can be seen at the canter of image of specimen surface. The scar can be seen on the image of damaged specimen with self-healing coating on anodized specimen, however, unique structure also can be observed at the bottom of scar, shown in Fig .1-b. This structure may be formed by the reaction between water in air and IPDI contained in the pore of porous film on Al alloy, thus, this coating has a self-healing property. Figure 1

Corrosion of 4043-Al alloy was examined by repeated wet–dry cycle tests with NaCl solutions at 323 K, and compared with immersion test corrosion in 0.2–5.5 kmol/m3 NaCl solutions. The Al alloy specimens after the immersion tests for 86.4 ks (1 day) or 604.8 ks (7 days) showed preferential dissolution of the aluminum matrix around Si-phase compounds, and the dissolution was more remarkable at lower NaCl concentrations. Mass loss of the specimens after the 604.8-ks immersion was also higher at lower NaCl concentrations. In the repeated wet–dry cycle tests, a 20 mm3 droplet of 0.2–5.5 kmol/m3 NaCl solution was initially dripped on the specimens, and left for 690 s to allow the drying up of the droplet, resulting in solid NaCl precipitation. Then, the dissolution and precipitation of NaCl were repeated a further 149 times by dripping 20-mm3 pure water at 690-s intervals. The specimens after the 150 cycles showed different corrosion modes at the center and edge of the droplets. At the edge, 40–80 × 10−6 pits/m2 of 20–50 µm diameter had formed, showing more corrosion with higher NaCl concentration droplets, and at the droplet center, the corrosion showed preferential dissolution of the aluminum matrix around the Si-phases, similar to the situation in the immersion tests. Copyright © 2015 John Wiley & Sons, Ltd.

Corrosion of Al alloys was examined by repeated wet-dry cycle tests with 5.5 M NaCl solution and pure water at 323 K and compared with immersion test corrosion. All Al alloy specimens after the immersion tests for 7 days in the NaCl solution showed preferential dissolution of the aluminum matrix around Si phases and Al3Fe intermetallic compounds, and in pure water showed formation of thick amorphous hydroxide films. The corrosion rate in pure water was higher than that in the NaCl solution. In the repeated wet-dry cycle test with NaCl solutions, a 0.02-ml droplet of 5.5 M NaCl solutions was initially dripped on specimens at 323 K and left for 690 s to allow the dry up of the droplet, resulting in solid NaCl precipitation. Then, the dissolution and precipitation of NaCl were repeated 150 times by dripping 0.02-ml pure water at 690-s intervals. At the edge of the droplet, pits with 20–100-μm diameter had formed after the 150 cycles, while, at the central areas, the corrosion behavior was similar to that observed in the NaCl immersion test. In similar cycle tests with pure water, dripping of water droplet was also repeated 150 times. Here, needle-like crystalline hydroxides formed at the edge of the droplet, while thick hydroxide films formed at the central areas, like in the pure water immersion test.

In a previous study, self-healing polyurethane coatings with microcapsules containing healing agents have been developed for the protection of metal from corrosion. At the initial stage of the development of these coatings, we synthesized the microcapsules containing healing agents by adding organic solvents to inhibit the solidification of the whole capsule. In this study, the structure of the capsules formed with different solvents, such as chlorobenzene, toluene and xylene was examined. We also evaluated the self-healing ability of coatings with these capsules after damaging the coating by scratching. The amount of healing agents contained in capsules depends on the kind and the amount of solvents added. In the capsule formed with 20 or 50 wt%-chlorobenzene, there is almost no healing agent of liquid phase, while in the capsule formed with 70 wt%-chlorobenzen healing agents are contained. Toluene and xylene are more effective inhibitors than chlorobenzene. The capsule formed with 70 wt%-toluene or xylene contains much more amounts of the healing agent of liquid phase than that formed with 70 %-chlorobenzene, and the coatings with the former capsules have an appreciable self-healing ability.

Self-healing coatings with capsules containing healing agents have been developed for the corrosion protection of metal. In this paper, polyurethane capsules were synthesized under different conditions to examine the size and shape of capsules, and selfhealing ability of coatings with capsules dispersed was examined after damaging the coated layer by scratching with a cutter blade. The size and shape of capsules depended on the concentration of chlorobenzene in cyclohexanone used as a solvent of prepolymer solution. The capsule formed with 70 % of chlorobenzene gave a self-healing capability to the coated layer by releasing the healing agent after damaging. The amount of glycerol added for the formation of the polyurethane capsule shell affected the self-healing ability of the coated layer. The coating with the capsule formed with small amounts of glycerol showed a high healing ability, while, with large amounts of glycerol, the selfhealing ability was relatively low.

Austenite formation on the surface of pure iron during nitriding in a mixture of NH3 and H2 gases and surface hardening due to formation of iron-nitrogen martensite by subsequent quenching were investigated. In nitriding at 973 K at a partial pressure of NH3(fNH3) of 5% and 10%, austenite layer is formed at the surface while double-layered structures consisting e-Fe2~3N and austenite are developed at fNH3 of 20%. In addition, at these high fNH3, voids are formed in e-Fe2~3N nitride as well as austenite with high nitrogen content. At fNH3 of 5% and 10%, the growth rates of austenite accords with parabolic growth law and become faster with increasing fNH3. On the other hand, after prolonged treatment at fNH3 of 20%, thickness of the nitrided zone is less than that for 10% due to substantial formation of voids and resultant emission of nitrogen from the surface. The hardness of the nitrided zone is nearly the constant at 800HV in the specimen nitrided at fNH3 of 5% whereas softening near the surface occurs in the specimens nitrided at fNH3 of 10% and 20% due to formation of the retained austenite and the voids.

The authors have examined changes in forearm blood flow during local intra-arterial infusion of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in patients with heart failure due to nonischemic heart disease. Incremental step-up doses of acetylcholine and nitroprusside were infused locally into the brachial artery in 10 healthy controls (group 1), 13 patients with no history of decompensated congestive heart failure (group 2), and 13 patients who exhibited congestive heart failure before admission (group 3). Forearm blood flow was measured by venous occlusion plethysmography. Systemic blood pressure and heart rate were not affected significantly by either infusion in any of the three groups. Groups 1 and 2 showed similar changes in forearm blood flow after endothelium-dependent and endothelium-independent vasodilation, but these changes were attenuated significantly in group 3 (both p

It has been reported that the transport function for organic anions on the kidney is maintained in multidrug resistance-associated protein 2 (Mrp2)-deficient rats. Different from Mrp2-deficient rats, Long–Evans Cinnamon (LEC) rats have impaired urinary excretion of Mrp2-substrate, phenolsulfonphthalein (PSP). PSP is transported by the potential-sensitive urate transport system in rat brush-border membranes. We analyzed the function of PSP transport system in LEC rats. Unlike Long–Evans Agouti (LEA) rats, the initial uptake of PSP and urate into the renal brush-border membrane vesicles of LEC rats were not significantly enhanced in the presence of positive intravesicular potential, suggesting that the potential-sensitive urate transport system is impaired in LEC rats. LEC rats should be useful for elucidating the potential-sensitive urate transport system in rats at the molecular level.

Wilson's disease is an inherited, autosomal recessive disorder of copper accumulation and toxicity. Lifelong chelation therapy is essential in all Wilson's disease patients. Intestinal absorption of some compounds is limited partly because they are preferentially transported in the secretory direction. Several ATP-binding cassette (ABC) transporters are expressed in the apical membrane of the small intestine and secrete various drugs into the lumen. In this study, we investigated the characteristics of the intestinal efflux ABC transporters in LEC rats. We found that the expression of multidrug resistance-associated protein 2 (Mrp2) in the jejunum of Long-Evans Cinnamon (LEC) rats, an animal model for Wilson's disease, is decreased.

Purpose: It has been reported that a significant portion of the lactone form of 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothecin (CPT-11) is excreted into the gastrointestinal lumen via the intestinal membrane and that carboxylesterase activity, which converts CPT-11 to SN-38, was detected in the intestine. It is possible that a reduction in the excretion of CPT-11 lactone into the gastrointestinal lumen induces the gastrointestinal toxicity. The purpose of this study was to investigate the characteristics of transporter(s) that contribute to the jejunal efflux of the lactone form of CPT-11. Methods: The serosal-to-mucosal permeation rate of CPT-11 lactone was investigated in everted sac studies. Results: The secretory transport required metabolic energy and was diminished by sulfobromophthalein (BSP) and 1-naphthol, inhibitors of the ME3277 transport system. However, inhibitors of breast cancer resistance protein (Bcrp), multidrug resistance-associated protein 2 (Mrp2) and P-glycoprotein (P-gp) did not affect the secretion of CPT-11 lactone. Conclusions: The results suggest that a specific transport system, which is identical to the ME3277 transport system, plays a major role in the secretion of CPT-11 lactone.

It is known that secretory transport limits the oral bioavailability of certain drugs. However, there is little information on the secretion of anionic compounds in the intestine. Phenolsulfonphthalein (PSP) and p-aminohippuric acid (PAH) have been used widely as substrates for organic anion transport systems. PAH is transported in the secretory direction in the intestine. It is possible that PSP and PAH share the same transport system at the mucosal membrane. The purpose of this study was to characterize the transport system for PSP in the intestine. In the jejunum, the serosal-to-mucosal permeation rate of PSP was significantly reduced in an ATP-depleted condition, whereas a significant difference was not observed in the ileum. Some multidrug resistance-associated protein 2 (Mrp2) inhibitors inhibited PSP permeation in the jejunum. However, pravastatin, a substrate of Mrp2, did not inhibit the PSP permeation. The jejunal secretory transport of pravastatin was significantly reduced in an ATP-depleted condition and by addition of probenecid, but PSP did not affect the jejunal permeation of pravastatin. These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane.

An in situ nanoindentation technique combined with an AFM was applied to evaluate the effects of dichromate treatment on the mechanical properties of the single crystal iron (1 0 0) and (1 1 0) surfaces passivated in pH 8.4 borate solution. The dichromate treatment was performed with natural immersion of the iron specimens in 5×10 −2 M K 2 Cr 2 O 7 solution for 24 h prior to passivation at 0.25 V (SHE) for 1 h. The hardness, H and the works (elastic work, W e , plastic work, W p , and total work, W t = W e + W p ) made during nanoindentation were obtained from the measured load–depth curves. The values of H and W e / W t at the indentation depth larger than 30 nm for the passivated single crystal iron surfaces were increased by the dichromate treatment. The increases in H and W e / W t due to the dichromate treatment were attributed to the promotion of repassivation at the sites of passive film ruptured during nanoindentation process.

In situ nanoindentation tests were performed to evaluate the mechanical properties of the iron (100) and (110) surfaces passivated potentiostatically for 1 h in pH 8.4 borate solution after or without immersion in 5 x 10 -2 M K 2 Cr 2 O 7 solution for 24 h. It was found from the measured load-depth curves at a maximum load of 400 μN that the hardness (3.2-3.3 GPa) of the passivated iron (110) surfaces was larger by 10% than that (2.9-3.1 GPa) of the passivated iron (100) surfaces. Moreover, the hardness of the passivated iron (100) and (110) surfaces increased slightly with increasing formation potential of passive film which was ascribed to the presence of passive film. The dichromate treatment increased the hardness of the iron (100) and (110) surfaces to some extent. The loading discontinuity appeared frequently at a load of about 90 μN in the load-depth curves for the passivated iron (110) surfaces as compared with the passivated iron (100) surfaces. The loading discontinuity in the load-depth curves for the iron (110) surface, however, disappeared completely due to the dichromate treatment.

An in-situ nanoindentation test using a Berkovich pyramidal diamond indenter was performed to examine the mechano-electro-chemical properties of the single crystal iron (100) surface passivated at a constant potential for 1 h in pH 8.4 borate solution. The load-depth curve measured at a maximum load, W max = 50 μN and a load speed of 50 μN s -1 showed an evidence of plasticity irrespective of the potential at which the passive film was formed. The average hardness of the iron surface obtained from the unloading curve ranged from 2.0 to 2.5 GPa and it increased with increasing potential in the passive region higher than 0.25 V versus SHE, indicating that the passive film contributes to the increase in hardness of the iron surface. Moreover, the indentation at a maximum load, W max = 200 μN and a load speed of 20 μN s -1 was performed in order to observe the time variation of the shape of the indent with AFM after the indentation. The indent shape for the iron surface cathodically reduced did not change significantly with time after the indentation. In contrast, the indent shape for the iron surface passivated at 1.0 V spread and became obscure with time, which was ascribed to the active dissolution of iron near and under the indenter, followed by the repassivation.

Previously, the surface acoustic wave linear motor has been demonstrated and its exact pre-load conditions investigated. Based on this previous research, multi-contact-point sliders were designed and tested. A maximum output force of 0.45 N, 450 times that obtained in preliminary experiments, was successfully obtained. Simple simulation results predicted that much larger thrust would be available by increasing the actual contact point area without changing the slider and the stator dimensions. The calculated output force was 10 N, roughly twenty times that observed experimentally. To realize the required stator texture of the contact surface, a silicon micro-machining technique or other conventional methods would be applicable.

We studied plasma levels of atrial and brain natriuretic peptides at rest and after exercise before and after intracardiac surgery with and without the maze procedure in patients with chronic heart failure secondary to valvular heart disease. The present study found that an increased response of both cardiac natriuretic peptides is attenuated with resulting water retention after the maze procedure.

Introduction Many kinds of metals are used as structural material in the building or other constructions. It is important to protect the metal from corrosion, because the corrosion of the metal may cause a significant damage of the building and the constructions. One way of the corrosion protection of the metal is to cover with organic or inorganic coatings, isolating the metal substrate from water or oxygen. When some parts of the coating is removed mechanically or chemically, the corrosion of the material may occur at the damaged areas. Therefore, it is necessary to keep the paint layer protective by a periodic painting that costs much labor and expense. From the point of view of time- and money-saving, we started to develop a “self-healing coating” on the metals for corrosion protection. When the organic coating is damaged by mechanical impulsions, the coating at the damaged areas is healed automatically without painting again, heating or any other external treatments.The above concept is accomplished by the following process. Micro capsules that contain reactive liquid agents are dispersed in coatings (Fig. 1-a). The reactive liquid agent in the capsule is easy to react with water or oxygen in the air to form an organic compound with properties similar to those of the coatings. When the coating is damaged to form flaws, the capsule is also destructed (Fig. 1-b). Then, the reactive liquid agent included in the capsule flows out, and the flaw is filled with the organic compound after reacting with water or oxygen in the air (Fig. 1-c). In the present investigation, capsules that contain a prepolymer agent were dispersed in polyurethane coatings to examine the self-healing ability of the coating. The effect of glycerol on the formation of the capsule was also examined. Experimental At First, 7.7 g of tolylene-2,4-diisocyanate (TDI) and 1.3 g of glycerol were added to 18 g of cyclohexanone, and mixed by stirring with a magnetic stirrer at 600 rpm and 75 ˚C for 24 h. In the period, a prepolymer is formed in cyclohexanone by the reaction shown in Fig. 2. Then, 9.5 g of isophorone diisocyanate and 17 g of chlorobenzene were added to 11 g of the prepolymer/cyclohexanone to obtain a prepolymer solution. Micro droplets of the prepolymer solution were dropped into an aqueous solution containing 3 g of sodium dodecyl sulfate (SDS) and 0.10 – 0.50 g of glycerol. The droplet of the prepolymer solution reacts with SDS/glycerol solution at the interface between two phases to form polyurethane capsules as shown in Fig. 3, since the prepolymer solution doesn’t dissolve in the toSDS/glycerol solution, As a result of the reaction, capsules, which have a polyurethane shell and contain high reactive liquid, were obtained. The capsules collected on a filter were observed by scanning electron microscopy (SEM).The polyurethane dispersed with the microcapsules was coated on Al substrate by spreading 1.5 g of the prepolymer solution containing 10 mg of the capsules after mixing with ethylene glycol ultrasonically, and then kept at room temperature for 48 h to allow the polymerization of the prepolymer and the evaporation of ethylene glycol. Self-healing ability of the coating was evaluated by SEM after damaging the coating with a sharp blade at the pressure of 6.1 MPa. Results and Discussions Fig. 4 shows SEM images of micro capsules synthesized with a) 0.5 and b) 0.1 g of glycerol. All the capsules are spherical, and some of them are coalescent, forming clusters. Fig. 5 shows distribution of the diameter of the micro capsules synthesized with different amounts of glycerol. The most frequent diameter of capsules synthesized with 0.5 g and 0.1 g of glycerol is 4.0 and 3.2 µm, suggesting the coalescence of capsules is easier with larger amounts of glycrol. All the coatings with capsules showed self-healing after damaging with the blade, and the healing effect was more remarkable with smaller amounts of glycerol. Figure 1

This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure.

In the novel hydrosilylation curing system, derived from an α,ω-bis(2,4,6,8-tetramethylcyclotetrasiloxan-2-yl) carbon chain crosslinker 1 and allyl-group-end-blocked oligomer 2, effervescence phenomena during curing were examined. We found that the main component of the gas formed was propylene when 1 and 2 were heated in the presence of H2PtCl6 for cure and that the amount of the gas was largely dependent on the structure of allyl functionality; in the system with allyl carbonate or allyl ester gas genaration was very distinctive and propylene formation was dominant well over the normal hydrosilylation.

We describe here the preparation and properties of a novel curing system, which has been derived from an SiH-containing organic oligomer 1 and an allyloxy end-blocked organic oligomer 2. The composition of these oligomers could be crosslinked via a platinum-catalyzed hydrosilylation reaction, that is, the addition reaction of the SiH bonds of 1 to the allyl functionality of 2, above 100°C, yields a rubbery material in a short period of time. The compatibility of the SiH-containing oligomer 1 with the allyloxy end-blocked oligomer 2 was governed by the oligomer main chain employed. Hence the SiH-containing oligomer 1 was completely miscible with 2, having the same main chain and, thus, the system yielded a homogeneously cured material. The poly(propylene oxide) curing system 1a/2a was systematically investigated in detail to manifest its curing behavior and crosslink structure. © 1993 John Wiley & Sons, Inc.

Several organic oligomers (Mw = 103–104 order) containing SiH bonds of the general formula 1 have been successfully synthesized by platinum-catalyzed partial hydrosilylation reaction of an allyloxy (or an allyl carbonate) end-blocked linear organic oligomer 2 with 2,4,6,8-tetramethylcyclotetrasiloxane, [CH3(H)SiO]4 (3) (hereafter called hydrocyclotetrasiloxane). 1H-NMR spectroscopy confirmed the introduction of hydrocyclotetrasiloxane moiety into the oligomers through SiC linkage by hydrosilylation reaction. 13C-NMR analysis revealed that the cyclic structure of the starting hydrocyclotetrasiloxane 3 was retained intact in product 1. As the precursor for 1, allyloxy (or allyl carbonate) end-blocked oligomers 2 could be prepared from hydroxyl-terminated oligomers 4. The storage stability of product 1 was significantly influenced by the platinum catalyst still remaining in it. The poor stability was improved by decreasing the amount of the platinum catalyst and/or by adding coordinating compounds. As a result, an excellent stability of product 1 was obtained. © 1993 John Wiley & Sons, Inc.

Synthesis of New Organic Crosslinking Reagents Containing SiH Bonds and Curing System Thereof

Several neurohormonal factors have been proposed as markers of the severity of acute myocardial infarction (MI). To determine whether plasma concentrations of atrial natriuretic factor (ANF) might predict post-MI prognosis, we studied 130 patients with acute MI (97 males and 33 females, mean age 62 years). Within one-half to one day after admission, a blood sample was taken for estimation of circulating ANF. The mean follow-up period was 37 months, and the follow-up rate was 97%. Of the 130 patients, 28 died from cardiac causes during the follow-up period. Patients were classified into three groups according to plasma ANF levels (group 1,99 pg/ml; group 2, 100-199 pg/ml; group 3;200 pg/ml). The survival curves were constructed by the Kaplan-Meier method. There were significant differences in the cumulative survival rate among the three groups (group 1group 2group 3; p0.001). The baseline characteristics (age, atrial pressure, and cardiac index) were different among the groups, therefore these variables were analyzed by a Cox multiple regression model. Significant predictors of cardiac mortality were plasma ANF class (p0.002) and pulmonary capillary wedge pressure (p0.007). In conclusion, these observations demonstrated that stratification of acute MI patients by plasma ANF level is a useful non-invasive method for predicting prognosis and for identifying individuals at high risk of cardiac death.

To examine whether atrial natriuretic factor (ANF) is secreted adequately in the early phase of myocardial infarction, plasma ANF concentration and clinical parameters, including hemodynamic variables, were studied in 118 patients with acute myocardial infarction (AMI). The patients were divided into 2 subgroups according to the absence (group A, n = 41) or presence (group B, n = 77) of a history of valvular heart disease, previous myocardial infarction, hypertension, or renal failure. Although no significant difference in atrial pressure after the infarction was found between the 2 groups, the plasma ANF level was significantly lower in group A than in group B (76 +/- 6 vs. 185 +/- 26 pg/ml; mean +/- SEM, p0.01). Plasma ANF was correlated with pulmonary capillary wedge pressure in group B (r = 0.54, p0.001), whereas no relationship with hemodynamic parameters was observed in group A. In 56 of the 118 patients (group A, n = 18; group B, n = 38), the pulmonary arterial plasma level was significantly higher in group A (p0.05), whereas the difference was not significant in group B. Seven of the 8 expired cases among these 56 patients had peripheral plasma ANF levels of more than 150 pg/ml, which were higher than those in pulmonary arterial plasma. These observations suggest firstly that the plasma level of ANF is lower in patients with a new onset of myocardial infarction compared to those with a history of cardiac or renal diseases, and secondly that stimulated ANF release originates not only from the right side of the heart, but also from additional site(s), particularly in patients with chronic ventricle overload and a poor prognosis.

Various mechanisms can influence the intestinal absorption and oral bioavailability of drugs. The barrier effects of efflux transporters may be one of the critical factors limiting the bioavailability of certain drugs. It has been reported that multidrug resistance-associated protein 2 (Mrp2) is expressed in the mucosal membrane of the epithelium of the small intestine and secretes various drugs into the jejunum lumen. However, it is possible that total intestinal secretion of Mrp2 substrates is accounted for the contribution of Mrp2 and other transporter(s) to the intestinal secretion of Mrp2 substrates. In this study, we found that phenolsulfonphthalein and pravastatin, both Mrp2 substrates, are transported by different transport systems in the intestine. These results suggest that contribution of transporters to the drug transport may be a critical factor affecting drug disposition and drug-drug interaction. In addition to evaluating the substrate specificity of a transporter, it is important to be aware of the contribution of a transporter to drug disposition.

The liver plays important roles in the detoxification of xenobiotics. Hepatobiliary transporters contribute to hepatic uptake and efflux processes of xenobiotecs. Expressions of these transporters may be modulated under the condition of hepatic failure. Long-Evans Cinnamon (LEC) rats provide a pertinent model for basic and clinical studies on hepatitis. However, only a few reports describing the properties of hepatobiliary transporters in LEC rats have appeared in the literature. We investigated the expression levels of hepatobiliary transporters in LEC rats by real-time RT-PCR. We found that hepatic expressions of three sinusoidal organic anion transporters, Ntcp, Oatp1a1 and Oatp1a4, were decreased in LEC rats. However, no significant difference of the expressions of Mrp2 and Bsep, organic anion transporters located on canalicular membrane, were found between Wistar rats and LEC rats.