Formation of Self-Healing Organic Coatings for Corrosion Protection of Al Alloys by Dispersion of Spherical and Fibrous Capsules.

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.

Correlation between antibiotic use and antibiotic resistance: A multicenter study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system in Hokkaido, Japan.

BACKGROUND: 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. METHODS: 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. RESULTS: 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]. CONCLUSIONS: 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.

Changes in the Structure and Corrosion Protection Ability of Porous Anodic Oxide Films on Pure Al and Al Alloys by Pore Sealing Treatment.

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.

Consistent removal of hair cells in vestibular end organs by time-dependent transtympanic administration of gentamicin in guinea pigs.

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.

Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions.

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.

Lactobacillus metriopterae sp. nov., a novel lactic acid bacterium isolated from the gut of grasshopper Metrioptera engelhardti.

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.

Contribution of multidrug resistance-associated protein 2 to secretory intestinal transport of organic anions.

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.

Functional analysis of phenolsulfonphthalein transport system in Long-Evans Cinnamon rats.

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.

Down-regulation of intestinal multidrug resistance-associated protein 2 in long-evans cinnamon rats.

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.

Characterization of hepatobiliary organic anion transporters in Long-Evans Cinnamon rats.

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.

Characterization of secretory intestinal transport of the lactone form of CPT-11.

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.

Characterization of secretory intestinal transport of phenolsulfonphthalein.

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.