Co-Self-Assembly of Amphiphiles into Nanocomposite Hydrogels with Tailored Morphological and Mechanical Properties.

As one of the most amazing aspects of life, all living organisms are formed by self-assembly, a fundamental biological design process in which ordered nanostructures are assembled from small parts. For example, most of the biological tissues contain structurally soft and hard parts that are usually hierarchically organized at nano or micro levels to achieve specific functions. Hydrogels are one of the most promising soft materials owing to their potential applications in building of biological tissues and stretchable sensors. In this work, a series of hydrogels are synthesized through the co-self-assembly of two types of amphiphiles in their aqueous solution prior to polymerization. Soft and hard parts with nanostructures of different order parameters are incorporated into the hydrogels. The hydrophilic segment (as soft phases) of the polymer network provides water absorption, fluid flow, and softness, whereas the hydrophobic segment (as hard phases) provides strength and tearing and fracture resistance. Appropriate soft/hard nanostructures and their interfaces allow for the tailoring of the desired morphological and mechanical properties, including a different wetting ability, toughness, energy dissipation, self-recovery, and fracture resistance arising from their nanostructures. This work provides insights into the design of nanostructured anisotropic hydrogels with controlled morphological and mechanical properties.

Biosynthesis of highly branched gold nanoparticles through structural engineering of fatty acids.

Biomimetic approaches have been used to develop inorganic nanomaterials with complex morphologies and functions. Fatty acids are among the most important and decomposable biomolecules in nature. However, the controlled synthesis of branched gold nanoparticles using these biomolecules has not been reported. Herein, we demonstrate a strategy to produce highly branched gold nanoparticles through structural engineering of fatty acids. Furthermore, we developed a method for tailoring fatty acid molecules by altering their aliphatic chains to facilitate the morphological evolution of gold nanoparticles from spherical to branched shape. It is found that the growth of the nanoparticles is sensitive to characteristics of fatty acids, such as saturation degrees. The growth of the nanoparticle is visualized by high-speed atomic force microscopy. The reaction mechanisms and growth processes of branched gold nanoparticles are proposed. This work may serve as a cornerstone to the design in a biomimetic fashion for the controllable synthesis of metallic nanomaterials.

[Combined effect of vancomycin or teicoplanin plus a beta-lactam antibiotic in mouse infection models caused by beta-lactam antibiotec-induced vancomycin resistant MRSA (BIVR)].

The concomitant use of low concentration beta-lactam antibiotics antagonizes the activity of vancomycin against some strains of MRSA. These strains, called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR), have been increasing for a number of years. We previously reported that the combination of VCM and ceftizoxime displayed this antagonism not only in vitro, but also in vivo, in a systemic infection caused by BIVR in mice. In the present study, we validated the antagonism in combinations of VCM with other beta-lactams, i.e., flomoxef (FMOX), ampicillin (AMPC), azthreonam (AZT) and imipenem/cilastatin (IPM/CS), in systemic infections and pneumoniain in mice. The survival rate of the mice with systemic infections caused by BIVR treated with combinations of FMOX, AMPC, AZT, and IPM/CS with VCM were significantly lower than with VCM monotherapy, and the number of residual viable cells in the kidneys of mice treated with combinations of FMOX and IPM/CS with VCM were significantly higher than with VCM monotherapy The number of residual viable cells in the lungs of mice with pneumonia caused by BIVR treated with the combination of IPM/CS and VCM was significantly higher than with VCM monotherapy. On the other hand, the survival rate with combination therapy consistings IPM/CS plus teicoplanin (T EIC) was significantly higher, and the number of residual viable cells in the kidney was significantly lower, than with TEIC monotherapy alone. In the mice with pneumonia, the number of residual viable cells in the lung after combination therapy with IPM/CS and TEIC was significantly lower than with TEIC monotherapy. Combination therapy with beta-lactams plus VCM showed antagonistic in models of systemic infection and pulmonary infection caused by BIVR, whereas combination therapy consisting of a beta-lactam plus TEIC had a synergistic effect in the same models, even though VCM and TEIC are member of the same glycopeptide antibiotic class.

A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein-2: A potential treatment for infected bone defects.

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.

Tissue distribution after intravenous dosing of micafungin, an antifungal drug, to rats.

The tissue distribution after an intravenous dose of micafungin (1 mg/kg), a new echinocandin-like lipopeptide antifungal agent, to male rats was investigated. Micafungin in plasma disappeared biexponentially with a terminal half-life of 5.03 h. Micafungin concentrations in liver, kidney, and lung at the first sampling time (5 min) after dosing were 1.15, 1.64, and 2.58-fold higher than the plasma concentration, and the AUC(0- infinity ) were 1.61, 3.42, and 2.89-fold higher than that for plasma. The terminal half-lives for these tissues were 5.14, 4.87, and 5.31 h, respectively, which were comparable to those for plasma. These results suggest that micafungin distributes rapidly and moderately into tissues such as the liver, kidney, and lungs, and that the concentrations in tissues decreased in parallel with the unchanged drug in plasma.

Purification and identification of a tributyltin-binding protein from serum of Japanese flounder, Paralichthys olivaceus.

Tributyltin (TBT) is an industrial chemical used as an antifoulant in marine environments. Previously, we reported that TBT accumulates in the serum or plasma of some fishes and is bound to a high molecular weight compound in the serum of the Japanese flounder, Paralichthys olivaceus. In this study, we succeeded in purifying the TBT-binding protein (TBT-bp) from the serum of Japanese flounder by using gel filtration chromatography, anion exchange chromatography, and polyacrylamide gel electrophoresis, with a 2.6% yield and a 77-fold purification. The molecular mass of TBT-bp was approximately 46.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its isoelectric point was approximately 3.0 on isoelectric focusing-polyacrylamide gel electrophoresis. The TBT-bp contained 42% N-glycan. The cDNA nucleotide sequence of TBT-bp was determined by reverse transcription-polymerase chain reaction of Japanese flounder liver, and we deduced a sequence of 191 amino acids of mature TBT-bp. No sequence identical to the TBT-bp amino acid sequence was found within the SWISS-PROT (http://www.nig. ac.jp/) protein database; however, a lipocalin-like sequence pattern was observed. We concluded that the TBT-bp was a novel protein that has not yet been reported, although some DNA sequences from expressed sequence tags (ESTs) of Japanese flounder liver had a high identity. A high expression level of TBT-bp gene was found in the liver, but the gene was slightly detectable in the kidney and brain.

Clonal association of Staphylococcus aureus causing bullous impetigo and the emergence of new methicillin-resistant clonal groups in Kansai district in Japan.

A molecular epidemiological analysis was performed to reveal the clonal association of Staphylococcus aureus strains isolated from patients with bullous impetigo. Pulsed-field gel electrophoresis with cluster analysis, genetic and phenotypic characterizations, and antimicrobial susceptibility profiling of 88 S. aureus strains isolated from outpatients at 4 hospitals in the Kansai district in Japan were undertaken. Three distinct clonal groups were identified: 2 of them carried the exfoliative toxin (ET) A gene (eta), and the other carried the ETB gene (etb). The former groups represent 2 eta-positive clonal groups that have not been described previously. All the strains in the more dominant eta-positive clonal group and some of the strains in the etb-positive clonal group were methicillin-resistant S. aureus (MRSA) showing borderline-to-moderate resistance to beta-lactams. These MRSA strains appear to be emerging clonal groups that have not been considered in previous epidemiological studies of ET-producing S. aureus in Japan and thus pose a significant threat for future treatment of patients with bullous impetigo and/or staphylococcal scalded-skin syndrome.