Extracting the redox orbitals in Li battery materials with high-resolution x-ray compton scattering spectroscopy.

We present an incisive spectroscopic technique for directly probing redox orbitals based on bulk electron momentum density measurements via high-resolution x-ray Compton scattering. Application of our method to spinel Li_{x}Mn_{2}O_{4}, a lithium ion battery cathode material, is discussed. The orbital involved in the lithium insertion and extraction process is shown to mainly be the oxygen 2p orbital. Moreover, the manganese 3d states are shown to experience spatial delocalization involving 0.16±0.05 electrons per Mn site during the battery operation. Our analysis provides a clear understanding of the fundamental redox process involved in the working of a lithium ion battery.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae.

The in vitro activity of benzylpenicillin in combination with fosfomycin against 51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was investigated. The fractional inhibitory concentration (FIC) index using the checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38). Fosfomycin inhibited the production of all penicillin-binding proteins (PBP) except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it was combined with benzylpenicillin. These results suggest that the combination of benzylpenicillin and fosfomycin could be considered as the alternative treatment of penicillin-resistant pneumococcal infections.

SF2487, a new polyether antibiotic produced by Actinomadura.

A new antibiotic SF2487 has been isolated from the culture broth of Actinomadura sp. SF2487. The structure of antibiotic SF2487 was determined by spectroscopic analyses of the sodium salt and X-ray diffraction analysis of the silver salt. The antibiotic represents a new member of polyether group antibiotics known as the acyltetronic acid type 4. The antibiotic is weakly active against Gram-positive bacteria and exhibits antiviral activity against influenza virus in vitro.

Effects of macrolides on ultrastructure of Staphylococcus aureus during postantibiotic phase.

The postantibiotic effects (PAEs) of macrolide antibiotics, such as midecamycin acetate (Miocamycin, MOM), erythromycin (EM), josamycin (JM) and clarithromycin (CAM), on Staphylococcus aureus and the ultrastructure of the pathogen during the postantibiotic phase were investigated. After exposure to 2 x MIC for 2 h, MOM showed the longest PAE of 3.9 h, while EM, JM and CAM showed PAE durations 1.2, 2.5 and 1.9 h, respectively. On examining the serum levels of these agents in man, the longest PAE of 2.4 h was induced by exposure to MOM. JM and CAM induced PAEs for durations of 1.4 and 1.3 h, but EM hardly induced the PAE. The ultrastructure was examined by transmission electron microscopy, and thick cell walls with an undulating outer layer and a multiple thick cross-section were observed for 4 h after exposure to 2 x MIC of MOM for 2 h. After exposure to 2 x MIC of EM, JM and CAM for 2 h, ultrastructural changes were observed for 1, 2 and 2 h, respectively. The size of these cells was about 1.5 to 2 times larger than the normal cells. Ultrastructural changes in S. aureus were observed during the PAE phase of each macrolide.

In vitro antimicrobial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, compared with that of ceftazidime, cefoperazone and aztreonam.

The antibacterial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, possessing a dihydroxypyridone moiety was compared in vitro with the activity of ceftazidime, cefoperazone, aztreonam and other beta-lactam antibiotics using seven bacterial species of a clinical origin. MT0703S showed the most potent activity against P. aeruginosa, including the ceftazidime-resistant strains, E. coli, K. pneumoniae and C. freundii. MT0703S was comparable to aztreonam but more active than ceftazidime and cefoperazone in its activity against K. oxytoca and E. cloacae, and comparable to ceftazidime against S. aureus and S. marcescens. MT0703S was more active than cefoperazone against S. marcescens but less active against S. aureus. The stability of MT0703S against various beta-lactamases appeared to be intermediate between the stability of ceftazidime and that of cefoperazone. The antimicrobial activity of MT0703S increased in a low-iron environment and decreased in a high ferric ion concentration.

In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent.

2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.

[Antibacteriological activities of arbekacin and vancomycin against strains of MRSA].

The activities of arbekacin (ABK) and vancomycin (VCM) against MRSA were compared, and the results are as follows. 1. In antibacterial activities (MIC value) against 142 strains of MRSA, MIC50 of ABK was two times less than that of VCM. MIC90's were both 1.56 micrograms/ml. 2. ABK was also superior to VCM in bactericidal activities within a short time against 100 strains of MRSA. After 4 hours, 42 strains were killed to below 10(-2) by 2 MIC of ABK, but 6 strains were killed to 10(-2) by 4 MIC of VCM. 3. Against the MRSA 1936 strain, neither ABK nor VCM was active, when an inoculum size of about 10(8) CFU/ml was used. At an inoculum size of 10(5) CFU/ml, ABK showed strong bactericidal activity in a dose dependent manner, while bacteria killing activity of VCM was time dependent. 4. In experimental infections with the MRSA 1936 strain, ABK showed high bactericidal activity rapidly, and area of body that showed bacterial inhibition appeared to be large compared to that obtained with VCM. 5. As to protection from MRSA infections, ABK was significantly superior to VCM in activities against 3 out of 4 strains of MRSA tested. ABK showed more pronounced efficacy when administered in a single dose than in divided doses. These results indicated that ABK would exhibit therapeutic efficacy in a short time.

Metabolism of 2(R,S)-1,2-bis(nicotinamido)propane, a new agent with anti-vasospasm activity, in rats and rabbits.

1. The metabolic fate of the new Anti-vasospasm Substance (AVS), 2(R,S)-1,2-bis(nicotinamido)propane (CAS 79455-30-4), was studied using 14C-labelled drug in rats and rabbits by thinlayer chromatography, mass spectrometry and nuclear magnetic resonance. 2. More than 75% of the radioactivity was observed in the urine when 14C-AVS was given intravenously to rabbits and rats, showing that the major route of excretion of AVS and its metabolites is via the kidney. 3. Marked species differences were observed in the metabolism of AVS in rats and rabbits. In rabbits, the major metabolites were 6- or 6'-monopyridone (23.5% of dose), and there were a few minor metabolites such as the mono N- or N1-oxide of two pyridine rings. In rats, however, only approximately 5% of the radioactivity was due to metabolites, mainly the N-oxide. 4. Formation of AVS monopyridone by rabbit liver cytosol was much higher than in rats, and was markedly inhibited by the aldehyde oxidase inhibitor, menadione. The difference between rats and rabbits in oxidase activity giving the AVS monopyridone metabolite correlated well with that measured by the general assay method for aldehyde oxidase. These results suggest that the species difference in AVS metabolism between rats and rabbits is mainly due to the difference in aldehyde oxidase activity, which is involved in formation of the monopyridone.

The in-vivo activity of an antifungal antibiotic, benanomicin A, in comparison with amphotericin B and fluconazole.

The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.

Characterization of the eicosapentaenoic acid biosynthesis gene cluster from Shewanella sp. strain SCRC-2738.

The 38 kb eicosapentaenoic acid (EPA) biosynthesis gene cluster of Shewanella sp. strain SCRC-2738 was cloned into the cosmid vector (pEPA). A 27 kb nucleotide sequence of the XhoI to SpeI region of pEPA showed EPA production (6.3%) in E. coli JM109. Among the nine open reading frames (ORFs) in this sequence, only five (ORFs 2 and 5-8) were essential for EPA production. High levels of production (16%-22%) were found in E. coli JM109 transformed with a multicopy pNEB vector carrying only the five essential ORFs and in that transformed with a pNEB vector that integrated ORFs 3, 5, 6, 7 and 8, and vector pSTV28 that integrated the ORF2 encoding phosphopantetheinyl transferase (PPTase). Thus, production of EPA appears to be regulated by the presence of all the biosynthesis gene products and by the ratio of PPTase to the other gene products. The temperature -EPA production relationship in E. coli strain DH5alpha varied between constructs, suggesting that it is controlled not only by EPA biosynthesis enzymes but also by other factors in vivo. There was a strict upper temperature limit for EPA biosynthesis: no EPA was synthesized at 30 degrees C in E. coli transformants carrying any gene construct for EPA biosynthesis.

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.