Scheme I 4 concomitantly, 2-methylene ketone 4g was formed (monitored by NMR). After 4 h, dehydrostannation was complete, and the precipitate was filtered off. Aqueous workup of the filtrate (pentane/aqueous NH4C1) followed by evaporation of the solvents and bulb-to-bulb distillation afforded 2-methylenecycloheptanone (4g) in 80% yield. Similarly, essentially quantitative conversion of 3 to 4 (eq 1) was observed in the reaction of 3 with Me2SO-d6/CDCl3 3 4 at 60 °C (by NMR) except for 3f which did not bear hydrogen ß to the stannyl group.9 The results are shown in Table I. The dehydrostannation of 3d,e,g,h proceeded with shorter reaction time than 3a-c. It seems that for dehydrostannation to occur, the intramolecular coordination of the carbonyl oxygen to the Sn atom (as indicated by IR) may play a key role. In fact, dehydrostannation did not take place with simple n-BuSnCl3 even under more forcing conditions (60 °C, 1 day). One plausible explanation for the present reaction is shown in Scheme I. The initial role of Me2SO may be the one as a base toward /3-hydrogen10 which may be sufficiently acidic due to the inductive effect of the adjacent carbonyl coordinated to the Sn. Thus, the deprotonation from 5 and subsequent destannylation via 6 would occur to lead to 4 and HSnCl3(Me2SO)" complex.11,12 Interestingly, the reaction of siloxycyclopropane 7 with SnCl4 in CH2C12 proceeded similarly and afforded ß-tríchlorostannyl aldehyde 8 (semisolid, vc=0 1680 cm-1). The (9) As the preparative method of /3-stannyl ketones 3, hydrostannation of ,/8-unsaturated ketones with HSnClg (in situ generated under acidic conditions: HC1 and SnCl2) has been known. The observed dehydrostannation promoted by Me2SO formally corresponds to its reverse reaction. See:

ATX‐S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second‐generation photosensitizer for use in photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using ATX‐S10(Na) and a diode laser for experimental tumors was evaluated in vitro and in vivo. In‐vitro PDT using ATX‐S10(Na) and the diode laser showed drug concentration‐, laser dose‐ and drug exposure time‐dependent cytotoxicity to various human and mouse tumor cell lines. In Meth‐A sarcoma‐implanted mice, optimal PDT conditions were found where tumors were completely eliminated without any toxicity. Against human tumor xenografts in nude mice, the combined use of 5 mg/kg ATX‐S10(Na) and 200 J/cm2 laser irradiation 3 h after ATX‐S10(Na) administration showed excellent anti‐tumor activity, and its efficacy was almost the same as that of PDT using 20 mg/kg porfimer sodium and a 100 J/cm2 excimer dye laser 48 h after porfimer sodium injection. Microscopic observation of tumor tissues revealed that PDT using ATX‐S10(Na) and the diode laser induced congestion, thrombus and degeneration of endothelial cells in tumor vessels, indicating that a vascular shutdown effect plays an important role in the anti‐tumor activity of PDT using ATX‐S10(Na) and the diode laser.

ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum at 670 nm, is a candidate second-generation photosensitizer for photodynamic therapy (PDT) for cancer treatment. In this study, we examined plasma protein binding, cellular uptake and subcellular targets of ATX-S10(Na) in vitro. Protein binding ratios of 50 µ µ µ µg/ml ATX-S10(Na) in rat, dog and human plasma were 73.0%, 87.2% and 97.7%, respectively. Gel filtration chromatography revealed that 1 mg/ml ATX-S10(Na) bound mainly to high-density lipoprotein (HDL) and serum albumin at the protein concentration of 0.4%, with binding ratios of 46% and 36%, respectively. The free form of ATX-S10(Na) was mostly incorporated into T.Tn cells, and its cellular uptake was partially but significantly inhibited by endocytosis inhibitors such as phenylarsine oxide, chloroquine, monensin and phenylglyoxal, and by chilling the cells to 4°C. However, ouabain, harmaline, sodium cyanide, probenecid and aspartic acid did not influence the uptake of ATX-S10(Na), suggesting that cellular uptake of ATX-S10(Na) was not related to sodium-potassium pump activity, sodium-dependent transporter activity, mitochondrial oxidative respiration, organic anion transporter activity or aspartic acid transporter activity. By fluorescence microscopy, lysosomal localization of ATX-S10(Na) was observed in T.Tn cells. However, electron microscopic observation revealed that many subcellular organelles such as mitochondria, endoplasmic reticulum, ribosomes, Golgi complex and plasma membrane were damaged by PDT using 25 µ µ µ µg/ml ATX-S10(Na) soon after laser irradiation at 50 J/cm 2 , and tumor necrosis was rapidly induced. This result indicated that ATX-S10(Na) was widely distributed within the cell.

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The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and-resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be b-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be b-lactamase-non-producing ABPC-resistant and 11.0% to be b-lac-tamase-producing ABPC-resistant strains. Extended spectrum b-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo b-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.