Utility of rekkotoken （Rhododendron anthopogonoides Maxim), Tibetan herbal medicine, as cosmetics

研究ノート (Note

Roundabout relaxation: collective excitation requires a detour to equilibrium

Relaxation to equilibrium after strong and collective excitation is studied, by using a Hamiltonian dynamical system of one dimensional XY model. After an excitation of a domain of $K$ elements, the excitation is concentrated to fewer elements, which are made farther away from equilibrium, and the excitation intensity increases logarithmically with $K$. Equilibrium is reached only after taking this ``roundabout'' route, with the time for relaxation diverging asymptotically as $K^\gamma$ with $\gamma \approx 4.2$.Comment: 4 pages, 5 figure

Parallel Transport in Gauge Theory on M4×Z2M_4 \times Z_2 Geometry

We apply the gauge theory on $M_4\times Z_2$ geometry previously proposed by Konisi and Saito to the Weinberg-Salam model for electroweak interactions, especially in order to clarify the geometrical meaning of curvatures in this geometry. Considering the Higgs field to be a gauge field along $Z_2$ direction, we also discuss the BRST invariant gauge fixing in this theory.Comment: 14 pages, LaTeX file. Change in title and minor changes in conten

胃部分切除一症例でのイトラコナゾール固形製剤と内用液剤投与後の血中濃度比較

In this paper, we report that in pulmonary aspergillosis patient who had history of resection of the stomach, the blood concentrations of itraconazole（ITCZ）and its active metabolite, hydroxy-ITCZ（OHITCZ） after taking oral solid formulation of ITCZ were remarkably low, whereas their blood concentrations significantly increased after switching from the solid formulation to the solution formulation.During administration of the ITCZ tablets（200 mg/day）, trough blood concentration of ITCZ and OH-ITCZ were 15 ng/mL and 18 ng/mL, respectively. On the other hand, when it was switched from the tablet to the oral solution（200 mg/day as ITCZ）, blood concentrations of ITCZ and OH-ITCZ increased to 1056 ng/mL and 1492 ng/mL, respectively. It was considered that the absorption of ITCZ tablets declined because the gastric acid secretion ability of the patients was decreased by gastrectomy.研究ノー

肺アスペルギルス症患者におけるイトラコナゾールおよび

A patient was given generic itraconazole (ITCZ) tablet, brand-name-ITCZ capsule, ITCZ oral solution and ITCZ injection to treat pulmonary aspergillosis. We monitored concentrations of ITCZ and its active metabolite hydroxy-ITCZ (OH-ITCZ) in plasma and lung tissues. During administration of the generic product (400 mg/day), trough plasma concentrations of ITCZ and OH-ITCZ were 76 ng/mL and 126 ng/mL, respectively. After administration of the brand-name product (200 mg/day), they increased to 229 ng/mL and 540 ng/mL, respectively. ITCZ and OH-ITCZ concentrations/dosage ratios were 6.1 and 8.4 times higher by switching to the brand-name product, respectively. It was suggested that there may be a difference in pharmacokinetics between the brand-name ITCZ and the generic. Also, we determined ITCZ and OH-ITCZ concentrations infected and uninfected tissues of resected lung simultaneously. The ITCZ concentration in the infected lesion of the lung was approximately 2.3 times higher than that in plasma and 1.6 times higher than in uninfected lung tissue. The OH-ITCZ concentration in the infected lesion was higher than ITCZ in the same region. It was considered that the high concentrations of ITCZ and its metabolite at infected lesion were due to their high affinities with ergosterol in fungal membrane.研究ノー

ナメクジウオmyc遺伝子の進化的解析

The proto-oncogene myc is one of the most important genes controlling cell proliferation. The vertebrate genome has four myc genes (c-, N-, L-, s-myc), whose evolutionary origin and relationship are unclear. Here, we isolated a myc gene from a protochordate, the amphioxus Branchiostoma belcheri, which is thought to be the nonvertebrate that is closest to the vertebrates. A 1480 bp cDNA sequence was determined and contains an ATGinitiated ORF consisting of 371 amino acids. The exon/intron structure was conserved. Southern blotting and degenerate PCR showed that the amphioxus genome contained only a single myc gene. A phylogenetic tree of Myc family genes based on the deduced amino acid sequences indicated that amphioxus Myc was located outside the vertebrate Myc family. These results suggest that myc gene duplication occurred after protochordate on phylogeny.がん原遺伝子myc は細胞増殖を制御する重要な遺伝子の一つである。脊椎動物では4種類のmycが存在しているが，その起源や類縁関係は明らかとなっていない。本研究で我々は，脊椎動物に最も近縁の無脊椎動物であるナメクジウオBranchiostoma belcheriからmyc遺伝子を単離した。全長1480塩基対のcDNA は371アミノ酸からなるORFを含んでいた。また，エキソン／イントロン構造は保存されていた。サザンブロット法およびdegenerate PCRの結果，ナメクジウオのゲノムは単一のmyc 遺伝子を持つことが明らかとなった。また，推定アミノ酸配列に基づいた系統解析の結果，ナメクジウオMyc は脊椎動物Mycファミリーの外側に位置していた。これらの結果から，myc ファミリーは原索動物以降に形成されたものと考えられた。東京海洋大学海洋科学部海洋生物資源学科東京海洋大学海洋科学部海洋生物資源学科コネチカット大学東京大学海洋研究所日本魚類生物科学研究所東京海洋大学海洋科学部海洋生物資源学

カルパペネム系抗菌薬・メロペネムの血液試料中での安定性に関する研究

Meropenem is a relatively unstable compound when dissolved; therefore, in studying pharmacokinetics (PK), accurate PK analysis may be interrupted depending on the handling of collected blood samples because it also rapidly degrades during processing and preserving of the blood samples. Thus, prior to PK studies, we determined the stability of meropenem in plasma with and without the same volume of 1 M 3-(N-morpholino)-propane-sulfonic acid (MOPS) buffer as a stabilizer were preserved under the conditions of -80℃, -20℃, 4℃ and 25℃, and the remaining meropenem level upon high-performance liquid chromatography at 1, 3, 7, 14, 30, 60, 120 and 180 days following preservation was measured to calculate the meropenem residual rate. The residual rate of plasma samples preserved at -80℃ was 95% or higher for 180 days. On the other hand, under the preservation condition over -20℃, the residual rate at 1 day following preservation was less than 95%. The stability of plasma sample was improved by adding MOPS buffer, and the residual rate was 95% or higher for 7 days at -20℃. Therefore, plasma samples for PK study of meropenem should be added MOPS buffer and preserved in a frozen state.研究ノー

血中濃度解析に基づくイトラコナゾール内用液剤の至適服用タイミングの検討

In this study, we examined the optimal time for taking itraconazole（ITCZ）oral solution based on the analysis of its blood concentration. The trough blood concentrations of both itraconazole and its active metabolite hydroxy-ITCZ were about twice higher under taking ITCZ oral solution between meals than under taking it before meals. The results of this study show that the absorption of ITCZ oral solution was affected not only by the meal before taking but also by the meal after taking it. Our findings suggest that the timing for taking ITCZ oral solution was better between meals than before meals.論

Evaluation of Multidrug Efflux Pump Inhibitors by a New Method Using Microfluidic Channels

Fluorescein-di-β-d-galactopyranoside (FDG), a fluorogenic compound, is hydrolyzed by β-galactosidase in the cytoplasm of Escherichia coli to produce a fluorescent dye, fluorescein. We found that both FDG and fluorescein were substrates of efflux pumps, and have developed a new method to evaluate efflux-inhibitory activities in E. coli using FDG and a microfluidic channel device. We used E. coli MG1655 wild-type, ΔacrB (ΔB), ΔtolC (ΔC) and ΔacrBΔtolC (ΔBC) harboring plasmids carrying the mexAB-oprM (pABM) or mexXY-oprM (pXYM) genes of Pseudomonas aeruginosa. Two inhibitors, MexB-specific pyridopyrimidine (D13-9001) and non-specific Phe-Arg-β-naphthylamide (PAβN) were evaluated. The effects of inhibitors on pumps were observed using the microfluidic channel device under a fluorescence microscope. AcrAB-TolC and analogous pumps effectively prevented FDG influx in wild-type cells, resulting in no fluorescence. In contrast, ΔB or ΔC easily imported and hydrolyzed FDG to fluorescein, which was exported by residual pumps in ΔB. Consequently, fluorescent medium in ΔB and fluorescent cells of ΔC and ΔBC were observed in the microfluidic channels. D13-9001 substantially increased fluorescent cell number in ΔBC/pABM but not in ΔBC/pXYM. PAβN increased medium fluorescence in all strains, especially in the pump deletion mutants, and caused fluorescein accumulation to disappear in ΔC. The checkerboard method revealed that D13-9001 acts synergistically with aztreonam, ciprofloxacin, and erythromycin only against the MexAB-OprM producer (ΔBC/pABM), and PAβN acts synergistically, especially with erythromycin, in all strains including the pump deletion mutants. The results obtained from PAβN were similar to the results from membrane permeabilizer, polymyxin B or polymyxin B nonapeptide by concentration. The new method clarified that D13-9001 specifically inhibited MexAB-OprM in contrast to PAβN, which appeared to be a substrate of the pumps and permeabilized the membranes in E. coli