著者

Shigeo Shinoda Takahiko Aoyama Yukio Aoyama Sachiko Tomioka Yoshiaki Matsumoto Yoko Ohe

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.1, pp.157-161, 2007 (Released:2007-01-01)

参考文献数

27

被引用文献数

31 38

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Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000 mg of APAP orally. Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000 mg to allow for an adequate analgesic effect. Plasma APAP and APAP metabolite concentrations were measured in the volunteers, plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain. Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment. A sigmoid Emax model was used as the pharmacodynamic model. Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than 0.2 μg/ml, but no side effects were observed. The pharmacokinetic and pharmacodynamic parameter (mean±S.D.) estimates were as follows: clearance, 18.7±4.7 l/h; distribution volume, 30.9±6.8 l; absorption rate constant, 2.4±1.3 h−1; rate constant for the elimination of APAP from the effect compartment, 1.3±0.5 h−1; maximum pain relief score, 4.6±2.2 units; effect compartment concentration at 50% maximum, 2.0±1.2 μg/ml; and sigmoid factor, 1.3±0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.

著者

Sachiko Tomioka Toshiro Aigaki Takashi Matsuo

出版者

日本遺伝学会

雑誌

Genes & Genetic Systems (ISSN:13417568)

巻号頁・発行日

vol.87, no.5, pp.323-329, 2012 (Released:2013-02-13)

参考文献数

13

被引用文献数

2 7

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Insect odorant-binding proteins function in the sensing of odors, tastes, and pheromones. Genes encoding two odorant-binding proteins, Obp57d and Obp57e, were identified to be involved in the behavioral adaptation of Drosophila sechellia to its host plant. The two genes are expressed in cells associated with taste sensilla on the legs, and the expression pattern in the legs is conserved among closely related species. To identify the cis-regulatory elements necessary for the expression in the leg sensilla, the promoter sequences of Obp57d and Obp57e were compared among species. Two types of conserved sequence-motifs were found as candidate cis-regulatory elements. Functions of these conserved elements in the promoters of D. melanogaster Obp57d and Obp57e were examined by using a newly constructed vector that combines the advantages of φC31 integrase-based transformation and gypsy transposable-element-derived insulators. By GFP-reporter assay using the new vector, it was confirmed that these conserved elements are necessary for the expression in the legs, working synergistically with each other to affect the expression level. Single-nucleotide substitutions in these elements dramatically changed the promoter activity. These results provide insight into the molecular mechanism for evolution of adaptive behavior via modulation of OBP expression levels.