記述言語：英語  

DOI： 10.1371/journal.pone.0119010

Open Access

記述言語：英語  

DOI： 10.1016/j.biomaterials.2012.12.013

記述言語：英語  

DOI： 10.2220/biomedres.34.13

Open Access

記述言語：日本語  

DOI： 10.4161/isl.24025

Open Access

Web of Science

記述言語：英語  

DOI： 10.4161/isl.3.3.15611

Web of Science

記述言語：英語  

DOI： 10.2220/biomedres.31.239

Open Access

記述言語：英語   出版者・発行元：Journal of Pharmacology and Experimental Therapeutics  

The present study examined the modulator role of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway activated by the α-1 adrenoceptor agonist phenylephrine in ATP-sensitive K⁺ channel function in intact vascular smooth muscle. We evaluated the ATP-sensitive K⁺ channel function and the activity of the PI3K-Akt pathway in the rat thoracic aorta without endothelium. The PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4- one hydrochloride (LY294002) (10^-5 M) augmented relaxation in response to the ATP-sensitive K⁺ channel opener levcromakalim (10^-8 to 3 × 10^-6 M) in aortic rings contracted with phenylephrine (3 × 10^-7 M) but not with 9,11-dideoxy- 11α,9α-epoxy-methanoprostaglandin F<inf>2α</inf> (U46619; 3 × 10^-8 M), although those agents induced similar contraction. ATP-sensitive K⁺ channel currents induced by levcromakalim (10 ^-6 M) in the presence of phenylephrine (3 × 10^-7 M) were enhanced by the nonselective α-adrenoceptor antagonist phentolamine (10^-7 M) and LY294002 (10^-5 M). Levels of the regulatory subunits of PI3K p85-α and p55-γ increased in the membrane fraction from aortas without endothelium treated with phenylephrine (3 × 10 ^-7 M) but not with U46619 (3 × 10^-8 M). Phenylephrine simultaneously augmented Akt phosphorylation at Ser473 and Thr308. Therefore, activation of the PI3K-Akt pathway seems to play a role in the impairment of ATP-sensitive K⁺ channel function in vascular smooth muscle exposed to α-1 adrenergic stimuli. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.

DOI： 10.1124/jpet.110.167775

Web of Science

Scopus

PubMed

記述言語：英語  

DOI： 10.1124/jpet.109.163543

記述言語：英語   出版者・発行元：公益社団法人 日本薬理学会  

Sepsis remains the leading cause of death in critically ill patients. A major problem contributing to sepsis-related high mortality is the lack of effective medical treatment. Thus, the key goal in critical care medicine is to develop novel therapeutic strategies that will impact favorably on septic patient outcome. While it is generally accepted that sepsis is an inflammatory state resulting from the systemic response to infection, apoptosis is implicated to be an important mechanism of the death of lymphocytes, gastrointestinal and lung epithelial cells, and vascular endothelial cells associated with the development of multiple organ failure in sepsis. The pivotal role of cell apoptosis is now highlighted by multiple studies demonstrating that prevention of cell apoptosis can improve survival in clinically relevant animal models of sepsis. In this review article, we address the scientific rationale for remedying apoptotic cell death in sepsis and propose that therapeutic efforts aimed at blocking cell signaling pathways leading to apoptosis may represent an attractive target for sepsis therapy. ©2010 The Japanese Pharmacological Society.

DOI： 10.1254/jphs.10r04cr

Web of Science

Scopus

PubMed

CiNii Research

記述言語：日本語   出版者・発行元：日本臨床麻酔学会  

全身性炎症反応症候群（SIRS）にはさまざまな病態が伴うが，頻脈性不整脈もこの経過中にしばしば遭遇する病態である．心筋においても他の臓器と同様に炎症による変化が観察され，不整脈や心不全発症の原因となる．心房細動などの頻脈性不整脈発症には，炎症による交感神経の過緊張状態，カテコラミンに対する反応性の変化，活動電位を構成するイオンチャネルの発現に対する影響，炎症により過剰産生されたNOによるイオンチャネル機能の修飾などさまざまな要因が関係している．このような状態においてはもはやカテコラミンのみによる治療は効果に限界があり，PDE III阻害薬とβ遮断薬を使った治療などの新しい治療戦略の構築が求められる．

DOI： 10.2199/jjsca.30.765

CiNii Research

記述言語：日本語  

DOI： 10.1254/fpj.134.198

担当区分：筆頭著者   記述言語：英語  

DOI： 10.1007/s00418-006-0207-0

出版者・発行元：Journal of Physical Chemistry B  

An ultraviolet photoelectron spectroscopic study was performed to examine the electronic structure of poly(1,1,2,2-tetramethyldisilylenemethylene), [(SiMe<inf>2</inf>)<inf>2</inf>CH<inf>2</inf>]<inf>n</inf>, which consists of repeating Si-Si-C units. We compared the observed spectra to reported gas-phase spectra of Si<inf>2</inf>Me<inf>6</inf> and Si<inf>4</inf>Me<inf>10</inf> and theoretical molecular orbital calculations. Theoretical calculations by the ab initio and PM3 methods agree well with the observed spectra, which enabled assignment of the observed spectral features. The broad peak derived from Si-Si bond orbitals in polycarbosilane suggests that Si-Si units, which are separated by carbon atoms, still interact with each other, to form σ-conjugation through the backbone. The observed ionization threshold energy of the polycarbosilane[(SiMe<inf>2</inf>)<inf>2</inf>CH<inf>2</inf>]<inf>n</inf> is 6.4 eV. The dispersion of the highest valence band of polycarbosilane is less than that of polysilane, indicating that the degree of σ-conjugation of polycarbosilane is smaller than that of polysilane.

DOI： 10.1021/jp0031698

Web of Science

Scopus