14 research outputs found
Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin
Improvement of pulmonary arterial hypertension, inflammatory response, and epithelium injury by dual activation of cAMP/cGMP pathway in a rat model of monocrotaline-induced pulmonary hypertension
Pharmacokinetic and Pharmacodynamic Modeling of Hedgehog Inhibitor TAK-441 for the Inhibition of Gli1 messenger RNA Expression and Antitumor Efficacy in Xenografted Tumor Model Mice
Cloning and Expression of a Novel Lysophospholipase Which Structurally Resembles Lecithin Cholesterol Acyltransferase
Ameliorative effect of phosphodiesterase 4 and 5 inhibitors in deoxycorticosterone acetate‐salt hypertensive uni‐nephrectomized KKA y
延岡市の福祉施設における言語聴覚障害児・者の実態について
A survey was conducted to understand the nature and management of persons with speech-language-hearing (SLH) and related disorders in facilities of child welfare and the elderly in Nobeoka city. The questionnaire was sent to 84 facilities and approximately a half of the facilities (51.2%) responded. No speech therapist (ST) was employed in these facilities. SLH disorders were identified in the 16.9% of individuals who resided in and commuted to these facilities. Overall, language disorders, i.c., language delay and aphasia, were the most frequently identified SLH disorder, followed by dysphagia and hearing disorders in the facilities for the elderly and articulation disorders in the child welfare facilities. The post-onset period of SLH and related disorders was seldom known. SLH therapy was taken only for 3.4% individuals. Paraprofessionals had involved for the management of SLH and related disorders. It is assumed that no formal evaluation was conducted in these facilities. Some paraprofessionals had joined a study group (16% of the facilities). It is hoped to establish the system of the evaluation and management of SLH and related disorders in these facilities in Nobeoka city
Discovery of Novel 5‑(Piperazine-1-carbonyl)pyridin-2(1<i>H</i>)‑one Derivatives as Orally eIF4A3-Selective Inhibitors
Starting
from our previous eIF4A3-selective inhibitor <b>1a</b>, a novel
series of (piperazine-1-carbonyl)pyridin-2(1<i>H</i>)-one
derivatives was designed, synthesized, and evaluated for identification
of orally bioavailable probe molecules. Compounds <b>1o</b> and <b>1q</b> showed improved physicochemical and ADMET profiles, while
maintaining potent and subtype-selective eIF4A3 inhibitory potency.
In accord with their promising PK profiles and results from initial
in vivo PD studies, compounds <b>1o</b> and <b>1q</b> showed
antitumor efficacy with T/C values of 54% and 29%, respectively, without
severe body weight loss. Thus, our novel series of compounds represents
promising probe molecules for the in vivo pharmacological study of
selective eIF4A3 inhibition