Phenotypic screening using waveform analysis of synchronized calcium oscillations in primary cortical cultures.

At present, in vitro phenotypic screening methods are widely used for drug discovery. In the field of epilepsy research, measurements of neuronal activities have been utilized for predicting efficacy of anti-epileptic drugs. Fluorescence measurements of calcium oscillations in neurons are commonly used for measurement of neuronal activities, and some anti-epileptic drugs have been evaluated using this assay technique.

A novel method for predicting the efficacy of topical drugs on onychomycosis: A comparison of efinaconazole and luliconazole.

To be effective against onychomycosis, topically applied drugs have to reach the infection site at an effective concentration to exert antifungal activity against the parasitic form of dermatophytes. We established a novel in vitro method for predicting drug efficacy at the infection site and verified the method by comparing the efficacy of two azole class topical anti-onychomycosis drugs. To predict drug efficacy in the nail plate, a human nail permeability test was conducted and the activities of the free-drugs in the upper, middle, and lowest layers of the nail plate were determined by measuring the growth inhibitory zone.

Scalable Total Syntheses and Structure-Activity Relationships of Haouamines A, B, and Their Derivatives as Stable Formate Salts.

Haouamines A, B, and their derivatives were synthesized via Suzuki-Miyaura coupling and three key cyclization reactions as follows: the newly developed palladium(0)-catalyzed arylative cyclization of phenylalanine-derived alkyne-aldehydes with 2-bromoarylboronic acid (an "anti-Wacker"-type cyclization); BF ⋅OEt -promoted Friedel-Crafts-type cyclization of symmetrical electron-rich aromatic rings adjacent to a tertiary allylic alcohol leading to the indeno-tetrahydropyridine skeleton; and (cyanomethyl)trimethylphosphonium iodide-mediated macrocyclization of amino alcohols to afford aza-paracyclophane precursors. The palladium-catalyzed reduction of mono- and di-triflate intermediates in the later stages enabled the alteration of both the position and number of hydroxyl groups on the C-ring. The instability of haouamine B was dramatically improved by salt formation with formic acid.

Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system.

The pathophysiological role of mammalian target of rapamycin complex 1 (mTORC1) in neurodegenerative diseases is established, but possible therapeutic targets responsible for its activation in neurons must be explored. Here we identified solute carrier family 38a member 1 (SNAT1, ) as a positive regulator of mTORC1 in neurons. and mice were crossed to generate mutant mice in which was selectively deleted in neurons.

A new strategy for taste masking on bitter drug by other combined drug in fixed-dose combination: bitterness of Amlodipine besylate could be masked efficiently by Valsartan.

Objectives: The aim of this study was to evaluate the bitterness of amlodipine besylate (AML) combined with other five antihypertensive drugs: alacepril, benazepril, hydrochlorothiazide, telmisartan (TEL) and valsartan (VAL), which have possibility of usage as a fixed-dose combination (FDC) drugs.

Methods: The bitterness of individual six drugs and AML combined with each of the five drugs was evaluated using taste sensor SA402B (Intelligent Sensor Technology Inc.).

Evaluation of the effects of ontogenetic or maturation functions and chronic heart failure on the model analysis for the dose-response relationship of warfarin in Japanese children.

Purpose: We previously demonstrated that the rational pediatric dosage of warfarin can be well-described by a SIZE parameter that includes an allometry exponent of weight. On the other hand, allometry alone is considered to be insufficient to predict drug clearance in neonates and infants. The primary purpose of the present study was to evaluate the effects of incorporation of the maturation process into the analysis model for the dose-response relationship of warfarin in Japanese children.

Couple Reports on Intimate Partner Violence and their Health Impact: Evidence From a Population-Based Survey in Japan.

Recent studies have shown that couples' reports of intimate partner violence (IPV) are not necessarily consistent. This study investigated the associations between patterns of partner victimization and perpetration reports and health and perceived wellbeing. Using household survey data from a probabilistic urban sample of adults aged 25 to 50 years and their partners, we identified 1,467 heterosexual pairs who completed the modified Japanese version of the Conflict Tactics Scale 2 Short Form.

Reduction in Vegetable Intake Disparities With a Web-Based Nutrition Education Intervention Among Lower-Income Adults in Japan: Randomized Controlled Trial.

Background: No existing Web-based nutrition education interventions have been evaluated in light of socioeconomic status just in Japan.

Objective: The aim was to investigate the effect of a Web-based intervention program on reducing vegetable intake disparities between low- and middle-income Japanese adults.

Methods: In this randomized controlled trial, participants were assessed at three time points-baseline, postintervention (5 weeks later), and a follow-up after 3 months-from October 2015 to March 2016.

The possible clinical impact of risperidone on P-glycoprotein-mediated transport of tacrolimus: A case report and in vitro study.

The authors encountered the case of an 8-fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). It was hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by voriconazole and P-glycoprotein (P-gp) inhibition of the small intestine by risperidone exerted a synergistic effect on the bioavailability of tacrolimus.

Cooling the lower abdomen to reduce postpartum blood loss: A randomized controlled trial.

Background: Cooling the lower abdomen is one of the Japanese traditional non-pharmacological prophylactic managements for postpartum hemorrhage. This study aimed to evaluate the effectiveness of cooling the lower abdomen in reducing postpartum blood loss compared with no intervention. In both cases, women delivered vaginally without prophylactic oxytocin in the third stage of labor.

Taste-Masking Effect of Chlorogenic Acid (CGA) on Bitter Drugs Evaluated by Taste Sensor and Surface Plasmon Resonance on the Basis of CGA-Drug Interactions.

The purpose of this study was to evaluate the taste-masking effects of chlorogenic acid (CGA) on bitter drugs using taste sensor measurements and surface plasmon resonance (SPR) analysis of CGA-drug interactions. Six different bitter drugs were used: amlodipine besylate (AMD), diphenhydramine hydrochloride (DPH), donepezil hydrochloride (DNP), rebamipide (RBM), diclofenac sodium (DCF) and etodolac (ETD). Taste sensor outputs were significantly inhibited by the addition of CGA to all drugs.

A randomized-controlled trial focusing on socio-economic status for promoting vegetable intake among adults using a web-based nutrition intervention programme: study protocol.

Background: Web-based nutritional education programmes appear to be comparable to those delivered face-to-face. However, no existing web-based nutrition education or similar programme has yet been evaluated with consideration of socio-economic status. The objective of a nutritional education programme of promoting vegetable intake designed a randomized controlled trial (RCT) is to evaluate the results of intervention and to determine how socio-economic status influences the programme effects.

Effects of Brief Communication Skills Training for Workers Based on the Principles of Cognitive Behavioral Therapy: A Randomized Controlled Trial.

Objective: Stimulating communication is an important workplace issue. We investigated the effects of a brief communication skills training (CST) program based on the principles of cognitive behavioral therapy (CBT).

Methods: A randomized controlled trial was conducted on 206 white-collar workers.

Bone Resorption Is Regulated by Circadian Clock in Osteoblasts.

We have previously shown that endochondral ossification is finely regulated by the Clock system expressed in chondrocytes during postnatal skeletogenesis. Here we show a sophisticated modulation of bone resorption and bone mass by the Clock system through its expression in bone-forming osteoblasts. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Period1 (Per1) were expressed with oscillatory rhythmicity in the bone in vivo, and circadian rhythm was also observed in cultured osteoblasts of Per1::luciferase transgenic mice.

An Alteration in the Cecal Microbiota Composition by Feeding of 1-Kestose Results in a Marked Increase in the Cecal Butyrate Content in Rats.

Functional food ingredients, including prebiotics, have been ardently developed for improving the intestinal environment. Fructooligosaccarides (FOS), including fructans, are the well researched and commercialized prebiotics. However, to our knowledge, few studies have been conducted on the physiological effects of each component of FOS as prebiotics.

The intrinsic microglial clock system regulates interleukin-6 expression.

Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin-6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses.

Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS.

Mammalian transient receptor potential ankyrin 1 (TRPA1) is a polymodal nociceptor that plays an important role in pain generation, but its role as a cold nociceptor is still controversial. Here, we propose that TRPA1 can sense noxious cold via transduction of reactive oxygen species (ROS) signalling. We show that inhibiting hydroxylation of a proline residue within the N-terminal ankyrin repeat of human TRPA1 by mutation or using a prolyl hydroxylase (PHD) inhibitor potentiates the cold sensitivity of TRPA1 in the presence of hydrogen peroxide.

In Vitro Enhancement of Carvedilol Glucuronidation by Amiodarone-Mediated Altered Protein Binding in Incubation Mixture of Human Liver Microsomes with Bovine Serum Albumin.

Carvedilol is mainly metabolized in the liver to O-glucuronide (O-Glu). We previously found that the glucuronidation activity of racemic carvedilol in pooled human liver microsomes (HLM) was increased, R-selectively, in the presence of amiodarone. The aim of this study was to clarify the mechanisms for the enhancing effect of amiodarone on R- and S-carvedilol glucuronidation.

A model analysis for dose-response relationship of warfarin in Japanese children: An introduction of the SIZE parameter.

The objective of the present study was to develop an optimal equation for the pediatric dose-response relationship of warfarin using a size parameter with an exponent of body weight (SIZE) which has been proposed for scaling drug clearance. Twenty patients with stable anticoagulation by warfarin were enrolled in the present study. During a mean follow-up period of 7.