This is a clinical safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) study of single ascending dose (SAD) multiple (MAD) the oral direct factor Xa inhibitor edoxaban in healthy males. The placebo-controlled, single-blind, randomized, 2-part consists SAD arm with 85 subjects (10, 30, 60, 90, 120, 150 mg) MAD 36 (90 mg daily, 60 twice 120 daily). Effects food formulation (tablet vs solution) are assessed crossover substudy. In SAD, doses well tolerated up to mg. Exposure...

This study determined the mass balance and pharmacokinetics of edoxaban in humans after oral administration [¹⁴C]edoxaban. After 60 mg (as active moiety) [¹⁴C]edoxaban to six healthy male subjects, serial blood/plasma urinary fecal samples were collected for up 168 h postdose. All analyzed total radioactivity by liquid scintillation counting concentrations four metabolites plasma, urine, either high-performance chromatography/tandem spectrometry method using multiple...

Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, rapidly reacts with peroxynitrite, the rate constant being of order 106 M-1 s-1; reaction yields selenoxide parent molecule, 2-phenyl-1,2-benzisoselenazol-3(2H)-one 1-oxide, as sole selenium-containing product; a stoichiometry 1 mol ebselen reacted and formed per mole peroxynitrite was observed. The studied in detail at neutral alkaline pH (pH 10−11). It also proceeds acidic where peroxynitrous acid (ONOOH) is predominant, yield lower because...

High Tc superconducting YBa2 Cu3 O7−x films were prepared by chemical vapor deposition using β-diketonates of Y, Ba, and Cu as source materials. The epitaxially grown on SrTiO3 (100) substrates. c-axis orientation perpendicular to the plane substrates was observed. A sharp resistive transition with (R=0) at 84 K obtained. maximum critical-current density 77 2×104 A/cm2 .

Edoxaban (the free base of DU-176b), an oral direct factor Xa inhibitor, is mainly excreted unchanged into urine and feces. Because active membrane transport processes such as renal secretion, biliary excretion, and/or intestinal the incomplete absorption edoxaban after administration have been observed, involvement drug transporters in disposition was investigated. Using a bidirectional assay human colon adenocarcinoma Caco-2 cell monolayers, we observed vectorial [¹⁴C]edoxaban,...

Bioactivation of a drug to reactive metabolite and its covalent binding cellular macromolecules is believed be involved in clinical adverse events, including idiosyncratic toxicities (IDTs). For the interpretation data terms risk assessment, vitro vivo variety drugs associated with IDTs or not were determined. Most "problematic" drugs, "withdrawn" "warning" exhibit higher human liver microsome (HLM) yields than "safe" drugs. Although some problematic that are known undergo bioactivation...

Abstract The electric and magnetic properties of matter are great interest for materials science their use in electronic applications. Large dielectric magnetoelectric responses at room temperature a advantage electromagnetic device Here we present study FeCo-MgF nanogranular films exhibiting giant temperature; with constant ε ′=490 response Δ ′/ ′ 0 =3%. In these films, Fe-Co alloy-based nanometer-sized granules dispersed Mg-fluoride-based insulator matrix. Insulating new class...

A Bi 2 O 3 -TiO phase diagram was determined using differential thermal analysis (DTA) apparatus. 4 Ti 12 (BIT) micalike single crystals grown by a flux method were clear and slightly grayish in color. Ferroelectric dielectric properties of BIT observed from measurements electric displacement vs field hysteresis loops the constant. Also, polarization switching characteristics investigated. The time current density read transient waveforms.

Calcium phosphate films were prepared on titanium substrates by radiofrequency (RF) magnetron sputtering at RF powers from 75 to 150 W. Hot-pressed β-tricalcium (β-TCP) plates with a high density (>99.6%) used as target. The substrate was not intentionally heated. consisted of amorphous calcium and oxyapatite (Ca10(PO4)6O) phases. ratio the phase depended conditions power, oxygen gas concentration in (CO2) total pressure chamber. (002) preferred orientation observed. deposition rate...

YBa 2 Cu 3 O 7- x thin films (0.8 µm in thickness) with c -axis orientation were prepared at 900°C on yttria-stabilized zirconia substrates by chemical vapor deposition using metal chelates as source materials. The onset and completion of the superconductive transition occurred 89 K 80 K, respectively, for film that received situ oxygen treatment. oxygen-treated had metallic resistivity resistance ratio (R 273 / R 100 ) was 2.

Developing optically transparent magnets at room temperature is an important challenge. They would bring many innovations to various industries, not only for electronic and magnetic devices but also optical applications. Here we introduce FeCo-(Al-fluoride) nanogranular films exhibiting ferromagnetic properties with high transparency in the visible light region. These have a nanocomposite structure, which nanometer-sized FeCo granules are dispersed Al-fluoride crystallized matrix. The...

Magneto-optical Faraday effect is widely applied in optical devices and indispensable for communications advanced information technology. However, the bismuth garnet Bi-YIG only material since 1972. Here we introduce (Fe, FeCo)-(Al-,Y-fluoride) nanogranular films exhibiting giant effect, 40 times larger than Bi-YIG. These have a nanocomposite structure, which nanometer-sized Fe, FeCo ferromagnetic granules are dispersed Al,Y-fluoride matrix.

We previously reported that centromere protein B (CENP-B) forms a stable complex (designated A) containing two alphoid DNAs in vitro. Domains the CENP-B polypeptide involved formation of A were determined present study with truncated derivatives expressed Escherichia coli and rabbit reticulocyte lysates. It was revealed by gel mobility shift analyses polypeptides NH2-terminal DNA-binding domain bind DNA molecule as monomer, while dimerizing at novel hydrophobic COOH-terminal region 59 amino...

The metabolic activation of a drug to an electrophilic reactive metabolite and its covalent binding cellular macromolecules is considered be involved in the occurrence idiosyncratic toxicity (IDT). As defense system against oxidative stress, phase II enzymes are known induced through Kelch-like ECH-associated protein 1/nuclear factor E2-related 2/antioxidant response element system. We presumed that it important for risk assessment drug-induced hepatotoxicity IDTs observe biological...

Thirty one layer TiO2/SiO2 optical filters with graded refractive index profiles were fabricated by helicon plasma sputtering at room temperature. Multilayer films deposited on glass (BK7) and Si (100) substrates simultaneously sequentially. The measured transmittance spectrum exhibited a reflectance of 99.8% central wavelength 730 nm high over the region outside reflected band as result suppression sidelobes. experimental corresponded almost completely that calculated based multilayer film...

Covalent binding of reactive metabolites to cytochrome P450s (P450s) often causes their mechanism-based inactivation (MBI), resulting in drug-drug interactions or toxicity. The detection and identification the P450 sites which bind would elucidate MBI mechanisms. We describe a proteomic approach using nano-LC/linear ion trap-Fourier transform cyclotron resonance (FTICR) mass spectrometry characterize metabolite raloxifene, is known 3A4 inhibitor, isozyme. LTQ-FT analyses revealed that...

Bi-Ti-O oxide thin films were prepared on a sapphire single-crystal substrate by electron cyclotron resonance (ECR) plasma sputtering. The target used was sintered Bi4Ti3O12(BIT) and the controlled in temperature range 400–640 °C(Tsub). film sputtered at Tsub=400 °C pyrochlore type oxide(Bi2Ti2O7), which changed to Bi4Ti3O12 polycrystalline state 500 single crystalline 640 °C. In °C, (001) plane of grew parallel (112̄0) (11̄02) planes substrate, (104) (0001) substrate. deposition rate about...

SrRuO3 (SRO) thin films were prepared by laser ablation, and the effects of deposition conditions on microstructure electrical conductivity these investigated changing substrate temperature (Tsub) atmosphere. The SRO deposited quartz substrates in a high vacuum (P=10−6 Pa) an oxygen partial pressure (PO2) 0.13 Pa amorphous, independent Tsub. Pseudo-cubic obtained at PO2=13 Tsub>773 K. Sr to Ru ratio increased with increasing Tsub, free was contained P=10−6 Pa. crystal grain coarsened Tsub...