Pharmacokinetics of Doxazosin Gastrointestinal Therapeutic System after Multiple Administration in Korean Healthy Volunteers

Doxazosin mesylate is a selective alpha-adrenoreceptor antagonist for the treatment of hypertension and benign prostatic hyperplasia. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of doxazosin in plasma. A reversed phase C18 column was used for the separation of doxazosin and prazosin (internal standard) with a mobile phase composed of water ? acetonitrile ? triethylamine (68:32:0.2 v/v, pH 5.0) at a flow rate of 1.2 mL/min. The fluorescence detector was operated at 246 (excitation) and 389 nm (emission). Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 1 ng/mL. Recovery of doxazosin from human plasma was greater than 93.4%. Doxazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of multiple 4-mg dose of doxazosin gastrointestinal therapeutic system formulation to 16 healthy volunteers. At steady state the mean area under the curve for a dosing interval and elimination half-life were calculated to be 367.0 ± 63.5 ng · hr/mL and 29.2 ± 4.5 hr, respectively. There was no difference in pharmacokinetic parameters between male and female.     

Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.     

Studies of the methanol crossover and cell performance behaviors of high temperature-direct methanol fuel cells (HT-DMFCs)

The high temperature-direct methanol fuel cell (HT-DMFC) based on phosphoric acid (PA)-doped polybenzimidazole (PBI) membranes shows promise as a passive-type DMFC system because it can operate using highly concentrated methanol fuel. In this paper, the methanol crossover and cell performance behaviors of the HT-DMFCs were investigated using a one-dimensional (1-D) HT-DMFC system model that fully accounts for the electrochemical reactions, key species transport and heat generation inside a cell, and the evaporation processes of liquid methanol/water fuel in the evaporator. The model was first validated against experimental HT-DMFC data measured over a wide range of methanol feed concentrations and operating current densities, and operating characteristics of HT-DMFCs were then explored in detail. Particular emphasis was placed on conducting a comparative study of HT-DMFCs with traditional liquid feed low temperature-DMFCs based on perfluorosulfonic acid membranes. The simulation results showed that a HT-DMFC can operate well under highly concentrated methanol fuel above 12 M due to the minimal degree of methanol crossover through the PA-doped PBI membrane.     

ITO-free inverted polymer solar cells using a GZO cathode modified by ZnO

A gallium-doped ZnO (GZO) layer was investigated and compared with a conventional indium-tin-oxide (ITO) layer for use as a cathode in an inverted polymer solar cell based on poly(3-hexylthiophene) (P3HT):[6,6]-phenyl-C₆₁ butyric acid methyl ester (PCBM) bulk heterojunctions (BHJ). By modifying the GZO cathode with a ZnO thin layer, a high power conversion efficiency (3.4%) comparable to that of an inverted solar cell employing the same P3HT:PCBM BHJ photoactive layer with a conventional ITO/ZnO cathode was achieved. This result indicates that GZO is a transparent electrode material that can potentially be used to replace high-cost ITO.     

Noise prediction of multi-rotor UAV by RPM fluctuation correction method

Journal of Mechanical Science and Technology - The multi-rotor type unmanned aerial vehicle (UAV) controls the movement through the rotational speed of each rotor. Since the phase of each rotor is...     

Microfabrication and optical properties of highly ordered silver nanostructures

ABSTRACT: Using thermal evaporation, we fabricated five uniform and regular arrays of Ag nanostructures with different shapes that were based on an anodized aluminum oxide template and analyzed their optical properties. Round-top-shaped structures are obtained readily, whereas to obtain needle-on-round-top-shaped and needle-shaped structures, control of the directionality of evaporation, pore size, length, temperature of the substrate, etc., was required. We then observed optical sensitivity of the nanostructures by using surface-enhanced Raman scattering, and we preliminarily investigated the dependency of Raman signal to the roughness and shape of the nanostructures.     

Simulation of the deflagration-to-detonation impact on a copper-based furnace injector

The deflagration-to-detonation transition (DDT) is accompanied by a strong pressure wave that can provide an adverse effect on nearby structures. The pressure generated from multiple detonative pulses is strong enough to cause metal surface erosion and bulk edge chipping. In this work, we investigate the damaging effect of the DDT phenomena and apply hydrocode simulation to evaluate the structural damage to a pulverized coal injector made of copper used in a pulverized coal-oxygen combustion furnace. Experimental conditions are imposed to improve the damage model of a metal injector exposed to multiple detonation pulses.     

Characterization of a C-Type Lectin Domain-Containing Protein with Antibacterial Activity from Pacific Abalone (Haliotis discus hannai)

Genes that influence the growth of Pacific abalone (Haliotis discus hannai) may improve the productivity of the aquaculture industry. Previous research demonstrated that the differential expression of a gene encoding a C-type lectin domain-containing protein (CTLD) was associated with a faster growth in Pacific abalone. We analyzed this gene and identified an open reading frame that consisted of 145 amino acids. The sequence showed a significant homology to other genes that encode CTLDs in the genus Haliotis. Expression profiling analysis at different developmental stages and from various tissues showed that the gene was first expressed at approximately 50 days after fertilization (shell length of 2.47 ± 0.13 mm). In adult Pacific abalone, the gene was strongly expressed in the epipodium, gill, and mantle. Recombinant Pacific abalone CTLD purified from Escherichia coli exhibited antimicrobial activity against several Gram-positive bacteria (Bacillus subtilis, Streptococcus iniae, and Lactococcus garvieae) and Gram-negative bacteria (Vibrio alginolyticus and Vibrio harveyi). We also performed bacterial agglutination assays in the presence of Ca²⁺, as well as bacterial binding assays in the presence of the detergent dodecyl maltoside. Incubation with E. coli and B. subtilis cells suggested that the CTLD stimulated Ca²⁺-dependent bacterial agglutination. Our results suggest that this novel Pacific abalone CTLD is important for the pathogen recognition in the gastropod host defense mechanism.