Pharmacological characterisation of electrocardiogram J-T interval in conscious Guinea pigs.

Drug-induced human ether-à-go-go-related gene (hERG) channel block and QT interval prolongation increase torsade de pointes (TdP) risk. However, some drugs block hERG channels and prolong QT interval with low TdP risk, likely because they block additional inward currents. We investigated the utility of J-T interval, a novel biomarker of inward current block and TdP risk, in conscious telemetered guinea pigs.

In vitro and in silico study on consequences of combined exposure to the food-borne alkenylbenzenes estragole and safrole.

Potential consequences of combined exposure to the selected food-borne alkenylbenzenes safrole and estragole or their proximate carcinogenic 1'-hydroxy metabolites were evaluated in vitro and in silico. HepG2 cells were exposed to 1'-hydroxyestragole and 1'-hydroxysafrole individually or in equipotent combination subsequently detecting cytotoxicity and DNA adduct formation. Results indicate that concentration addition adequately describes the cytotoxic effects and no statistically significant differences were shown in the level of formation of the major DNA adducts.

Histopathological and electron microscopic study in dogs with patellar luxation and skin hyperextensibility.

Patellar luxation is abnormal displacement of the patella from the femoral trochlear groove. It is seen primarily in small breed dogs and causes pain and limited mobility of the stifle joint. This study aimed to investigate the relationship among patellar luxation, skin extension, and skin collagen fibril diameter.

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states.

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models.

Modulation of afferent nerve activity by prostaglandin E2 upon urinary bladder distension in rats.

What is the central question of this study? It has been widely assumed that C fibres innervating the bladder are mainly excited in overactive bladder syndrome. However, it remains unclear whether Aδ fibres are also activated in pathological conditions. What is the main finding and its importance? We found that a certain population of Aδ fibres, which become active specifically at a bladder pressure of more than 15 cmH2 O in normal conditions, showed increased excitability in conditions of prostaglandin E2 -induced overactive bladder.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance.

Effects of probucol, a typical hERG expression inhibitor, on in vivo QT interval prolongation in conscious dogs.

The cholesterol-lowering drug, probucol, is known to induce QT interval prolongation and torsades de pointes in patients. Recent in vitro studies have indicated that probucol reduces hERG expression in the plasma membrane and does not directly block human ether-a-go-go-related gene (hERG) channels. The present study was performed to investigate the effects of probucol on in vivo QT interval prolongation.

Structure of a UDP-glucose dehydrogenase from the hyperthermophilic archaeon Pyrobaculum islandicum.

The crystal structure of an extremely thermostable UDP-glucose dehydrogenase (UDP-GDH) from the hyperthermophilic archaeon Pyrobaculum islandicum was determined at a resolution of 2.0 Å. The overall fold was comprised of an N-terminal NAD(+) dinucleotide binding domain and a C-terminal UDP-sugar binding domain connected by a long α-helix, and the main-chain coordinates of the enzyme were similar to those of previously studied UDP-GDHs, including the enzymes from Burkholderia cepacia, Streptococcus pyogenes and Klebsiella pneumoniae.

Expression, purification, crystallization and preliminary X-ray diffraction analysis of a galactose 1-phosphate uridylyltransferase from the hyperthermophilic archaeon Pyrobaculum aerophilum.

A galactose 1-phosphate uridylyltransferase from the hyperthermophilic archaeon Pyrobaculum aerophilum was crystallized using the sitting-drop vapour-diffusion method with polyethylene glycol 8000 as the precipitant. The crystals belonged to the tetragonal space group P4(1), with unit-cell parameters a = b = 73.3, c = 126.

Crystal structure of UDP-galactose 4-epimerase from the hyperthermophilic archaeon Pyrobaculum calidifontis.

The crystal structure of a highly thermostable UDP-galactose 4-epimerase (GalE) from the hyperthermophilic archaeon Pyrobaculum calidifontis was determined at a resolution of 1.8Å. The asymmetric unit contained one subunit, and the functional dimer was generated by a crystallographic two-fold axis.

Feedback stabilization involving redox states of c-type cytochromes in living bacteria.

The formal potential of c-type cytochromes expressed in the bacterial outer membrane was dependent on their redox state functioning in mediating extracellular electron transfer. Its negative (positive) shifting accompanying with the oxidization (reduction) of c-type cytochromes can serve to stabilize the redox states in a feedback manner.

Anterior cruciate ligament reconstruction using chitin-coated fabrics in a rabbit model.

Experimental anterior cruciate ligament (ACL) reconstruction was carried out in a rabbit model, in which a chitin-coated polyester graft was used as the scaffold, and a noncoated graft was used as a control graft. After 8 weeks implantation, a mechanical test of the knee and histometric measurement of the graft and surrounding tissues were carried out. A tensile test of the femur-graft-tibia specimen showed that the knee treated with the coated graft had a peak resistance force of 42.

Biological fixation of fibrous materials to bone using chitin/chitosan as a bone formation accelerator.

Biological fixation or anchorage of fibrous materials to bone by bone ingrowth into the spaces between fibers is a major concern in developing novel medical implants, including artificial ligaments. Toward this end, we evaluated the efficacy of chitin/chitosan as a bone formation accelerator. Specimens of polyester nonwoven fabric coated with chitin/chitosan were implanted into holes drilled into the distal ends of rat femora.

A practical solution for eliminating artificial image contrast in aberration-corrected TEM.

We propose a simple and practical solution to remove artificial contrast inhibiting direct interpretation of atomic arrangements in aberration-corrected TEM. The method is based on a combination of "image subtraction" for elimination of nonlinear components in images and newly improved "image deconvolution" for proper compensation of nonflat phase contrast transfer function. The efficiency of the method is shown by experimental and simulation data of typical materials such as gold, silicon, and magnesium oxide.

Neuroprotective effects of KCL-440, a new poly(ADP-ribose) polymerase inhibitor, in the rat middle cerebral artery occlusion model.

It is reported that ischemic brain injury is mediated by the activation of poly(ADP-ribose) polymerase (PARP). In this study, we examined the pharmacological profile of KCL-440, a new PARP inhibitor, and its neuroprotective effects in the rat acute cerebral infarction model induced by photothrombotic middle cerebral artery (MCA) occlusion. In an in vitro study, KCL-440 exhibited potency with regard to inhibition of PARP activity, with an IC50 value of 68 nM.

A simple method for minimizing non-linear image contrast in spherical aberration-corrected HRTEM.

A simple and practical method for minimizing non-linear image contrast in spherical aberration-corrected (C(S)-corrected) high-resolution transmission electron microscopy is presented. The effectiveness of the method is considered from the viewpoints of theoretical formulations and image simulations including second-order imaging effects. The method is one of the advantages of C(S)-correction and applied to high-resolution images down to 0.

The first observation of carbon nanotubes by spherical aberration corrected high-resolution transmission electron microscopy.

High-resolution transmission electron microscopy (HRTEM) of multi-wall carbon nanotubes using a spherical aberration correction of the objective lens has shown a new possibility for the observation of nanometre-sized tubular materials. Improvement of the image resolution along a direction parallel to that of electron incidence enables one to obtain some information on the local height of the tubes, and in lateral directions better than 0.14 nm at 200 kV accelerating voltage, the possibility of direct determination of the chirality of the tubes and the observation of finer atomic structures of carbon atoms such as 'hexagon' ones is suggested.

Direct observation of a stacking fault in Si(1 - x)Ge(x) semiconductors by spherical aberration-corrected TEM and conventional ADF-STEM.

Spherical aberration (C(S))-corrected transmission electron microscopy (TEM) and annular dark-field scanning TEM (ADF-STEM) are applied to high-resolution observation of stacking faults in Si(1 - x)Ge(x) alloy films prepared on a Si(100) buffer layer by the chemical vapor deposition method. Both of the images clarify the individual nature of stacking faults from their directly interpretable image contrast and also by using image simulation in the case of the C(S)-corrected TEM. Positions of the atomic columns obtained in the ADF-STEM images almost agree with a projection of the theoretical model studied by Chou et al.