Combination of TS-021 with metformin improves hyperglycemia and synergistically increases pancreatic β-cell mass in a mouse model of type 2 diabetes.

Aims: The objectives of this study were to elucidate the effects of a potent dipeptidyl peptidase (DPP)-IV inhibitor, TS-021, combined with/without metformin on glycemic control and pathological changes in pancreatic islets in high-fat diet and streptozotocin-induced (HFD-STZ) diabetic mice.

Main Methods: The anti-diabetic effects of TS-021 and/or metformin in HFD-STZ mice were examined in both acute and chronic treatment studies. In addition, we performed immunohistochemical analysis after repeated administration of TS-021 and/or metformin to HFD-STZ mice twice a day for 5 weeks.

Electrophysiological characteristics of idiopathic ventricular tachycardia in children.

Background: Idiopathic ventricular tachycardia (VT) has been reported to have a good prognosis, but there still might be the potential risk of sudden death.

Methods And Results: The 46 consecutive children (mean age 11.7 ± 3.

Quantitative evaluation of coronary artery wall echogenicity by integrated backscatter analysis in Kawasaki disease.

Background: Coronary artery wall echogenicity increases on echocardiograms during the acute phase of Kawasaki disease (KD). According to this background, echogenicity of the coronary artery wall in patients with KD is quantified by using integrated backscatter (IB) analysis.

Methods: IB analysis is a quantitative method for evaluating echogenicity.

Development of a microfocus x-ray tube with multiple excitation sources.

A microfocus x-ray tube with multiple targets and an electron gun with a focal spot size of 10 microm in diameter has been developed. The electron gun contains a LaB(6) cathode and an Einzel lens. The x-ray tube can be operated at 50 W (50 kV, 1 mA) and has three targets, namely, Cr, W, and Rh on the anode that can be selected completely by moving the anode position.

Dual myocardial scintigraphy mismatch in an infant with Bland-White-Garland syndrome.

Bland-White-Garland syndrome (BWG) is a rare disorder that includes abnormalities of the coronary arteries that cause severe myocardial ischemia or infarction in infancy. In this case report, we describe an infant with BWG evaluated by dual single photon emission computed tomography using thallium-201 and I-123 beta-methyl-p-iodophenyl-pentadecanoic acid before and after surgery.

Association of sinus node dysfunction, atrioventricular node conduction abnormality and ventricular arrhythmia in patients with Kawasaki disease and coronary involvement.

Background: This study was performed to investigate the incidence of arrhythmias in patients with Kawasaki disease (KD).

Methods And Results: Electrophysiologic studies (EPS) were performed in 40 patients (mean age: 10.3+/-5.

Clinical importance of Koch's triangle size in children: a study using 3-dimensional electroanatomical mapping.

Background: Catheter ablation inside the Koch's triangle has a risk for complete atrioventricular block.

Methods And Results: The anatomic size of the coronary sinus (CS) and His bundle (HB) in children and the distance between them was studied using a 3-dimensional electroanatomical mapping system (CARTO). Fifty-three children (mean age, 11.

Association of atrial arrhythmia and sinus node dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia.

Background: This study was performed to investigate the frequency and importance of supraventricular arrhythmia and sinus node (SN) dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).

Methods And Results: Eight patients with CPVT (mean age: 16.8+/-8.

[Advantages of multislice spiral computed tomography for evaluation of serious coronary complications after Kawasaki disease].

Objectives: Novel multislice spiral computed tomography (MSCT) findings were identified in patients after Kawasaki disease that could not be detected by coronary angiography (CAG).

Methods: Eighteen patients had suffered from serious coronary arterial lesions after Kawasaki disease (mean age 21.7 years, range 13-34 years).

Usefulness of real-time 3-dimensional echocardiography for the evaluation of coronary artery morphology in patients with Kawasaki disease.

Objectives: This study was designed to evaluate the usefulness of real-time 3-dimensional echocardiography (RT-3DE) for evaluating coronary artery morphology in patients with Kawasaki disease.

Background: The diagnosis of coronary artery morphology in the acute phase of the disease is of prime importance for evaluating the likelihood of cardiovascular sequelae. Occasionally, visualization of the right coronary artery and bifurcated regions, including the circumflex artery, has proved challenging with traditional echocardiographic methods.

Excitation energy dependence for the Li 1s X-ray photoelectron spectra of LiMn2O4.

The Li 1s XPS (X-ray Photoelectron Spectroscopy) spectra of LiMn2O4, which is one of the major positive-electrode materials in lithium-ion rechargeable batteries, and MnO2 as a reference material, were measured by a laboratory-type XPS spectrometer. The Li 1s peak was not observed in the spectra excited by the Mg Kalpha line (1253.6 eV), because the Li 1s peak overlapped the background of the Mn 3p peak of LiMn2O4.

Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], on hemorrhagic and ischemic stroke.

The present study characterized the effects of TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N'-hydroxyimido formamide], a new selective inhibitor of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), on the metabolism of arachidonic acid by human and rat renal microsomes and the inhibitory effects of this compound on hepatic cytochrome P450 enzymes involved in drug metabolism. The effects of TS-011 on the fall in cerebral blood flow following subarachnoid hemorrhage (SAH) and in reducing infarct size in ischemic stroke models were also examined since 20-HETE may contribute to the development of cerebral vasospasm. TS-011 inhibited the synthesis of 20-HETE by human renal microsomes and recombinant CYP4A11 and 4F2, 4F3A, and 4F3B enzymes with IC50 values around 10 to 50 nM.

Increased excretion of urinary 20-HETE in rats with cyclosporine-induced nephrotoxicity.

The present study examined the contribution of 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) in cyclosporine A (CsA)-induced renal nephrotoxicity. Treatment of rats with CsA (50 mg/kg) for 9 days induced renal damage as indicated by marked increase in urine flow (from 9.0 +/- 0.

Pyrazole derivatives as new potent and selective 20-hydroxy-5,8,11,14-eicosatetraenoic acid synthase inhibitors.

Improvement of the physical properties of pyrazole derivative 1, which we reported previously as a potent and selective 20-HETE synthase inhibitor (IC(50) 5.7 nM), is described. Introduction of a sufficient substituted-amino group on the side chain enhanced the water-solubility of 1 (0.

Design and synthesis of 1-(4-benzoylphenyl)imidazole derivatives as new potent 20-HETE synthase inhibitors.

Structural modification of the novel 20-HETE synthase inhibitor 1 (IC(50) 310nM) is described. Introduction of a side chain with a carboxylic acid at the terminal position to 1 resulted in increased ability to inhibit human renal microsomal production of 20-HETE (7c: IC(50) 7.9nM), with good selectivity toward CYP2D6 and cyclooxygenases (COX)-1 and -2.

The role of histidine residues conserved in the putative ATP-binding region of macrolide 2'-phosphotransferase II.

Macrolide 2'-phosphotransferase (MPH(2')) catalyzes the transfer of the gamma-phosphate of ATP to the 2'-hydroxyl group of macrolide antibiotics. In this study, H198 and H205, conserved in the ATP-binding region motif 1 in the putative amino acid sequence of MPH(2')II, were replaced by Ala to investigate their role. H205 was also subsequently replaced by Asn.

Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors.

In a previous paper, we reported that an imidazole derivative 1 exhibited a potent inhibitory activity of 20-HETE synthase (1; IC(50) value of 5.7 nM), but this compound also exhibited little selectivity for cytochrome P450s (CYPs). We examined some derivatives of imidazole 1 which had an amino group on the side chain, and found that a dimethylaminohexyloxy derivative (3g; IC(50) value of 8.

Pyrazole and isoxazole derivatives as new, potent, and selective 20-hydroxy-5,8,11,14-eicosatetraenoic acid synthase inhibitors.

In a previous paper, we reported the N-hydroxyformamidine derivative HET0016 as a potent and selective 20-HETE synthase inhibitor. Despite its attraction as a potential therapeutic agent for cerebral diseases, the preparation of an injectable formulation of HET0016 was limited by its poor solubility under neutral conditions and instability under acidic conditions. The instability of HET0016 in acidic conditions is due to the N-hydroxyformamidine moiety, which is considered to be essential for the potent and selective activity seen in our previous study.

Detection of myocardial contractile reserve by low-dose dobutamine quantitative gated single-photon emission computed tomography in patients with Kawasaki disease and severe coronary artery lesions.

We studied 24 patients with severe coronary artery lesions to assess myocardial perfusion and left ventricular contractile reserve simultaneously using low-dose dobutamine quantitative electrocardiographically gated single-photon emission computed tomography in patients with Kawasaki disease. Low-dose dobutamine infusion was started after an injection of technetium-99m tetrofosmin at rest. Myocardial contractile reserve was evaluated using the post-stress and low-dose dobutamine images, and myocardial perfusion was evaluated using the stress and rest images.