Randomized, Double-Blind, Controlled Study to Evaluate Safety and Pharmacokinetics of Single Ascending Doses of ASP5354, an Investigational Imaging Product, in Healthy Adult Volunteers.

Intraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real-time ureter visualization are approved. ASP5354 (TK-1) is a novel indocyanine green derivative.

Preclinical Development and Validation of ASP5354: A Near-Infrared Fluorescent Agent for Intraoperative Ureter Visualization.

Purpose: Iatrogenic ureteral injury (IUI) can complicate minimally invasive and open abdominopelvic surgery. The incidence of IUI is low and dependent on the type of surgery (< 10 %), but it is associated with high morbidity. Therefore, intraoperative visualization of the ureter is critical to reduce the incidence of IUI, and some methodologies for ureter visualization have been developed.

Three-dimensional Pseudo-continuous Arterial Spin-labeling Using Turbo-spin Echo with Pseudo-steady State Readout: A Comparison with Other Major Readout Methods.

We evaluated 3D pseudo-continuous arterial spin labeling (pCASL) using turbo spin echo with a pseudo-steady-state (PSS) readout in comparison with the other major readout methods of 3D spiral and 2D echo-planar imaging (EPI). 3D-PSS produced cerebral blood flow (CBF) values well correlated to those of the 3D spiral readout. By visual evaluation, the image quality of 3D-PSS pCASL was superior to that of 2D-EPI.

Acceleration of ASL-based time-resolved MR angiography by acquisition of control and labeled images in the same shot (ACTRESS).

Purpose: Noncontrast 4D-MR-angiography (MRA) using arterial spin labeling (ASL) is beneficial because high spatial and temporal resolution can be achieved. However, ASL requires acquisition of labeled and control images for each phase. The purpose of this study is to present a new accelerated 4D-MRA approach that requires only a single control acquisition, achieving similar image quality in approximately half the scan time.

Distinct properties of telmisartan on agonistic activities for peroxisome proliferator-activated receptor γ among clinically used angiotensin II receptor blockers: drug-target interaction analyses.

A proportion of angiotensin II type 1 receptor blockers (ARBs) improves glucose dyshomeostasis and insulin resistance in a clinical setting. Of these ARBs, telmisartan has the unique property of being a partial agonist for peroxisome proliferator-activated receptor γ (PPARγ). However, the detailed mechanism of how telmisartan acts on PPARγ and exerts its insulin-sensitizing effect is poorly understood.

Glucose regulates RMI1 expression through the E2F pathways in adipose cells.

RecQ-mediated genome instability 1 (RMI1) has been identified as a novel energy homeostasis-related molecule. While recent studies have suggested that change in RMI1 expression levels in adipose tissue may affect the body's energy balance, no reports have identified the mechanism behind this expression regulation. In the present study, we found that RMI1 expression increased on differentiation of 3T3-L1 fibroblasts to adipocytes.

Adipocyte hyperplasia and RMI1 in the treatment of obesity.

The escalating prevalence of obesity is one of the most pressing health concerns of the modern era, yet existing medicines to combat this global pandemic are disappointingly limited in terms of safety and effectiveness. The inadequacy of currently available therapies for obesity has made new drug development crucial. In the past several decades, however, major progress has been achieved in understanding adipocyte hyperplasia associated with the pathogenesis of obesity, and consequently new potential targets for the medical treatment of obesity have been identified.

Glucose metabolism activation by SHIP2 inhibitors via up-regulation of GLUT1 gene in L6 myotubes.

Lipid phosphatase SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of insulin signaling. In this report, we identified AS1938909, a novel small-molecule SHIP2 inhibitor. AS1938909 showed potent inhibition of SHIP2 (Ki=0.

SHIP2 and its involvement in various diseases.

Importance Of The Field: Inositol polyphosphate 5-phosphatase (SHIP2) is an important negative regulator of intracellular phosphatidylinositol phosphate, a key second messenger of various intracellular signaling pathways. The functional upregulation of SHIP2 results in signaling blockade, leading to related disorders.

Areas Covered In This Review: We first summarize the role of SHIP2 in the regulation of insulin signaling and type 2 diabetes, including remarkable advances in pharmacological approaches.

RMI1 deficiency in mice protects from diet and genetic-induced obesity.

The aim of this study is to discover and characterize novel energy homeostasis-related molecules. We screened stock mouse embryonic stem cells established using the exchangeable gene trap method, and examined the effects of deficiency of the target gene on diet and genetic-induced obesity. The mutant strain 0283, which has an insertion at the recQ-mediated genome instability 1 (RMI1) locus, possesses a number of striking features that allow it to resist metabolic abnormalities.

[Development of fat suppressed three-dimensional T1-weighted image using linear filling order for K-space].

We have developed a sequence for abdominal examination that fat suppressed 3D-T1W by a linear filling order using an adiabatic pulse for frequency selective fat suppression. We simulated the change in fat signal using a linear method and checked the starting point of data filling for the null point using a phantom of different T1 values. We then checked the contrast between the fat signal and liver.

[Benefits and risks of glucocorticoid therapy for the treatment of rheumatoid arthritis and management of glucocorticoid-induced osteoporosis].

More than 50 years have passed since glucocorticoid (GC) therapy was introduced into the treatment of rheumatoid arthritis (RA) . Although the effect of GC monotherapy on RA is limited to short-term and long-term GC treatment carries the risks of adverse effects and rebound phenomenon after the discontinuation, disease-modifying action of GC have been recently reported when used in combination with DMARDs. One of the important side effects associated with GC therapy is osteoporosis, and Japanese guidelines on the management and treatment of glucocorticoid -induced osteoporosis have been published recently.

Automated microfluidic assay system for autoantibodies found in autoimmune diseases using a photoimmobilized autoantigen microarray.

Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation.

Clinical and histopathological features of myopathies in Japanese patients with anti-SRP autoantibodies.

To elucidate the clinical and histopathological features associated with autoantibodies to the signal recognition particle (SRP), we have studied 23 Japanese patients with this specificity among 3,500 patients with polymyositis/dermatomyositis and other connective tissue diseases. Anti-SRP antibodies were determined based on analysis of RNA and protein components by immunoprecipitation assays. The pathological analysis was performed by using special stainings including alkaline phosphatase, myosin ATPase, and modified Gomori trichrome stainings.

Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight.

While the brain does not utilize fatty acids as a primary energy source, recent evidence shows that intermediates of fatty acid metabolism serve as hypothalamic sensors of energy status. Increased hypothalamic malonyl-CoA, an intermediate in fatty acid synthesis, is indicative of energy surplus and leads to the suppression of food intake and increased energy expenditure. Malonyl-CoA functions as an inhibitor of carnitine palmitoyl-transferase 1 (CPT1), a mitochondrial outer membrane enzyme that initiates translocation of fatty acids into mitochondria for oxidation.

Longterm effect of intermittent cyclical etidronate therapy on corticosteroid-induced osteoporosis in Japanese patients with connective tissue disease: 7-year followup.

Objective: To determine the efficacy and safety of intermittent cyclical etidronate therapy of up to 7 years for corticosteroid-induced osteoporosis.

Methods: One hundred two Japanese patients who originally participated in a 3-year prospective randomized study were enrolled into an open-label followup study. All patients had received > 7.

[Prevention and treatment of NSAIDs-induced gastrointestinal complications by prostaglandin derivatives].

Non-steroidal anti-inflammatory drugs(NSAIDs) are widely used for the treatment of many rheumatic diseases. Gastrointestinal ulcers are the most important complication during long-term NSAIDs therapy and sometimes, serious complications, such as perforation, stenosis, and bleeding occurs. Recently, use of COX-2 selective NSAIDs reduced such complications, however the increase of cardiovascular risks has been reported.

[Pathologic condition of osteoporosis in rheumatoid arthritis].

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis which causes osteoporosis and joint destruction. Recently, it has been well understood that pro-inflammatory cytokine plays a pivotal role in disease progression. These pro-inflammatory cytokine induces activation of osteoclasts, resulting in paraarticular osteoporosis and joint destruction.

[Inhibition of radiographic progression in rheumatoid arthritis by anti-rheumatic drugs (DMARDs)].

From the results of recent randomized controlled clinical trials of disease modifying antirheumatic drugs (DMARDs), slowing radiographic progression has been documented with the use of methotrexate, leflunomide, salazusulfapyridine, IM gold, and cyclosporine. Although the effects of DMARDs is inferior to that of anti-tumor necrosis factor (TNF) agents, DMARDs can stop the progression of joint damage with the achievement of remission or good response.

Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase.

Objective: We have previously described anti-KS autoantibodies and provided evidence that they are directed against asparaginyl-transfer RNA (tRNA) synthetase (AsnRS). The aim of the present study was to identify patients with anti-AsnRS autoantibodies and elucidate the clinical significance of this sixth antisynthetase antibody. In particular, we studied whether it was associated with the syndrome of myositis (polymyositis or dermatomyositis [DM]), interstitial lung disease (ILD), arthritis, and other features that had been previously associated with the 5 other anti-aminoacyl-tRNA synthetase autoantibodies.