Automated analysis of a novel object recognition test in mice using image processing and machine learning.

The novel object recognition test (NORT) is one of the most commonly employed behavioral tests in experimental animals designed to evaluate an animal's interest in and recognition of novelty. However, manual procedures, which rely on researchers' observations, prevent high throughput analysis. In this study, we developed an automated analysis method for NORT utilizing machine learning-assisted exploratory behavior detection.

Therapeutic Effect of Colony Stimulating Factor 1 Receptor Kinase Inhibitor, JTE-952, on Methotrexate-Refractory Pathology in a Rat Model of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and the destruction of bone and cartilage in affected joints. One of the unmet medical needs in the treatment of RA is to effectively prevent the structural destruction of joints, especially bone, which progresses because of resistance to conventional drugs that mainly have anti-inflammatory effects, and directly leads to a decline in the QOL of patients. We previously developed a novel and orally available type II kinase inhibitor of colony-stimulating factor-1 receptor (CSF1R), JTE-952.

JTE-952 Suppresses Bone Destruction in Collagen-Induced Arthritis in Mice by Inhibiting Colony Stimulating Factor 1 Receptor.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and structural destruction of the joints. Bone damage occurs in an early stage after onset and osteoclast activation plays a substantial role in its progression. Colony stimulating factor 1 receptor (CSF1R) is a receptor protein tyrosine kinase specifically expressed in monocytic-lineage cells such as macrophages and osteoclasts.

Pharmacological Properties of JTE-952, an Orally Available and Selective Colony Stimulating Factor 1 Receptor Kinase Inhibitor.

Colony stimulating factor 1 (CSF1) receptor (CSF1R) is a receptor protein-tyrosine kinase specifically expressed in monocyte-lineage cells, such as monocytes and macrophages. In this study, we characterized the pharmacological properties of an azetidine compound, JTE-952 ((2S)-3-{[2-({3-[4-(4-cyclopropylbenzyloxy)-3-methoxyphenyl]azetidine-1-yl}carbonyl)pyridin-4-yl]methoxy}propane-1,2-diol), which is a novel CSF1R tyrosine kinase inhibitor. JTE-952 potently inhibited human CSF1R kinase activity, with a half maximal inhibitory concentration of 11.

Optimal home SBP targets for preventing the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

Objectives: Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined.

Methods: We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus.

[Contribution of clinical laboratory to the diabetes care team: efforts in physiological laboratory].

A large number of clinical laboratory technologists are qualified as diabetes educators; however, few of them actually participate in teaching patients. This is partially because it is difficult to balance their routine laboratory tasks and the work of a diabetes educator. We have introduced ultrasonic examinations of the ophthalmic artery, inspection of the R-R interval and current perceptual-threshold inspection for the early diagnosis of diabetic complications, and we have been contributing to the good medical care for diabetes.

Orally administered selective TRPV1 antagonist, JTS-653, attenuates chronic pain refractory to non-steroidal anti-inflammatory drugs in rats and mice including post-herpetic pain.

Chronic pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs) is a major problem and drugs for such pain are needed. Many studies suggest that transient receptor potential vanilloid type 1 (TRPV1) is associated with NSAID-refractory chronic pain. Therefore, we investigated the involvement of TRPV1 in NSAID-refractory chronic pain using experimental models for NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain.

Inhibition of CCL20 increases mortality in models of mouse sepsis with intestinal apoptosis.

Background: CC chemokine ligand 20 (CCL20) and CC chemokine receptor 6 are believed to stimulate the recruitment of neutrophils and activation of macrophages against bacterial pathogens through the activation of T helper cells. We analyzed the role of CCL20 in the acute phase of sepsis.

Methods: The effect of a neutralizing, anti-mouse CCL20 monoclonal antibody (mAb) was examined in 2 murine models of sepsis: Cecal ligation and puncture (CLP) and Escherichia coli peritonitis.

JTS-653 blocks afferent nerve firing and attenuates bladder overactivity without affecting normal voiding function.

Purpose: We evaluated the role of TRPV1 in bladder overactivity based on afferent nerve firing and urodynamic parameters using the selective TRPV1 antagonist JTS-653.

Materials And Methods: We evaluated the effects of JTS-653 on the increased pelvic nerve discharge and intravesical pressure induced by intravesical infusion of 100 μM capsaicin in anesthetized rats. The effects of JTS-653 on the urodynamic parameters of bladder overactivity induced by intravesical infusion of 30 nM resiniferatoxin or 0.

Pharmacological characterization of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel transient receptor potential vanilloid 1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) activation in peripheral sensory nerve is known to be associated with various pain-related diseases, thus TRPV1 has been the focus as a target for drug discovery. In this study, we characterized the pharmacological profiles of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel TRPV1 antagonist. JTS-653 displaced [(3)H]resiniferatoxin binding to human and rat TRPV1.

Five-item version of the international index of erectile function correlated with albuminuria and subclinical atherosclerosis in men with type 2 diabetes.

Aim: There is increasing evidence of a strong link between erectile dysfunction and atherosclerosis. The aim of this study was to evaluate the relationships between the 5-item version of the International Index of Erectile Function (IIEF-5) score and albuminuria as well as markers of subclinical atherosclerosis in men with type 2 diabetes.

Methods: We evaluated the relationship of the IIEF-5 score with the degree of urinary albumin excretion, pulse wave velocity, ankle-brachial index or toe-brachial index (n = 125) as well as with major cardiovascular risk factors, including age, blood pressure, serum lipid concentration and hemoglobin A1c, body mass index, severity of diabetic retinopathy or nephropathy, and presence of neuropathy or cardiovascular disease in 197 men with type 2 diabetes.

Uncontrolled home blood pressure in the morning is associated with nephropathy in Japanese type 2 diabetes.

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH).

Effect of pioglitazone on various parameters of insulin resistance including lipoprotein subclass according to particle size by a gel-permeation high-performance liquid chromatography in newly diagnosed patients with type 2 diabetes.

Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects. The aim of this study was to obtain a better understanding of the mechanism involved in the insulin sensitizing effect of pioglitazone. A total of 50 newly diagnosed patients with type 2 diabetes were enrolled in this study and divided into two groups, 25 of who were treated with 15 mg/day pioglitazone and 25 with 500 mg/day metformin for 12 weeks.

Synergistic effect of HLA class II loci and cytokine gene polymorphisms on the risk of gastric cancer in Japanese patients with Helicobacter pylori infection.

It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H.

Role of endogenous androgen against insulin resistance and athero- sclerosis in men with type 2 diabetes.

Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men.

Association between serum estradiol concentrations and carotid atherosclerosis in men with type 2 diabetes mellitus.

The aim of this study was to evaluate relationships between serum estradiol concentration and carotid atherosclerosis in addition to major cardiovascular risk factors in men with type 2 diabetes mellitus because previous reports concerning the role of estrogen on atherosclerosis in men are conflicting. Serum estradiol concentrations were measured in 305 consecutive men with type 2 diabetes mellitus. Relationships were evaluated between serum estradiol concentration and carotid atherosclerosis, as determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score, in a subgroup of 144 diabetic patients, as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations.

Hypereosinophilic syndrome accompanied by Buerger's disease-like femoral arterial occlusions.

A case of hypereosinophilic syndrome (HES) with a rare complication of Buerger's disease-like large arterial occlusion (AO) was successfully treated with emergent percutaneous transluminal angioplasty and anticoagulants plus corticosteroid. By reviewing 15 reported cases of HES with AO including the present case, we found man predominance but no other consistent characteristics in HES with AO, such as age, smoking history, eosinophil counts or previous treatments, thus, predicting AO in HES patients appears to be difficult. Vessel intervention should be considered as a treatment option, since treatment delay in some patients has resulted in the amputation of extremities.

Low serum testosterone concentration in middle-aged men with type 2 diabetes.

Low concentrations of endogenous androgens have been linked with insulin resistance and atherosclerosis. Men with diabetes have been reported to have lower serum testosterone concentration than non-diabetic men; however, there has never been a large study. The aim of this study was to investigate if endogenous androgen concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men, and to identify what factors may be associated with low serum testosterone concentrations in men with type 2 diabetes.

Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus.

The aim of this study was to evaluate the relationship between arterial stiffness determined by pulse wave velocity (PWV) and serum endogenous androgen concentrations as well as major cardiovascular risk factors in men with type 2 diabetes mellitus. Serum free testosterone and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured in 268 men with type 2 diabetes mellitus. Relationships between PWV and serum endogenous androgen concentrations as well as major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, glycemic control (hemoglobin A(1c)), body mass index, and degree of albuminuria, were evaluated.

Low serum dehydroepiandrosterone sulfate concentration is a predictor for deterioration of urinary albumin excretion in male patients with type 2 diabetes.

We recently found that serum dehydroepiandrosterone sulfate (DHEA-S) concentration correlated inversely with the degree of urinary albumin excretion in a cross-sectional study. We therefore performed an observational study to investigate the relationship between serum DHEA-S concentrations and changes in urinary albumin excretion in male patients with type 2 diabetes to answer the question as to whether DHEA is a causal rather than simply coincidental intermediate linking urinary albumin excretion to cardiovascular disease (CVD). The relationship between serum DHEA-S concentration and changes in urinary albumin excretion was investigated in 207 consecutive male patients with type 2 diabetes.

Efficacy of glimepiride in patients with poorly controlled insulin-treated type 2 diabetes mellitus.

We retrospectively investigated the effects of adding glimepiride in patients with type 2 diabetes showing suboptimal control by insulin therapy. Of 63 patients with poorly controlled insulin-treated type 2 diabetes (baseline HbA1c, 8.4 +/- 0.

Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes.

Decreased serum dehydroepiandrosterone (DHEA) concentrations may be associated with an increased risk of cardiovascular disease (CVD) in men. We evaluated relationships between serum DHEA sulfate (DHEA-S) concentration and carotid atherosclerosis, as well as major cardiovascular risk factors, in men with type 2 diabetes. Serum DHEA-S concentrations were measured in 206 consecutive men with type 2 diabetes.

Clinical and genetic characteristics of diabetic patients with high-titer (>10,000 U/ml) of antibodies to glutamic acid decarboxylase.

We investigated the clinical aspects and genetic background of 13 diabetic patients with high-titers (>10,000 U/ml) of anti-glutamic acid decarboxylase antibody (Group A) and compared these 28 middle-aged (35-51 years, Group B) and 13 elderly (66-79 years, Group C) patients with anti-GAD(+) (<1100 U/ml) who were diagnosed initially as having type 2 diabetes. The mean age and mean age at onset of Group A were 70.8 +/- 3.

Association between urinary albumin excretion and serum dehydroepiandrosterone sulfate concentration in male patients with type 2 diabetes: a possible link between urinary albumin excretion and cardiovascular disease.

Objective: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD.

Idiopathic sudden hearing loss in patients with type 2 diabetes.

The aim of the present study was to identify clinical and audiologic characteristics of idiopathic sudden hearing loss (ISHL) in patients with type 2 diabetes. We retrospectively investigated 148 cases of ISHL, whose age was more than 40 years, comparing clinical and audiologic valuables between diabetic and non-diabetic patients. Twenty-four patients (16.