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Neuroendocrine regulatory peptide (NERP)-2 is derived from a distinct region of VGF, a neurosecretory protein originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. Colocalization of NERP-2 with orexin-A in the lateral hypothalamus increases orexin-A-induced feeding and energy expenditure in both rats and mice. Orexigenic and anorectic peptides in the hypothalamus modulate gastric function. In this study, we investigated the effect of NERP-2 on gastric function in rats. Intracerebroventricular administration of NERP-2 to rats increased gastric acid secretion and gastric emptying, whereas peripheral administration did not affect gastric function. NERP-2-induced gastric acid secretion and gastric emptying were blocked by an orexin 1 receptor antagonist, SB334867. NERP-2 also induced Fos expression in the lateral hypothalamus and the dorsomotor nucleus of the vagus X, which are key sites in the central nervous system for regulation of gastric function. Atropine, a blocker of vagal efferent signal transduction, completely blocked NERP-2-induced gastric acid secretion. These results demonstrate that central administration of NERP-2 activates the orexin pathway, resulting in elevated gastric acid secretion and gastric emptying., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

Aim: The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities., Methods: Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated., Results: The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN., Conclusion: These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN., (© 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.)

Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion, hypothalamus, and skeletal muscles, is closely associated with obesity and diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice were treated with canagliflozin for 8 weeks. Canagliflozin attenuated the HFD-mediated increases in body weight, liver weight, and visceral and subcutaneous fat weight. Additionally, canagliflozin decreased blood glucose as well as the fat, triglyceride, and glycogen contents of the liver. Along with these metabolic corrections, canagliflozin attenuated the increases in the mRNA levels of the proinflammatory biomarkers Iba1 and Il6 and the number of macrophages/microglia in the nodose ganglion and hypothalamus. In the skeletal muscle of HFD-fed obese mice, canagliflozin decreased inflammatory cytokine levels, macrophage accumulation, and the mRNA level of the specific atrophic factor atrogin-1. Canagliflozin also increased the mRNA level of insulin-like growth factor 1, protected against muscle mass loss, and restored the contractile force of muscle. These findings suggested that SGLT2 inhibition disrupts the vicious cycle of obesity and inflammation, not only by promoting caloric loss, but also by suppression of obesity-related inflammation in both the nervous system and skeletal muscle., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and its progression significantly worsens the patient's quality of life. Although several drugs are available for DPN, all of these provide only symptomatic relief. We investigated the therapeutic effects of ghrelin for DPN, based on its various physiological functions. Seven patients with type 2 diabetes with typical clinical signs and symptoms of DPN were hospitalized. Synthetic human ghrelin (1.0 μg/kg) was administered intravenously for 14 days. Motor nerve conduction velocity (MCV) of the posterior tibial nerve improved significantly after the treatment, compared to that at baseline (35.1 ± 1.8 to 38.6 ± 1.8 m/s, p < 0.0001), while the MCV in six untreated patients did not change throughout hospitalization. The subjective symptoms assessed based on the total symptom score also significantly improved (15.6 ± 3.1 to 11.1 ± 2.2, p = 0.047). Although sensory nerve conduction velocity (SCV) of the sural nerve could not be detected in three patients at baseline, it was detected in two of the three patients after 14 days of ghrelin administration. Overall, SCV did not change significantly. Plasma glucose, but not serum C peptide, levels during a liquid meal tolerance test significantly improved after treatment. These results suggest that ghrelin may be a novel therapeutic option for DPN; however, a double-blind, placebo-controlled trial is needed in the future.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced in the human stomach. Although ghrelin has therapeutic potential for cancer cachexia, ghrelin treatment may have a concern about accelerating cancer progression. Here, using the human lung adenocarcinoma cell line HLC-1, we investigated the effects of ghrelin on molecular mechanisms linked to cancer progression, including cell viability, proliferation, resistance to apoptosis, and mitochondrial activity. Both types of mouse alveolar epithelial cells (types I and II) expressed the GHSR, as did the human normal airway cell lines BEAS-2B and HLC-1. Treatment with ghrelin (10 -2 , 10 -1 , 1, 10 μM) did not affect cell viability or proliferation. Pretreatment of HLC-1 cells with ghrelin (10 μM) did not affect resistance to paclitaxel-induced apoptosis. The parameters of mitochondrial respiration, including basal respiration, proton leak, ATP production, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration, of the HLC-1 cells pretreated with or without ghrelin were unchanged. Taken together, ghrelin does not influence cancer progression in lung adenocarcinoma cells.

An LC-MS/MS method for the determination of diniconazole in agricultural products, livestock and marine products was developed. Diniconazole in agricultural products was extracted with acetone. The extract was concentrated and partitioned with n-hexane and 10% sodium chloride solution. Agricultural products such as grains and beans were defatted using n-hexane-acetonitrile. Livestock and marine products were extracted with a mixture of acetone and n-hexane, and the organic layer was evaporated to dryness. The residue was defatted using n-hexane-acetonitrile. Cleanup was carried out using a Florisil cartridge column and a graphitized carbon cartridge column for these samples. The LC separation was carried out on an Inertsil ODS-3 column with a linear gradient of 0.1% formic acid and acetonitrile containing 0.1% formic acid. MS was carried out in the positive ion electrospray ionization mode. The calibration curve was linear between 0.00125 to 0.00750 mg/L. Average recoveries (n=5) of diniconazole from 16 kinds of agricultural products, livestock and marine products fortified at the MRLs (0.01 ppm) were 88.3-108%, and the relative standard deviations were 0.5-5.1%. The limits of quantitation were 0.01 mg/kg.

Chronic respiratory failure, which is often caused by chronic obstructive pulmonary disease, chronic lower respiratory tract infection, or interstitial pneumonia, often leads to cachexia with disease progression. Patients who have chronic respiratory failure with cachexia exhibit increased morbidity. Although cachectic status is an important clinical problem, there are no effective therapies for cachexia. Ghrelin has various effects, including increasing food intake, attenuating sympathetic nerve activity, inhibiting inflammation, increasing cardiac output, and controlling fat utilization. These effects of ghrelin are ideal targets for the treatment of severely wasting chronic respiratory disease. In a few clinical studies, including a small randomized controlled trial, ghrelin administration to cachectic patients with chronic respiratory failure improved exercise tolerance, dyspnea, and appetite. The patients in these studies gained muscle mass and weight. In another study of chronic lower respiratory tract infection with cachexia, ghrelin suppressed airway inflammation by decreasing neutrophil accumulation in the airway, resulting in improvements in oxygenation and exercise tolerance. Although further clinical investigations are needed to clarify its usefulness, ghrelin is expected to become a novel therapy for cachectic patients with chronic respiratory failure.

The hypothalamus is a center of food intake and energy metabolism regulation. Information signals from peripheral organs are mediated through the circulation or the vagal afferent pathway and input into the hypothalamus, where signals are integrated to determine various behaviors, such as eating. Numerous appetite-regulating peptides are expressed in the central nervous system and the peripheral organs, and interact in a complex manner. Of such peptides, gut peptides are known to bind to receptors at the vagal afferent pathway terminal that extend into the mucosal layer of the digestive tract, modulate the electrical activity of the vagus nerve, and subsequently send signals to the solitary nucleus and furthermore to the hypothalamus. All peripheral peptides other than ghrelin suppress appetite, and they synergistically suppress appetite through the vagus nerve. In contrast, the appetite-enhancing peptide, ghrelin, antagonizes the actions of appetite-suppressing peptides through the vagus nerve, and appetite-suppressing peptides have attenuated effects in obesity as a result of inflammation in the vagus nerve. With greater understanding of the mechanism for food intake and energy metabolism regulation, medications that apply the effects of appetite-regulating peptides or implantable devices that electrically stimulate the vagus nerve are being investigated as novel treatments for obesity in basic and clinical studies., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF., Methods: We conducted an open-label randomized trial in routine psychiatric practice settings. Seventy-seven MDD outpatients were randomly assigned to the mirtazapine or predetermined SSRIs groups, and investigators arbitrarily selected sertraline or paroxetine. The primary outcome was the proportion of benzodiazepine users at weeks 6, 12, and 24 between the groups. We defined patients showing a ≥50 % reduction in Hamilton depression rating scale (HDRS) scores from baseline as responders. Blood samples were collected at baseline, weeks 6, 12, and 24., Results: Sixty-five patients prescribed benzodiazepines from prescription day 1 were analyzed for the primary outcome. The percentage of benzodiazepine users was significantly lower in the mirtazapine than in the SSRIs group at weeks 6, 12, and 24 (21.4 vs. 81.8 %; 11.1 vs. 85.7 %, both P  < 0.001; and 12.5 vs. 81.8 %, P  = 0.0011, respectively). No between-group difference was observed in HDRS score changes. Serum proBDNF levels were significantly decreased ( χ 2  = 8.5, df  = 3, P  = 0.036) and serum mature BDNF levels were temporarily significantly decreased ( F  = 3.5, df  = 2.4, P  = 0.027) in the responders of both groups at week 24., Conclusion: This study demonstrated mirtazapine as the first-choice antidepressant for current depressive episodes may reduce benzodiazepine use in patients with MDD. Trial registration UMIN000004144. Registered 2nd September 2010. The date of enrolment of the first participant to the trial was 24th August 2010. This study was retrospectively registered 9 days after the first participant was enrolled.

Background: In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD) is not well established. Therefore, a feasibility study of the clinical effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting is urgently required. This was a pilot uncontrolled trial and the intervention consisted of a 16-week CBT program. The primary outcome was Panic Disorder Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ-5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end of the study. Fifteen subjects completed outcome measures at all assessment points., Results: At post-CBT, the mean reduction in PDSS scores from baseline was -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88-2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By calculating areas under the curve for EQ-5D index changes, we estimated that patients gained a minimum of 0.102 QALYs per 1 year due to the CBT., Conclusions: This study demonstrated that individual CBT for PD may be useful in Japanese clinical settings but further randomized control trials are needed., Trial Registration: UMIN-CTR UMIN000022693 (retrospectively registered).

Background: The lowering of the age of onset and chronicity have been key problems related to eating disorders (EDs). As the proportion of teens in the estimated onset ages has increased, it has become important to detect students with EDs and to clarify how they can be supported. Though epidemiological surveys of Yogo teachers (school nurse/health science teachers) have been conducted to inquire about the number of such students, none of these were done according to ED type based on DSM-5. Thus, we conducted a wide area survey in Japan with the goal of proposing a better framework of support for Yogo teachers in their efforts to care for students with EDs., Methods: A questionnaire survey organized by ED type (based on DSM-5) was administered to Yogo teachers working at elementary/junior high/senior high/special needs schools in four prefectures of Japan in 2015, and 1,886 responses were obtained. Based on the results, the encounter rates (the proportion of Yogo teachers who had encountered a student with an ED) were calculated, and factors that could affect the rates were examined by logistic regression analysis., Results: The order of the encounter rates of the ED types was as follows: Anorexia Nervosa (AN) > Bulimia Nervosa (BN) > Avoidant/Restrictive Food Intake Disorder (ARFID) > Binge Eating Disorder (BED) > Others. The factors significantly affecting the rates were "location, school type, number of students, experience years, and AN knowledge" for AN, "school type, experience years, and BN knowledge" for BN, "school type, experience years, and BED knowledge" for BED, "location, experience years, and ARFID knowledge" for ARFID, and "school type, experience years, and Others knowledge" for Others., Conclusions: Because the encounter rate of AN was the highest, providing support for AN would be the most effective. Moreover, one factor that affected the encounter rate of all ED types was ED knowledge. In addition to this, senior high schools had the highest encounter rates for AN, BN and BED, and special needs schools had the highest rates for Others. These findings imply that, in order to detect and support ED students at an early stage, it is necessary to offer knowledge of the most prevalent ED types to Yogo teachers at the corresponding school type.

Case 1: A 66-year-old man was admitted because of progressive gait disturbance and dysphagia after developing red rash. He was diagnosed as Guillain-Barré syndrome (GBS) and treated by intravenous immunoglobulin therapy (IVIg). Two weeks later, he could swallow and walk without any abnormalities. Case 2: A 58-year-old woman was admitted because of gait disturbance, bilateral peripheral facial nerve palsies, and respiratory failure one week after developing fever and rash. She was diagnosed as GBS and treated with IVIg. She underwent mechanical ventilation, while she could wean off it one month later and her limb strengths improved. We confirmed both patients had scrub typhus by serological studies. Peripheral neuropathy is one of the complications of scrub typhus. In addition, this disease sometimes leads to severe GBS. GBS should be included in differential diagnosis when peripheral neuropathies develop in the course of treating scrub typhus, and we should keep in mind that scrub typhus is one of the causes of GBS.

Ghrelin was reported to enhance GLP-1 secretion after glucose load in mice., (© 2015 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: Glutamatergic neurotransmission via the N-methyl-d-aspartate (NMDA) receptor is integral to the pathophysiology of depression. This study was performed to examine whether amino acids related to NMDA receptor neurotransmission are altered in the serum of patients with depression., Method: We measured the serum levels of d-serine, l-serine, glycine, glutamate and glutamine in patients with depression (n=70), and age-matched healthy subjects (n=78)., Results: Serum levels of d-serine and l-serine in patients with depression were significantly higher than those of healthy controls (p<0.001). In contrast, serum levels of glycine, glutamate and glutamine did not differ between the two groups. Interestingly, the ratio of l-serine to glycine in patients was significantly higher than that of healthy controls (p<0.001)., Conclusion: This study suggests that serine enantiomers may be peripheral biomarkers for depression, and that abnormality in the d-serine-l-serine-glycine cycle plays a role in the pathophysiology of depression.

Background: Many studies have focused on the decreasing age of onset of eating disorders (EDs). Because school-age children with EDs are likely to suffer worse physical effects than adults, early detection and appropriate support are important. The cooperation of Yogo teachers is essential in helping these students to find appropriate care. To assist Yogo teachers, it is helpful to clarify the encounter rates (the proportion of Yogo teachers who have encountered ED students) and kinds of requested support (which Yogo teachers felt necessary to support ED students). There are no studies that have surveyed the prevalence rates of ED children by ED type as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), nor were we able to find any quantitative study surveying the kinds of support Yogo teachers feel helpful to support ED students., Methods: A questionnaire survey was administered to 655 Yogo teachers working at elementary/junior high/senior high/special needs schools in Chiba Prefecture. The questionnaire asked if the respondents had encountered students with each of the ED types described in DSM-5 (anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), avoidant/restrictive food intake disorder (ARFID), and other types of EDs (Others)), and the kinds of support they felt necessary to support these students. The encounter rates and the kinds of requested were obtained and compared, taking their confidence intervals into consideration., Results: The encounter rates for AN, BN, BED, ARFID, and Others were 48.4, 14.0, 8.4, 10.7, and 4.6 %, respectively. When classified by school type, AN, BN, BED, and ARFID had their highest encounter rates in senior high schools. Special needs schools had the highest rate for Others. The support most required for all ED types was "a list of medical/consultation institutions.", Conclusions: Our results have clarified how to support Yogo teachers in the early detection and support of ED students. We found that the encounter rate of AN was the highest, and that it is effective to offer "a list of medical/consultation institutions" to junior and senior high schools where the encounter rates for AN are high.

Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via α7-nicotinic acetylcholine receptors (α7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity. Indeed, central insulin-mediated hepatic IL-6/STAT3 activation and gluconeogenic gene suppression were impeded in mice with hepatic vagotomy, pharmacological cholinergic blockade, or α7-nAchR deficiency. In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines. These findings suggest that dysregulation of the α7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between Parkinson's disease (PD) and body mass index (BMI) has not been established. In this study, we investigated the correlation between BMI and autonomic dysfunction in patients with PD., Methods: Clinical features, BMI, cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy and the coefficient of variation of the electrocardiographic R-R interval (CVRR) were analyzed in 124 patients with PD who were naïve to anti-parkinsonian drugs., Results: BMI was negatively correlated with early heart-to-mediastinum ratio and CVRR in patients with PD, regardless of disease duration and severity., Conclusions: Autonomic dysfunction and BMI increase were associated with each other. Physicians should consider the possibility of autonomic dysfunction in PD patients with high BMI., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Many patients from Toroku, Japan, who have chronic arsenic exposure demonstrate whole-body sensory disturbance that is slightly more pronounced in the extremities. Although previous research in this population showed a mild peripheral neuropathy, it is unknown whether these patients have central nervous system impairment. To investigate the lesion sites underlying sensory disturbance related to chronic arsenic poisoning, we analyzed somatosensory evoked potentials (SEP)., Methods: Clinical features, nerve conduction study results, and median and/or tibial SEP were analyzed in patients with chronic arsenic exposure (total, 13 patients; median & tibial, 4; median, 5; tibial, 4) retrospectively. The SEP findings in patients were compared with those in normal controls., Results: The median SEP results indicated a conduction delay between the proximal brachial plexus and the primary sensory cortex, and tibial SEP findings indicated a delay between the dorsal gray matter of the lumbosacral cord and the primary sensory cortex., Conclusion: This is the first study to identify an impairment of the central somatosensory pathway in patients with chronic arsenic exposure. Sensory disturbance in these patients is related not only to peripheral neuropathy but also to impairment of the central nervous system., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We previously reported on the positive association of hemoglobin with hypertension and atherosclerosis. On the other hand, hepatocyte growth factor (HGF) has been evaluated as a possible biochemical index of hypertension-induced vascular damage. However, no studies have reported on a correlation between hemoglobin and HGF accounting for hypertension status., Methods: A cross-sectional study of 1108 subjects (392 men and 716 women, 40-93 years old) who were undergoing a general checkup in 2014 was conducted., Results: Multiple linear regression analysis adjustment for known cardiovascular risk factors showed no significant correlation between hemoglobin and HGF in non-hypertensive subjects, but a significant positive correlation in hypertensive subjects; β (parameter estimate) = 0.3 (p = 0.975) for non-hypertensive men, β = 0.4 (p = 0.925) for non-hypertensive women, β = 32.7 (p < 0.001) for hypertensive men, and β = 18.7 (p = 0.002) for hypertensive women., Conclusion: We found a significant positive correlation between hemoglobin and HGF among hypertensive men and women. Like HGF, hemoglobin may be a useful indicator to evaluate hypertension-induced vascular damage. Since hemoglobin can easily be measured, these results support hemoglobin as an efficient tool to evaluate vascular damage induced by hypertension in daily medical practice.

A 73-year-old woman was admitted to our hospital due to a decreased conscious level and a high fever. Six days before her admission, she felt transient numbness in her right lower limb. Brain MRI taken by her local doctor revealed only right parietal cortex lesions. She was diagnosed with transient ischemic attack and started on anti-platelet therapy. One day before her admission, she became drowsy, and left-side weakness developed. She was admitted to a community hospital for treating stroke. On the next day, she was referred to our hospital because of a high fever. Our brain MRI showed new lesions in her right temporal lobe. She had no stroke risk factors, and embolic sources were not detected. Cerebrospinal fluid analysis detected herpes simplex virus DNA. She was diagnosed with herpes simplex encephalitis (HSE). HSE is common encephalitis which develops fever, headache and alteration in mental status. It often involves temporal lobe, but extratemporal lesions alone are not uncommon. Diffusion-weighted images (DWI) of brain are of importance to differentiate HSE from stroke. When it is questionable to diagnose with stroke for patients with cerebral cortex lesions, they must be monitored with close observation. There is the possibility of initial presentation of HSE in that situation even if patients have no typical symptoms.

Background: Although antidepressants are still a commonly used treatment for social anxiety disorder (SAD), a significant proportion of patients fail to remit following antidepressants. However, no standard approach has been established for managing such patients. This study aimed to examine the effectiveness of cognitive behavioral therapy (CBT) as an adjunct to usual care (UC) compared with UC alone in SAD patients who remain symptomatic following antidepressant treatment., Methods: This was a prospective randomized open-blinded end-point study with two parallel groups (CBT + UC, and UC alone, both for 16 weeks) conducted from June 2012 to March 2014. SAD patients who remain symptomatic following antidepressant treatment were recruited, and a total sample size of 42 was set based on pilot results., Results: Patients were randomly allocated to CBT + UC (n = 21) or UC alone (n = 21). After 16 weeks, adjusted mean reduction in the Liebowitz Social Anxiety Scale from baseline for CBT + UC and UC alone was -40.87 and 0.68, respectively; the between-group difference was -41.55 (-53.68 to -29.42, p < 0.0001). Response rates were 85.7 and 10.0% for CBT + UC and UC alone, respectively (p < 0.0001). The corresponding remission rates were 47.6 and 0.0%, respectively (p = 0.0005). Significant differences were also found in favor of CBT + UC for social anxiety symptoms, depressive symptoms, and functional impairment., Conclusions: Our results suggest that in SAD patients who have been ineffectively treated with antidepressants, CBT is an effective treatment adjunct to UC over 16 weeks in reducing social anxiety and related symptoms., (© 2016 S. Karger AG, Basel.)

Azodicarbonamide (ADA) is used in some countries as a flour bleaching agent and a dough conditioner. However, ADA is prohibited for use as a food additive in Japan. Therefore, it is necessary to establish an efficient and sensitive method to determine ADA in wheat flour. A simple and practical procedure to analyze ADA in wheat flour and prepared flour mixes was developed. ADA was extracted from samples by ultrasonication with acetone. ADA in the solution was derivatized with triphenylphosphine (TPP). The ADA-TPP derivative was concentrated and cleaned up using a reversed-phase solid-phase extraction cartridge, and the ADA-TPP derivative was analyzed using HPLC for determination and LC-MS/MS for identification. Good linearity was achieved over the concentration range of 0.25-100 ppm ADA in wheat flour and prepared flour mixes. The mean recoveries from wheat flour and prepared flour mixes fortified at the levels of 1 and 10 ppm ranged from 86.9 to 101.0%, and the coefficients of variation ranged from 1.9 to 3.4%.

Previous studies showed that food craving in eating disorders can be weakened with high-frequency repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC). The aims of this study were to assess cerebral oxygenation change induced with rTMS and to assess the short-term impact of rTMS on food craving and other bulimic symptoms in patients with bulimia nervosa (BN). Eight women diagnosed with BN according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria participated in this study. We measured haemoglobin concentration changes in the DLPFC with near-infrared spectroscopy during cognitive tasks measuring self-regulatory control in response to food photo stimuli, both at baseline and after a single session of rTMS. Subjective ratings for food cravings demonstrated significant reduction. A significant decrease in cerebral oxygenation of the left DLPFC was also observed after a single session of rTMS. Measurement with NIRS after rTMS intervention may be applicable for discussing the mechanisms underlying rTMS modulation in patients with BN., (Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.)

Obesity has been increasing not only in Japan but also in both developed and developing countries. Mean body mass index of Japanese patients with type 2 diabetes has been increasing, and it reached 25.0 in 2013. If body weight decreases more than 3% of initial body weight in patients with metabolic syndrome, not only glucose metabolism but also dyslipidemia and hypertension improve. To reduce the excess body weight, behavior therapy, calorie restriction, and exercise are necessary. The next strategies are drugs including mazindol, glucose-like peptide-1 receptor agonist and sodium-dependent glucose cotransporter 2 inhibitor, and bariatric surgery. Because it is often difficult to reduce body weight using only present non-invasive therapies, clarification of appetite mechanisms and development of novel anti-obesity drugs with few side effects are needed.

In previous studies of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), areas of slow blood flow in the spinal cord were related to pathological changes. While the pathological changes in the brain are milder than those in the spinal cord, they are also more significant in sites with slow blood flow. In this study, we investigated brain glucose metabolism in slow blood flow areas using fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Clinical features and brain (18)F-FDG-PET parameters were analyzed in six patients with HAM/TSP. For comparison of PET data, eight healthy volunteers were enrolled as normal controls (NLs). Glucose metabolism in the watershed areas of the middle and posterior cerebral arteries, as compared with that in the occipital lobes as a control, was significantly lower in HAM/TSP patients than in NLs. This result confirmed the relationship between slow blood flow areas and hypometabolism in HAM/TSP, and is consistent with previous findings that pathological changes are accentuated in sites with slow blood flow.

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding. This treatment increased the number of macrophages/microglia in the nodose ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll-like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfα in the nodose ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered inflammatory responses in the gut, nodose ganglion, and subsequently in the hypothalamus within 24 h. These findings suggest that the vagal afferent nerve may transfer gut-derived inflammatory signals to the hypothalamus via the nodose ganglion, and that ghrelin may protect against HFD-induced inflammation., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Ghrelin is a 28-amino-acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia-cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced inflammation-associated colon carcinogenesis model and the second was the Apc(Min/+) genetic cancer susceptibility model. In AOM/DSS-treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in Apc(Min/+) mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS-treated mice or Apc(Min/+) mice, though tumor size tended to be larger in Ghrl(-/-) colons in the AOM/DSS model. No tumor-promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation-associated colorectal carcinogenesis and may suggest its safety in patients under colitis-associated cancer susceptibility conditions., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Background: No epidemiologic survey examining eating disorders in Japan has been done at a national level since 1992. The prevalence of anorexia nervosa, as assessed by questionnaires to hospitals, is thought to be underestimated because patients with anorexia nervosa tend to avoid consultations. In conformity with the School Health and Safety Act of Japan, schools are required to have physicians perform a medical examination of students every year. The teachers in charge of health education and school physicians determine the height, weight, and health condition, and examine the medical records of each student. Therefore, we as members of the Survey Committee for Eating Disorders of the Japanese Ministry of Health, Labour, and Welfare conducted an epidemiologic survey using questionnaires sent to schools in seven prefectures to determine the current prevalence of anorexia nervosa among adolescents., Methods: We sent a questionnaire to elementary, junior high, and senior high schools. Questionnaires contained items on the number of students, patients with anorexia nervosa in each grade who were diagnosed by specialists, and students who the school physician strongly suspected to have anorexia nervosa but who did not undergo a clinical examination in a medical institution., Results: We found patients of both sexes with anorexia nervosa aged 9-10 years in elementary schools. The point prevalence of anorexia nervosa for girls, including strongly suspected cases, in the three grades of junior high school and three grades of senior high school were 0-0.17 %, 0-0.21 %, 0.17-0.40 %, 0.05-0.56 %, 0.17-0.42 % and 0.09-0.43 %, respectively. We also confirmed a prominent sex difference in the prevalence of anorexia nervosa. The prevalence of boys was one third that of girls in some prefectures. One third to one half of diagnosed and strongly suspected students with anorexia nervosa had not received medical consultation or treatment., Conclusions: Although the prevalence of anorexia nervosa had regional differences in Japan, it has reached levels comparable to those in Western societies. Because no eating disorder center exists and the treatment environment is poor, national action to address this disease is a pressing need in Japan.

Aim: Antioxidant activities and cytokine levels in human body fluids are considered to be strongly associated with periodontitis. The aim of this study was to elucidate the relationship between salivary antioxidant activities against superoxide or hydroxyl radical, cytokines, and periodontal conditions through a community-based cross-sectional study conducted in Goto city, Japan., Materials and Methods: Saliva samples were analysed for superoxide or hydroxyl radical scavenging activities and cytokine levels from 160 participants. We demonstrated that saliva contained superoxide and hydroxyl radical scavenging activities by using electron spin resonance with a spin-trapping agent. The concentrations of eight cytokines were measured using multiplex bead assays., Results: There were significant differences in salivary superoxide or hydroxyl radical scavenging activity, and the levels of Interleukin-1β, Interleukin-6, and Interleukin-8 between periodontitis classifications. Multivariate stepwise logistic regression model showed that salivary superoxide and hydroxyl radical scavenging activities were significantly associated with the classification of periodontitis. In addition, salivary superoxide scavenging activity was found to have significant association with all periodontal parameters using multiple linear regression analysis., Conclusions: These findings suggest that the evaluation of salivary antioxidant activities, as assessed by electron spin resonance, are associated with periodontitis and various clinical variables in community-dwelling participants (ClinicalTrials.gov number NCT01742728)., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway. Administration (s.c.) of ghrelin did not induce food intake, suppression of oxygen consumption, electrical activity of the vagal afferent nerve, phosphorylation of ERK2 and AMP-activated protein kinase alpha in the nodose ganglion, or Fos expression in hypothalamic arcuate nucleus of mice fed a HFD for 12 weeks. Administration of anti-ghrelin IgG did not induce suppression of food intake in HFD-fed mice. Expression levels of ghrelin receptor mRNA in the nodose ganglion and hypothalamus of HFD-fed mice were reduced. Inflammatory responses, including upregulation of macrophage/microglia markers and inflammatory cytokines, occurred in the nodose ganglion and hypothalamus of HFD-fed mice. A HFD blunted ghrelin signaling in the nodose ganglion via a mechanism involving in situ activation of inflammation. These results indicate that ghrelin resistance in the obese state may be caused by dysregulation of ghrelin signaling via the vagal afferent., (© 2015 The authors.)

Background: Several studies have reported that height is inversely associated with risk of cardiovascular disease but positively associated with cancer risk. On the other hand, evidence has been accumulating that anemia reflects poor health and increased vulnerability to poor outcomes in older persons. Moreover, alcohol consumption has also been reported to be associated with mortality. However, no studies have reported on a possible association between height and risk of anemia in relation to drinking status., Methods: We conducted a cross-sectional study of 1287 men aged 40-89 years undergoing general health check-ups., Results: Independent from classic cardiovascular risk factors, we found a significant inverse association between height and anemia for non-drinkers and a J-shaped association for drinkers. The multivariable odds ratio (ORs) of an increment of 1 SD (standard deviation) in height (6.68 cm) for anemia for non-drinkers was 0.59 (0.45-0.77). For drinkers, with the second quartile of height (Q2) as the reference group, the multivariable OR of anemia was 2.68(0.90-7.96) (p = 0.075) for the lowest height quartile (Q1), 2.73(0.92-8.08) for the third quartile (Q3) and 4.82(1.65-14.10) for the highest quartile (Q4) (p = 0.004)., Conclusion: Height was found to be associated with anemia for rural Japanese men and drinking status is likely to affect those associations.

Introduction: Both dipeptidyl peptidase-4 inhibitors and α-glucosidase inhibitors (α-GI) have been reported to change the incretin and insulin secretion. To examine the effects of acarbose, miglitol, and sitagliptin on glucose metabolism and secretion of gut peptides, we conducted a crossover study in patients with type 2 diabetes mellitus (T2DM)., Methods: Eleven Japanese patients with T2DM underwent four meal tolerance tests with single administration of acarbose, miglitol, sitagliptin, or nothing. Fasting and postprandial plasma levels of glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were measured., Results: Early-phase insulin secretion was reduced following acarbose and miglitol, and the areas under the curve (AUC) of insulin at 180 min following acarbose and miglitol were significantly lower than sitagliptin. AUC of plasma glucose at 180 min after acarbose, miglitol, and sitagliptin tended to be lower than in controls, and plasma glucose levels at 30-60 min following miglitol were significantly lower than in controls. Plasma glucagon, ghrelin, and des-acyl ghrelin levels did not differ among the four conditions. Postprandial plasma active GLP-1 levels and AUC of GLP-1 increased significantly in both the sitagliptin and miglitol groups compared to control. Postprandial plasma total GIP levels increased following sitagliptin but decreased after acarbose and miglitol. Changes in incretin levels tended to be greater with miglitol than acarbose., Conclusion: These results showed that sitagliptin and α-GIs, miglitol more so than acarbose, improved hyperglycemia in patients with T2DM after single administration, and had different effects on insulin and incretin secretion., Trial Registration: UMIN-CTR number, UMIN000009981.

Background: Decision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability., Methods: Patients suffering from AN (n = 22), BN (n = 36) and age-matched HC (n = 51) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings., Results: Significant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making., Conclusion: Different patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

Background: Recent studies have reported an association between both higher and lower levels of hemoglobin A1c (HbA1c) and higher mortality of diabetes patients. Like diabetes, carotid atherosclerosis is a well known lifestyle-related disease. However, no studies have yet reported an association between HbA1c levels and carotid atherosclerosis., Methods: We conducted a cross-sectional study of 1,150 Japanese elderly men aged ≥60 years who were undergoing general health checkups. Carotid atherosclerosis was defined as a carotid intima-media thickness (CIMT) ≥1.1 mm. Since body mass index (BMI) is regarded as a cardiovascular risk factor that exerts a strong influence on both HbA1c levels and carotid atherosclerosis, we performed a stratified analysis of this risk based on BMI., Results: Using the intermediate HbA1c quintile as a reference group, the groups in the lowest HbA1c quintiles showed a significantly higher risk of carotid atherosclerosis in patients with low BMI (≤23 kg/m(2)) vs. no increased risk in those with high BMI (>23 kg/m(2)). The association of HbA1c with carotid atherosclerosis became slightly stronger when these analyses were limited to subjects who were not taking glucose-lowering medications or medications for hyperlipidemia and cardiovascular disease. After adjusting for classical cardiovascular risk factors, adjusted odds ratios (ORs) for carotid atherosclerosis were 1.36 (0.84 to 2.20) for total subjects, 2.29 (1.12 to 4.66) for low-BMI groups, and 0.68 (0.33 to 1.41) for high-BMI groups., Conclusions: Lower HbA1c level is a significant risk factor for carotid atherosclerosis in rural community-dwelling elderly Japanese men with low, but not high BMI, particularly in those not taking glucose-lowering medication.

Background: Repeated ghrelin administration leads to improvements in symptoms, muscle wasting and exercise tolerance in cachectic patients with pulmonary disease. We investigated the optimal ghrelin dose for underweight patients with chronic respiratory failure., Methods: In this multicenter, randomized, dose-comparison exploratory study, 44 cachectic patients with chronic respiratory failure were randomly assigned pulmonary rehabilitation with intravenous twice-daily administration of 1 or 2 μg/kg ghrelin for 3 weeks. The primary endpoint was improvement in 6-min walking distance (6 MWD). The secondary endpoint was change in peak VO2., Results: Twenty-one patients were assigned to the 1 μg/kg ghrelin group and 23 to the 2 μg/kg ghrelin group. Change from baseline 6 MWD after treatment was similar between groups(1 μg/kg: 53.9 m, 2 μg/kg: 53.9 m, p = 0.99). Mean change in peak VO2 was significantly greater in the 2 μg/kg group (63.1 ml/min) than in the 1 μg/kg group (-63.8 ml/min, p = 0.048). Food intake and lean body mass significantly increased in both groups, and the St. George Respiratory Questionnaire score, body weight, and body mass index were remarkably improved in only the 2 μg/kg group, although there was no significant difference between groups. No treatment-related serious events were reported for either group., Conclusion: Improvements in the oxygen uptake capacity were greater in patients receiving 2 μg/kg ghrelin twice daily for 3 weeks than in those receiving 1 μg/kg, although exercise tolerance was similar between groups at the end of the 3-week treatment period. Thus, a twice daily dose of 2 μg/kg ghrelin is recommended over 1 μg/kg ghrelin for patients with chronic respiratory failure and weight loss.

Neuroendocrine regulatory peptides (NERP-1 and -2) are novel amidated peptides derived from VGF, a polypeptide secreted from neurons and endocrine cells through a regulated pathway. Dr. Nakazato Masamitsu reported that NERP-1 and -2 may have a local modulator function on the human endocrine system, and clearly showed expression of NERP-1 and -2 in human pancreas islets. Based on these data, we investigated the alteration of insulin secretion, insulin granule-related protein, and pancreas-specific transcription factors in response to NERPs expression. We confirmed the expression of NERP-1 and -2 in the pancreas of a human diabetes patient, in addition to diabetic animal models. When INS1 cells and primary rat islets were incubated with 10nM NERPs for 3 days, glucose-stimulated insulin secretion levels were blunted by NERP-1 and -2. The number of insulin granules released from the readily releasable pool, which is associated with the first phase of glucose-stimulated insulin release, was decreased by NERP-1 and -2. Insulin granule-related proteins and mRNAs were down-regulated by NERP-2 treatment. NERP-2 decreased the expression of BETA2/NeuroD and insulin and controlled the nucleo-cytoplasmic translocation of FOXO1 and Pdx-1. We observed that NERP-2 levels were dramatically increased in diabetic pancreas. In conclusion, NERP-2 may play an important role in insulin secretion through the regulation of insulin secretory granules and β-cell transcription factors. In addition, NERP-2 expression is increased in diabetic conditions. Therefore, we suggest that NERPs may be potent endogenous suppressors of glucose-dependent insulin secretion., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A 64-year-old woman with diffuse large B-cell Lymphoma (DLBCL) complained of double vision and pain sensation in her limbs after eight cycles of chemotherapy. F-fluorodexyglucose-positron emission tomography (FDG-PET) 7 days after the onset of double vision showed no abnormal accumulation and confirmed remission of DLBCL according to the international criteria. However, she developed limb weakness and severe paresthesia. The second FDG-PET 41 days after onset showed increased uptake at the both the brachial and lumbar plexuses, suggesting neurolymphomatosis. Although FDG-PET appears to be a highly sensitive diagnostic method for neurolymphomatosis, it is sometimes difficult to detect neurolymphomatosis in early diagnose, such as with this case. Therefore, multiple examinations are necessary to determine neurolymphomatosis.

Background: Cardiac 123I-metaiodobenzylguanidine scintigraphy (MIBG) previously demonstrated an uptake reduction in patients with Parkinson's disease (PD). However, epidemiologic research showed that electrocardiography (ECG) abnormalities occurred prior to motor signs in PD. Here we investigated whether the electrical conduction system of the heart was impaired in PD., Methods: Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD, 42 with multiple system atrophy (MSA) and 124 normal controls (NL)., Results: The PR interval was significantly longer in patients with PD than in NL. The PR interval was significantly negatively correlated with early and delayed heart-to-mediastinum ratios in MIBG scintigraphy in PD and MSA patients. In 19 PD patients with PR prolongation, 17 patients also had abnormal MIBG findings, and the other 2 showed normal MIBG., Conclusions: The PR prolongation must show some sympathetic system abnormality because it is mainly controlled by the sympathetic nervous system. PR prolongation supports the objective biomarker value of MIBG for PD diagnosis., (© 2015 S. Karger AG, Basel.)

Objectives: Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric disorders, with some speculating that a reason for difficulty in its treatment might be its coexistence with autism spectrum. We investigated the tendency for autistic spectrum disorders (ASD) in patients with OCD from a neuroimaging point of view using voxel-based morphometry., Methods: We acquired T1-weighted images from 20 patients with OCD and 30 healthy controls and investigated the difference in regional volume between the groups as well as the correlation between Autism-Spectrum Quotient (AQ) scores and regional cerebral volumes of patients with OCD., Results: Volumes in the bilateral middle frontal gyri were significantly decreased in patients with OCD compared to controls. Correlational analysis showed significant positive correlations between AQ scores and regional gray matter (GM) volumes in the left dorsolateral prefrontal cortex (DLPFC) and left amygdala. Furthermore, GM volumes of these regions were positively correlated with each other., Conclusions: The positive correlation of ASD traits in patients with OCD with regional GM volumes in the left DLPFC and amygdala could reflect the heterogeneity of patient symptoms. Our results suggest that differences in GM volume might allow classification of patients with OCD for appropriate therapy based on their particular traits.

Teneligliptin is a novel peptidomimetic-chemotype prolylthiazolidine-based inhibitor of dipeptidyl peptidase-4 (DPP-4). The aim of this study was to evaluate the effects of teneligliptin on 24 h blood glucose control and gastrointestinal hormone responses to a meal tolerance test, and to investigate the glucose-lowering mechanisms of teneligliptin. Ten patients with type 2 diabetes mellitus (T2DM) were treated for 3 days with teneligliptin (20 mg/day). Postprandial profiles for glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose-dependent insulinotropic polypeptide (GIP), ghrelin, des-acyl ghrelin, and 24 h glycemic fluctuations were measured via continuous glucose monitoring for 4 days. Once daily teneligliptin administration for 3 days significantly lowered postprandial and fasting glucose levels. Significant elevations of fasting and postprandial active GLP-1 and postprandial active GIP levels were observed. Teneligliptin lowered postprandial glucose elevations, 24 h mean blood glucose levels, standard deviation of 24 h glucose levels and mean amplitude of glycemic excursions (MAGE) without hypoglycemia. Serum insulin levels in the fasting state and 30 min after a meal were similar before and after teneligliptin treatment; however significant reductions at 60 to 180 min after treatment were observed. A significant elevation in early-phase insulin secretion estimated by insulinogenic and oral disposition indices, and a significant reduction in postprandial glucagon AUC were observed. Both plasma ghrelin and des-acyl ghrelin levels were unaltered following teneligliptin treatment. Teneligliptin improved 24 h blood glucose levels by increasing active incretin levels and early-phase insulin secretion, reducing the postprandial insulin requirement, and reducing glucagon secretion. Even short-term teneligliptin treatment may offer benefits for patients with T2DM.