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Iwadate Y.,Chiba University | Fukuda K.,Chiba Chuo Medical Center | Matsutani T.,Chiba University | Saeki N.,Chiba University
Journal of Clinical Neuroscience | Year: 2016

Gliomas arising in the brain parenchyma infiltrate into the surrounding brain and break down established complex neuron-glia networks. However, mounting evidence suggests that initially the network microenvironment of the adult central nervous system (CNS) is innately non-permissive to glioma cell invasion. The main players are inhibitory molecules in CNS myelin, as well as proteoglycans associated with astrocytes. Neural stem cells, and neurons themselves, possess inhibitory functions against neighboring tumor cells. These mechanisms have evolved to protect the established neuron-glia network, which is necessary for brain function. Greater insight into the interaction between glioma cells and the surrounding neuron-glia network is crucial for developing new therapies for treating these devastating tumors while preserving the important and complex neural functions of patients. © 2015 Elsevier Ltd. All rights reserved. Source


Okumi H.,Josai International University | Okumi H.,Chiba University | Tashima K.,Josai International University | Matsumoto K.,Josai International University | And 3 more authors.
Planta Medica | Year: 2012

Capsaicin and 6-gingerol, pungent components of chilli pepper and ginger, are known as dietary agonists of transient receptor potential vanilloid-1. Transient receptor potential vanilloid-1 nerve fibers are recognized to play a role in gastric mucosal integrity in rats. In the present studies, we examined the acute effects of peroral administration of capsaicin and 6-gingerol on gastric acid secretion in conscious mice. These agents were given p.o. 30min before the pylorus was ligated. Oral administration of capsaicin (1.0-100mg/kg) or 6-gingerol (1.5-50mg/kg) significantly and dose-dependently inhibited basal acid secretion. Pretreatment with BCTC, a transient receptor potential vanilloid-1 antagonist, significantly reversed the reduced basal acid secretion by capsaicin or 6-gingerol. The combination of the lowest doses of capsaicin and 6-gingerol markedly inhibited basal acid secretion in conscious mice and this was also significantly reversed by BCTC. Moreover, the combination of the maximal dose of capsaicin and 6-gingerol inhibited basal acid secretion only to the level of a single administration of the maximal dose of capsaicin. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on the inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1. In separate experiments, intraduodenal administration of either capsaicin (30mg/kg) or 6-gingerol (15mg/kg), whose doses were observed to have a significant inhibitory effect by oral administration, tended to inhibit basal acid secretion compared with the vehicle. These results suggest that the combination of capsaicin and 6-gingerol has an additive effect on inhibition of gastric acid secretion through activation of transient receptor potential vanilloid-1, and oral administration of transient receptor potential vanilloid-1 agonists directly stimulates transient receptor potential vanilloid-1 in the gastric lumen, resulting in a potent reduction of gastric acid secretion. © Georg Thieme Verlag KG Stuttgart · New York. Source


Iwadate Y.,Chiba University | Fukuda K.,Chiba Chuo Medical Center | Matsutani T.,Chiba University | Saeki N.,Chiba University
Japanese Journal of Neurosurgery | Year: 2014

Gliomas arising in the brain parenchyma infiltrate into the surrounding brain to breakdown the established complex neuron-glia network. Mounting evidences suggests that the adult brain parenchyma innately restricts axonal regrowth and cellular infiltrations including those of glioma cells mainly by inhibitory molecules in CNS myelin as well as the proteoglycans associated with astrocytes. These mechanisms have been shown to be a major hurdle for successful axon regeneration at the time of brain injury. However, these innate inhibitory mechanisms may be injured by radiation therapy, which could compromise patients’ survival periods as well as lead to long-term cognitive impairment. Herein, we review the molecular basis of the innate inhibitory mechanisms of the neuron-glia network and discuss its clinical implications. Greater insight into the interaction of glioma cells and the surrounding brain parenchyma is crucial for developing new therapies for theating these devastating tumors while still preserving the complex neuron-glia network. © 2014 The Japanese Congress of Neurological Surgeons. Source


Kobayashi K.,Chiba University | Yokoh H.,Chiba University | Sato Y.,Chiba University | Takemoto M.,Chiba University | And 10 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12weeks, sitagliptin reduced HbA1c by -0.44% (p<0.001) relative to αGI. At 24weeks, the reduction was almost identical between the groups (-0.091%, p=0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia. © 2014 John Wiley & Sons Ltd. Source

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