Gifu-shi, Japan
Gifu-shi, Japan

Asahi University is a private university in Mizuho, Gifu Prefecture, Japan. The school was first founded in 1971 as Gifu Dental University . It was renamed Asahi University in 1985 when the management department was added. Wikipedia.

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Obata T.,Osaka Aoyama University | Nakashima M.,Asahi University
European Journal of Pharmacology | Year: 2017

Examined in the present study, allopurinol are xanthine oxidase inhibitors for use in rat hearts in vivo dialysis technology and ventricular myocardial intersitial adenosine production can increase. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and the tissue in the vicinity of the dialysis was perfused with Tyrode's solution containing adenosine 5’-monophosphate (AMP) through the dialysis probe at a rate of 1.0 ml/min to assess the activity of ecto-5’-nucleotidase. Allopurinol (10 μM) significantly increased the level of adenosine in rat heart dialysate (n=6, p<0.05), which was inhibited by chelerythrine, 10 μM, an antagonist of protein kinase C (PKC). Another free radical scavenger, coenzyme Q10 (CoQ10, 100 μM) or ascorbic acid (Vitamin C; 100 μM) also increased adenosine production. In addition, allopurinol enhanced the diacylglycerol (DAG; 50 μM)-induced also increases in adenosine production by 71.5±12.0% (n=6, P<0.05), to a level significantly (P<0.05) greater than the increase caused by DAG alone (33.0±10.6%). In the presence of allopurinol (10 μM), a marked elevation of AMP-primed dialysate adenosine in ischemia/reperfused rat hearts was observed. Free radical generation may suppress adenosine production via activation of PKC. The results suggest that oxidative stress may cause inactivation of nucleotidase, adenosine production in rat heart. © 2017

Obata T.,Osaka Aoyama University | Nakashima M.,Asahi University
European Journal of Pharmacology | Year: 2016

The present study examined whether ischemia-reperfusion-induced hydroxyl radical (·OH) generation was attenuated by myo-inositol hexaphosphoric acid (phytic acid). A flexibly mounted microdialysis technique was used to detect the generation of ·OH in in vivo rat hearts. To measure the level of ·OH, sodium salicylate in Ringer's solution (0.5 mM or 0.5 nmol/μl/min) was infused directly through a microdialysis probe to detect the generation of ·OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). To confirm the generation of ·OH by Fenton-type reaction, iron(II) was infused through a microdialysis probe. A positive linear correlation between iron(II) and the formation of 2,3-DHBA (R2=0.983) was observed. However, the level of 2,3-DHBA in norepinephrine (100 μM) plus phytic acid (100 μM) treated group were significantly lower than those observed in norepinephrine-only-treated group (n=6,∗p<0.05). To examine the effect of phytic acid on ischemia-reperfusion-induced ·OH generation, the heart was subjected to myocardial ischemia for 15 min by occlusion of the left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with phytic acid. These results suggest that phytic acid is associated with antioxidant effect due to the suppression of iron-induced ·OH generation. © 2016 Published by Elsevier B.V.

Onishi M.,Asahi University | Iinuma M.,Asahi University | Tamura Y.,Asahi University | Kubo K.-Y.,Seijoh University
Neuroscience Letters | Year: 2014

Prenatal stress in dams induces learning deficits and suppresses neurogenesis in the hippocampal dentate gyrus (DG) of offspring via increasing corticosterone levels in the dam. Chewing under stressful conditions prevents stress-induced behavioral impairments and morphologic changes. Here, we examined whether chewing during prenatal stress prevents the stress-induced learning deficits and the suppression of cell proliferation in the hippocampal DG in adult offspring. Pregnant mice were exposed to restraint stress beginning on day 12 of pregnancy and continuing until delivery. Half of the dams were given a wooden stick to chew on during restraint. The pups were raised to adulthood, and learning ability and cell proliferation in the hippocampal DG were assessed. In dams, chewing during prenatal stress attenuated the stress-induced increase in plasma corticosterone levels. In the adult offspring, prenatal stress impaired learning and decreased cell proliferation in the DG, whereas maternal chewing during prenatal stress significantly attenuated the prenatal stress-induced learning deficits and decreased cell proliferation in the DG in their offspring. These findings suggest that maternal chewing during prenatal stress is an effective stress-coping method for the dam to prevent learning deficits and suppression of cell proliferation in offspring. © 2013 Elsevier Ireland Ltd.

Tsuchiya H.,Asahi University
Journal of Toxicology | Year: 2011

Cigarette smoking and alcohol consumption possibly affect platelet functions. To verify the hypothesis that some α-, β-, and γ-carboline components in cigarette smoke and alcoholic beverages may change platelet aggregability, their effects on human platelets were determined by aggregometry together with investigating their membrane effects by turbidimetry. Carbolines inhibited platelet aggregation induced by five agents with the potency being 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole 3-amino-1-methyl-5H-pyrido[4,3-b]indole 1-methyl-9H-pyrido[3,4-b]indole. The most potent 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole showed 50 aggregation-inhibitory concentrations of 6-172 μM. Both -carbolines interacted with phosphatidylcholine membranes to lower the lipid phase transition temperature with the potency correlating to the antiplatelet activity, suggesting that the interaction with platelet membranes to increase their fluidity underlies antiplatelet effects. Given their possible concentration and accumulation in platelets, γ- and β-carbolines would provide cigarette smokers and alcohol drinkers with reduced platelet aggregability, and they may be responsible for the occurrence of hemorrhagic diseases associated with heavy smoking and alcoholics. © 2011 Hironori Tsuchiya.

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme (Thymus vulgaris, Lamiaceae) and clove (Syzygium aromaticum, Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na+ channels, γ-aminobutyric acid type A receptors, N-methyl-D-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin. © 2017 by the author.

Tsuchiya H.,Asahi University
International Journal of Pharmacology | Year: 2012

Propofol induces general anesthesia through binding to GABA A receptors. It is inhibited by interacting with benzodiazepine inverse agonist tetrahydro-β-carbolines present in the human body. Aside from acting on receptor proteins, both propofol and tetrahydro-β-carbolines act on membrane lipid bilayers. In this study, the hypothetical inhibitory relation on membrane biophysical modification was verified between propofol and tetrahydro-β-carbolines. Lipid bilayer membranes were prepared with phospholipids and cholesterol. The membrane preparations were reacted with propofol, 1-methyl-1,2,3,4-tetrahydro-β-carboline and its metabolites 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline and 7-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline, followed by measuring fluorescence polarization to determine their induced changes in membrane fluidity. In the pilot experiments using model membranes prepared with 100 mol% 1,2-dipalmitoyl phosphatidylcholine, 1-methyl-1,2,3,4-tetrahydro-β-carboline showed a concentration-dependent biphasic effect to increase membrane fluidity at high micromolar concentrations but decrease at <50 μM. In the lower concentration range of 0.01-0.5 μM, 1-methyl-1,2,3,4-tetrahydro-β-carboline was effective in rigidifying the membranes, whereas neither 6-hydroxyl nor 7-hydroxyl metabolite showed any membrane effects. Based on these results, biomimetic membranes consisting of 60 mol% 1-palmitoyl-2-oleoylphosphatidylcholine and 40 mol% cholesterol were pretreated with 1-methyl-1,2,3,4-tetrahydro-β-carboline of physiologically presumable concentrations and then reacted with propofol of clinically relevant concentrations. Propofol fluidized the membranes at 0.125-1 μM. However, the membrane-fluidizing effects of 0.125 and 0.25 μM propofol were inhibited by 0.01-5 nM 1-methyl-1,2,3,4-tetrahydro-β-carboline. In addition to their interaction at a receptor level, propofol and 1-methyl-1,2,3,4-tetrahydro-β-carboline show the inhibitory relation on membrane fluidity changes. Such a relation may be hypothetically associated with the anesthetic tolerance. © 2012 Asian Network for Scientific Information.

Into T.,Asahi University | Inomata M.,Asahi University | Takayama E.,Asahi University | Takigawa T.,Asahi University
Cellular Signalling | Year: 2012

Toll-like receptors (TLRs) serve as the major innate immune sensors for detection of specific molecular patterns on various pathogens. TLRs activate signaling events mainly by utilizing ubiquitin-dependent mechanisms. Recent research advances have provided evidence that TLR signaling is linked to induction of autophagy. Autophagy is currently known to affect both of the immune defense and suppression of inflammatory responses. In TLR-associated immune responses, autophagic lysis of intracellular microbes (called xenophagy) contributes to the former mechanism, while the latter seems to be mediated by the control of the mitochondrial integrity or selective autophagic clearance of aggregated signaling proteins (called aggrephagy). Several autophagy-related ubiquitin-binding proteins, such as SQSTM1/p62 and NDP52, mediate xenophagy and aggrephagy. In this review, we summarize the expanded knowledge regarding TLR signaling and autophagy signaling. After that, we will focus on autophagy-associated signaling downstream of TLRs and the effect of autophagy on TLR signaling, thus highlighting the signaling crosstalk between the TLR-associated innate immune responses and the regulation of innate immunity by xenophagy and aggrephagy. © 2012 Elsevier Inc..

Tsuchiya H.,Asahi University | Mizogami M.,Asahi University
Anesthesia and Analgesia | Year: 2012

It remains questionable whether local anesthetics can interact with membrane lipids at clinically relevant concentrations to show the difference between enantiomers. We compared the effects of bupivacaine stereoisomers on biomimetic membranes containing cardiolipin and cholesterol. Bupivacaine interacted with the membranes at cardiotoxic 5 μM with the potency being S(-)-enantiomer < racemate < R(+)-enantiomer, which agreed with the rank order of their cardiotoxicity. Such differences became greater with decreasing drug concentrations, possibly explaining the inconsistent cardiotoxic potencies of bupivacaine stereoisomers reported previously. The interactivity with biomembranes may in part contribute to the mode of toxic action of local anesthetics. Copyright © 2012 International Anesthesia Research Society.

Inomata M.,Asahi University | Niida S.,National Institute for Longevity science | Shibata K.-I.,Hokkaido University | Into T.,Asahi University
Cellular and Molecular Life Sciences | Year: 2012

Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly (I: C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin- editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting 'autophagy receptors' in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly (I: C) - induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF-TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling. © 2011 Springer Basel AG.

Tsuchiya H.,Asahi University
Food Chemistry | Year: 2010

Plant foods contain various flavonoids with nutraceutical and health benefits. Structurally different flavonoids were compared by the potency to interact with liposomal membranes in the context of their mode of action. A series of fluorescence polarisation measurements showed that flavonoids (1-10 μM) structure-dependently acted on the deeper regions of lipid bilayers to decrease membrane fluidity. Their comparative effects on cell-mimetic membranes, consisting of unsaturated phospholipids and cholesterol, characterised the structure-membrane interactivity relationship: 3-hydroxylation of the C ring, non-modification of the B ring and 5,7-dihydroxylation of the A ring led to the greatest membrane interactivity, followed by 3′,4′-dihydroxylation of the B ring. Galangin and quercetin, meeting such a structural requirement, inhibited the proliferation of tumour cells at 10-100 μM, together with rigidifying cell membranes, but not membrane-inactive flavonoids. The structure-dependent membrane interaction, which modifies the fluidity, is mechanistically associated with flavonoid bioactivity in a membranous lipid phase. © 2009 Elsevier Ltd. All rights reserved.

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