Kyushu University of Health and Welfare
Nobeoka, Japan

Kyushu University of Health and Welfare is a private university in Nobeoka, Miyazaki, Japan, established in 1999. Wikipedia.

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Tokunaga J.,Kyushu University of Health and Welfare
American journal of pharmaceutical education | Year: 2010

To develop, implement, and assess an experience-based education program using human patient simulators to instruct pharmacy students in monitoring vital signs to identify drug treatment effects and adverse events. Medical emergency care programs using human patient simulators were prepared and facilitated practical clinical training in resuscitation, which required selecting drugs while monitoring changes in blood pressure, pulse, and arterial blood oxygen saturation. Training encompassed the monitoring of routes of drug administration, drawing of simulated blood, vital-sign monitoring based on a pharmaceutical universal training model, vital-sign monitoring devices and simulators, and medical emergency education using biological simulators. Before and after bedside training, students were asked to complete a questionnaire to assess their understanding of vital sign monitoring and emergency care. Students successfully learned how to monitor routes of drug administration, vital signs, and pathological conditions. There was a significant increase in students' recognition of the importance of vital-sign monitoring. Experienced-based training using patient simulators successfully prepared pharmacy students to monitor vitals signs and identify drug treatment effects and adverse events.

Gamoh S.,Kyushu University of Health and Welfare | Hisa H.,Kyushu University of Health and Welfare | Yamamoto R.,Kyushu University of Health and Welfare
Biological and Pharmaceutical Bulletin | Year: 2013

5-Hydroxytryptamine (5-HT) is involved in regulation of both physiological and pathophysiological conditions in tissues throughout the body. 5-HT induces vascular smooth muscle constriction in most vessels. The vasoconstrictive effects of 5-HT are mediated by 5-HT1B and 5-HT2A receptors located on the membrane of smooth muscle cells, except in the intracranial arteries which constrict only through 5-HT1B receptors. 5-HT also acts as vasodilator because it releases nitric oxide from endothelial cells. This response is dominantly mediated by 5-HT1B receptors but not by 5-HT2A receptors. In this review, we focus on the action of 5-HT via G protein-coupled 5-HT receptors involved in some vascular-related pathophysiological responses. Furthermore, we describe the possibilities of 5-HT receptors as targets for drug therapy against saphenous vein grafts diseases (especially in patients with diabetes mellitus), migraine and pulmonary arterial hypertension. © 2013 The Pharmaceutical Society of Japan.

Mutoh J.,Kyushu University of Health and Welfare | Ohsawa M.,Kyushu University of Health and Welfare | Ohsawa M.,Nagoya City University | Hisa H.,Kyushu University of Health and Welfare
Neuropharmacology | Year: 2013

Renal ischemia produces sympathoexcitation, which is responsible for the development of ischemic acute kidney injury. Stimulation of central opioid receptors activates the renal sympathetic nerve. The present study examined the effect of an opioid receptor antagonist naloxone on the ischemia/reperfusion- induced renal dysfunction in mice. Blood urea nitrogen (BUN) and plasma creatinine increased 24 h after the renal ischemia/reperfusion. Intraperitoneal or intracerebroventricular, but not intrathecal, pretreatment with naloxone suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. This effect of naloxone was reversed by subcutaneous pretreatment with morphine. Selective MOP receptor antagonist β-funaltrexamine (FNA) also suppressed the renal ischemia/reperfusion-induced increases in BUN and plasma creatinine. Moreover, tyrosine hydroxylase expression in the renal tissue increased 24 h after renal ischemia/reperfusion, which was abolished by intraperitoneal or intracerebroventricular pretreatment with naloxone and FNA. Immunohistochemical experiments revealed a significant increase in the number of the Fos family proteins (c-Fos, FosB, Fra-1, and Fra-2) positive cells in the paraventricular nucleus of hypothalamus and supraoptic nucleus 24 h after the renal ischemia/reperfusion. Intracerebroventricular pretreatment with naloxone attenuated the renal ischemia/reperfusion-induced increase in the number of the Fos family proteins positive cells in these areas. Finally, we observed that i.c.v. pretreatment with antiserum against β-endorphin also suppressed the increased blood urea and plasma creatinine. These results suggest that the blockade of central opioid receptors can attenuate the ischemic acute kidney injury through the inhibition of renal sympathoexcitation. The central opioid receptors may thus be a new target for the treatment of ischemic organ failures. © 2013 Elsevier Ltd. All rights reserved.

Uchiyama T.,Kyushu University of Health and Welfare | Toda K.-I.,Kitano Hospital | Takahashi S.,Kyushu University of Health and Welfare
Biological and Pharmaceutical Bulletin | Year: 2010

Resveratrol, a natural polyphenol in grapes, is known to prevent the cardiovascular diseases and to exert the antiangiogenic effect in in vivo models with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF). We examined the effect of resveratrol on tubule formation of cultured endothelial F-2 cells. In collagen gel matrix, F-2 cells formed an extended network of tubular structures in response to VEGF or bFGF. Resveratrol dose-dependently prevented the VEGF-induced tubule formation, but failed to inhibit the angiogenic response to bFGF. We next examined whether the inhibition of nitric oxide (NO) production is linked to the antiangiogenic effect of resveratrol on VEGF-stimulated F-2 cells, because NO plays a crucial role in VEGFinduced tubular network formation. NO production was increased by VEGF, but not by bFGF, and resveratrol inhibited VEGF-stimulated NO production. N G-nitro-L-arginine methyl ester (l-NAME) potently inhibited NO production under all conditions, including VEGF stimulation, and abrogated VEGF-induced tubule formation. However, l-NAME did not inhibit bFGF-induced tubule formation. To investigate the bFGF-induced in vivo antiangiogenic effect of resveratrol, we examined the effect of resveratrol on prostaglandin E2 (PGE 2) production and cyclooxygenase (COX) expression in NRK-F fibroblasts. COX-2 and its derived PGE 2 are important factors for bFGF-induced in vivo angiogenesis. Resveratrol dose-dependently prevented both COX-2 induction and PGE 2 production in bFGF-stimulated fibroblasts. These results suggest that resveratrol exerts the inhibitory effects on VEGF- and bFGF-induced angiogenesis through different mechanisms including inhibition of NO production in VEGF-stimulated endothelial cells and inhibition of COX-2 induction in bFGF-stimulated fibroblasts. © 2010 Pharmaceutical Society of Japan.

Kawahara M.,Kyushu University of Health and Welfare
Current Pharmaceutical Design | Year: 2010

Numerous studies have indicated that Alzheimer's amyloid-protein (Aβ) causes the degeneration of synapses and neurons, finally inducing the pathogenesis of Alzheimer's disease (AD). Recent approaches have emphasized the importance of Aβ oligomerization which enhances its neurotoxicity and synaptotoxicity. Our work as well as other groups' research have demonstrated that Aβ oligomers are directly incorporated into neuronal membranes and form calcium-permeable ion channels (amyloid channels). Although the precise molecular mechanism of Aβ neurotoxicity remains elusive, the formation of amyloid channels and the resultant abnormal elevation of the intracellular calcium levels might be the primary event for neurodegeneration, considering that calcium dyshomeostasis triggers various apoptotic pathways. This article reviews the current understanding of AD pathology based on the hypothesis that the disruption of calcium homeostasis through amyloid channels may be the molecular basis of Aβ neurotoxicity. The potential development of preventive agents for new therapeutic targets is also discussed. © 2010 Bentham Science Publishers Ltd.

Yamaori S.,Hokuriku University | Okamoto Y.,Hokuriku University | Yamamoto I.,Kyushu University of Health and Welfare | Watanabe K.,Hokuriku University
Drug Metabolism and Disposition | Year: 2011

Δ 9-Tetrahydrocannabinol, cannabidiol (CBD), and cannabinol are the three major cannabinoids contained in marijuana, which are devoid of nitrogen atoms in their structures. In this study, we investigated the inhibitory effects of the major phytocannabinoids on the catalytic activity of human CYP2D6. These major cannabinoids inhibited the 3-[2-(N,N-diethyl-N- methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) and dextromethorphan O-demethylase activities of recombinant CYP2D6 and pooled human liver microsomes in a concentration-dependent manner (IC 50 =4.01-24.9 μM), indicating the strongest inhibitory potency of CBD. However, these cannabinoids showed no or weak metabolism-dependent inhibition. CBD competitively inhibited the CYP2D6 activities with the apparent K i values of 1.16 to 2.69 μM. To clarify the structural requirement for CBD-mediated CYP2D6 inhibition, effects of CBD-related compounds on the AMMC O-demethylase activity of recombinant CYP2D6 were examined. Olivetol (IC 50 =7.21 μM) inhibited CYP2D6 activity as potently as CBD did (IC 50 =6.52 μM), whereas d-limonene did not show any inhibitory effect. Pentylbenzene failed to inhibit CYP2D6 activity. Furthermore, neither monomethyl nor dimethyl ethers of CBD inhibited the activity. Cannabidivarin having a propyl side chain inhibited CYP2D6 activity; its inhibitory effect (IC 50 = 10.2 μM) was less potent than that of CBD. On the other hand, orcinol and resorcinol showed lack of inhibition. The inhibitory effect of CBD on CYP2D6 activity was more potent than those of 16 compounds without nitrogen atoms tested, such as progesterone. These results indicated that CBD caused potent direct CYP2D6 inhibition, in which two phenolic hydroxyl groups and the pentyl side chain of CBD may play important roles. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.

Nagai T.,National Hospital Organization | Nagai M.,Kyushu University of Health and Welfare
European Archives of Oto-Rhino-Laryngology | Year: 2012

Labyrinthine window rupture (LWR) is one cause of acute sensorineural hearing loss and need for early exploration is clear for good improved hearing. Acute sensorineural hearing loss of 60 dB or more treated from May 2006 to May 2010 were retrospectively analyzed. There were 21 ears of severe deafness, 18 ears of profound deafness, and 10 ears of total deafness. All patients were examined with temporal bone CT. Space-occupying lesions around the labyrinthine windows were suggestive images of LWR. Thirty-five ears were operated for LWR while 14 ears of SHL received conservative treatments. Fifty-seven percent of LWR improved 30 dB or more after sealing of both labyrinthine windows. Of the 15 markedly recovered ears, 14 ears were operated within 2 weeks from the onset. Of the five cured ears, four ears were operated within a week from the onset. As for the hearing prognosis of SHL, 88% of severe and profound deafness improved 30 dB or more but total deafness did not improve more than 30 dB. Exclusion of LWR from SHL and early surgical intervention in LWR will bring about good hearing prognosis to both LWR and SHL. © 2011 The Author(s).

Kawahara M.,Kyushu University of Health and Welfare | Kato-Negishi M.,University of Tokyo
International Journal of Alzheimer's Disease | Year: 2011

Whilst being environmentally abundant, aluminum is not essential for life. On the contrary, aluminum is a widely recognized neurotoxin that inhibits more than 200 biologically important functions and causes various adverse effects in plants, animals, and humans. The relationship between aluminum exposure and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii Peninsula and Guam, and Alzheimer's disease (AD) has been suggested. In particular, the link between aluminum and Alzheimer's disease has been the subject of scientific debate for several decades. However, the complex characteristics of aluminum bioavailability make it difficult to evaluate its toxicity and therefore, the relationship remains to be established. Mounting evidence has suggested that significance of oligomerization of β-amyloid protein and neurotoxicity in the molecular mechanism of AD pathogenesis. Aluminum may play crucial roles as a cross-linker in β-amyloid oligomerization. Here, we review the detailed characteristics of aluminum neurotoxicity based on our own studies and the recent literatures. Our aim is to revisit the link between aluminum and AD and to integrate aluminum and amyloid cascade hypotheses in the context of β-amyloid oligomerization and the interactions with other metals. © 2011 Masahiro Kawahara and Midori Kato-Negishi.

Takahashi S.,Mukogawa Women's University | Takahashi S.,Kyushu University of Health and Welfare | Nakashima Y.,Kyushu University of Health and Welfare
British Journal of Nutrition | Year: 2012

In the present study, we examined the effect of repeated and long-term treatment with resveratrol on NO production in endothelial cells as a model of routine wine consumption. Repeated treatment with resveratrol for 5 d resulted in an increase in endothelial NO synthase (eNOS) protein content and NO production in human umbilical vein endothelial cell (HUVEC) in a concentration-dependent manner. A significant increase in functional eNOS protein content was observed with resveratrol, even at 50 nm. In contrast, eNOS phosphorylation was not stimulated and inducible NO synthase (iNOS) was not detected after resveratrol treatment. Both eNOS protein and mRNA expression were promoted by 50 nm-resveratrol in a time-dependent manner. Increased eNOS mRNA expression in response to resveratrol was not decreased by an oestrogen receptor (ER) antagonist ICI182780, a PPARα inhibitor MK886 or a sirtuin inhibitor Salermide. However, a combination of ICI182780 and MK886 significantly inhibited resveratrol-induced eNOS mRNA expression. Salermide had no effect even in the presence of ICI182780 or MK886. These results demonstrate that resveratrol within the physiological range increases eNOS mRNA and protein expression through ER and PPARα activation, thereby promoting NO production in endothelial cells. eNOS induction might result from the accumulative effect of nanomolar concentrations of resveratrol. The present study results can account in part for the observation that cardiovascular benefits of red wine are experienced with routine consumption, but not with acute consumption. © 2011 The Authors.

Yamaori S.,Hokuriku University | Kushihara M.,Hokuriku University | Yamamoto I.,Kyushu University of Health and Welfare | Watanabe K.,Hokuriku University
Biochemical Pharmacology | Year: 2010

Inhibitory effects of Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated. These cannabinoids inhibited 7-ethoxyresorufin O-deethylase activity of recombinant CYP1A1, CYP1A2, and CYP1B1 in a competitive manner. CBD most potently inhibited the CYP1A1 activity; the apparent Ki value (0.155μM) was at least one-seventeenth of the values for other CYP1 isoforms. On the other hand, CBN more effectively decreased the activity of CYP1A2 and CYP1B1 (Ki=0.0790 and 0.148μM, respectively) compared with CYP1A1 (Ki=0.541μM). Δ9-THC less potently inhibited the CYP1 activity than CBD and CBN, and showed low selectivity against the CYP1 inhibition (Ki=2.47-7.54μM). The preincubation of CBD resulted in a time- and concentration-dependent decrease in catalytic activity of all the recombinant CYP1 enzymes and human liver microsomes. Similarly, the preincubation of Δ9-THC or CBN caused a time- and concentration-dependent inhibition of recombinant CYP1A1. The inactivation of CYP1A1 by CBD indicated the highest kinact/KI value (540l/mmol/min) among the CYP1 enzyme sources tested. The inactivation of recombinant CYP1A1 and human liver microsomes by CBD required NADPH, was not influenced by dialysis and by glutathione, N-acetylcysteine, and superoxide dismutase as trapping agents. These results indicated that CBD and CBN showed CYP1 isoform-selective direct inhibition and that CBD was characterized as a potent mechanism-based inhibitor of human CYP1 enzymes, especially CYP1A1. © 2010 Elsevier Inc.

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