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Nobeoka, Japan

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

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

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). Source

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

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. Source

Yamazaki Y.,Shimadzu Corporation | Fujii N.,Kyoto University | Sadakane Y.,Kyushu University of Health and Welfare
Analytical Chemistry

α-Crystallin, which forms a huge multimeric complex that is essential for maintaining eye lens transparency, is one of the major proteins in the lens. The protein, which exists as isoforms αA and αB, functions as a molecular chaperone to restore the original conformations of distorted constituent proteins in the lens. This function is important to maintain the transparency of the lens, because there is no protein turnover in the lens. Abnormal aggregation of constituent proteins in the lens has been reported in cataract patients, and deamidation of Asn as well as racemization and isomerization of Asp have been found in the α-Crystallin of these patients. While the establishment of a quick and facile analytical method is eagerly anticipated to investigate the relevance of the isomerization to pathological states such as cataracts, differentiating the isomerization states is still not performed routinely. Here, we report the differentiation and semiquantitative analysis of an isoaspartic acid (βAsp) in human α-Crystallin using postsource decay on a MALDI-TOF mass spectrometer incorporating a curved field reflectron. Our reproducible results of analyzing synthetic and tryptic peptides containing βAsp corroborated results obtained using a previously reported diagnostic ion, y l-n+1-46, for the differentiation of βAsp. The relative content of βAsp in the peptide was successfully estimated from a unique ratio, y l-n:y l-n+1, corresponding to cleavages at the C- and N-termini, respectively, of the isomeric residues. The βAsp content was consistent with measurements obtained independently by reversed phase HPLC analysis. Experiments in which neighboring amino acids adjacent to βAsp/Asp were substituted revealed that the ratio between y l-n and y l-n+1 reflected the isomerization status, while the diagnostic ion was observed only in the peptides that included an arginine residue at their C-terminus. Postsource decay experiments utilizing both the diagnostic ion and the characteristic fragment pattern could be applied to various kinds of peptides containing βAsp. © 2010 American Chemical Society. Source

Jiang R.,Hokuriku University | Yamaori S.,Hokuriku University | Okamoto Y.,Hokuriku University | Yamamoto I.,Kyushu University of Health and Welfare | Watanabe K.,Hokuriku University
Drug Metabolism and Pharmacokinetics

The present study investigated the inhibitory effect of cannabidiol (CBD), a major constituent of marijuana, on the catalytic activity of cytochrome P450 2C19 (CYP2C19). (S)-Mephenytoin 4′-hydroxylase activities of human liver microsomes (HLMs) and recombinant CYP2C19 were inhibited by CBD in a concentration-dependent manner (IC50 = 8.70 and 2.51 μM, respectively). Omeprazole 5-hydroxylase and 3-O-methylfluorescein O-demethylase activities in recombinant CYP2C19 were also strongly inhibited by CBD (IC50 = 1.55 and 1.79 μM, respectively). Kinetic analysis for inhibition revealed that CBD showed a mixed-type inhibition against (S)-mephenytoin 4′-hydroxylation by recombinant CYP2C19. To clarify the structural requirements for CBD-mediated CYP2C19 inhibition, the effects of CBD-related compounds on CYP2C19 activity were examined. Olivetol inhibited the (S)-mephenytoin 4′-hydroxylase activity of recombinant CYP2C19 with the IC50 value of 15.3 μM, whereas d-limonene slightly inhibited the activity (IC50 > 50 μM). The inhibitory effect of CBD-2′-monomethyl ether (IC50 = 1.88 μM) on CYP2C19 was comparable to that of CBD, although the inhibitory potency of CBD-2′,6′-dimethyl ether (IC50 = 14.8 μM) was lower than that of CBD. Cannabidivarin, possessing a propyl side chain, showed slightly less potent inhibition (IC50 = 3.45 μM) as compared with CBD, whereas orcinol and resorcinol did not inhibit CYP2C19 activity at all. These results indicate that CBD caused potent CYP2C19 inhibition, in which one free phenolic hydroxyl group and the pentyl side chain of CBD may play important roles. © 2013 by the Japanese Society for the Study of Xenobiotics (JSSX). Source

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

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. Source

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