断酒しているアルコール依存症者に対する一般住民の態度改善に関する研究

広島大学(Hiroshima University)博士(学術)Philosophydoctora

Biochemical Functions and mRNA Expression of Rat Hepatocytes in a Bioartificial Liver Module

Evaluation of hepatic functions of the bioartificial liver (BAL) module is essential for developing an optimal BAL system which can be applied to a patient with fulminant hepatic failure. Although hepatic function in BALs has been evaluated only in biochemical activities in previous reports, we assessed a newly designed BAL from a hollow fiber type not only in biochemical activities such as gluconeogenesis, ureogenesis and albumin synthesis but also in the expressions of albumin messenger RNA (mRNA) and cytochrome P450 2B1 mRNA by Northern blot analysis. One to 3 × 108 hepatocytes isolated from adult rats were suspended in hydrated collagen, loaded into a hollow fiber module and perfused with L-15 medium supplemented with various hormones for 2 to 13 days. Both production rates of glucose and urea nitrogen were highest on day 1 (610 ?g glucose/107 cells/h and 76.1 ?g urea nitrogen/107 cells/h, respectively). Ureogenesis was maintained for 8 days in BAL, but gluconeogenesis decreased after 7 days. Albumin production rate increased to day 3, reached its maximum (11.0 ?g/107 cells/h) and then gradually decreased. The expression of albumin mRNA was highest on day 2 and detectable until day 11. Cytochrome P450 2B1 mRNA was detected only on day 2. Northern blot analysis showed that the maintenance period in each hepatic function was different. These results suggested that assessment of the functions at a molecular level was invaluable in the development of a potential BAL for clinical use. It might be necessary to reconstruct the lobular system as well as a 3-dimensional environment for hepatocytes in the BAL to maintain the ability of detoxification such as cytochrome P450s

Gadolinium modulates gentamicin uptake via an endocytosis-independent pathway in HK-2 human renal proximal tubular cell line

The aim of this study was to characterize the uptake mechanism of gentamicin, an aminoglycoside antibiotic, in human renal proximal tubular cell line HK-2. Sodium-dependent uptake of D-[H-3]glucose and L-[H-3]alanine was observed in HK-2 cells, indicating that the cells employed in this study retain functional characteristics of the renal proximal tubular cells. On the other hand, mRNA and protein expression of megalin, an endocytic receptor which is responsible for the internalization of gentamicin into the renal proximal tubular cells, was very faint in HK-2 cells. Various aminoglycoside antibiotics including amikacin and kanamycin inhibited the uptake of [H-3]gentamicin. Colchicine and cytochalasin D, general endocytosis inhibitors, had no significant effect on [H-3]gentamicin uptake in HK-2 cells, which was in contrast to the results observed in OK cells, a renal proximal tubular cell line expressing megalin. Furthermore, unlike OK cells, [H-3]gentamicin uptake in HK-2 cells was not inhibited by N-WASP181-200, a cationic 20-amino acid peptide. Ruthenium red, a nonspecific cation channel blocker, decreased the uptake of [H-3]gentamicin in HK-2 cells. In contrast, the trivalent cation gadolinium biphasically modulated [H-3]gentamicin uptake with a maximum increase at 0.3 mM gadolinium. The enhanced effect of gadolinium on [H-3]gentamicin uptake was independent of gadolinium-induced increase in intracellular calcium concentration. These findings indicate that gentamicin is primarily taken up via an endocytosis-independent pathway in HK-2 cells with very low expression of megalin, and that the uptake of gentamicin is modulated by gadolinium

Long-range transportation of polyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons from China to Japan

金沢大学大学院自然科学研究科Promoting Environmental Pesearch in Pan-Japan Sea Area : Young Researchers\u27 Network, Schedule: March 8-10,2006,Kanazawa Excel Hotel Tokyu, Japan, Organized by: Kanazawa University 21st-Century COE Program, Environmental Monitoring and Prediction of Long- & Short- Term Dynamics of Pan-Japan Sea Area ; IICRC(Ishikawa International Cooperation Research Centre), Sponsors : Japan Sea Research ; UNU-IAS(United Nations University Institute of Advanced Studies)+Ishikawa Prefecture Government ; City of Kanazaw

Methadone in post-herpetic neuralgia: A pilot proof-of-concept study

OBJECTIVE: This research was designed as a pilot proof-of-concept study to evaluate the use of low-dose methadone in post-herpetic neuralgia patients who remained refractory after first and second line post-herpetic neuralgia treatments and had indications for adding an opioid agent to their current drug regimens. METHODS: This cross-over study was double blind and placebo controlled. Ten opioid naïve post-herpetic neuralgia patients received either methadone (5 mg bid) or placebo for three weeks, followed by a 15-day washout period and a second three-week treatment with either methadone or placebo, accordingly. Clinical evaluations were performed four times (before and after each three-week treatment period). The evaluations included the visual analogue scale, verbal category scale, daily activities scale, McGill pain questionnaire, adverse events profile, and evoked pain assessment. All patients provided written informed consent before being included in the study. ClinicalTrials.gov: NCT01752699 RESULTS: Methadone, when compared to placebo, did not significantly affect the intensity of spontaneous pain, as measured by the visual analogue scale. The intensity of spontaneous pain was significantly decreased after the methadone treatment compared to placebo on the category verbal scale (50% improved after the methadone treatment, none after the placebo, p = 0.031). Evoked pain was reduced under methadone compared to placebo (50% improved after the methadone treatment, none after the placebo, p = 0.031). Allodynia reduction correlated with sleep improvement (r = 0.67, p = 0.030) during the methadone treatment. The side effects profile was similar between both treatments. Conclusions: Methadone seems to be safe and efficacious in post-herpetic neuralgia. It should be tried as an adjunctive treatment for post-herpetic neuralgia in larger prospective studies

Bioluminescent system for dynamic imaging of cell and animal behavior

AbstractThe current utility of bioluminescence imaging is constrained by a low photon yield that limits temporal sensitivity. Here, we describe an imaging method that uses a chemiluminescent/fluorescent protein, ffLuc-cp156, which consists of a yellow variant of Aequorea GFP and firefly luciferase. We report an improvement in photon yield by over three orders of magnitude over current bioluminescent systems. We imaged cellular movement at high resolution including neuronal growth cones and microglial cell protrusions. Transgenic ffLuc-cp156 mice enabled video-rate bioluminescence imaging of freely moving animals, which may provide a reliable assay for drug distribution in behaving animals for pre-clinical studies

Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

植物由来成分であるプテロシンBはSIK3を阻害し変形性関節症の治療薬開発のリード化合物となる. 京都大学プレスリリース. 2016-03-31.Yahara, Y., Takemori, H., Okada, M. et al. Correction: Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3. Nat Commun 7, 12117 (2016).Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic

Atmospheric behaviors of polycyclic aromatic hydrocarbons at a Japanese remote background site, Noto peninsula, from 2004 to 2014

Total suspended particulates were collected at a Japanese remote background site (Noto Air Monitoring Station; NAMS) on the Noto Peninsula from September 2004 to June 2014. Nine polycyclic aromatic hydrocarbons (PAHs) in the particulates (fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, benzo[ghi]perylene and indeno[1,2,3-cd]pyrene) were determined by HPLC with fluorescence detection. The mean total concentrations of the nine PAHs in the cold season (November to May for the years 2004-2014) was 670 pg m-3 (range 37-4100 pg m-3). The mean total concentration in the warm season (June to October for the same period) was 170 pg m-3 (range 31-960 pg m-3). The atmospheric PAH level at NAMS decreased in recent years, although no significant change was found in the warm season. An analysis of meteorological conditions showed that the atmospheric PAHs at NAMS were long range transported from Northeast China in the cold seasons and were contributed to by Japanese domestic sources in the warm seasons. Lower concentration ratios of reactive PAHs to their isomers at NAMS also supported these results. Activities associated with the Beijing Olympic and Paralympic Games in 2008 and reconstruction after the 2007 Noto Hanto earthquake may have contributed to the yearly variations of atmospheric PAH levels at NAMS during the period 2007-2009. Source control measures implemented by the Chinese and Japanese governments appear to have been effective in decreasing the atmospheric PAH levels at NAMS in recent years. © 2015 Elsevier Ltd.Embargo Period 24 month