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  • 1
    ISSN: 1420-908X
    Keywords: Key words: Cyclooxygenase-1 — Cyclooxygenase-2 — NSAIDs — Selective inhibition — NS-398
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: The role of cyclooxygenase (COX)-2 was examined using a rat endotoxin shock model and the potency and selectivity of NS-398, a COX-2 selective inhibitor in vitro, for COX-2 activity was examined in vivo.¶Material: Male Wistar rats (weighing 140–180 g) were used.¶Methods: Lipopolysaccharide (LPS, 1 mg/kg, i.v.) was administered to rats (LPS-treated rats) and expression of COX-1 mRNA and COX-2 mRNA in the aorta and peripheral blood leukocytes was examined by RT-PCR. COX activity was assessed by measuring the plasma 6-keto prostaglandin (PG) F1 α, PGE2 and thromboxane (TX) B2 30 s after administration of arachidonic acid (AA, 3 mg/kg, i.v.). NS-398 (0.3–100 mg/kg, p.o.) or indomethacin (0.3–3 mg/kg, p.o.) was administered 1 h before the AA injection.¶Results: COX-2 mRNA was detectable in the aorta and peripheral blood leukocytes at least from 3 to 9 h after the LPS injection but not in non-LPS-treated rats. Plasma 6-keto PGF1 α, PGE2 and TXB2 levels after AA injection into LPS-treated rats were significantly enhanced compared to findings in non-LPS-treated rats. NS-398 showed significant inhibition of the increase in PGs in LPS-treated rats, the ED50 values being 0.35 mg/kg for 6-keto PGF1 α, 1.5 mg/kg for PGE2 and 〈 0.3 mg/kg for TXB2. NS-398 even at 100 mg/kg did not significantly suppress the increased PGs levels in non-LPS-treated rats. In contrast, indomethacin significantly inhibited plasma PGs levels after AA injection into LPS-treated rats and non-LPS-treated rats. The ED50 values in LPS-treated rats, determined by 6-keto PGF1 α, PGE2 and TXB2 production, were 1.0, 1.3 and 2.3 mg/kg and those in non-LPS-treated rats were 0.42, 0.24 and 0.93 mg/kg, respectively.¶Conclusions: In a rat endotoxin shock model, expression of COX-2 plays a role in an increase in COX activity. NS-398 showed preferential inhibitory effects on COX-2 activity in vivo. This approach is useful to directly analyze the inhibitory activity of NSAIDs for COX-1 and COX-2 in vivo.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Spontaneous and 2,4,6-trinitrochlorobenzene (TNCB)-induced dermatitis models using NC/Nga mice have been recognized as animal models of atopic dermatitis. We reported that scratching behavior leads to dermatitis in a spontaneous dermatitis but not in a TNCB-induced dermatitis. Prostaglandin D2 (PGD2) suppressed the scratching behavior of NC/Nga mice, suggesting that PGD2 plays a physiological role on inhibiting pruritus. We studied whether there was a difference in skin PG contents between spontaneous and TNCB-induced dermatitis. Spontaneous dermatitis was induced by cohabitation with NC/Nga mice having severe skin lesions. TNCB-induced dermatitis was caused by applications of TNCB. PGD2, PGE2, 6keto-PGF1α, and PGF2α contents in the skin were examined using enzyme-immunoassay kits. For studying ability to produce skin PGs, PG contents were evaluated after topical treatment of arachidonic acid (AA) or mechanical scratching. In spontaneous dermatitis, PGE2, 6keto-PGF1α, and PGF2α contents increased with dermatitis, but only PGD2 did not do so. In TNCB-induced dermatitis, PGD2, PGE2, 6keto-PGF1α, and PGF2α increased. Determination of skin PG contents after AA treatment or mechanical scratching revealed that skin PGD2 production of conventional group of spontaneous dermatitis was lower than the specific pathogen-free group. It seemed that ability of skin PGD2 production was attenuated in spontaneous dermatitis. These results suggest that enhancement of scratching behavior in spontaneous dermatitis was caused by the defect of ability to produce PGD2, which plays a physiological role in inhibiting pruritus, resulting in development of dermatitis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0090-6980
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Biaxially aligned YBa2Cu3O7−x (YBCO) thin films were produced on polycrystalline Ni-based alloy, by using biaxial yttria-stabilized-zirconia (YSZ) intermediate layers formed by off-normal ion-beam-assisted deposition. Most explicit in-plane alignment was obtained when the YSZ layer formed with the beam-incident angle of 55° from substrate normal. Jc-B characteristics and angular dependence of Jc on the magnetic field were measured. 5.0×105 and 5.5×104 A/cm2 were obtained at 77 K with 0 and 8 T, respectively. The distribution of misorientation angles of in-plane a and b axes between YBCO grains was evaluated by both x-ray pole figure measurement and planar observations of transmission electron microscopy. 50% of the grains had the misorientation angles restricted within ±5°. From the image of dislocations, the elastic strains at grain boundaries were estimated to be relaxed with lower misorientation angle. The high-Jc properties are understood to be obtained by the current paths through low-angle grain boundaries.
    Type of Medium: Electronic Resource
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