Prevalence of atopic dermatitis and serum IgE of Yusho patients born before 1967

Dioxins may have an impact on the human immunological system, which would increase the risk to develop allergic diseases, such as atopic dermatitis. In order to determine the lifetime prevalence of atopic dermatitis in Yusho patients, a questionnaire-based survey was conducted in 2008. One thousand and seventy-one out of 1430 certified yusho patients who were born before Yusho accident answered the questionnaires, and the prevalence of atopic dermatitis in Yusho patients was 5.5%. We also measured serum IgE in 515 Yusho patients who attended annual medical check-ups from 2007 to 2009 and in 172 control subjects. Serum levels of IgE in Yusho patients were 250.7 +/- 663.4 IU/ml, whereas those in control subjects were 265.0 +/- 602.0 IU/ml. There was no significant difference in serum levels of IgE between Yusho patients and control subjects. In addition, no significant correlation was observed between serum levels of IgE and blood levels of dioxins in Yusho patients.     

Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect

Ketoconazole (KCZ) has been shown to exhibit anti-inflammatory effects in addition to its inhibitory effects against fungi; however, the underlying molecular mechanism remains poorly understood. Aryl hydrocarbon receptor (AhR), a receptor that is activated by polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons such as dioxin, is a sensor of the redox system against oxidative stress and regulates nuclear factor-erythroid 2-related factor-2 (Nrf2), a master switch of the redox machinery. To clarify whether KCZ modulates AhR-Nrf2 function leading to redox system activation, cultured human keratinocytes were treated with KCZ. Confocal microscopic analysis revealed that KCZ induced AhR nuclear translocation, resulting in the upregulation of CYP1A1 mRNA and protein expression. Furthermore, KCZ actively switched on Nrf2 nuclear translocation and quinone oxidoreductase 1 expression. Tumor necrosis factor-α- and benzo(a)pyrene (BaP)-induced reactive oxidative species (ROS) and IL-8 production were effectively inhibited by KCZ. Knockdown of either AhR or Nrf2 abolished the inhibitory capacity of KCZ on ROS and IL-8 production. In addition, KCZ-induced Nrf2 activation was canceled by AhR knockdown. Moreover, KCZ inhibited BaP-induced 8-hydroxydeoxyguanosine and IL-8 production. In conclusion, the engagement of AhR by KCZ exhibits the cytoprotective effect mediated by the Nrf2 redox system, which potently downregulates either cytokine-induced (AhR-independent) or PAH-induced (AhR-dependent) oxidative stress.     

N-ethylmaleimide-sensitive fusion protein (NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after inflammation

Central sensitization, similar to long-term potentiation in the hippocampus, refers to the increased synaptic efficacy established in somatosensory neurons in the dorsal horn of the spinal cord following tissue injury or nerve damage. In the course of inflammation, many proteins including glutamate receptors are assumed to be dynamically reorganized in the postsynaptic density (PSD) and involved in persistent pain. Mechanical hyperalgesia induced by intraplantar injection of complete Freund's adjuvant (CFA) was inhibited at 4 h, but not at 24 h, by indomethacin, an inhibitor of prostanoid synthesis. To elucidate the nature of the molecule(s) involved in the late phase of inflammatory pain, we analysed the PSD fraction prepared from the lumbar spinal cord of rats before and 24 h after CFA injection by conducting two-dimensional differential gel electrophoresis. N -ethylmaleimide-sensitive fusion protein (NSF) was identified as a downregulated protein in the PSD by MALDI-TOF MS and immunoblotting. Concomitant with the decrease in NSF, GluR2 and GluR3 were decreased and GluR1 was conversely increased in the PSD fraction 24 h after CFA injection. In vivo patch-clamp recordings of rats 24 h after CFA injection showed that excitatory postsynaptic currents of dorsal horn neurons evoked by pinch stimuli to inflamed skin were inwardly rectified and inhibited by 60% by philanthotoxin-433, a selective inhibitor of the Ca²⁺ -permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These results suggest that peripheral inflammation gives rise to central sensitization in the spinal cord through subunit composition switch of AMPA receptors in the late phase.     

前列腺特异性抗原和雄激素受体在乳房外paget病中的表达

目的：了解前列腺特异性抗原（prostate specific antigen,PSA）和雄激素受体（androgen receptor,AR）在乳房外Paget病（EMPD）中的表达及其意义。方法：采用免疫组化ABC法检测PSA和AR在30例EMPD患者皮损中的表达情况。结果：①在30例EMPD患者皮损中13例PSA表达阳性,14例AR表达阳性,且在男性患者中PSA和AR的表达均明显高于女性患者（P〈0．01）;②在男性EMPD患者中,PSA和AR阳性表达间有明显相关性。结论：PSA和AR在男性EMPD患者中过度表达．PSA和（或）AR信号传导通路可能在男性EMPD形成机制中起重要作用。