SummarySystemic sclerosis (SSc) is an autoimmune disease characterized by fibrotic changes in skin and other organs involving excessive collagen deposition. Here we investigated the effect of intravenous immunoglobulin (IVIG) on fibrosis in a murine model of bleomycin (BLM)-induced scleroderma. Scleroderma was induced in C3H/He J mice by subcutaneous BLM injections daily for 35 days. The collagen content in skin samples from the BLM-injected group (6·30 Ϯ 0·11 mg/g tissue) was significantly higher than the PBS group (5·80 Ϯ 0·10 mg/g tissue), and corresponded with dermal thickening at the injection site. In contrast, mice treated with IVIG for 5 consecutive days after initiating BLM injection showed lesser collagen content significantly (IVIG group, 5·61 Ϯ 0·09 mg/g tissue; BLM vs. IVIG). In order to investigate the cellular and protein characteristics in the early stage of the model, the skin samples were obtained 7 days after the onset of experiment. Macrophage infiltration to the dermis, monocyte chemoattractant protein (MCP-1)-positive cells, and increased TGF-b1 mRNA expression were also observed in the BLM group. IVIG inhibited these early fibrogenic changes; MCP-1 expression was significantly lesser for the IVIG group (1·52 Ϯ 0·19 pg/mg tissue) than for the BLM group (2·49 Ϯ 0·26 pg/mg tissue). In contrast, TGF-b1 mRNA expression was significantly inhibited by IVIG. These results suggest that IVIG treatment may inhibit macrophage recruitment to fibrotic sites by down regulating MCP-1 and TGF-b production, and thus could be a potential drug for managing fibrotic disorders such as SSc.
Purpose To evaluate the reproducibility and consistency of the new mydriasis-free electroretinogram (ERG) with a skin electrode (RETeval) device, to determine the normative values of parameters, and to clarify the usefulness of pupil records to colored-light stimulus. Methods A total of 100 eyes of 50 healthy subjects (mean age, 21.4 years) were enrolled. The diagnostic parameters obtained by the RETeval device were examined under the following conditions. The reproducibility was determined with the coefficient of variation (CV). The consistency was examined by intraclass correlation coefficients (ICCs). The mean value and the normal range were analyzed with a 95% confidence interval as the normative values of parameters. The correlation of parameters to pupil records (area ratio, constriction ratio) and flicker ERG was also examined in the diabetic retinopathy assessment protocol. Results From the CV for each of the two measurements, the amplitude has a low reproducibility compared with the implicit time. Generally good consistency was obtained with both ERG parameters (ICCs = 0.48–0.92). Moderate correlations were found for the white-, red-, and blue-light stimulus in the area ratio and the constriction ratio, respectively (r = 0.44–0.62; P = 0.010–<0.0001). No correlation was observed between pupil and flicker parameters (r = 0.06–0.34; P = 0.646–0.051). Conclusions The RETeval device was suggested as a possible screening device to detect the visual afferent diseases by evaluating in combination with the ERG recording and the colored-light pupil response.
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