Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Environmental crystalline silica exposure has been associated with formation of autoantibodies and development of systemic autoimmune disease, but the mechanisms leading to these events are unknown. Silica exposure in autoimmune-prone New Zealand mixed (NZM) mice results in a significant exacerbation of systemic autoimmunity as measured by increases in autoantibodies and glomerulonephritis. Previous studies have suggested that silica-induced apoptosis of alveolar macrophages (AM) contributes to the generation of the autoantibodies and disease. Rottlerin has been reported to inhibit apoptosis in many cell types, possibly through direct or indirect effects on PKCdelta. In this study, rottlerin reduced silica-induced apoptosis in bone marrow-derived macrophages as measured by DNA fragmentation. In NZM mice, RNA and protein levels of PKCdelta were significantly elevated in AM 14 wk after silica exposure. Therefore, rottlerin was used to reduce apoptosis of AM and evaluate the progress of silica-exacerbated systemic autoimmune disease. Fourteen weeks after silica exposure, NZM mice had increased levels of anti-histone autoantibodies, high proteinuria, and glomerulonephritis. However, silica-instilled mice that also received weekly instillations of rottlerin had significantly lower levels of proteinuria, anti-histone autoantibodies, complement C3, and IgG deposition within the kidney. Weekly instillations of rottlerin in silica-instilled NZM mice also inhibited the upregulation of PKCdelta in AM. Together, these data demonstrate that in vivo treatment with rottlerin significantly decreased the exacerbation of autoimmunity by silica exposure.
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PMID:Effects of rottlerin on silica-exacerbated systemic autoimmune disease in New Zealand mixed mice. 1604 Jun 31

Silicosis has progressive, but unpredictable development. There are no markers routinely available to measure the activity and prognosis of silicosis. 8-isoprostane, a marker of oxidative stress and leukotrienes B4, C4, D4, and E4 were measured in exhaled breath condensate in patients with silicosis. Sixty subjects were examined, with mean age 66.7+/-2.0 yr and mean exposure to silica 23.6+/-2.5 yr. The control group had 25 subjects, with mean age 64.7+/-4.8 yr. Exhaled breath was collected using the EcoScreen (Jaeger, Germany); 8-isoprostane and leukotrienes were analyzed by high-performance liquid chromatography/mass spectrometry. Several lung functions parameters were impaired in silicotics in comparisons with the controls; ESR, alpha1-antitrypsin and proteinuria were higher in the silicotics. Antineutrophilic cytoplasmic antibodies were more frequent in the silicotics (39%) than in the controls (4%), (p=0.0017). The mean level of 8-isoprostane in the patients with silicosis was 73.6+/-9.9 vs. 43+/-10 pg/ml (p=0.0001) in the controls. Silica exposure category (high, medium, none) was positively associated with the level of 8-isoprostane. In the patients with complicated silicosis, a high level of 8-isoprostane was found more frequently (p=0.0194). Leukotriene D4 was also increased in the silicotics (21.1+/-2.7 pg/ml) vs. the controls (14.7+/-2.7 pg/ml), (p=0.001). No significant effect of smoking or alcohol consumption on the markers examined was seen. This is the first study using exhaled breath condensate analysis in patients with silicosis.
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PMID:8-isoprostane and leukotrienes in exhaled breath condensate in Czech subjects with silicosis. 1821 71