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)

A 15-year-old girl had a history of diffuse goiter and received methimazole treatment 2 months before admission to the hospital. She developed bilateral lower leg edema 5 days before admission and the laboratory examinations revealed leukopenia, anemia, proteinuria, and granular cast. Positive antinuclear antibodies and anti-double strand (anti-ds) DNA antibodies were noted, although complement levels were not reduced. Myeloperoxidase antineutrophil cytoplasmic antibody was positive. A renal biopsy disclosed that there was focal segmental glomerulosclerosis. Methimazole was discontinued, and she was treated with prednisolone and Plaquenil, after which the symptoms and laboratory tests became normal within 40 days. The prednisolone was discontinued after treatment for seven months. Currently, the anti-dsDNA, C3, C4, CBC, urinalysis, and thyroid function tests are within normal limits. With hydroxychloroquine and levothyroxine, she was free of symptoms after discontinuation of methimazole until now (about 21 months).
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PMID:Methimazole-induced lupus erythematosus: a case report. 1472 59

The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N,N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR)7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti-double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs.
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PMID:Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. 2434 72