RESUMO
To identify potential biomarkers in immune-mediated nephritis, urine from mice subjected to an augmented passive model of anti-glomerular basement membrane (GBM)-induced experimental nephritis was resolved using two-dimensional gels. The urinary proteome in these diseased mice was comprised of at least 71 different proteins. Using orthogonal assays, several of these molecules, including serum amyloid P (SAP), PG D synthase, superoxide dismutase, renin, and total protease were validated to be elevated in the urine and kidneys of mice during anti-GBM disease, as well as in mice with spontaneously arising lupus nephritis. Among these, urinary protease was the only marker that appeared to be exclusively renal in origin, whereas the others were partly serum-derived. Longitudinal studies in murine lupus demonstrated that total urinary protease had better predictive value for histologically active nephritis (r = 0.78) compared with proteinuria (r = -0.04), azotemia (r = 0.28), or the other markers examined, whereas urine SAP emerged as the single most predictive marker of histological glomerulonephritis. Collectively, these studies uncover total urinary protease, PG D synthase, SAP, and superoxide dismutase as novel biomarkers of anti-GBM disease and lupus nephritis, with stronger correlation to renal disease compared with currently employed biomarkers. These findings could have important diagnostic and prognostic ramifications in the management of these renal diatheses.
Assuntos
Modelos Animais de Doenças , Oxirredutases Intramoleculares/urina , Lipocalinas/urina , Nefrite Lúpica/enzimologia , Nefrite Lúpica/urina , Peptídeo Hidrolases/urina , Proteoma/análise , Componente Amiloide P Sérico/urina , Superóxido Dismutase/urina , Sequência de Aminoácidos , Animais , Doença Antimembrana Basal Glomerular/enzimologia , Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/urina , Autoanticorpos/fisiologia , Biomarcadores/urina , Feminino , Humanos , Oxirredutases Intramoleculares/imunologia , Rim/enzimologia , Rim/imunologia , Rim/patologia , Lipocalinas/imunologia , Estudos Longitudinais , Nefrite Lúpica/imunologia , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Dados de Sequência Molecular , Peptídeo Hidrolases/imunologia , Valor Preditivo dos Testes , Proteoma/imunologia , Componente Amiloide P Sérico/imunologia , Superóxido Dismutase/imunologia , Regulação para Cima/imunologiaRESUMO
OBJECTIVE: To test the retention of smooth-surface sealants bonded with different etching protocols against toothbrushing and, secondarily, to characterize the type and location of sealant loss. MATERIALS AND METHODS: Eighty-nine extracted human teeth were randomly assigned one of two etching protocols: 37% phosphoric acid etch (ETCH) or self-etching primer (SEP). Six specimens at a time were placed in a toothbrushing machine to simulate 4, 8, 12, and 24 months of toothbrush abrasion. Using black-light photographs of each specimen taken before and after brushing, four blinded coinvestigators determined new sealant loss, loss along the edge of an initial defect, and the location of sealant loss. RESULTS: Overall, there were significantly (P < .05) more teeth with sealant loss in the SEP group (38.6%) than in the ETCH group (15.5%). New loss of sealant was significantly (P < .05) more likely in the SEP group (27.2%) than in the ETCH group (2.2%). Of the teeth with new loss of sealant, all (100%) had loss at the edge, and 23% had progressive loss. There was no significant group difference in sealant loss from initial defects. Of the teeth that showed enlargement of initial defects, 91% had loss at the edge and 91% had progressive loss. CONCLUSIONS: Using SEP to apply facial sealants results in lower retention rates than using ETCH. The vast majority of sealant loss occurs at the edges. Loss of sealant due to enlargement of an initial defect is highly progressive over time.