It was reported on studies of an in vitro model that

It was reported on studies of an in vitro model that in the course 1379592 of kidney reabsorption the transport of FDG was predominantly mediated by sodium glucose co-transporters (SGLTs), while the transport of D-glucose is mediated by both sodium-independent glucose transport proteins (GLUTs) and SGLTs [13]. Therefore, we analyzed the temporal expression of the known SGLT1, 2, 3a, and 3b. Relative to day 0 expression levels, there was a significant decline in SGLT1 expression in kidney 7 days after anti-GBM AN-3199 biological activity treatment (Figure 6A). SGLT2 also declined but the drop was not significant (Figure 6B). On the other hand, there was progressively increased expression of all SGLTs on days 10 and 14 (Figure 6A ). With the exception of SGLT2 the increase began to reverse on day 21.Imaging Assessment of Lupus NephritisFigure 1. Renal dysfunction and pathological changes during anti-GBM antibody nduced nephritis. Following the challenge with antiGBM serum, 12961/SvJ mice (n = 3? per group) showed increased serum creatinine (sCr) levels (A) and proteinuria (B); Kidney specimens from all anti-GBM nephritis mice were examined by light microscopy for evidence of glomerular nephritis (GN score) (C), and glomerular crescent formation (D). Representative Periodic Acid Schiff (PAS) staining on day 0 (E) and day 14 (F) (yellow dash line indicates the formation of crescent). F also shows severe inflammatory cell infiltration in the tubular-interstitial area of anti-GBM nephritic mice as indicated by yellow arrows. The severity of GN score was graded on a 0? scale as follows: 0, normal; 1, mild increase in mesangial cellularity and matrix; 2, moderate increase in mesangial cellularity and matrix, with thickening of the GBM; 3, focal endocapillary hypercellularity with obliteration of capillary lumina and a substantial increase in the thickness and irregularity of the GBM; and 4, diffuse endocapillary hypercellularity, segmental necrosis, crescents, and hyalinized end-stage glomeruli. doi:10.1371/journal.pone.0057418.gImaging Assessment of Lupus NephritisImaging Assessment of Lupus NephritisFigure 2. Representative coronal PET-CT images of mice following FDG injection. Images were obtained 0 (A), 7 (B), 10 (C), 14 (D) and 21 days (E) post-administration of rabbit IgG injection. They were derived from the 0?0 min dynamic scans (5 min per frame and 12 frames in total). L: left kidney; R: right kidney. The yellow dashed circle delineates the substantial enlargement of the abdominal cavity on day 21. doi:10.1371/journal.pone.0057418.gDiscussionCurrently, the gold standard for diagnosis and the treatment follow up of patients with lupus nephritis is histologic evaluation of invasive biopsies, which often results in patient morbidity, especially when multiple biopsies are performed. Therefore, there is an unmet clinical need for non-invasive imaging techniques that would enable longitudinal assessment of disease progression, evaluation of acute flares, and response to treatment in the same subject. Ideally the imaging study would take advantage of current understanding of the underlying pathophysiology. Lupus nephritis is initiated by the glomerular deposition of 58-49-1 biological activity autoantibodies (e.g. anti-GBM antibodies) and immune complexes. This triggers a cascade of inflammatory events including upregulation of adhesion molecules on endothelial cells (including VCAM-1), activation of intrinsic renal cells, recruitment of inflammatory cells, release of various inflammatory mediators, and.It was reported on studies of an in vitro model that in the course 1379592 of kidney reabsorption the transport of FDG was predominantly mediated by sodium glucose co-transporters (SGLTs), while the transport of D-glucose is mediated by both sodium-independent glucose transport proteins (GLUTs) and SGLTs [13]. Therefore, we analyzed the temporal expression of the known SGLT1, 2, 3a, and 3b. Relative to day 0 expression levels, there was a significant decline in SGLT1 expression in kidney 7 days after anti-GBM treatment (Figure 6A). SGLT2 also declined but the drop was not significant (Figure 6B). On the other hand, there was progressively increased expression of all SGLTs on days 10 and 14 (Figure 6A ). With the exception of SGLT2 the increase began to reverse on day 21.Imaging Assessment of Lupus NephritisFigure 1. Renal dysfunction and pathological changes during anti-GBM antibody nduced nephritis. Following the challenge with antiGBM serum, 12961/SvJ mice (n = 3? per group) showed increased serum creatinine (sCr) levels (A) and proteinuria (B); Kidney specimens from all anti-GBM nephritis mice were examined by light microscopy for evidence of glomerular nephritis (GN score) (C), and glomerular crescent formation (D). Representative Periodic Acid Schiff (PAS) staining on day 0 (E) and day 14 (F) (yellow dash line indicates the formation of crescent). F also shows severe inflammatory cell infiltration in the tubular-interstitial area of anti-GBM nephritic mice as indicated by yellow arrows. The severity of GN score was graded on a 0? scale as follows: 0, normal; 1, mild increase in mesangial cellularity and matrix; 2, moderate increase in mesangial cellularity and matrix, with thickening of the GBM; 3, focal endocapillary hypercellularity with obliteration of capillary lumina and a substantial increase in the thickness and irregularity of the GBM; and 4, diffuse endocapillary hypercellularity, segmental necrosis, crescents, and hyalinized end-stage glomeruli. doi:10.1371/journal.pone.0057418.gImaging Assessment of Lupus NephritisImaging Assessment of Lupus NephritisFigure 2. Representative coronal PET-CT images of mice following FDG injection. Images were obtained 0 (A), 7 (B), 10 (C), 14 (D) and 21 days (E) post-administration of rabbit IgG injection. They were derived from the 0?0 min dynamic scans (5 min per frame and 12 frames in total). L: left kidney; R: right kidney. The yellow dashed circle delineates the substantial enlargement of the abdominal cavity on day 21. doi:10.1371/journal.pone.0057418.gDiscussionCurrently, the gold standard for diagnosis and the treatment follow up of patients with lupus nephritis is histologic evaluation of invasive biopsies, which often results in patient morbidity, especially when multiple biopsies are performed. Therefore, there is an unmet clinical need for non-invasive imaging techniques that would enable longitudinal assessment of disease progression, evaluation of acute flares, and response to treatment in the same subject. Ideally the imaging study would take advantage of current understanding of the underlying pathophysiology. Lupus nephritis is initiated by the glomerular deposition of autoantibodies (e.g. anti-GBM antibodies) and immune complexes. This triggers a cascade of inflammatory events including upregulation of adhesion molecules on endothelial cells (including VCAM-1), activation of intrinsic renal cells, recruitment of inflammatory cells, release of various inflammatory mediators, and.

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