High-dose folic acid supplements and responsiveness to rHu-EPO in HD patients.
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Biomedical subjects
Publications and source records attributed to Antonio Dal Canton.
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Since the early description of Randall plaques in 1937, studies of the pathogenesis of stone formation mainly focused on the chemistry involving salt precipitation and crystallization, rather than tubular and interstitial medullar mechanisms of calcium concentration and supersaturation. In 2003, Bushinsky published a suggestive and inspiring sequence of events aimed to show that the basement membrane of the thin limb of the loop of Henle can be the first site of nucleation, as recently shown by the impressive work by Evan et al. The aim of this minireview is to verify the consistency of the Evan and Bushinsky theory with the current literature in the field.
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BACKGROUND: In experimental extracapillary glomerulonephritis (EG) podocytes migrate, proliferate and change phenotype, and play a pivotal role in crescent formation. Hepatocyte Growth Factor (HGF) is an injury-induced effector of tissue repair that causes cell migration, growth and transdifferentiation via its receptor Met. METHODS: In 11 patients with EG we measured serum levels of HGF and investigated whether serum induces the release of HGF by Peripheral Blood Mononuclear Cells (PBMC). In renal biopsies we studied the expression of Met. In cultured podocytes we studied Met expression, migration, growth and morphological changes induced by recombinant (r) HGF. RESULTS: In patients with EG average serum levels of HGF (0.73 ng/ml) were higher than in normal volunteers (N, 0.10 ng/ml, p<0.01) and in patients with non-crescentic glomerular disease (GD, 0.18 ng/ml, p<0.01). Serum of EG induced a significant HGF release by PBMC (mean 0.58 ng/ml) in comparison with serum of N and GD (0.07 and 0.06 ng/ml, respectively, both p<0.001). Met was strongly expressed in crescents. Cultured podocytes expressed Met, and rHGF induced in podocytes a time- and dose-dependent migration, growth and epithelial to mesenchymal transdifferentiation. CONCLUSIONS: These results suggest that HGF/Met system participates in the process of crescent formation by inducing podocyte migration, growth and mesenchymal transformation.
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BACKGROUND: The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli. METHODS: Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (alpha2) IV collagen, transforming growth factor-beta (TGF-beta), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). beta-actin was used as housekeeping gene. The production of collagen type IV and TGF-beta was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography. RESULTS: (alpha2) IV collagen, TGF-beta, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-beta. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion. CONCLUSION: HGF reduced expression and synthesis of TGF-beta and collagen type IV and increased MMP-2 mRNA level in normal human glomeruli. These results suggest an antifibrotic effect of HGF on glomerular cells and may explain its beneficial role in glomerulosclerosis.
BACKGROUND: Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. PATIENTS AND METHODS: From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. RESULTS: Perfusate volume used was significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively; PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS). CONCLUSIONS: CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.
BACKGROUND: In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. METHODS: Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. RESULTS: The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). CONCLUSION: The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.
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The proto-oncogene product Ron is the receptor for macrophage stimulating protein, a scatter factor that stimulates cell proliferation, prevents apoptosis, and induces an invasive cell phenotype. We investigated the expression of Ron, Ki-67 (proliferation index), p53, and bcl-2 (proapoptotic and antiapoptotic proteins, respectively) in 50 renal tumors (19 clear cell carcinomas, 18 oncocytomas, 7 papillary cell carcinomas, 5 chromophobe cell carcinomas, and 1 carcinoma with sarcomatoid areas). In addition, we studied Ron in normal kidney and in the renal carcinoma cell line Caki-1. Immunostaining and Western blot showed Ron in normal kidney and in all oncocytomas but never in renal cell carcinomas or in Caki-1. In addition, Western blot showed that Ron was expressed in phosphorylated, i.e., active, form. Bcl-2 was strongly expressed in oncocytomas, whereas Ki-67 and p53 were much less expressed in oncocytomas than in carcinomas. These results indicate in Ron a marker that differentiates oncocytoma from the other renal epithelial tumors. We therefore think that Ron may prove to be a new tool for a sound and precise diagnosis of oncocytoma, a benign tumor that cannot always be distinguished from carcinomas at histologic examination. The overexpression of bcl-2, but not p53 in oncocytoma, suggests that the MSP/Ron system sustains the growth of oncocytoma by opposing apoptosis.
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