Race and renal cell carcinoma stage at diagnosis: an analysis of the Surveillance, Epidemiology, and End Results data.

To study racial differences in tumor stage at diagnosis among Black and White patients with renal cell carcinoma (RCC) by histologic type and time period. The patients were Black and White patients with RCC from 1999 to 2011 derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Multinomial logistic regression was used to assess the associations between cancer stage and race and then stratified by histology and diagnosis year. Compared to Whites, Blacks were less likely to be diagnosed with regional disease [odds ratio (OR)=0.67; 95% confidence interval (CI)=0.60-0.73] or distant disease (OR=0.82; 95% CI=0.74-0.90) after adjusting for age, sex, year of diagnosis, and tumor grade. When stratified by RCC histology, similar results were observed for clear cell (OR=0.71; 95% CI=0.63-0.80), chromophobe (OR=0.51; 95% CI=0.32-0.81), and other histologic type (OR=0.63; 95% CI=0.42-0.96) while the association was not significant for papillary histology. The analyses by time showed a lower likelihood to have regional disease in Black than White in 2003-2006 (OR=0.66; 95% CI=0.55-0.79) and 2007-2011 (OR=0.57; 95% CI=0.49-0.67). Black patients were also less likely to have distant disease in 2007-2011 period (OR=0.76; 95% CI=0.65-0.88). In conclusion, blacks were less likely to be diagnosed at a later stage RCC than Whites regardless of cancer histology. This racial disparity may exist over time during the study period.

A low-cost method to test cytotoxic effects of Crotalus vegrandis (Serpentes: Viperidae) venom on kidney cell cultures.

The pathogenesis of the renal lesion upon envenomation by snakebite has been related to myolysis, hemolysis, hypotension and/or direct venom nephrotoxicity caused by the venom. Both primary and continuous cell culture systems provide an in vitro alternative for quantitative evaluation of the toxicity of snake venoms. Crude Crotalus vegrandis venom was fractionated by molecular exclusion chromatography. The toxicity of C. vegrandis crude venom, hemorrhagic, and neurotoxic fractions were evaluated on mouse primary renal cells and a continuous cell line of Vero cells maintained in vitro. Cells were isolated from murine renal cortex and were grown in 96 well plates with Dulbecco's Modified Essential Medium (DMEM) and challenged with crude and venom fractions. The murine renal cortex cells exhibited epithelial morphology and the majority showed smooth muscle actin determined by immune-staining. The cytotoxicity was evaluated by the tetrazolium colorimetric method. Cell viability was less for crude venom, followed by the hemorrhagic and neurotoxic fractions with a CT50 of 4.93, 18.41 and 50.22 microg/mL, respectively. The Vero cell cultures seemed to be more sensitive with a CT50 of 2.9 and 1.4 microg/mL for crude venom and the hemorrhagic peak, respectively. The results of this study show the potential of using cell culture system to evaluate venom toxicity.

A low-cost method to test cytotoxic effects of Crotalus vegrandis (Serpentes: Viperidae) venom on kidney cell cultures

La patogénesis de la lesion renal ha sido relacionada a la miolisis, hemólisis, hipotensión y/o el efecto directo del veneno. Tanto el cultivo primario o el cultivo celular continuo proveen una alternativa in vitro para la evaluación cuantitativa de la toxicidad de venenos de serpiente. El veneno crudo de Crotalus vegrandis fue fraccionado por una cromatografía de exclusión molecular. La toxicidad del veneno crudo de C. vegrandis, sus fracciones hemorrágicas y neurotóxicas fueron evaluadas en células renales primarias de ratón y una línea continua de células Vero mantenidas in vitro. Las células fueron aisladas de la corteza renal murina y se cultivaron en placas de 96 pozos con medio Dulbecco (DMEM). Allí fueron tratadas con el veneno crudo y sus fracciones. Las células de la corteza renal murina tuvieron una morfología de células epiteliales y la mayoría se tiñeron con un anticuerpo anti-músculo actina. La citotoxicidad fue evaluada por el método colorimétrico del tetrazolium. La viabilidad de las células fue menor en las células tratadas con el veneno crudo, seguida por la fracción hemorrágica y neurotóxica, con un CT50 de 4.93, 18.41 y 50.22 µg/mL, respectivamente. Los cultivos de células Vero parecieron ser más sensibles con un CT50 de 2.9 y 1.4 µg/mL para el veneno crudo y el pico hemorrágico, respectivamente. Los resultados de este estudio muestran la potencialidad de usar sistemas de cultivo celular para evaluar la toxicidad de los venenos.

Glomerular permeability barrier in the rat. Functional assessment by in vitro methods.

The formation of glomerular ultrafiltrate is dependent on the prevailing hemodynamic forces within the glomerular microcirculation and the intrinsic properties of the filtration barrier. However, direct assessment of the permeability barrier is difficult with most available techniques. We used confocal microscopy to image 1-micron thick optical cross-sections of isolated intact glomeruli and glomeruli denuded of cells and quantitated dextran (70,000 mol wt) diffusion from the capillary lumen. Dextran permeance was 11 times greater for the acellular filtration barrier than the intact peripheral capillary. Consideration of the basement membrane and cells as series resistors demonstrated that cells of the filtration barrier contribute 90% of the total resistance to macromolecular permeance. Using a different approach, dextran sieving coefficients for acellular glomeruli consolidated as a multilayer sheet in a filtration cell were similar to those for intact glomeruli in vivo at radii 30-36 A and approximately 50 times greater at a dextran radius of 60 A. The presence of cells significantly reduced hydraulic permeability determined on consolidated intact or acellular glomeruli in an ultrafiltration cell with 50 mmHg applied pressure. The glomerular basement membrane does restrict macromolecular permeability but cells are important determinants of the overall macromolecular and hydraulic permeability of the glomerulus.