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Aims/hypothesis Podocyte loss by apoptosis, in addition to favouring progression of established diabetic nephropathy, has been recently indicated as an early phenomenon triggering the initiation of glomerular lesions. This study aimed to assess the rate of glomerular cell death and its relationship with renal functional, structural and molecular changes in rats with experimental diabetes. Methods Male Sprague-Dawley rats with streptozotocininduced diabetes and coeval non-diabetic control animals were killed at 7 days and at 2, 4 and 6 months for the assessment of apoptosis, renal function, renal structure and the expression of podocyte markers and apoptosis-and cell cycle-related proteins. Results Glomerular cell apoptosis was significantly increased in diabetic vs non-diabetic rats at 4 months and to an even greater extent at 6 months, with podocytes accounting for 70% of apoptosing cells. The increase in apoptosis was preceded by increases in proteinuria, albuminuria and mean glomerular and mesangial areas, and by reductions in glomerular cell density and content of synaptopodin and Wilms' tumour protein-1. It coincided with the development of mesangial expansion and glomerular sclerosis, and with the upregulation/activation both of tumour protein p53, which increased progressively throughout the study, and of p21 (also known as cyclin-dependent kinase inhibitor 1A, CIP1 and WAF1), which peaked at 4 months and decreased thereafter. Conclusions/interpretation Glomerular cell (podocyte) apoptosis is not an early feature in the course of experimental diabetic glomerulopathy, since it is preceded by glomerular hypertrophy, which may decrease glomerular cell density to the point of inducing compensatory podocyte hypertrophy. This is associated with reduced podocyte protein expression (podocytopathy) and proteinuria, and ultimately results in apoptotic cell loss (podocytopenia), driving progression to mesangial expansion and glomerular sclerosis.

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The aim of this study was to measure interaction forces between surfaces with high electric potentials in aqueous electrolyte solutions. Therefore, the force between a platinum or gold sample, which served as the working electrode, and a silicon nitride tip of an atomic force microscope was measured. Various potentials were applied between the sample and a reference electrode. Experimental results were compared to forces calculated with the Poisson-Boltzmann equation. As predicted by theory, the electrostatic double-layer force changed only in a narrow potential range of about 300 mV and saturated below and above this range. Within this range the repulsion grew with more negative sample potentials. This was expected, since the tip was negatively charged at the high pH chosen. At strong negative sample potentials this saturation was not complete and the force continued to rise slightly when lowering the potential. Another surprising and yet unexplained observation was a weak long-range attraction at positive sample potentials. This attraction decayed with a decay length of typically 50 nm. In parallel, the structure of Au(111) was imaged. We confirmed a ( 3 × p, p > 10) reconstruction at potentials below about -0.3 V SHE and the normal (1 × 1) hexagonal packing above this potential. Above about +0.8 V SHE the (1 × 1) structure disappeared and no crystalline packing was observed anymore.

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