Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy

Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Fractional clearances of uncharged dextran 40 and anionic proteins were performed in an attempt to elucidate the defect in glomerular barrier function responsible for heavy proteinuria in diabetic nephropathy. Notwithstanding urinary albumin excretion (UalbV) at 3634 ± 608 µg/min, the fractional clearance for dextran molecules with Einstein-Stokes radii (r) between 22 and 36 Å was depressed in 12 patients with advanced diabetic nephropathy, which suggests a reduction in mean glomerular pore size or density. Equivalent restriction to transglomerular passage of dextrans with a r < 36 Å in 7 patients with minimal change nephropathy was associated with a similarly enhanced proteinuria (UalbV, 3333 ± 759 µg/min). The dissociation between fractional clearances for neutral and anionic macromolecules in both disorders is consistent with loss of glomerular electrostatic charge. In diabetic nephropathy, however, the fractional clearances for large dextrans and test proteins considerably exceeded corresponding values in minimal change nephropathy when r ≥ 36 Å. Furthermore, the fractional clearances for test proteins were two orders of magnitude smaller than that for equivalent-sized dextrans in minimal change nephropathy, whereas this difference was much less in diabetic nephropathy. Thus, a selective increase in transglomerular passage of large molecules and a progressive loss of ability to discriminate between large molecules of different configuration distinguish the glomerular capillary wall in diabetic nephropathy from that in minimal change nephropathy.Protéinurie et caractéristiques fonctionnelles de la barrière glomérulaire dans la néphropathie diabétique. Les clearances fractionnelles de dextran 40 neutre et de protéines anioniques ont été mesurées afin d'étudier le défaut de la fonction de la barrière glomérulaire responsable de la protéinurie massive au cours de la néphropathie diabétique. Malgré une excrétion urinaire d'albumine (UalbV) de 3634 ± 608 µg/min, la clearance fractionnelle pour les molécules de dextran dont le rayon d'Einstein-Stokes (r) était compris entre 22 et 36 Å était abaissé chez 12 malades atteints de néphropathie diabétique avancée, ce qui suggère une diminution de la taille moyenne ou de la densité des pores. Une diminution équivalente de la restriction au franchissement du glomérule de dextran r < 36 Å chez 7 malades atteints de néphropathie à modifications minimes était associée à une protéinurie du même ordre (UalbV, 3333 ± 759 /µg/min). La dissociation entre les clearances fractionnelles des macromolécules neutres et anioniques dans les deux affections est compatible avec une perte des charges électrostatiques glomérulaires. Dans la néphropathie diabétique, cependant les clearances fractionnelles des dextrans de grande taille et des protéines étudiées était plus élevé que les valeurs obtenues dans les néphropathies à modifications minimes quand r ≥ 36 Å. De plus, les clearances fractionnelles pour les protéines étudiées sont plus es petit de deux ordres de grandeur que les clearances fractionnelles pour les dextrans de taille équivalente dans la néphropathie à modifications minimes, alors que cette différence était bien moindre dans la néphropathie diabétique. Ainsi une augmentation sélective du passage transglomérulaire des grosses molécules et une perte progressive de la capacité de discriminer entre les grosses molécules selon leur configuration différencie la paroi du capillaire glomérulaire de la néphropathie diabétique de celle de la néphropathie à modifications minimes

Emergent regularities and scaling in armed conflict data

Armed conflict exhibits regularities beyond known power law distributions of fatalities and duration over varying culture and geography. We systematically cluster conflict reports from a database of $10^5$ events from Africa spanning 20 years into conflict avalanches. Conflict profiles collapse over a range of scales. Duration, diameter, extent, fatalities, and report totals satisfy mutually consistent scaling relations captured with a model combining geographic spread and local conflict-site growth. The emergence of such social scaling laws hints at principles guiding conflict evolution

Podocytopenia and disease severity in IgA nephropathy

Podocytopenia and disease severity in IgA nephropathy.BackgroundIgA nephropathy is a common form of progressive glomerular disease, associated with proliferation of mesangial cells and mesangial deposition of IgA. The present study was designed to investigate functional and morphological covariates of disease severity in patients with IgA nephropathy.MethodsGlomerular hemodynamics, permselectivity and ultrastructure were studied in 17 adult patients with IgA nephropathy using inulin, para-aminohippuric acid (PAH) and 3H-Ficoll clearances and morphometric methods. A mathematical model of macromolecule permeation through a heteroporous membrane was used to characterize glomerular permselectivity. Controls consisted of 14 healthy living kidney donors and 12 healthy volunteers.ResultsThe patients were heterogeneous in their disease severity, but as a group had a decreased glomerular filtration rate (GFR) and increased urinary protein excretion compared to controls [63 ± 29 SD vs. 104 ± 23 mL/min/1.73 m2, P < 0.001, and (median) 1.34 vs. 0.11 g/day, P < 0.0001, respectively). A multivariate analysis of structural and functional relationships revealed GFR depression to be most strongly correlated with the prevalence of global glomerular sclerosis (t = -4.073, P = 0.002). Those patients with the most severe glomerular dysfunction had a reduced number of glomerular visceral epithelial cells (podocytes) per glomerulus. The degree of podocytopenia was related to the extent of glomerular sclerosis and of impairment of permselectivity and GFR, with worsening injury below an apparent threshold podocyte number of about 250 cells per glomerulus. There were no corresponding correlations between these indices of injury and the number of mesangial and endothelial cells.ConclusionsOur findings show that podocyte loss is a concomitant of increasing disease severity in IgA nephropathy. This suggests that podocyte loss may either cause or contribute to the progressive proteinuria, glomerular sclerosis and filtration failure seen in this disorder

Engineering shallow spins in diamond with nitrogen delta-doping

We demonstrate nanometer-precision depth control of nitrogen-vacancy (NV) center creation near the surface of synthetic diamond using an in situ nitrogen delta-doping technique during plasma-enhanced chemical vapor deposition. Despite their proximity to the surface, doped NV centers with depths (d) ranging from 5 - 100 nm display long spin coherence times, T2 > 100 \mus at d = 5 nm and T2 > 600 \mus at d \geq 50 nm. The consistently long spin coherence observed in such shallow NV centers enables applications such as atomic-scale external spin sensing and hybrid quantum architectures.Comment: 14 pages, 4 figures, 11 pages of additional supplementary materia