Children and Their Parents: A Comparative Study of the Legal Position of Children with Regard to Their Intentional and Biological Parents in English and Dutch Law

This is a book about children and their parents. There are many different kinds of children and at least about as many different kinds of parents. In addition to the many different disciplines that study children and their parents, such as sociology, psychology, child studies and gender studies, to name but a few, this study concerns a legal question with regard to the parent-child relationship, namely how the law assigns parents to children. This subject is approached in a comparative legal perspective and covers England and The Netherlands. The book contains a detailed comparison and analysis of the manner in which the law in the two jurisdictions assigns the status of legal parent and/or attributes parental responsibility to the child’s biological and intentional parents. The concept ‘procreational responsibility’, which is introduced in the concluding chapter of the book, may be used as a tool to assess and reform existing regulations on legal parent-child relationships. The structure of the book, which is based on a categorisation of different family types in a ‘family tree’, enables the reader to have easy access to family-specific information.FdR – Publicaties zonder aanstelling Universiteit Leide

Heparanase: an essential factor for the development of proteinuria

Contains fulltext : 160306.pdf (publisher's version ) (Open Access)RU Radboud Universiteit, 11 oktober 2016Promotor : Berden, J.H.M. Co-promotor : Vlag, J. van de

The role of heparanase and the endothelial glycocalyx in the development of proteinuria

Item does not contain fulltextProteinuria is a hallmark of many glomerular diseases and an independent risk factor for the progression of renal failure. Proteinuria results from damage to the glomerular filtration barrier (GFB), which plays a critical role in size- and charge-selective filtration. The GFB consists of three layers, which is the fenestrated endothelium that is covered by the glycocalyx, the podocytes and the intervening glomerular basement membrane. Defects in one of the three layers in the GFB can lead to the development of proteinuria. Heparan sulphate (HS) is a negatively charged polysaccharide that is abundantly expressed in all layers of the GFB. HS expression in the GFB is reduced in the majority of patients with proteinuria, which is associated with an increased glomerular expression of the HS-degrading enzyme heparanase. The primary role of HS in the development of proteinuria has been challenged after the establishment of several genetically engineered mouse models with an altered HS expression that did not display development of overt proteinuria. However, in a recent study, we showed that heparanase is essential for the development of proteinuria in diabetic nephropathy, which suggests that loss of HS contributes to the development of proteinuria. Recent studies also further highlight the importance of the glomerular endothelial glycocalyx in charge-selective filtration and the development of proteinuria. This review aims to summarize our current knowledge on the role of in particular HS and heparanase in the development of proteinuria

Heparanase-2 protein and peptides have a protective effect on experimental glomerulonephritis and diabetic nephropathy.

Introduction: The endothelial glycocalyx degrading enzyme heparanase-1 (HPSE1) is a major contributor to kidney diseases, such as glomerulonephritis and diabetic nephropathy. Therefore, inhibition of HPSE1 could be an interesting therapeutic strategy to treat glomerular diseases. A possible HPSE1 inhibitor is heparanase-2 (HPSE2) because HPSE2 is a structural homolog of HPSE1 without enzymatic activity. The importance of HPSE2 has been recently demonstrated in HPSE2-deficient mice, since these mice developed albuminuria and died within a few months after birth. We postulate that inhibition of HPSE1 activity by HPSE2 is a promising therapeutic strategy to target albuminuria and resulting renal failure. Methods: First, we evaluated the regulation of HPSE2 expression in anti-GBM and LPS-induced glomerulonephritis, streptozotocin-induced diabetic nephropathy, and adriamycin nephropathy by qPCR and ELISA. Second, we measured the HPSE1 inhibiting capacity of HPSE2 protein and 30 different HPSE2 peptides and assessed their therapeutic potential in both experimental glomerulonephritis and diabetic nephropathy using kidney function and cortical mRNA expression of HPSE1 and cytokines as outcome parameters. Results: HPSE2 expression was downregulated under inflammatory and diabetic conditions, whereas this effect on HPSE2 expression was absent with HPSE1 inhibition and in HPSE1-deficient mice. Both HPSE2 protein and a mixture of the three most potent HPSE1 inhibitory HPSE2 peptides could prevent LPS and streptozotocin induced kidney injury. Discussion: Taken together, our data suggest a protective effect of HPSE2 in (experimental) glomerular diseases and support the therapeutic potential of HPSE2 as HPSE1 inhibitor in glomerular diseases

Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis

Vascular nephrologyNephrolog

Endothelial Nitric Oxide Synthase Prevents Heparanase Induction and the Development of Proteinuria

NephrologyVascular nephrolog

Vitamin D attenuates proteinuria by inhibition of heparanase expression in the podocyte

Contains fulltext : 152933.pdf (publisher's version ) (Closed access)The glomerular filtration barrier consists of podocytes, the glomerular basement membrane, and endothelial cells covered with a glycocalyx. Heparan sulphate (HS) in the glomerular filtration barrier is reduced in patients with proteinuria, which is associated with increased expression of the HS-degrading enzyme heparanase. Previously, we showed that heparanase is essential for the development of proteinuria in experimental diabetic nephropathy. Vitamin D supplementation reduces podocyte loss and proteinuria in vitro and in vivo. Therefore, we hypothesize that vitamin D reduces proteinuria by reducing glomerular heparanase. Adriamycin-exposed rats developed proteinuria and showed increased heparanase expression, which was reduced by 1,25-dihydroxyvitamin D3 (1,25-D3 ) treatment. In vitro, adriamycin increased heparanase mRNA in the podocyte, which could be corrected by 1,25-D3 treatment. In addition, 1,25-D3 treatment reduced transendothelial albumin passage after adriamycin stimulation. In line with these results, we showed direct binding of the vitamin D receptor to the heparanase promoter, and 1,25-D3 dose-dependently reduced heparanase promoter activity. Finally, 1,25-D3 -deficient 25-hydroxy-1alpha-hydroxylase knockout mice developed proteinuria and showed increased heparanase, which was normalized by 1,25-D3 treatment. Our data suggest that the protective effect of vitamin D on the development of proteinuria is mediated by inhibiting heparanase expression in the podocyte. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Endothelial Nitric Oxide Synthase Prevents Heparanase Induction and the Development of Proteinuria

Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart. In vitro, the eNOS inhibitor asymmetric dimethylarginine (ADMA) induced heparanase expression in cultured mouse glomerular endothelial cells. Moreover, ADMA enhanced transendothelial albumin passage in a heparanase-dependent manner. We conclude that eNOS prevents heparanase induction and the development of proteinuria