Interleukin-6 stimulates gene expression of extracellular matrix components in bovine mesangial cells in culture

The effect of interleukin-6 (IL-6) on gene expression of extracellular matrix components in bovine mesangial cells in culture has been investigated. IL-6 (100 U/ml) time dependently increased the steady state expression of mRNAs coding for α1 collagen III and fibronectin, both transcripts being 1.5- and 2.5-fold higher than basal level at 24 and 48 h, respectively. In contrast, IL-6 stimulated laminin mRNA expression only after 48 h incubation (2.5-fold upon basal level). These results suggest that IL-6 could favour glomerular matrix accumulation thus contributing to the development of glomerulosclerosis

PUK12 COST-EFFECTIVENESS OF ACE INHIBITOR THERAPY TO PREVENT DIALYSIS IN NON-DIABETIC NEPHROPATHY—INFLUENCE OF THE ACE INSERTION / DELETION POLYMORPHISM

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Imatinib ameliorates renal disease and survival in murine lupus autoimmune disease

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Validation of a patient-specific hemodynamic computational model for surgical planning of vascular access in hemodialysis patients

Vascular access dysfunction is one of the main causes of morbidity and hospitalization in hemodialysis patients. This major clinical problem points out the need for prediction of hemodynamic changes induced by vascular access surgery. Here we reviewed the potential of a patient-specific computational vascular network model that includes vessel wall remodeling to predict blood flow change within 6 weeks after surgery for different arteriovenous fistula configurations. For model validation, we performed a multicenter, prospective clinical study to collect longitudinal data on arm vasculature before and after surgery. Sixty-three patients with newly created arteriovenous fistula were included in the validation data set and divided into four groups based on fistula configuration. Predicted brachial artery blood flow volumes 40 days after surgery had a significantly high correlation with measured values. Deviation of predicted from measured brachial artery blood flow averaged 3% with a root mean squared error of 19.5%, showing that the computational tool reliably predicted patient-specific blood flow increase resulting from vascular access surgery and subsequent vascular adaptation. This innovative approach may help the surgeon to plan the most appropriate fistula configuration to optimize access blood flow for hemodialysis, potentially reducing the incidence of vascular access dysfunctions and the need of patient hospitalization

Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations

Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations. Two patients with a clinical history of D+ hemolytic uremic syndrome associated with Shiga-toxin-producing 0157:H7 E. coli and recurrence in the kidney graft carry heterozygous mutations in the genes encoding complement factor I (patient 1) and membrane cofactor protein (patient 2). © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons

Thymic Dendritic Cells Express Inducible Nitric Oxide Synthase and Generate Nitric Oxide in Response to Self- and Alloantigens

Thymocytes maturing in the thymus undergo clonal deletion/apoptosis when they encounter self- or allo-Ags presented by dendritic cells (DCs). How this occurs is a matter of debate, but NO may play a role given its ability of inducing apoptosis of these cells. APC (a mixed population of macrophages (Mφ) and DCs) from rat thymus expressed high levels of inducible NO synthase (iNOS) and produced large amounts of NO in basal conditions whereas iNOS expression and NO production were very low in thymocytes. Analysis by FACS and by double labeling of cytocentrifuged preparations showed that DCs and MΦ both express iNOS within APC. Analysis of a purified preparation of DCs confirmed that these cells express high levels of iNOS and produce large amounts of NO in basal conditions. The capacity of DCs to generate NO was enhanced by exposure to rat albumin, a self-protein, and required a fully expressed process of Ag internalization, processing, and presentation. Peptides derived from portions of class II MHC molecules up-regulate iNOS expression and NO production by DCs as well, both in self and allogeneic combinations, suggesting a role of NO in both self and acquired tolerance. We also found that NO induced apoptosis of rat double-positive thymocytes, the effect being more evident in anti-CD3-stimulated cells. Altogether, the present findings might suggest that DC-derived NO is at least one of the soluble factors regulating events, in the thymus, that follow recognition of self- and allo-Ags

A Novel Strategy to Enhance Mesenchymal Stem Cell Migration Capacity and Promote Tissue Repair in an Injury Specific Fashion

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