Neutrophil-dependent pentraxin-3 and reactive oxygen species production modulate endothelial dysfunction in haemodialysis patients.

BACKGROUND: The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. METHODS: Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l-selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). RESULTS: The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l-selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. CONCLUSIONS: Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved

steroid resistant minimal change disease with ballooned podocytes

n/

Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review on incidence, risk factors, pathophysiology and management of immunosuppressive therapy

Abstract Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications

Early and Late Infections in Newborns: Where Do We Stand? A Review

Neonatal sepsis still represents an important cause of mortality and morbidity among infants. According to the onset, we can distinguish "early onset sepsis" when microbiological cultures positive for external pathogens come from newborns during the first 7 days of life (maternal intrapartum transmission); "late onset sepsis" when microbiological cultures positive for external pathogens come from newborns after the first 7 days from delivery (postnatal acquisition). In this review we synthesize the incidence, risk factors, clinical manifestations, and methods of diagnosis and treatment of each type of neonatal infection, in order to better define such a pathological condition which is of great importance in common clinical practice

Coronary tortuosity: normal variant or pathological condition?

HighlightsCoronary tortuosity is a common coronary angiography finding. The aetiology and the clinical significant are not well defined, generally considered a normal variant. We showed a case of marked tortuosity of all coronary arteries associated with myocardial ischemia. </p

Effects of the Calix[4]arene Derivative Compound OTX008 on High Glucose-Stimulated ARPE-19 Cells: Focus on Galectin-1/TGF-β/EMT Pathway

Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5-5-10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial-mesenchymal transition markers were reduced by OTX008 5 μM and 10 μM. The inhibition of galectin-1 by OTX008 in DR may preserve retinal pigment epithelial cell integrity and functionality by reducing their pro-fibrotic phenotype and epithelial-mesenchymal transition phenomenon induced by diabetes

CORRIGENDUM to The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

In this article, the authors’ first names and surnames were incorrectly listed in the wrong order. The correct author list is: Marco Tucci, Anna Passarelli, Annalisa Todisco, Francesco Mannavola, Luigia Stefania Stucci, Stella D’Oronzo, Michele Rossini, Marco Taurisano, Loreto Gesualdo and Franco Silvestris

Doppler ultrasound venous mapping of the lower limbs

Aldo Innocente Galeandro1, Giovanni Quistelli2, Pietro Scicchitano2, Michele Gesualdo2, Annapaola Zito2, Paola Caputo2, Rosa Carbonara2, Giuseppe Galgano3, Francesco Ciciarello4, Sandro Mandolesi4, Claude Franceschi5, Marco Matteo Ciccone21Centro Diagnostica Globale and ASL-TA, Taranto, Italy; 2Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy; 3Cardiovascular Diseases Section, Ente Ecclesiastico Ospedale Generale Regionale F Miulli, Acquaviva delle Fonti, Bari, Italy; 4Cardiology Department, Policlinico Umberto I, Sapienza University of Rome, Italy; 5Vascular Laboratories of Hospitals Saint Joseph and Piti&amp;eacute;-Salp&amp;eacute;tri&amp;egrave;re, Paris, FranceBackground: The study aim was to test the accuracy (intra and interobserver variability), sensitivity, and specificity of a simplified noninvasive ultrasound methodology for mapping superficial and deep veins of the lower limbs.Methods: 62 consecutive patients, aged 62 &amp;plusmn; 11 years, were enrolled. All underwent US-examinations, performed by two different investigators, of both legs, four anatomical parts, and 17 veins, to assess the interobserver variability of evaluation of superficial and deep veins of the lower limbs.Results: Overall the agreement between the second versus the first operator was very high in detecting reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar test). The higher CEAP classification stages were significantly associated with reflux (odds ratio: 1.778, 95% confidence interval: 1.552&amp;ndash;2.038; P &amp;lt; 0.001) as well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741&amp;ndash;4.389; P &amp;lt; 0.001). Thus, our findings show a strict association between the symptoms of venous disorders and ultrasound evaluation results for thrombosis or reflux.Conclusion: This study demonstrated that our venous mapping protocol is a reliable method showing a very low interobserver variability, which makes it accurate and reproducible for the assessment of the morphofunctional status of the lower limb veins.Keywords: venous mapping, new methodology, sensitivity, specificity, accurac