A5041554168- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Blood groups and transfusion
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Iron Metabolism and Disorders
- Adenosine and Purinergic Signaling
- Chronic Kidney Disease and Diabetes
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Advanced Glycation End Products research
- Cell Adhesion Molecules Research
- Pregnancy and preeclampsia studies
- Renin-Angiotensin System Studies
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- COVID-19 Clinical Research Studies
- Systemic Lupus Erythematosus Research
- Nitric Oxide and Endothelin Effects
- Macrophage Migration Inhibitory Factor
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Interference and Gene Delivery
- Diabetes Treatment and Management
Mario Negri Institute for Pharmacological Research
2015-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2024
Scripps Research Institute
2004-2005
Radboud University Nijmegen
2002
Azienda Ospedaliero Universitaria Ospedali Riuniti
2000
Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused Shiga toxin-producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of has a poor prognosis. Genetic complement abnormalities have been found in aHUS.We screened 273 consecutive patients with aHUS studied their role predicting clinical phenotype response to treatment. We compared mutation frequencies localization...
Abstract In the present study, we examined hypothesis that dynamic characteristics of flow modulate production vasoactive mediators, namely nitric oxide (NO) and endothelin-1 (ET-1), by human umbilical vein endothelial cells (HUVECs). Cells were exposed for 6 hours in a cone-and-plate apparatus to different types flow: steady laminar, with shear stresses 2, 8, 12 dyne/cm 2 ; pulsatile stress from 8.2 16.6 frequency Hz; periodic square wave cycles 15 minutes 8 turbulent, on average. A second...
We addressed the role of hyperglycemia in leukocyte-endothelium interaction under flow conditions by exposing human umbilical vein endothelial cells for 24 h to normal (5 mM), high concentration glucose (30 advanced glycosylation end product-albumin (100 microg/ml), or hyperglycemic (174-316 mg/dl) sera from patients with diabetes and abnormal hemoglobin A1c (8.1+/-1.4%). At incubation were perfused total leukocyte suspension a parallel plate chamber laminar (1.5 dyn/cm2). Rolling adherent...
Focal segmental glomerulosclerosis is a kidney disease that manifested as the nephrotic syndrome. It often resistant to glucocorticoid therapy and progresses end-stage renal in 50 70% of patients. Genetic studies have shown familial focal podocytes, which are major components glomerular filtration barrier. However, molecular cause over half cases primary unknown, effective treatments been elusive.
Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway complement. Four gain-of-function mutations that form hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied functional consequences 10 FB changes recently from different aHUS cohorts. Using several tests for and C5 formation regulation, two potentially disease-relevant formed either an...
Microvascular thrombosis is associated with multiorgan failure and mortality in coronavirus disease 2019 (COVID-19). Although thrombotic complications may be ascribed to the ability of SARS-CoV-2 infect replicate endothelial cells, it has been poorly investigated whether, complexity viral infection human host, specific elements alone can induce damage. Detection circulating spike protein sera severe COVID-19 patients was evaluated by ELISA.
Glomerulopathy with fibronectin (FN) deposits (GFND) is an autosomal dominant disease age-related penetrance, characterized by proteinuria, microscopic hematuria, hypertension, and massive glomerular of FN that lead to end-stage renal failure. The genetic abnormality underlying GFND was still unknown. We hypothesized mutations in FN1, which encodes FN, were the cause GFND. In a large Italian pedigree eight affected subjects, we found linkage at FN1 locus 2q32. sequenced 15 unrelated...
Thrombotic thrombocytopenic purpura is a rare disorder of small vessels that associated with deficiency the von Willebrand factor-cleaving protease ADAMTS13, which favors platelet adhesion and aggregation in microcirculation. The disease manifests mainly central nervous system symptoms, but cases renal insufficiency have been reported. Presented are findings genetic basis phenotype heterogeneity thrombotic two sisters within one family. patients had ADAMTS13 as result heterozygous mutations...
Investigated was the effect of high albumin concentrations on proximal tubular cell expression fractalkine. Human cells (HK-2) were incubated with human serum (HSA), which induced a dose-dependent increase in fractalkine mRNA associated increased levels both membrane-bound and soluble forms protein. To evaluate role nuclear factor kappaB (NF-kappaB) activation HSA-induced mRNA, HK-2 infected recombinant adenovirus encoding natural inhibitor NF-kappaB, IkBalpha; 43% reduction resulted....
Abstract von Willebrand factor (VWF), a multimeric protein with central role in hemostasis, has been shown to interact complement components. However, results are contrasting and inconclusive. By studying 20 patients congenital thrombotic thrombocytopenic purpura (cTTP) who cannot cleave VWF multimers because of genetic ADAMTS13 deficiency, we investigated the mechanism through which modulates its pathophysiological implications for human diseases. Using assays ex vivo serum-induced C3 C5b-9...
Genetic and acquired abnormalities causing dysregulation of the complement alternative pathway contribute to atypical hemolytic uremic syndrome (aHUS), a rare disorder characterized by thrombocytopenia, nonimmune microangiopathic anemia, acute kidney failure. However, in substantial proportion patients disease-associated alterations are still unknown.Whole-exome whole-genome sequencing were performed two unrelated families with infantile recessive aHUS. Sequencing cDNA from affected...
Membranoproliferative glomerulonephritis (MPGN) was recently classified as C3 glomerulopathies (C3G), and immune-complex (IC) mediated MPGN. Dysregulation of the complement alternative pathway, driven by acquired and/or genetic defects, plays a pathogenetic role in C3G. However, pathway abnormalities were also found IC-MPGN. The most common drivers are nephritic factors (C3NeFs), heterogeneous autoantibodies that stabilize convertase, C3bBb. C3NeFs traditionally detected hemolytic assays...
Background Complement activation contributes to lung dysfunction in coronavirus disease 2019 (COVID-19). We assessed whether C5 blockade with eculizumab could improve outcome. Methods In this single-centre, academic, unblinded study two 900 mg doses were added-on standard therapy ten COVID-19 patients admitted from February 2020 April and receiving Continuous-Positive-Airway-Pressure (CPAP) ventilator support ≤24 hours. compared their outcomes those of 65 contemporary similar controls....
We have previously documented that cyclosporine exerts a direct cytotoxic effect on endothelial cells and causes an increase in renal vascular resistance (RVR) the rat. In present study we investigated whether FK506, novel immunosuppressive agent thought to be less nephrotoxic than CsA, impairs cell function vitro affects RVR vivo. eicosanoid release endothelin were measured bovine aortic culture exposed for 1, 6, 24 hr increasing concentrations of FK506 (1 nM 10 μM) or CsA (0.5, μM). No...