97 results on '"Armelloni S"'
Search Results
2. Glomerular barrier dysfunction in glomerulosclerosis- resistant Milan rats with experimental diabetes: the role of renal haemodynamics
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Pugliese, G, Ricci, C, Iacobini, C, Menini, S, Fioretto, P, Ferrandi, M, Giardino, L A, Armelloni, S, Mattinzoli, D, Rastaldi, M P, and Pugliese, F
- Published
- 2007
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3. Glomerular clusterin is associated with PKC-α/β regulation and good outcome of membranous glomerulonephritis in humans
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Rastaldi, M P, Candiano, G, Musante, L, Bruschi, M, Armelloni, S, Rimoldi, L, Tardanico, R, Cherchi, S Sanna, Ferrario, F, Montinaro, V, Haupt, R, Parodi, S, Carnevali, M L, Allegri, L, Camussi, G, Gesualdo, L, Scolari, F, and Ghiggeri, G M
- Published
- 2006
4. Supplementary Material for: Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet
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Armelloni, S., Calvaresi, N., Ikehata, M., Corbelli, A., Mattinzoli, D., Giardino, L.A., Li, M., Messa, P., and Rastaldi, M.P.
- Abstract
Background/Aims: The relative contribution of genetic factors and dietary patterns to glomerular damage in healthy individuals and prediabetic conditions is currently unclear. All Rab3A knockout (KO) mice spontaneously develop macroalbuminuria, but only male mice exhibit a glucose-intolerant phenotype, thus making the model suitable to examine the impact of a diet on preexisting podocyte damage. Methods: Male and female Rab3A KO and wild-type (WT) mice were chronically fed a high-glucose diet (HGD). Biochemical tests, histology and immunohistochemistry were periodically performed whilst primary podocytes served for in vitro analyses. Results: Chronic administration of an HGD did not induce de novo alterations in WT kidneys but caused progressive worsening of podocyte and glomerular damage in both male and female Rab3A KO. Though glomerular lesions, reminiscent of human diabetic nephropathy, were more severe in male mice, overt proteinuria and renal damage were also evident in female mice. The in vitro analysis of Rab3A WT and KO podocytes revealed diminished actin plasticity in the cell processes of KO podocytes. Furthermore, a modest increase in glucose concentration induced profound cytoskeletal changes only in Rab3A KO cells. Conclusions: Our data show that chronic administration of an HGD to Rab3A KO mice that have a genetic defect that impairs podocyte actin plasticity results in increased podocyte damage and leads to overt proteinuria. If the same diet is given to male Rab3A KO animals, with additionally altered glucose homeostasis, this results in renal lesions similar to those of human diabetic nephropathy.
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- 2017
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5. Corrigendum to FGF23-regulated production of fetuin-A (AHSG) in osteocytes [Bone 83 (2016) 35–47]
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Mattinzoli, D., primary, Rastaldi, M.P., additional, Ikehata, M., additional, Armelloni, S., additional, Pignatari, C., additional, Giardino, L.A., additional, Li, M., additional, Alfieri, C.M., additional, Regalia, A., additional, Riccardi, D., additional, and Messa, P., additional
- Published
- 2016
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6. alpha- and beta-Adducin polymorphisms affect podocyte proteins and proteinuria in rodents and decline of renal function in human IgA nephropathy
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FERRANDI M, CUSI D, MOLINARI I, DEL VECCHIO L, BARLASSINA C, RASTALDI MP, SCHENA FP, MACCIARDI F, MARCANTONI C, ROCCATELLO D, PETERS LL, ARMELLONI S, MIN L, GIARDINO L, MATTINZOLI D, CAMISASCA C, PALAZZO F, FERRARI P, BIANCHI G., MANUNTA , PAOLO, Ferrandi, M, Cusi, D, Molinari, I, DEL VECCHIO, L, Barlassina, C, Rastaldi, Mp, Schena, Fp, Macciardi, F, Marcantoni, C, Roccatello, D, Peters, Ll, Armelloni, S, Min, L, Giardino, L, Mattinzoli, D, Camisasca, C, Palazzo, F, Manunta, Paolo, Ferrari, P, and Bianchi, G.
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Adducins - Abstract
Adducins are cytoskeletal actin-binding proteins (α, β, γ) that function as heterodimers and heterotetramers and are encoded by distinct genes. Experimental and clinical evidence implicates α- and β-adducin variants in hypertension and renal dysfunction. Here, we have addressed the role of α- and β-adducin on glomerular function and disease using β-adducin null mice, congenic substrains for α- and β-adducin from the Milan hyperten- sive (MHS) and Milan normotensive (MNS) rats and patients with IgA nephropathy. Targeted deletion of β- adducin in mice reduced urinary protein excretion, preceded by an increase of podocyte protein expression (phosphonephrin, synaptopodin, α-actinin, ZO-1, Fyn). The introgression of polymorphic MHS β-adducin locus into MNS (Add2, 529R) rats was associated with an early reduction of podocyte protein expression (nephrin, synaptopodin, α- actinin, ZO-1, podocin, Fyn), followed by severe glomerular and interstitial lesions and increased urinary protein excretion. These alterations were markedly attenuated when the polymorphic MHS α-adducin locus was also present (Add1, 316Y). In patients with IgA nephropathy, the rate of decline of renal function over time was associated to polymorphic β-adducin (ADD2, 1797T, rs4984) with a significant interaction with α-adducin (ADD1, 460W, rs4961). These findings suggest that adducin genetic variants participate in the development of glomerular lesions by modulating the expression of specific podocyte proteins.
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- 2010
7. Albuminuria and glomerular damage in mice lacking the Metabotropic Glutamate Receptor Type 1 (GRM1)
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Puliti, Aldamaria, Rossi, Pia, Caridi, G, Corbelli, A, Ikehata, M, Armelloni, S, Li, M, Zennaro, C, Conti, V, Vaccari, Carlotta, Cassanello, M, Calevo, Mg, Emionite, L, Ravazzolo, Roberto, and Rastaldi, M. P.
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- 2011
8. Nephrin expression in adult rodent central nervous system and its interaction with glutamate receptors J Pathol. 2011 Sep;225(1):118-28
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Li, M, Armelloni, S, Ikehata, M, Corbelli, A, Pesaresi, M, Calvaresi, N, Giardino, L, Mattinzoli, D, Nisticò, F, Andreoni, S, Puliti, Aldamaria, Ravazzolo, Roberto, Forloni, G, Messa, P, and Rastaldi, M. P.
- Published
- 2011
9. Glomerular oxidative damage and podocyte alterations in type 2 diabetic nephropathy
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Rastaldi, M, Calvetta, A., Calvaresi, N., Armelloni, S., Berra, S., Corbelli, Sa, Mariani, G., Corneglia, L., Garibotto, Giacomo, Bertani, T., Fornasieri, A., Ferrario, F., Tonolo, G., Nosadini, R., Holthofer, H., and D'Amico, G.
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diabetic nephropathy - Published
- 2004
10. Podocytes: A new player for glutamate signaling
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Armelloni, S., primary, Li, M., additional, Messa, P., additional, and Rastaldi, M.P., additional
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- 2012
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11. Glomerular podocytes contain neuron-like functional synaptic vesicles
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Rastaldi, M, Armelloni, S, Berra, S, Calvaresi, N, Corbelli, A, Giardino, L, Li, M, Wang, G, Fornasieri, A, Villa, A, Heikkila, E, Soliymani, R, Boucherot, A, Cohen, C, Kretzler, M, Nitsche, A, Ripamonti, M, Malgaroli, A, Pesaresi, M, Forloni, G, Schlöndorff, D, Holthofer, H, D'Amico, G, Rastaldi, MP, Giardino, LA, Wang, GQ, Cohen, CD, Forloni, GL, D'Amico, G., VILLA, ANTONELLO, Rastaldi, M, Armelloni, S, Berra, S, Calvaresi, N, Corbelli, A, Giardino, L, Li, M, Wang, G, Fornasieri, A, Villa, A, Heikkila, E, Soliymani, R, Boucherot, A, Cohen, C, Kretzler, M, Nitsche, A, Ripamonti, M, Malgaroli, A, Pesaresi, M, Forloni, G, Schlöndorff, D, Holthofer, H, D'Amico, G, Rastaldi, MP, Giardino, LA, Wang, GQ, Cohen, CD, Forloni, GL, D'Amico, G., and VILLA, ANTONELLO
- Abstract
Although patients with chronic renal failure are increasing worldwide, many aspects of kidney biology remain to be elucidated. Recent research has uncovered several molecular properties of the glomerular filtration barrier, in which podocytes, highly differentiated, ramified cells that enwrap the glomerular basement membrane, have been reported to be mainly responsible for filter's selectivity. We previously described that podocytes express Rab3A, a GTPase restricted to cell types that are capable of highly regulated exocytosis, such as neuronal cells. Here, we first demonstrate by a proteomic study that Rab3A in podocytes coimmmunoprecipitates with molecules once thought to be synapse specific. We then show that podocytes possess structures resembling synaptic vesicles, which contain glutamate, coexpress Rab3A and synaptotagmin 1, and undergo spontaneous and stimulated exocytosis and recycling, with glutamate release. Finally, from the results of a cDNA microarray study, we describe the presence of a series of neuron- and synapse-specific molecules in normal human glomeruli and confirm the glomerular protein expression of both metabotropic and ionotropic glutamate receptors. These data point toward a synaptic-like mechanism of communication among glomerular cells, which perfectly fits with the molecular composition of the glomerular filter and puts in perspective several previous observations, proposing a different working hypothesis for understanding glomerular signaling dynamics.
- Published
- 2006
12. A novel model of in vitro osteocytogenesis
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Mattinzoli⁎, D., primary, Messa, P., additional, Corbelli, A., additional, Ikehata, M., additional, Zennaro, C., additional, Armelloni, S., additional, Li, M., additional, Giardino, L., additional, and Rastaldi, M.P., additional
- Published
- 2012
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13. High binding of immunoglobulin M kappa rheumatoid factor from type II cryoglobulins to cellular fibronectin: a mechanism for induction of in situ immune complex glomerulonephritis?
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Fornasieri, A, Armelloni, S, Bernasconi, P, Li, M, de Septis, C, Sinico, R, D'Amico, G, D'Amico, G., SINICO, RENATO ALBERTO, Fornasieri, A, Armelloni, S, Bernasconi, P, Li, M, de Septis, C, Sinico, R, D'Amico, G, D'Amico, G., and SINICO, RENATO ALBERTO
- Abstract
In our previous experimental work we suggested that the frequent nephritogenicity of type II cryoglobulins could depend on a particular affinity of the immunoglobulin (Ig) M kappa rheumatoid factor (RF) component for mesangial matrix. Since cellular fibronectin (cFN) in the human kidney is mainly represented in glomerular mesangium, we studied the binding capacity to cFN of IgM kappa RFs from type II cryoglobulins compared with other different monoclonal and polyclonal IgM and IgM RFs. We purified 13 IGM kappa from human IgM kappa/IgG cryoglobulins, eight monoclonal IgM from patients with Waldenström's macroglobulinemia, nine polyclonal IgM from normal donors, and eight polyclonal IgM RFs from patients with rheumatoid arthritis. Purified IgM were used at the same concentration in enzyme-linked immunosorbent assay (ELISA) on cFN-coated plates. All the cryoglobulin IgM showed high specific binding to cFN while IgM from Waldenström's macroglobulinemia, normal IgM, and polyclonal IgM RFs had low or absent binding. These data were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cFN followed by Western blot analysis with purified IgM. The IgM kappa binding to cFN persisted using IgM kappa monomers, and was inhibited by cFN but not by plasma FN in a specific inhibition test. Further enzyme-linked immunosorbent assay studies showed that cryoglobulin IgM kappa RFs are still able to bind IgG in a dose-dependent manner once linked to solid-phase cFN. The data suggest that the affinity of cryoglobulin IgM kappa RFs for immobilized cFN could be involved in the particular high nephritogenicity of type II cryoglobulins and might lead to in situ immune complex formation.
- Published
- 1996
14. Electron microscopy study of genesis and dynamics of immunodeposition in IgMk-IgG cryoglobulin-induced glomerulonephritis in mice
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Fornasieri, A, primary, Tazzari, S, additional, Li, M, additional, Armelloni, S, additional, Tarelli, LT, additional, Sessa, A, additional, and D'Amico, G, additional
- Published
- 1998
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15. Characterization of nephropathy induced by immunization with high molecular weight dextran
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Pasi, A., primary, Dendorfer, U., additional, Holthofer, H., additional, Nelson, P., additional, Tazzari, S., additional, Armelloni, S., additional, Fornasieri, A., additional, D'Amico, G., additional, and Schlondorff, D., additional
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- 1997
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16. Interference of cephalosporins with immune response: Effects of cefonicid on human T-helper cells
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Villa, M.L., primary, Armelloni, S., additional, Ferrario, E., additional, Ottaviani, F., additional, and Clerici, M., additional
- Published
- 1991
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17. Podocytes: recent biomolecular developments
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Armelloni Silvia, Corbelli Alessandro, Giardino Laura, Li Min, Ikehata Masami, Mattinzoli Deborah, Messa Piergiorgio, Pignatari Chiara, Watanabe Shojiro, and Rastaldi Maria Pia
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actin cytoskeleton ,foot processes ,nephrin ,podocyte ,proteinuria ,slit diaphragm ,Biology (General) ,QH301-705.5 - Abstract
Podocytes are postmitotic renal glomerular cells with multiple ramifications that extend from the cell body. Processes departing from a podocyte interdigitate with corresponding projections from neighboring cells and form an intricate web that enwraps the glomerular capillary completely. Podocyte processes are interconnected by the slit diaphragm, an adhesion junction mostly formed by Ig-like molecules, cadherins/protocadherins, ephrin/eph, and neurexin molecules organized in an assembly that resembles synaptic junctions. Podocyte failure is primarily or secondarily implicated in all forms of proteinuric glomerular diseases, as confirmed by the morphological changes of their elaborate cell architecture detectable by electron microscopy. Importantly, mutations of podocyte proteins are responsible for the most severe forms of congenital nephrotic syndrome. In the last 15 years, progressive technological advances have aided the study of podocyte biology and pathology, confirming the relevance of podocyte molecules and signaling pathways for the function of the glomerular filter. This review will examine the most important and newest discoveries in the field, which is rapidly evolving, hopefully leading to a detailed knowledge of this fascinating cell and to the development of specific therapeutic options for proteinuric diseases.
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- 2014
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18. Podocytes possess Rab3A and Rabphilin-3A, synaptic proteins required for regulated processes of exocytosis and endocytosis
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Rastaldi, Mp, Armelloni, S., Li, M., Silvia Berra, Pesaresi, M., Colasanti, G., and D Amico, G.
19. [The renal biopsy in the post-genomic era.]
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Mattinzoli, D., Giardino, L. A., Corbelli, A., Armelloni, S., Li, M., Silvia Berra, and Rastaldi, M. P.
20. The renal biopsy in the post-genomic era,L'approccio alla biopsia renale e le nuove possibilita' diagnostiche: cosa cambia nell'era postgenomica
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Mattinzoli, D., Giardino, L. A., Corbelli, A., Armelloni, S., Li, M., Silvia Berra, and Rastaldi, M. P.
21. Glomerular oxidative damage and podocyte alterations in type 2 diabetic nephropathy
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Rastaldi, M., Calvetta, A., Calvaresi, N., Armelloni, S., Li, M., Silvia Berra, Corbelli, A., Mariani, G., Corneglia, L., Garibotto, G., Bertani, T., Fornasieri, A., Ferrario, F., Tonolo, G., Nosadini, R., Holthofer, H., and D Amico, G.
22. Podocytes: genetics and biology,Biologia e genetica del podocita
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Zennaro, C., Armelloni, S., Li, M., Watanabe, S., Pignatari, C., MASAMI IKEHATA, Giardino, L., Mattinzoli, D., Corbelli, A., and Rastaldi, M. P.
23. Graphene quantum dots: From efficient preparation to safe renal excretion
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Tatiana Da Ros, Carlo Alfieri, Piergiorgio Messa, Silvia Armelloni, Francesco Cellesi, Deborah Mattinzoli, Jose M. González-Domínguez, Belén Ballesteros, Adrian Ostric, Masami Ikehata, Akcan Istif, Caroline Hadad, Ministerio de Economía, Industria y Competitividad (España), European Commission, Ministero dell'Istruzione, dell'Università e della Ricerca, Università degli studi di Trieste, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), González Domínguez, José Miguel [0000-0002-0701-7695], Armelloni, Silvia [0000-0001-6431-2642], Ikehata, Masami [0000-0001-9835-9991], Istif, Akcan [0000-0001-6245-8998], Cellesi, Francesco [0000-0001-6106-9317], Alfieri, Carlo Maria [0000-0003-3860-5219], Messa, Piergiorgio [0000-0002-1512-559X], Ballesteros, Belén [0000-0002-1958-8911], Da Ros, Tatiana [0000-0003-1932-1560], Hadad, C., Gonzalez-Dominguez, J. M., Armelloni, S., Mattinzoli, D., Ikehata, M., Istif, A., Ostric, A., Cellesi, F., Alfieri, C. M., Messa, P., Ballesteros, B., Da Ros, T., González Domínguez, José Miguel, Armelloni, Silvia, Ikehata, Masami, Istif, Akcan, Cellesi, Francesco, Alfieri, Carlo Maria, Messa, Piergiorgio, Ballesteros, Belén, and Da Ros, Tatiana
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Biodistribution ,podocyte ,Biocompatibility ,graphene quantum dot ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,law.invention ,Uptake pathway ,biodistribution ,graphene quantum dots ,nanocarrier ,podocytes ,renal clearance ,uptake pathway ,law ,General Materials Science ,Electrical and Electronic Engineering ,Chemistry ,Graphene ,Graphene quantum dots ,Podocytes ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Ultrafiltration (renal) ,Quantum dot ,Renal physiology ,Nanocarrier ,Nanocarriers ,0210 nano-technology ,Renal clearance ,Clearance - Abstract
7 figures.-- Supplementary material available on line (6 figures).-- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder., Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation., J. M. G.-D. acknowledges Spanish Ministry of Science, Innovation and Universities for his Juan de la Cierva Incorporación research contract (No. IJCI-2016-27789). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No. 734834 (INFUSION) and No. 734381 (CARBO-IMmap), and from MIUR. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (No. SEV-2017-0706)., Funding note : Open Access funding provided by Università degli Studi di Trieste within the CRUICARE Agreement.
- Published
- 2021
24. Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans.
- Author
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Rastaldi MP, Candiano G, Musante L, Bruschi M, Armelloni S, Rimoldi L, Tardanico R, Cherchi SS, Ferrario F, Montinaro V, Haupt R, Parodi S, Carnevali ML, Allegri L, Camussi G, Gesualdo L, Scolari F, and Ghiggeri GM
- Published
- 2006
- Full Text
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25. Application of Retinoic Acid to Obtain Osteocytes Cultures from Primary Mouse Osteoblasts
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Laura Giardino, Alessandro Corbelli, Piergiorgio Messa, Anna Mondini, Maria Pia Rastaldi, Silvia Armelloni, Cristina Zennaro, Min Li, Deborah Mattinzoli, Masami Ikehata, Mattinzoli, D, Messa, P, Corbelli, A, Ikehata, M, Mondini, A, Zennaro, Cristina, Armelloni, S, Li, M, Giardino, L, and Rastaldi, M. P.
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Pathology ,medicine.medical_specialty ,Cellular differentiation ,General Chemical Engineering ,Cell ,Population ,Retinoic acid ,Cell Culture Techniques ,Primary Osteoblast ,Mice, Transgenic ,Tretinoin ,Biology ,Osteocytes ,General Biochemistry, Genetics and Molecular Biology ,Extracellular matrix ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,education ,Bone ,education.field_of_study ,Osteoblasts ,General Immunology and Microbiology ,General Neuroscience ,Osteoblast ,Cell Differentiatin ,Cell biology ,Culture Media ,Cellular Biology ,medicine.anatomical_structure ,chemistry ,Cell culture ,Osteocyte - Abstract
The need for osteocyte cultures is well known to the community of bone researchers; isolation of primary osteocytes is difficult and produces low cell numbers. Therefore, the most widely used cellular system is the osteocyte-like MLO-Y4 cell line. The method here described refers to the use of retinoic acid to generate a homogeneous population of ramified cells with morphological and molecular osteocyte features. After isolation of osteoblasts from mouse calvaria, all-trans retinoic acid (ATRA) is added to cell medium, and cell monitoring is conducted daily under an inverted microscope. First morphological changes are detectable after 2 days of treatment and differentiation is generally complete in 5 days, with progressive development of dendrites, loss of the ability to produce extracellular matrix, down-regulation of osteoblast markers and up-regulation of osteocyte-specific molecules. Daily cell monitoring is needed because of the inherent variability of primary cells, and the protocol can be adapted with minimal variation to cells obtained from different mouse strains and applied to transgenic models. The method is easy to perform and does not require special instrumentation, it is highly reproducible, and rapidly generates a mature osteocyte population in complete absence of extracellular matrix, allowing the use of these cells for unlimited biological applications.
- Published
- 2014
26. Albuminuria and glomerular damage in mice lacking the metabotropic glutamate receptor 1
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Pia Irene Anna Rossi, Min Li, Valerio Conti, Roberto Ravazzolo, Maria Grazia Calevo, Masami Ikehata, Cristina Zennaro, Aldamaria Puliti, Gianluca Caridi, Michela Cassanello, Silvia Armelloni, Carlotta Maria Vaccari, Laura Emionite, Maria Pia Rastaldi, Alessandro Corbelli, Puliti, 1, Rossi, Pi, Caridi, G, Corbelli, A, Ikehata, M, Armelloni, S, Li, M, Zennaro, Cristina, Conti, V, Vaccari, Cm, Cassanello, M, Calevo, Mg, Emionite, L, Ravazzolo, R, and Rastaldi, Mp
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medicine.medical_specialty ,Kidney Cortex ,Blotting, Western ,Kidney Glomerulus ,Fluorescent Antibody Technique ,metabotropic receptor 1 ,nephrin ,albuminuria ,podocytes ,Receptors, Metabotropic Glutamate ,Transfection ,Pathology and Forensic Medicine ,Podocyte ,Nephrin ,Mice ,Internal medicine ,medicine ,Albuminuria ,Animals ,Humans ,Gene Silencing ,Cells, Cultured ,biology ,Podocytes ,Reverse Transcriptase Polymerase Chain Reaction ,Glutamate receptor ,Regular Article ,medicine.anatomical_structure ,Endocrinology ,Metabotropic receptor ,Phenotype ,Gene Expression Regulation ,Metabotropic glutamate receptor ,Doxorubicin ,biology.protein ,Glomerular Filtration Barrier ,Metabotropic glutamate receptor 1 ,Kidney Diseases ,Signal transduction - Abstract
The metabotropic glutamate (mGlu) receptor 1 (GRM1) has been shown to play an important role in neuronal cells by triggering, through calcium release from intracellular stores, various signaling pathways that finally modulate neuron excitability, synaptic plasticity, and mechanisms of feedback regulation of neurotransmitter release. Herein, we show that Grm1 is expressed in glomerular podocytes and that a glomerular phenotype is exhibited by Grm1(crv4) mice carrying a spontaneous recessive inactivating mutation of the gene. Homozygous Grm1(crv4/crv4) and, to a lesser extent, heterozygous mice show albuminuria, podocyte foot process effacement, and reduced levels of nephrin and other proteins known to contribute to the maintenance of podocyte cell structure. Overall, the present data extend the role of mGlu1 receptor to the glomerular filtration barrier. The regulatory action of mGlu1 receptor in dendritic spine morphology and in the control of glutamate release is well acknowledged in neuronal cells. Analogously, we speculate that mGlu1 receptor may regulate foot process morphology and intercellular signaling in the podocyte.
- Published
- 2009
27. Podocyte glutamatergic signaling contributes to the function of the glomerular filtration barrier
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Piergiorgio Messa, Alessandro Corbelli, Maria Pia Rastaldi, Silvia Armelloni, Deborah Mattinzoli, Fabien Tourrel, Michele Carraro, Min Li, Dominique Guerrot, Silvia Berra, Laura Giardino, Cristina Zennaro, Masami Ikehata, Giardino, L, Armelloni, S, Corbelli, A, Mattinzoli, D, Zennaro, Cristina, Guerrot, D, Tourrel, F, Ikehata, M, Li, M, Berra, S, Carraro, Michele, Messa, P, and Rastaldi, Mp
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Male ,medicine.medical_specialty ,glutamatergic signaling ,Glutamic Acid ,Biology ,Receptors, N-Methyl-D-Aspartate ,Exocytosis ,Podocyte ,Rats, Sprague-Dawley ,Nephrin ,Mice ,Glutamatergic ,Internal medicine ,medicine ,Animals ,podocytes, glomerular filtration barrier,glutamatergic signaling ,Cells, Cultured ,Cytoskeleton ,Mice, Knockout ,Mice, Inbred BALB C ,Glutamate receptor ,Membrane Proteins ,General Medicine ,Rab3A GTP-Binding Protein ,Actin cytoskeleton ,rab3A GTP-Binding Protein ,Rats ,Basic Research ,medicine.anatomical_structure ,Endocrinology ,podocytes ,Nephrology ,glomerular filtration barrier ,Glomerular Filtration Barrier ,biology.protein ,NMDA receptor ,Female ,Ketamine ,Kidney Diseases ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists ,Glomerular Filtration Rate ,Signal Transduction - Abstract
Podocytes possess the complete machinery for glutamatergic signaling, raising the possibility that neuron-like signaling contributes to glomerular function. To test this, we studied mice and cells lacking Rab3A, a small GTPase that regulates glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-d-aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of Rab3A and blockade of NMDAR both associated with an increased urinary albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A-null podocytes displayed a dysregulated release of glutamate with higher rates of spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism led to profound cytoskeletal remodeling and redistribution of nephrin in cultured podocytes; the addition of the agonist NMDA reversed these changes. In summary, these results suggest that glutamatergic signaling driven by podocytes contributes to the integrity of the glomerular filtration barrier and that derangements in this signaling may lead to proteinuric renal diseases.
- Published
- 2009
28. Glomerular podocytes contain neuron-like functional synaptic vesicles
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Maria Pia Rastaldi, Silvia Armelloni, Silvia Berra, Novella Calvaresi, Alessandro Corbelli, Laura Anna Giardino, Min Li, Guo Quin Wang, Alessandro Fornasieri, Antonello Villa, Eija Heikkila, Rabah Soliymani, Anissa Boucherot, Clemens David Cohen, Matthias Kretzler, Almut Nitsche, Maddalena Ripamonti, Antonio Malgaroli, Marzia Pesaresi, Gian Luigi Forloni, Detlef Schlöndorff, Harry Holthofer, Giuseppe D'Amico, Rastaldi, M, Armelloni, S, Berra, S, Calvaresi, N, Corbelli, A, Giardino, L, Li, M, Wang, G, Fornasieri, A, Villa, A, Heikkila, E, Soliymani, R, Boucherot, A, Cohen, C, Kretzler, M, Nitsche, A, Ripamonti, M, Malgaroli, A, Pesaresi, M, Forloni, G, Schlöndorff, D, Holthofer, H, D'Amico, G, Rastaldi, Mp, Giardino, La, Wang, Gq, Cohen, Cd, Malgaroli, Antonio, Forloni, Gl, and D'Amico, G.
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Synaptic Vesicle ,Glutamic Acid ,Spider Venoms ,Biology ,Biochemistry ,Synaptic vesicle ,Synaptotagmin 1 ,Exocytosis ,Exocytosi ,Synapse ,Mice ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Cells, Cultured ,Endocytosi ,Animal ,Podocytes ,Glomerular basement membrane ,Gene Expression Profiling ,Synaptotagmin I ,Rab3A GTP-Binding Protein ,Endocytosis ,rab3A GTP-Binding Protein ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Glomerular Filtration Barrier ,Synaptic Vesicles ,Spider Venom ,Human ,Biotechnology - Abstract
Although patients with chronic renal failure are increasing worldwide, many aspects of kidney biology remain to be elucidated. Recent research has uncovered several molecular properties of the glomerular filtration barrier, in which podocytes, highly differentiated, ramified cells that enwrap the glomerular basement membrane, have been reported to be mainly responsible for filter's selectivity. We previously described that podocytes express Rab3A, a GTPase restricted to cell types that are capable of highly regulated exocytosis, such as neuronal cells. Here, we first demonstrate by a proteomic study that Rab3A in podocytes coimmmunoprecipitates with molecules once thought to be synapse specific. We then show that podocytes possess structures resembling synaptic vesicles, which contain glutamate, coexpress Rab3A and synaptotagmin 1, and undergo spontaneous and stimulated exocytosis and recycling, with glutamate release. Finally, from the results of a cDNA microarray study, we describe the presence of a series of neuron- and synapse-specific molecules in normal human glomeruli and confirm the glomerular protein expression of both metabotropic and ionotropic glutamate receptors. These data point toward a synaptic-like mechanism of communication among glomerular cells, which perfectly fits with the molecular composition of the glomerular filter and puts in perspective several previous observations, proposing a different working hypothesis for understanding glomerular signaling dynamics.
- Published
- 2006
29. Podocyte Developmental Defects Caused by Adriamycin in Zebrafish Embryos and Larvae: A Novel Model of Glomerular Damage
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Piergiorgio Messa, Massimo Mariotti, Sara Pasqualetti, Masami Ikehata, Silvia Armelloni, Michele Carraro, Mary Artero, Cristina Zennaro, Maria Pia Rastaldi, Milan Clai, Alessandro Corbelli, Min Li, G. Boscutti, Zennaro, Cristina, Mariotti, M, Carraro, Michele, Pasqualetti, S, Corbelli, A, Armelloni, S, Li, M, Ikehata, M, Clai, M, Artero, M, Messa, P, Boscutti, G, and Rastaldi, Mp
- Subjects
Glomerulu ,medicine.medical_specialty ,Nephrotic Syndrome ,Kidney Glomerulus ,lcsh:Medicine ,Embryonic Development ,Podocyte ,Permeability ,Nephrin ,Adriamycin ,In vivo ,Internal medicine ,Chronic Kidney Disease ,Medicine and Health Sciences ,medicine ,Animals ,lcsh:Science ,Zebrafish ,Basement membrane ,Multidisciplinary ,Dose-Response Relationship, Drug ,Heart development ,biology ,Podocytes ,Pediatric Nephrology ,lcsh:R ,Biology and Life Sciences ,Heart ,Developmental Nephrology ,biology.organism_classification ,Cell biology ,Pronephros ,Endocrinology ,medicine.anatomical_structure ,Doxorubicin ,Nephrology ,Larva ,Embryogenesis ,Toxicity ,Glomerulus ,biology.protein ,lcsh:Q ,Research Article ,Developmental Biology - Abstract
The zebrafish pronephros is gaining popularity in the nephrology community, because embryos are easy to cultivate in multiwell plates, allowing large number of experiments to be conducted in an in vivo model. In a few days, glomeruli reach complete development, with a structure that is similar to that of the mammalian counterpart, showing a fenestrated endothelium and a basement membrane covered by the multiple ramifications of mature podocytes. As a further advantage, zebrafish embryos are permeable to low molecular compounds, and this explains their extensive use in drug efficacy and toxicity experiments. Here we show that low concentrations of adriamycin (i.e. 10 and 20 µM), when dissolved in the medium of zebrafish embryos at 9 hours post-fertilization and removed after 48 hours (57 hpf), alter the development of podocytes with subsequent functional impairment, demonstrated by onset of pericardial edema and reduction of expression of the podocyte proteins nephrin and wt1. Podocyte damage is morphologically confirmed by electron microscopy and functionally supported by increased clearance of microinjected 70 kDa fluorescent dextran. Importantly, besides pericardial edema and glomerular damage, which persist and worsen after adriamycin removal from the medium, larvae exposed to adriamycin 10 and 20 µM do not show any myocardiocyte alterations nor vascular changes. The only extra-renal effect is a transient delay of cartilage formation that rapidly recovers once adriamycin is removed. In summary, this low dose adriamycin model can be applied to analyze podocyte developmental defects, such as those observed in congenital nephrotic syndrome, and can be taken in consideration for pharmacological studies of severe early podocyte injury.
- Published
- 2014
30. High binding of immunoglobulin M kappa rheumatoid factor from type II cryoglobulins to cellular fibronectin: a mechanism for induction of in situ immune complex glomerulonephritis?
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Min Li, Cristina Pinerolo de Septis, Giuseppe D'Amico, A Fornasieri, Silvia Armelloni, Renato Alberto Sinico, Paola Bernasconi, Fornasieri, A, Armelloni, S, Bernasconi, P, Li, M, de Septis, C, Sinico, R, and D'Amico, G
- Subjects
Male ,Immunoglobulin kappa-Chain ,Blotting, Western ,Enzyme-Linked Immunosorbent Assay ,Immune complex formation ,Cryoglobulins ,Immunoglobulin G ,Statistics, Nonparametric ,Immunoglobulin kappa-Chains ,Glomerulonephritis ,Rheumatoid Factor ,Medicine ,Rheumatoid factor ,Humans ,Immune Complex Diseases ,Glomerulonephriti ,Autoantibodies ,biology ,business.industry ,Cryoglobulin ,medicine.disease ,Autoantibodie ,Molecular biology ,Cryoglobulinemia ,Immunoglobulin M ,Nephrology ,Polyclonal antibodies ,Immune Complex Disease ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Female ,Binding Sites, Antibody ,Waldenstrom Macroglobulinemia ,business ,Immune complex disease ,Human - Abstract
In our previous experimental work we suggested that the frequent nephritogenicity of type II cryoglobulins could depend on a particular affinity of the immunoglobulin (Ig) M kappa rheumatoid factor (RF) component for mesangial matrix. Since cellular fibronectin (cFN) in the human kidney is mainly represented in glomerular mesangium, we studied the binding capacity to cFN of IgM kappa RFs from type II cryoglobulins compared with other different monoclonal and polyclonal IgM and IgM RFs. We purified 13 IGM kappa from human IgM kappa/IgG cryoglobulins, eight monoclonal IgM from patients with Waldenström's macroglobulinemia, nine polyclonal IgM from normal donors, and eight polyclonal IgM RFs from patients with rheumatoid arthritis. Purified IgM were used at the same concentration in enzyme-linked immunosorbent assay (ELISA) on cFN-coated plates. All the cryoglobulin IgM showed high specific binding to cFN while IgM from Waldenström's macroglobulinemia, normal IgM, and polyclonal IgM RFs had low or absent binding. These data were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cFN followed by Western blot analysis with purified IgM. The IgM kappa binding to cFN persisted using IgM kappa monomers, and was inhibited by cFN but not by plasma FN in a specific inhibition test. Further enzyme-linked immunosorbent assay studies showed that cryoglobulin IgM kappa RFs are still able to bind IgG in a dose-dependent manner once linked to solid-phase cFN. The data suggest that the affinity of cryoglobulin IgM kappa RFs for immobilized cFN could be involved in the particular high nephritogenicity of type II cryoglobulins and might lead to in situ immune complex formation.
- Published
- 1996
31. Glomerulonephritis induced by human IgMK-IgG cryoglobulins in mice
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Fornasieri, A., Li, M., Silvia Armelloni, Septis, C. P., Schiaffino, E., Sinico, R. A., Schmid, C., D Amico, G., Fornasieri, A, Li, M, Armelloni, S, de Septis, C, Schiaffino, E, Sinico, R, Schmid, C, and D'Amico, G
- Subjects
Male ,Immunoglobulin kappa-Chain ,Time Factors ,Fluorescent Antibody Technique ,Enzyme-Linked Immunosorbent Assay ,Injections, Intravenou ,Antigen-Antibody Complex ,Immunoglobulin kappa-Chains ,Mice ,Glomerulonephritis ,Rheumatoid Factor ,Animals ,Humans ,Isoelectric Point ,Glomerulonephriti ,Cryoglobulins ,Aged ,Aged, 80 and over ,Mice, Inbred BALB C ,Animal ,Temperature ,Cryoglobulin ,Middle Aged ,Glomerular Mesangium ,Disease Models, Animal ,Proteinuria ,Immunoglobulin M ,Immunoglobulin G ,Injections, Intravenous ,Female ,Human ,Chromatography, Liquid - Abstract
BACKGROUND: Human cryoglobulinemia is sometimes associated with glomerulonephritis (GN) due to deposition of cryoglobulins (cryos). To see whether human cryos can induce GN in mice and to study time-related changes of glomerular lesions and possible factors of cryos' nephritogenicity, we developed an experimental passive model of cryoglobulinemic GN. EXPERIMENTAL DESIGN: Two cryos IgMk-IgG from 2 patients with active GN (OLD and SOR), 2 cryos IgMk-IgG (TAC and GRO) and 1 IgMλ (CHI) from 3 patients without GN were purified, solubilized at 37° C and injected intravenously into BALB/c mice, 4 mg, twice a day. To study the possible factors of cryo nephritogenicity, we analyzed: (a) the presence, amount, and size of complexed IgMk-IgG at 37° C by fast flow liquid chromatography; (b) the Cc1 or Lc1 subclass of rheumatoid factors; (c) the isoelectric points of the IgMks; (d) The proportion of IgG subclasses in cryos. RESULTS: On day 1 from the beginning of intravenous injections, cryos OLD had induced mesangial deposits of human IgM, human IgG, mouse C3 and mesangial hypercellularity. On day 2, phagocytizing cells were found along with massive endoluminal and subendothelial deposits of IgM, IgG, and C3. On day 6, perivascular infiltrates of mononuclear cells were also seen. Cryos SOR induced a similar but milder form of GN. After administration of purified OLD IgMk, OLD IgG, GRO IgMk or GRO IgG, only OLD IgMk was deposited in the mesangium. Analysis of all the cryos revealed that: the amount of complexed IgMk-IgG at 37° C was always less than 1% of cryos; Cc1 and Lc1 idiotypes were not related to the nephritogenicity of cryos, the isoelectric points of IgMks were 4.5 to 5.5 and IgG1 was the prevalent subclass. CONCLUSIONS: Data demonstrate that human cryos from patients with GN can induce GN in mice that resembles the corresponding human pathology. The affinity of IgMk for glomeruli and the unexpectedly small amounts of IgMk-IgG complexes at 37° C suggest that there is a role of in situ binding in nephritogenicity which is independent of the isoelectric point, rheumatoid factor idiotype, or IgG subclass
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- 1993
32. A novel model of in vitro osteocytogenesis
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⁎, D., Messa, P., Corbelli, A., Ikehata, M., Zennaro, C., Armelloni, S., Li, M., Giardino, L., and Rastaldi, M.P.
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- 2012
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33. Novel model of in vitro osteocytogenesis induced by retinoic acid treatment
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Min Li, Alessandro Corbelli, Cristina Zennaro, Piergiorgio Messa, Laura Giardino, Silvia Armelloni, Deborah Mattinzoli, Masami Ikehata, M.P. Rastaldi, Mattinzoli, D, Messa, P, Corbelli, A, Ikehata, M, Zennaro, Cristina, Armelloni, S, Li, M, Giardino, L, and Rastaldi, Mp
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lcsh:Diseases of the musculoskeletal system ,Population ,lcsh:Surgery ,Retinoic acid ,Tretinoin ,sclerostin ,Matrix (biology) ,Models, Biological ,Osteocytes ,Cell Line ,Extracellular matrix ,chemistry.chemical_compound ,Mice ,Osteogenesis ,Sclerotonin ,medicine ,Animals ,Osteoblasts ,Osteocyte ,Melatonin ,education ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Glycoproteins ,education.field_of_study ,Extracellular Matrix Proteins ,Osteoblast ,lcsh:RD1-811 ,Cell biology ,Up-Regulation ,medicine.anatomical_structure ,chemistry ,Cell culture ,osteoblast ,Sclerostin ,Intercellular Signaling Peptides and Proteins ,lcsh:RC925-935 - Abstract
Despite recent research which more and more stresses the importance of osteocytes in regulating bone and systemic mineral metabolism, current molecular and functional knowledge of osteocyte properties are still incomplete, mostly due to limited availability of in vitro models. Osteocytes are terminally differentiated dendritic cells, and therefore are not easy to obtain and maintain in primary cultures. As an alternative, osteocyte differentiation can be induced by progressive osteoblast embedding in mineralised extracellular matrix. In this model, which is suitable for reproduction of bone development, the presence of calcified matrix prevents several cell biological methods from being used. Therefore, the osteocyte-like MLO-Y4 cell line continues to be the most widely used cellular system. Here we show that treatment of primary osteoblasts or MC3T3-E1 cells with retinoic acid generates a homogeneous population of ramified cells with osteocyte features, as confirmed by morphological and molecular analyses. The first morphological changes are detectable in primary cells after 2 days of treatment, and in the cell line after 4 days of treatment. Differentiation is complete in 5 and 10 days, respectively, with progressive development of dendrites, loss of the ability to produce extracellular matrix, down-regulation of osteoblast markers, and up-regulation of osteocyte-specific molecules, most notably among them sclerostin. Compared to other published protocols, our method has a number of advantages. It is easy to perform and does not require special instrumentation, it is highly reproducible, and rapidly generates a mature osteocyte population in the complete absence of extracellular matrix, allowing the use of these cells for unlimited biological applications.
34. Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients.
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Molinari P, Caldiroli L, Abinti M, Nardelli L, Armelloni S, Cesari M, Castellano G, and Vettoretti S
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- Humans, Male, Female, Aged, Cross-Sectional Studies, Aged, 80 and over, Frail Elderly, Cytokines blood, Glomerular Filtration Rate, Geriatric Assessment methods, Interleukin-6 blood, Syndrome, Chemokine CCL2 blood, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic blood, Malnutrition blood, Frailty blood, Frailty complications, Inflammation blood
- Abstract
Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m
2 ; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 ( p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.- Published
- 2024
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35. Clinical Factors and Biomarkers Associated with Depressive Disorders in Older Patients Affected by Chronic Kidney Disease (CKD): Does the Advanced Glycation End Products (AGEs)/RAGE (Receptor for AGEs) System Play Any Role?
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Buoli M, Dozio E, Caldiroli L, Armelloni S, Vianello E, Corsi Romanelli M, Castellano G, and Vettoretti S
- Abstract
Depressive disorders are highly prevalent among subjects suffering from chronic kidney disease (CKD). The aim of the present study is to evaluate clinical and biochemical factors associated with depressive disorders in a sample of older CKD patients, with a focus on advanced glycation end products (AGEs) and their soluble receptors (sRAGEs). A total of 115 older subjects affected by CKD (stages 3 to 5, not in dialysis) were selected for this study. These patients were divided into two groups according to the presence of depressive disorders defined by a score ≥ 10 on the 30-item Geriatric Depression Scale (GDS). The two groups were compared by independent sample t tests for continuous variables and χ
2 tests for qualitative ones. Significant variables at univariate analyses were then inserted as predictors of a binary logistic regression model, with the presence or absence of depressive disorders as a dependent variable. The binary logistic regression model showed that patients with concomitant depressive disorders were more frequently of female gender ( p < 0.01) and had lower MCP1 ( p < 0.01) and AGE circulating levels ( p < 0.01) than their counterparts. Depressive disorders in older CKD patients are more prevalent in women and seem to be inversely associated with systemic inflammation and circulating AGEs.- Published
- 2024
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36. Associations of Intact and C-Terminal FGF23 with Inflammatory Markers in Older Patients Affected by Advanced Chronic Kidney Disease.
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Abinti M, Vettoretti S, Caldiroli L, Mattinzoli D, Ikehata M, Armelloni S, Molinari P, Alfieri CM, Castellano G, and Messa P
- Abstract
Background : In patients with chronic kidney disease (CKD), Fibroblast Growth Factor 23 (FGF23) is markedly increased and has been proposed to interact with systemic inflammation. Methods : In this cross-sectional study, we evaluated the correlations of intact FGF23, c-terminal FGF23, and the FGF23 ratio (c-terminal to intact) with some inflammatory cytokines in 111 elderly patients with advanced CKD not yet in dialysis. Results : Estimated glomerular filtration rate (eGFR) was inversely correlated with intact FGF23 and c-terminal FGF23, as well as with interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP-1). Intact FGF23 levels were directly correlated with IL-6 (r = 0.403; p < 0.001) and TNFα (r = 0.401; p < 0.001) while c-terminal FGF23 was directly correlated with MCP-1 (r = 0.264; p = 0.005). The FGF23 ratio was, instead, inversely correlated with IL-6 (r = -0.326; p < 0.001). Multivariate analysis revealed that intact FGF23 was directly associated with TNFα [B = 0.012 (95% CI 0.006, 0.019); p = 0.003] and c-terminal FGF23 was directly associated with MCP-1 [B = 0.001 (95% CI 0.000, 0.002); p = 0.038], while the FGF23 ratio was inversely correlated with IL-6 [B = -0.028 (95% CI -0.047, -0.010); p = 0.002]. Conclusions : Our data demonstrate that, in CKD patients, intact FGF23 and the metabolites deriving from its proteolytic cleavage are differently associated with some inflammatory pathways. In particular, intact FGF23 is mainly associated with IL-6 and TNFα, c-terminal FGF23 with MCP-1, and the FGF23 ratio with IL6.
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- 2024
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37. Spontaneous low-protein intake in older CKD patients: one diet may not fit all.
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Vettoretti S, Molinari P, Armelloni S, Castellano G, and Caldiroli L
- Abstract
Competing Interests: SV served as consultant at advisory boards for Merk Sharp & Dohme and held a sponsorized lecture by Shär. LC worked as a consultant for Shär. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2024
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38. Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation.
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Li M, Armelloni S, Mattinzoli D, Ikehata M, Chatziantoniou C, Alfieri C, Molinari P, Chadjichristos CE, Malvica S, and Castellano G
- Abstract
The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.
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- 2024
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39. Update on current and potential application of extracellular vesicles in kidney transplantation.
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Abinti M, Favi E, Alfieri CM, Zanoni F, Armelloni S, Ferraresso M, Cantaluppi V, and Castellano G
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- Humans, Kidney, Graft Rejection diagnosis, Graft Rejection etiology, Graft Rejection prevention & control, Kidney Transplantation adverse effects, Kidney Failure, Chronic surgery, Extracellular Vesicles
- Abstract
Kidney transplantation (KT) is the best treatment for end-stage kidney disease. However, early diagnosis of graft injury remains challenging, mainly because of the lack of accurate and noninvasive diagnostic techniques. Improving graft outcomes is equally demanding, as is the development of innovative therapies. Many research efforts are focusing on extracellular vesicles, cellular particles free in each body fluid that have shown promising results as precise markers of damage and potential therapeutic targets in many diseases, including the renal field. In fact, through their receptors and cargo, they act in damage response and immune modulation. In transplantation, they may be used to determine organ quality and aging, the presence of delayed graft function, rejection, and many other transplant-related pathologies. Moreover, their low immunogenicity and safe profile make them ideal for drug delivery and the development of therapies to improve KT outcomes. In this review, we summarize current evidence about extracellular vesicles in KT, starting with their characteristics and major laboratory techniques for isolation and characterization. Then, we discuss their use as potential markers of damage and as therapeutic targets, discussing their promising use in clinical practice as a form of liquid biopsy., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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40. Fibroblast growth factor 23 level modulates the hepatocyte's alpha-2-HS-glycoprotein transcription through the inflammatory pathway TNFα/NFκB.
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Mattinzoli D, Li M, Castellano G, Ikehata M, Armelloni S, Elli FM, Molinari P, Tsugawa K, Alfieri CM, and Messa P
- Abstract
Introduction: High serum levels of fibroblast growth factor 23 (FGF23) characterize chronic kidney disease (CKD) since its early stages and have been suggested to contribute to inflammation and cardiovascular disease. However, the mechanisms linking FGF23 with these pathological conditions remain still incompletely defined. The alpha-2-HS-glycoprotein (AHSG), a liver-produced anti-inflammatory cytokine, is highly modulated by inflammation itself, also through the TNFα/NFκB signaling pathway. In our previous study, we found that FGF23 modulates the production of AHSG in the liver in a bimodal way, with stimulation and inhibition at moderately and highly increased FGF23 concentrations, respectively., Methods: The present study, aiming to gain further insights into this bimodal behavior, was performed in hepatocyte human cells line (HepG2), using the following methods: immunochemistry, western blot, chromatin immunoprecipitation, fluorescence in situ hybridization (FISH), qRT-PCR, and gene SANGER sequencing., Results: We found that FGF23 at 400 pg/ml activates nuclear translocation of NFκB, possibly increasing AHSG transcription. At variance, at 1,200 pg/ml, FGF23 inactivates NFκB through the activation of two specific NFκB inhibitors (IκBα and NKIRAS2) and induces its detachment from the AHSG promoter, reducing AHSG transcription., Conclusion: These results add another piece to the puzzle of FGF23 involvement in the multifold interactions between CKD, inflammation, and cardiovascular disease, suggesting the involvement of the NFκB pathway, which might represent a potential therapeutic target in CKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mattinzoli, Li, Castellano, Ikehata, Armelloni, Elli, Molinari, Tsugawa, Alfieri and Messa.)
- Published
- 2022
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41. MCP1 Could Mediate FGF23 and Omega 6/Omega 3 Correlation Inversion in CKD.
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Mattinzoli D, Turolo S, Alfieri CM, Ikehata M, Caldiroli L, Armelloni S, Montini G, Agostoni C, Messa P, Vettoretti S, and Castellano G
- Abstract
Fibroblast growth factor 23 (FGF23) concentrations rise after the early stages of chronic kidney disease (CKD). FGF23 is involved in inflammatory reactions closely associated with an incremented risk of cardiovascular disease (CVD). There is growing evidence that omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA) can modulate inflammation through several mediators producing an opposite effect on cardiovascular (CV) risks. In this study, we explore whether there is any correlation between PUFA, FGF23, and inflammation in CKD patients. We evaluated, cross-sectionally, 56 patients at different stages of CKD. Monocyte chemoattractant protein 1 (MCP1), and intact and c-terminal FGF23 (iFGF23, cFGF23) were quantified by the ELISA, and the fatty acids (FA) profile was analyzed by gas chromatography. Concurrently with an eGFR decrease (p < 0.01) and an MCP1 increase (p = 0.031), we observed an inversion of the correlation between FGF23 and the n-6/n-3 ratio. This last correlation was inversed in CKD stage 3 (r2 (−) 0.502 p = 0.029) and direct in stage 5 (r2 0.657 p = 0.020). The increase in MCP1 seems to trigger events in the inversion of the correlation between FGF23 and the n-6/n-3 PUFA ratio. This result strongly encourages future studies on basal pathways, on possible pharmacological interventions, and on managing kidney transplant patients treated with immunosuppressive therapy.
- Published
- 2022
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42. Carbon dots conjugated to SN38 for improved colorectal anticancer therapy.
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Mattinzoli D, Cacioppo M, Ikehata M, Armelloni S, Alfieri CM, Castellano G, Barilani M, Arcudi F, Messa P, and Prato M
- Abstract
Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
- Published
- 2022
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43. Possible Benefits of a Low Protein Diet in Older Patients With CKD at Risk of Malnutrition: A Pilot Randomized Controlled Trial.
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Caldiroli L, Vettoretti S, Armelloni S, Mattinzoli D, Ikehata M, Molinari P, Alfieri C, Messa P, and Castellano G
- Abstract
Background: Current guidelines do not clarify whether older patients with advanced chronic kidney disease (CKD) may benefit of low protein (LP) diet if they are at risk of malnutrition. We compared the effects of normocalorie/normoprotein (NP) and normocalorie/LP diet on nutritional status and metabolic complications related to the progression of kidney damage in these patients., Methods: This pilot study had an open-label randomized-controlled design (ClinicalTrials.gov Id: NCT05015647). Thirty-five patients were treated for 6 months with two different diets (LP = 17) and (NP = 18). Malnutrition was assessed by the Malnutrition Inflammation Score and International Society of Renal Nutrition and Metabolism criteria. Renal function was assessed by creatinine and cystatin-C-based estimated glomerular filtration rate (eGFR)., Results: At the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 vs. 6 ± 1.5, p = 0.020 and 3 ± 2.5 vs. 6 ± 2, p = 0.012), prevalence of protein energy wasting syndrome decreased only in LP. LP group had higher eGFRcys-C (17 ± 6 vs. 12 ± 4 ml/min/1.73 m
2 ; p < 0.05), lower serum urea (105 ± 65 vs. 138 ± 30 mg/dl; p < 0.05) and lower parathormone (68 ± 10 vs. 99 ± 61 ng/L; p < 0.05) than NP. Serum and urinary phosphorous did not change while fibroblast growth factor 23 (FGF23)-intact and FGF23 c-terminal increased in both groups [FGF23-intact in LP: 70 (48; 98) vs. 126 (90; 410) pg/ml, p < 0.01 and in NP: 86 (57; 194) vs. 143 (119; 186) pg/ml, p < 0.01; FGF23 c-terminal in LP: 77 (30.3; 112) vs. 111 (63; 384) RU/ml, p < 0.01 and in NP: 142 (56.6; 175) vs. 157 (76.7; 281) RU/ml, p < 0.01]., Conclusions: LP diet has a favorable impact on nutritional status as much as NP diet with possible greater benefits on the progression of kidney disease and some of its metabolic complications., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05015647, identifier: NCT05015647., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Caldiroli, Vettoretti, Armelloni, Mattinzoli, Ikehata, Molinari, Alfieri, Messa and Castellano.)- Published
- 2022
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44. Urinary mRNA Expression of Glomerular Podocyte Markers in Glomerular Disease and Renal Transplant.
- Author
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Armelloni S, Mattinzoli D, Ikehata M, Alfieri C, Belingheri M, Moroni G, Cresseri D, Passerini P, Cerutti R, and Messa P
- Abstract
The research of novel markers in urinary samples, for the description of renal damage, is of high interest, and several works demonstrated the value of urinary mRNA quantification for the search of events related to renal disease or affecting the outcome of transplant kidneys. In the present pilot study, a comparison of the urine mRNA expression of specific podocyte markers among patients who had undergone clinical indication to renal transplanted (RTx, n = 20) and native (N, n = 18) renal biopsy was performed. The aim of this work was to identify genes involved in podocytes signaling and cytoskeletal regulation ( NPHS1, NPHS2, SYNPO, WT1, TRPC6, GRM1 , and NEUROD ) in respect to glomerular pathology. We considered some genes relevant for podocytes signaling and for the function of the glomerular filter applying an alternative normalization approach. Our results demonstrate the WT1 urinary mRNA increases in both groups and it is helpful for podocyte normalization. Furthermore, an increase in the expression of TRPC6 after all kinds of normalizations was observed. According to our data, WT1 normalization might be considered an alternative approach to correct the expression of urinary mRNA. In addition, our study underlines the importance of slit diaphragm proteins involved in calcium disequilibrium, such as TRPC6.
- Published
- 2021
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45. Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress.
- Author
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Margiotta E, Caldiroli L, Callegari ML, Miragoli F, Zanoni F, Armelloni S, Rizzo V, Messa P, and Vettoretti S
- Subjects
- Aged, Bacteria, Humans, Indican, Inflammation, Interleukin-6, Malondialdehyde, Middle Aged, Oxidative Stress, Renal Dialysis, Sarcopenia metabolism, Uremia, Uremic Toxins analysis, Gastrointestinal Microbiome, Renal Insufficiency, Chronic microbiology, Sarcopenia epidemiology, Uremic Toxins metabolism
- Abstract
Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m
2 , not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera , Rothia , Veillonella , Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.- Published
- 2021
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46. Bone Effect and Safety of One-Year Denosumab Therapy in a Cohort of Renal Transplanted Patients: An Observational Monocentric Study.
- Author
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Alfieri C, Binda V, Malvica S, Cresseri D, Campise M, Gandolfo MT, Regalia A, Mattinzoli D, Armelloni S, Favi E, Molinari P, and Messa P
- Abstract
In 32-kidney transplanted patients (KTxps), the safety and the effects on BMD and mineral metabolism (MM) of one-year treatment with denosumab (DB) were studied. Femoral and vertebral BMD and T-score, FRAX score and vertebral fractures (sVF) before (T0) and after 12 months (T12) of treatment were measured. MM, renal parameters, hypocalcemic episodes (HpCa), urinary tract infections (UTI), major graft and KTxps outcomes were monitored. The cohort was composed mainly of females, n = 21. We had 29 KTxps on steroid therapy and 22 KTxps on vitamin D supplementation. At T0, 25 and 7 KTxps had femoral osteoporosis (F-OPS) and osteopenia (F-OPS), respectively. Twenty-three and six KTxps had vertebral osteoporosis (V-OPS) and osteopenia (V-OPS), respectively. Seventeen KTxps had sVF. At T12, T-score increased at femoral and vertebral sites ( p = 0.05, p = 0.008). The prevalence of F-OPS and V-OPS reduced from 78% to 69% and from 72% to 50%, respectively. Twenty-five KTxps ameliorated FRAX score and two KTxps had novel sVF. At T12, a slight reduction of Ca was present, without HpCa. Four KTxps had UTI. No graft rejections, loss of graft or deaths were reported. Our preliminary results show a good efficacy and safety of DB in KTxps. Longer and randomized studies involving more KTxps might elucidate the possible primary role of DB in the treatment of bone disorders in KTxps.
- Published
- 2021
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47. Association between the uremic toxins indoxyl-sulfate and p-cresyl-sulfate with sarcopenia and malnutrition in elderly patients with advanced chronic kidney disease.
- Author
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Caldiroli L, Armelloni S, Eskander A, Messa P, Rizzo V, Margiotta E, Cesari M, and Vettoretti S
- Subjects
- Aged, Cresols, Humans, Indican, Indoles, Sulfates, Malnutrition, Renal Insufficiency, Chronic complications, Sarcopenia
- Abstract
Background: in patients with chronic kidney disease (CKD) indoxyl sulfate (IS) and p-cresyl sulfate (PCs) may induce sarcopenia either directly or via systemic inflammation. We evaluated whether IS and PCs were associated with: sarcopenia, systemic inflammation and nutritional status., Methods: we examined cross sectionally 93 patients with advanced CKD. Sarcopenia was identified according to EWGSOP2 definition. Malnutrition was assessed by Malnutrition Inflammation Score (MIS) and Protein Energy Wasting syndrome (PEW). Inflammatory status was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, IL12p70., Results: we did not find any association of sarcopenia with IS and PCs. IS was associated with LogTNFα and LogMCP-1 in the overall cohort (r = 0.30, p = 0.0043; r = 0.22 p = 0.047) and in not sarcopenic patients (r = 0.32, p = 0.0077; r = 0.25, p = 0.041). PCs was associated with LogIL10 and LogIL12p70 in sarcopenic patients (r = 0.58, p = 0.0042; r = 0.52, p = 0.013). IS was higher in patients without PEW (p = 0.029), while PCs was higher in patients with PEW (p = 0.0040). IS and PCs were not different in patients with normal or increased MIS., Conclusions: IS and PCs were not associated with sarcopenia, although they were both associated with some inflammatory pathways. Notably, we found a positive association of PCs with PEW syndrome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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48. Assessment of increased glomerular permeability associated with recurrent focal segmental glomerulosclerosis using an in vitro model of the glomerular filtration barrier.
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Li M, Alfieri CM, Morello W, Cellesi F, Armelloni S, Mattinzoli D, Montini G, and Messa P
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- Cell Membrane Permeability, Endothelial Cells, Humans, Kidney Glomerulus, Podocytes, Glomerular Filtration Barrier pathology, Glomerulosclerosis, Focal Segmental metabolism, Glomerulosclerosis, Focal Segmental pathology
- Abstract
The presence of circulating permeability factors (cPFs) has been hypothesized to be associated with recurrence of focal segmental glomerulosclerosis (rFSGS) in renal allografts. The available methods to detect cPFs are complex, not easily repeatable and inappropriate to represent the anatomical characteristics of the three-layer glomerular filtration barrier (GFB). Here we describe a novel method which measures the permeability to bovine serum albumin (BSA) through a three-layer device (3LD). The 3 layers comprise: (1) conditionally immortalized human podocytes (HCiPodo), (2) collagen type IV coated porous membrane and (3) human glomerular endothelial cells (HCiGEnC). Using this method, we found that sera from all rFSGS patients increased albumin permeability, while sera from non recurrent (nrFSGS) and genetic (gFSGS) forms of FSGS did not. The mechanisms underlying the increase of albumin permeability are probably due to endothelial cell damage as an initial event, which was demonstrated by the decrease of Platelet endothelial cell adhesion molecule (PECAM-1 or CD31), while the podocytes' expressions of synaptopodin and podocin were normal. Furthermore, we also found that the plasmapheretic treatment (PPT) eliminated the effect of increasing BSA permeability in sera from rFSGS patients. These preliminary data suggest that our in vitro GFB model could not only be useful in predicting the recurrence of FSGS after renal transplantation (RTx), but also be a valuable in vitro model to study podocyte and endothelial cell biology.
- Published
- 2020
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49. Malnutrition and inflammation are associated with severity of depressive and cognitive symptoms of old patients affected by chronic kidney disease.
- Author
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Guenzani D, Buoli M, Caldiroli L, Carnevali GS, Serati M, Vezza C, Armelloni S, Messa P, and Vettoretti S
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- Aged, Cohort Studies, Female, Humans, Inflammation complications, Male, Renal Insufficiency, Chronic physiopathology, Renal Insufficiency, Chronic psychology, Cognitive Dysfunction complications, Depression complications, Malnutrition complications, Renal Insufficiency, Chronic complications
- Abstract
Objective: Chronic kidney disease (CKD) is a disabling condition associated with different medical comorbidities including depression and cognitive impairment. We investigated the association between malnutrition, inflammation and depressive/cognitive symptoms in elderly subjects with advanced CKD., Methods: We evaluated cross-sectionally 132 elderly subjects (age ≥65 years) with advanced CKD (stage 4-5, non-dialytic-ND) in regular follow up at the outpatient clinic of nephrology. Blood and urinary samples were collected after an overnight fast. All patients were evaluated by Geriatric Depression Scale (GDS)-30 items for severity of depressive symptoms, Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT) for cognition. Nutritional status was assessed by Malnutrition Inflammation Score (MIS). Different linear regression models were performed to study the association between clinical variables, diet and inflammatory parameters with the above mentioned rating scale scores. A final linear regression model with only previous statistically significant variables was performed for GDS scores., Results: Our cohort consisted of 95 males and 37 females with a mean age of 78 ± 7. Female gender (B = 3.20, p < .01), higher MIS (B = 0.29, p = .02) and higher IL-12p70 serum levels (pg/mL) (B = 0.37, p = .03) were associated with severity of depressive symptoms. MIS was associated with the severity of cognitive impairment as assessed by MMSE (B = -0.19, p < .01) and CDT (B = 0.10, p = .03)., Conclusion: In elderly subjects affected by CKD the severity of depressive symptoms and cognitive impairment is associated with specific inflammatory and nutritional parameters. These results have to be considered as preliminary and need replication by further studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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50. Sarcopenia is Associated with Malnutrition but Not with Systemic Inflammation in Older Persons with Advanced CKD.
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Vettoretti S, Caldiroli L, Armelloni S, Ferrari C, Cesari M, and Messa P
- Subjects
- Age Factors, Aged, Aged, 80 and over, Biomarkers blood, Body Composition, Body Mass Index, Creatinine, Cross-Sectional Studies, Female, Humans, Inflammation blood, Inflammation diagnosis, Inflammation Mediators blood, Italy epidemiology, Male, Prevalence, Protein-Energy Malnutrition diagnosis, Protein-Energy Malnutrition physiopathology, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic diagnosis, Risk Factors, Sarcopenia diagnosis, Inflammation epidemiology, Nutritional Status, Protein-Energy Malnutrition epidemiology, Renal Insufficiency, Chronic epidemiology, Sarcopenia epidemiology
- Abstract
Background: In patients with chronic kidney disease (CKD), sarcopenia can be determined by a wide spectrum of risk factors. We evaluated the association of sarcopenia with nutritional, behavioral and inflammatory patterns in older patients with advanced CKD., Methods: we cross-sectionally evaluated 113 patients with CKD stages 3b-5. Sarcopenia was defined according to the EWGSOP2 criteria. We assessed: anthropometry, bioelectrical impedance analysis, physical, and psychological performance. Nutritional status was assessed using the Malnutrition Inflammation Score (MIS) and by verifying the eventual presence Protein Energy Wasting syndrome (PEW). Systemic inflammation was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, fetuin, IL12., Results: 24% of patients were sarcopenic. Sarcopenic individuals had lower creatinine clearance (18 ± 11 vs. 23 ± 19 mL/min; p = 0.0087) as well as lower BMI (24.8 ± 3.0 vs. 28.4 ± 5.5 Kg/m
2 ; p < 0.0001) and a lower FTI (11.6 ± 3.9 vs. 14.4 ± 5.1 kg/m2 , p = 0.023). Sarcopenic persons had higher prevalence of PEW (52 vs. 20%, p < 0.0001) and a tendency to have higher MIS (6.6 ± 6.5 vs. 4.5 ± 4.0, p = 0.09); however, they did not show any difference in systemic inflammation compared to non-sarcopenic individuals., Conclusions: CKD sarcopenic patients were more malnourished than non-sarcopenic ones, but the two groups did not show any difference in systemic inflammation.- Published
- 2019
- Full Text
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