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Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Mallamaci F.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Blood Purification | Year: 2013

High FGF23 predicts renal function loss in chronic kidney disease (CKD) patients and graft failure in transplant patients. FGF23, parathyroid hormone and serum phosphate are all interrelated but among these CKD-MBD biomarkers only FGF23 is independently related with CKD progression. High FGF23 associates with endothelial dysfunction in CKD patients and in elderly individuals in the general population. Furthermore, independently of serum phosphate, high FGF23 associates with mortality and left ventricular hypertrophy in dialysis patients and with atherosclerosis in elderly individuals in the general population. FGF23 also predicts a high risk for death and cardiovascular events in predialysis CKD patients and in subjects with coronary artery disease. A recent trial in CKD patients showed that low phosphate intake associated with a phosphate binder produces a 35% decrease in plasma FGF23. Yet in this and in another trial testing several phosphate binders, FGF23 levels remained well beyond the upper limit of the normal range. Of note, in this latter study, calcification of the coronary arteries and abdominal aorta actually increased, rather than decreased, during treatment with these drugs in the face of evidence of negative phosphate balance and amelioration of hyperparathyroidism. Mechanistic studies are still needed before testing the hypothesis that FGF23 is implicated in a causal manner in cardiovascular and renal diseases. Given the modest effects of phosphate binders on serum FGF23 in CKD patients, pharmacologic interventions antagonizing the effects of this growth factor rather than phosphate-lowering interventions should be put in place to properly test this hypothesis in the clinical scenario in CKD. © 2013 S. Karger AG, Basel.


Bonsignore M.R.,University of Palermo | Bonsignore M.R.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | McNicholas W.T.,St Vincents University Hospital | Montserrat J.M.,Hospital Clinic IDIBAPS CIBERES | Eckel J.,German Diabetes Center
European Respiratory Journal | Year: 2012

A European Respiratory Society research seminar on "Metabolic alterations in obstructive sleep apnoea (OSA)" was jointly organised in October 2009 together with two EU COST actions (Cardiovascular risk in the obstructive sleep apnoea syndrome, action B26, and Adipose tissue and the metabolic syndrome, action BM0602) in order to discuss the interactions between obesity and OSA. Such interactions can be particularly significant in the pathogenesis ofmetabolic abnormalities and in increased cardiovascular risk in OSA patients. However, studying the respective role of OSA and obesity is difficult in patients, making it necessary to refer to animal models or in vitro systems. Since most OSA patients are obese, their management requires a multidisciplinary approach. This review summarises some aspects of the pathophysiology and treatment of obesity, and the possible effects of sleep loss on metabolism. OSA-associated metabolic dysfunction (insulin resistance, liver dysfunction and atherogenic dyslipidaemia) is discussed from the perspective of both obesity and OSA in adults and children. Finally, the effects of treatment for obesity or OSA, or both, on cardio-metabolic variables are summarised. Further interdisciplinary research is needed in order to develop new comprehensive treatment approaches aimed at reducing sleep disordered breathing, obesity and cardiovascular risk. Copyright©ERS 2012.


Pinsino A.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Roccheri M.C.,University of Palermo | Matranga V.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Marine Environmental Research | Year: 2014

In the marine environment, manganese represents a potential emerging contaminant, resulting from an increased production of manganese-containing compounds. In earlier reports we found that the exposure of Paracentrotus lividus sea urchin embryos to manganese produced phenotypes with no skeleton. In addition, manganese interfered with calcium uptake, perturbed extracellular signal-regulated kinase (ERK) signaling, affected the expression of skeletogenic genes, and caused an increase of the hsc70 and hsc60 protein levels. Here, we extended our studies focusing on the temporal activation of the p38 mitogen-activated protein kinase (p38 MAPK) and the proteolytic activity of metalloproteinases (MMPs). We found that manganese affects the stage-dependent dynamics of p38 MAPK activation and inhibits the total gelatin-auto-cleaving activity of MMPs, with the exclusion of the 90-85kDa and 68-58kDa MMPs, whose levels remain high all throughout development. Our findings correlate, for the first time to our knowledge, an altered activation pattern of the p38 MAPK with an aberrant MMP proteolytic activity in the sea urchin embryo. © 2013 Elsevier Ltd.


Profita M.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
International journal of immunopathology and pharmacology | Year: 2010

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral and nasal FENO concentrations were increased in children with PER, IA, mA and MA when compared with HCs. Nasal 8-isoprostane was higher in EBC of children with PER and asthma than in HCs. Oral and nasal LTB4 were higher in EBC of children with PER and mA than in HCs. Oral and nasal PGE2 concentrations were higher in EBC of children with PER than in HCs. Positive correlations between oral and nasal biomarkers were found in IA for LTB4 and PGE2, in mA for FENO, 8-isoprostane, LTB4 and PGE2, and in MA for PGE2. No correlations were observed in children with PER and HCs. Our results suggest that non-invasive markers of inflammation and oxidative stress might be useful to study the relationships between oral and nasal compartments in allergic children with PER and concomitant asthma with the aim of defining the UAD.


Lampiasi N.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Montana G.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Immunobiology | Year: 2015

Identification of new antioxidant and anti-inflammatory bioactive molecules is an important tool for selecting effective formulations for the treatment of inflammation. The mouse macrophage cell line RAW 264.7, lipopolysaccharide (LPS)-activated, is associated with an inflammation response. Activated macrophages produce reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines such as IL-6, TNF-α and IL-10. In the present study we have showed that pre-treatment with Ferulic Acid (FA) reduces NO accumulation in the culture medium of LPS-induced macrophage cells. Moreover, real-time experiments have revealed that FA has an inhibitory effect at the transcriptional level on the expression of some inflammatory mediators such as IL-6, TNF-α and iNOS and an activation effect on the expression of some antioxidant molecules such as Metallothioneins (MT-1, MT-2). Importantly, we have found that FA reduced the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-κB (NF-κB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-κB promoter activity in a luciferase assay. Our data clearly suggest that FA anti-inflammatory effects are mainly mediated through IKK/NF-κB signalling pathway. Therefore, FA could represent a new natural drug extremely useful to improve anti-inflammatory treatment. © 2015.


Bolignano D.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Nephrology Dialysis Transplantation | Year: 2013

Obesity is an independent risk factor for the development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in obese subjects with altered glomerular filtration rate (GFR), proteinuria or albuminuria. MEDLINE, EMBASE and CENTRAL databases were searched for articles reporting longitudinal data on the effect of weight loss on renal parameters in obese patients with altered kidney function. Thirty-one (2013 subjects) were included. In the 13 studies where weight loss was achieved by bariatric surgery, body mass index (BMI) significantly decreased in all studies; GFR decreased in six studies on hyperfiltration patients and increased in one study on patients with CKD Stage 3-4. Albuminuria decreased in six studies and proteinuria decreased in five studies. In six studies, weight loss was achieved by antiobesity agents: BMI decreased in all studies; GFR decreased in four studies and albuminuria in three. Eleven studies analysed the effects of diet, alone or in combination with lifestyle modifications. A significant decrease in BMI was reported in all studies; GFR increased in two studies, remained stable in four studies and decreased in two studies on hyperfiltration patients. Albuminuria decreased in six studies and remained stable in one study. Proteinuria decreased in five studies. In obese patients with altered renal function, weight loss, particularly if achieved by surgical interventions, improves proteinuria, albuminuria and normalizes GFR. Larger, long-term studies are needed to analyse the durability of this improvement and the effects on renal outcomes, such as CKD progression and the development of ESKD. © The Author 2013. Published by Oxford University Press on behalf of ERAEDTA. All rights reserved.


Bolignano D.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Current Opinion in Nephrology and Hypertension | Year: 2010

Purpose of review: This review aims to analyze the relationships between arginine vasopressin (AVP) and chronic kidney disease (CKD) and to define the potential of vasopressin receptor antagonists beyond the treatment of water metabolism disorders. Recent findings: Experimental studies in rat and observational studies in humans suggest that AVP may play a role in the genesis and exacerbation of renal damage and chronic renal insufficiency. Summary: A sustained stimulation of vasopressin receptors induces intrarenal renin-angiotensin system activation, podocyte alterations, glomerular hyperfiltration and hypertrophy eventuating in proteinuria and kidney damage. Furthermore, AVP directly stimulates contraction and proliferation of mesangial cells and accumulation of extracellular matrix and glomerulosclerosis. Whether a chronic increase in water intake (determining a reduction in endogenous AVP levels) and/or the administration of vasopressin receptor antagonists are useful for the prevention and treatment of CKD remains to be tested in clinical trials. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Bolignano D.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2012

Aims: Glitazones rank now among the most used hypoglycemic agents in patients with type-2 diabetes. This systematic review focuses on the cardiovascular and renal outcomes in chronic kidney disease (CKD) patients treated with these drugs. Data synthesis: Data from randomized clinical trials and a meta-analysis indicate that glitazones (particularly rosiglitazone) may increase the risk of myocardial infarction, heart failure and cardiovascular death in type-2 diabetics. Observational studies looking at survival and cardiovascular outcomes in diabetic patients with kidney failure show controversial results. Studies in experimental models and clinical studies suggest that glitazones may have favorable effects on renal disease progression, because these drugs coherently reduce urinary albumin excretion and proteinuria in diabetic and non-diabetic nephropathies. No clinical trial based on clinical end-points like kidney failure has until now tested the effect of glitazones on the evolution of chronic renal failure in these patients. Conclusions: Whether the use of glitazones has a positive or a negative impact upon major cardiovascular and renal outcomes in diabetic patients remains an open, unanswered question. Specific studies are needed to assess the efficacy and safety of glitazones in a high risk population like type-2 diabetics with chronic kidney disease. © 2011 Elsevier B.V.


Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Mallamaci F.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Journal of Renal Nutrition | Year: 2011

Experimental and clinical evidence implicates the 2 major adipose tissue cytokines, adiponectin (ADPN) and leptin (LEP), in renal damage. The interpretation of the link between these cytokines and renal outcomes is strictly context-sensitive. Albuminuria is a feature of renal disease in the ADPN null mouse and this alteration can be reversed by supplementing ADPN. Accordingly, in young normoalbuminuric obese individuals low ADPN is associated with higher albumin excretion rate. Conversely, high ADPN is associated with more severe proteinuria in chronic kidney disease patients, possibly underlying a protective response aimed at countering the high renal and cardiovascular risk of high proteinuria. LEP administration ameliorates insulin resistance in insulin-resistant patients with hereditary lipodystrophy - a disease characterized by severe LEP deficiency and renal disease- and the same intervention reverses both, insulin resistance and renal damage in a mouse model of LEP deficiency. However, LEP may exert noxious effects on the kidney (particularly renal fibrosis) if administered in conditions of LEP sufficiency or excess. © 2011 National Kidney Foundation, Inc.


Zoccali C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Torino C.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Tripepiand G.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Mallamaci F.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy
Current Opinion in Nephrology and Hypertension | Year: 2012

Purpose of Review: Obesity is a major driver of the current epidemic of chronic kidney disease (CKD), but metrics of obesity in the CKD population have been studied sparsely. This review updates knowledge on this issue. Recent Findings: Measures of abdominal obesity, waist circumference and waist-to-hip ratio (WHR), are better predictors than BMI of the high risk of mortality in predialysis and dialysis patients and waist circumference reliably reflects visceral fat in CKD patients. Skinfold thickness and WHR are superior to BMI for the classification of obesity in CKD patients. Multifrequency body impedance analysis (BIA) provides valid estimates of fat mass in hemodialysis patients. Summary: Skinfold thickness,WHR and multifrequency BIA are superior to BMI for measuring body fat in CKD patients and measures of abdominal obesity are stronger predictors of adverse clinical outcomes than the BMI. These metrics should be preferentially applied for the assessment of obesity in CKD, but it remains unproven that these techniques offer real advantages over the BMI in clinical practice in CKD patients. © 2012 Wolters Kluwer Health | Lippincott Williams and Wilkins.

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