Childrens Hospital and Research Institute Bambino Gesu

Rome, Italy

Childrens Hospital and Research Institute Bambino Gesu

Rome, Italy
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Pompilio A.,University of Chieti Pescara | Crocetta V.,University of Chieti Pescara | De Nicola S.,University of Chieti Pescara | Verginelli F.,University of Chieti Pescara | And 2 more authors.
Frontiers in Microbiology | Year: 2015

The present study was undertaken in order to understand more about the interaction occurring between S. maltophilia and P. aeruginosa, which are frequently co-isolated from CF airways. For this purpose, S. maltophilia RR7 and P. aeruginosa RR8 strains, co-isolated from the lung of a chronically infected CF patient during a pulmonary exacerbation episode, were evaluated for reciprocal effect during planktonic growth, adhesion and biofilm formation onto both polystyrene and CF bronchial cell monolayer, motility, as well as for gene expression in mixed biofilms. P. aeruginosa significantly affected S. maltophilia growth in both planktonic and biofilm cultures, due to an inhibitory activity probably requiring direct contact. Conversely, no effect was observed on P. aeruginosa by S. maltophilia. Compared with monocultures, the adhesiveness of P. aeruginosa on CFBE41o- cells was significantly reduced by S. maltophilia, which probably acts by reducing P. aeruginosa's swimming motility. An opposite trend was observed for biofilm formation, confirming the findings obtained using polystyrene. When grown in mixed biofilm with S. maltophilia, P. aeruginosa significantly over-expressed aprA, and algD-codifying for protease and alginate, respectively-while the quorum sensing related rhlR and lasI genes were down-regulated. The induced alginate expression by P. aeruginosa might be responsible for the protection of S. maltophilia against tobramycin activity we observed in mixed biofilms. Taken together, our results suggest that the existence of reciprocal interference of S. maltophilia and P. aeruginosa in CF lung is plausible. In particular, S. maltophilia might confer some selective 'fitness advantage' to P. aeruginosa under the specific conditions of chronic infection or, alternatively, increase the virulence of P. aeruginosa thus leading to pulmonary exacerbation. © 2015 Pompilio, Crocetta, De Nicola, Verginelli, Fiscarelli and Di Bonaventura.

Carletti B.,Childrens Hospital and Research Institute Bambino Gesu | Piemonte F.,Childrens Hospital and Research Institute Bambino Gesu | Rossi F.,University of Turin
Current Neuropharmacology | Year: 2011

During the past decades Neural Stem Cells have been considered as an alternative source of cells to replace lost neurons and NSC transplantation has been indicated as a promising treatment for neurodegenerative disorders. Nevertheless, the current understanding of NSC biology suggests that, far from being mere spare parts for cell replacement therapies, NSCs could play a key role in the pharmacology of neuroprotection and become protagonists of innovative treatments for neurodegenerative diseases. Here, we review this new emerging concept of NSC biology. © 2011 Bentham Science Publishers Ltd.

Passarelli C.,Childrens Hospital and Research Institute Bambino Gesu | Di Venere A.,University of Rome Tor Vergata | Piroddi N.,University of Florence | Pastore A.,Childrens Hospital and Research Institute Bambino Gesu | And 7 more authors.
Cytoskeleton | Year: 2010

In this study we investigated the molecular mechanism of glutathionylation on isolated human cardiac myofibrils using several pro-glutathionylating agents. Total glutathionylated proteins appeared significantly enhanced with all the pro-oxidants used. The increase was completely reversed by the addition of a reducing agent, demonstrating that glutathione binding occurs by a disulfide and that the process is reversible. A sensitive target of glutathionylation was α-actin, showing a different reactivity to the several pro-glutathionylating agents by ELISA. Noteworthy, myosin although highly sensitive to the in vitro glutathionylation does not represent the primary glutathionylation target in isolated myofibrils. Light scattering measurements of the glutathionylated α-actin showed a slower polymerisation compared to the non-glutathionylated protein and force development was depressed after glutathionylation, when the myofibrils were mounted in a force recording apparatus. Interestingly, confocal laser scanning microscopy of cardiac cryosections indicated, for the first time, the constitutive glutathionylation of α-cardiac actin in human heart. Due to the critical location of α-actin in the contractile machinery and to its susceptibility to the oxidative modifications, glutathionylation may represent a mechanism for modulating sarcomere assembly and muscle functionality under patho-physiological conditions in vivo. © 2009 Wiley-Liss, Inc.

PubMed | G Gaslini Institute, University of Florence, Childrens Hospital and Research Institute Bambino Gesu, Meyer Hospital and ENEA
Type: Journal Article | Journal: PloS one | Year: 2015

Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the development of predictive biomarkers of substantial decline in lung function.

Pastore A.,Childrens Hospital and Research Institute Bambino Gesu | Ciampalini P.,Childrens Hospital and Research Institute Bambino Gesu | Tozzi G.,Childrens Hospital and Research Institute Bambino Gesu | Pecorelli L.,Childrens Hospital and Research Institute Bambino Gesu | And 3 more authors.
Pediatric Diabetes | Year: 2012

Background: Oxidative stress plays an important role in the pathogenesis of type 1 diabetes (T1D), where an increase in reactive oxygen species may contribute to the initial destruction of β-cells. Accumulating evidence also suggests a role for oxidative stress in obesity, where it may potentiate the development of complications. Objective: To analyze the in vivo homeostasis of glutathione in children with T1D at onset and in children who are obese, to evaluate the systemic content of all glutathione forms (total, reduced, oxidized, and protein-bound glutathione) and the balance among them. Moreover, since glutathione bound to hemoglobin is a clinical marker of oxidative stress in human blood, we analyzed glutathionyl-hemoglobin in T1D and in obese children. Subjects: Children with T1D at onset (n = 30) or obesity (n = 30) at the first observation, and 30 healthy subjects chosen from the children who attended the outpatient clinic for minor problems. Methods: We assessed circulating levels of various glutathione forms by performing reverse-phase high performance liquid chromatography. Glutathionyl-hemoglobin analysis was carried out by cation-exchange chromatography. Results: In children with T1D and in obese children, we found a significant decrease of all glutathione forms including, for the first time, the content of total glutathione and glutathionylated proteins. The comparison among forms shows no significant imbalance in T1D patients, whereas in obese children it seems to suggest an attempt to rebalance the glutathione system homeostasis. Conclusions: Our findings consistently show in vivo evidence of glutathione depletion upon early onset of T1D and in obese children, thus evidencing glutathione as an early marker in these two metabolic conditions. © 2011 John Wiley & Sons A/S.

Salerno T.,Childrens Hospital and Research Institute Bambino Gesu | Guccione P.,Childrens Hospital and Research Institute Bambino Gesu | Malena S.,Childrens Hospital and Research Institute Bambino Gesu | Cutrera R.,Childrens Hospital and Research Institute Bambino Gesu
Pediatric Cardiology | Year: 2010

Horseshoe lung is a rare malformation that is often associated with lung hypoplasia and/or vascular anomalies. We describe a 10-year-old girl with horseshoe lung and unique left pulmonary vein. This is the first reported case with this vascular feature. The patient presented with signs and symptoms of severe pulmonary hypertension and was treated with sildenafil. © 2010 Springer Science+Business Media, LLC.

Passarelli C.,Childrens Hospital and Research Institute Bambino Gesu | Tozzi G.,Childrens Hospital and Research Institute Bambino Gesu | Pastore A.,Childrens Hospital and Research Institute Bambino Gesu | Bertini E.,Childrens Hospital and Research Institute Bambino Gesu | Piemonte F.,Childrens Hospital and Research Institute Bambino Gesu
International Journal of Molecular Medicine | Year: 2010

The mitochondrial respiratory chain represents the major source of reactive oxygen species (ROS) in cells and its dysfunction may contribute to the pathogenesis of several diseases. In mitochondria, glutathione is the major redox buffer and is a good indicator for the redox environment of the cell. Indeed, overproduction of ROS decreases the ratio between reduced and oxidized glutathione leading the latter to bind to proteins by a mechanism called glutathionylation. In this study, we demonstrate that in isolated cardiac mitochondria the respiratory chain enzyme Complex I is highly susceptible to glutathionylation under conditions of oxidative stress, showing a significant dose- and time-dependent decrease of the activity after treatment with oxidized glutathione. Among respiratory chain enzymes, Complex I appears the most affected by the oxidant-mediated inactivation in isolated mitochondria. Also, in cultured cardiomyocytes CI activity was strongly inhibited after in vivo treatment with hydrogen peroxide. Noteworthy, HPLC analysis showed a significant increase of protein glutathionylation in oxidatively stressed cells and this rise is in vivo reverted after incubation of cells with anti-oxidant N-acetylcysteine. These findings take particular importance given that CI represents the entry point of electrons into oxidative phosphorylation and that the threshold at which CI dysfunction affects ATP production is lower than that of any other OXPHOS complexes, making the enzyme particularly critical for the health of cells.

PubMed | University of Rome La Sapienza and Childrens Hospital and Research Institute Bambino Gesu
Type: Journal Article | Journal: EBioMedicine | Year: 2015

Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61-1.01), p<0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p<0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p<0.05) and LDL-c (p<0.05), and increased serum liver enzymes (ALT, p<0.001; AST, p<0.01; GGT, p<0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004-1.032, p=0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241-5.245, p=0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248-0.866, p=0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.

PubMed | Childrens Hospital and Research Institute Bambino Gesu
Type: Journal Article | Journal: Antioxidants (Basel, Switzerland) | Year: 2016

A prominent feature of Friedreichs ataxia (FRDA) is the neurodegeneration of the central and peripheral nervous systems, but little information is available about the mechanisms leading to neuronal damage in this pathology. Currently, no treatments delay, prevent, or reverse the inexorable decline that occurs in this condition. Evidence of oxidative damage has been demonstrated in Friedreichs ataxia, and this damage has been proposed as the origin of the disease. Nevertheless, the role of oxidative stress in FRDA remains debatable. The lack of direct evidence of reactive oxygen species overproduction in FRDA cells and tissues and the failure of exogenous antioxidants to rescue FRDA phenotypes questions the role of oxidative stress in this pathology. For example, the antioxidant idebenone ameliorates cardiomyopathy in FRDA patients, but this therapy does not improve neurodegeneration. To date, no known pharmacological treatment with antioxidant properties cures or delays FRDA neuropathology. This review reports and discusses the evidence of oxidative stress in FRDA and focuses on the existing knowledge of the apparent ineffectiveness of antioxidants for the treatment of neuronal damage.

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