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Conti V.,University of Salerno | Corbi G.,University of Molise | Simeon V.,Scientific Institute of Hospitalization and Treatment | Russomanno G.,University of Salerno | And 4 more authors.
Aging Clinical and Experimental Research | Year: 2015

Background: Oxidative stress is strongly associated with aging and age-related diseases and plays a crucial role in endothelial dysfunction development. Aim: To better understand the molecular mechanisms of aging and stress response in humans, we examined changes to young and older human endothelial cells over time (72, 96 and 120 h), before and after H2O2-induced stress. Methods: We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation. Moreover, we quantified levels of cellular senescence by senescence-associated β galactosidase (SA-βgal) assay. Results: Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels. In addition cellular senescence drastically increased in older cells compared with Young cells both in presence and in the absence of oxidative stress. Discussion: By following the cell behavior during the time course, we can hypothesize that while in young cells an oxidative stress induction stimulated an adequate response through activation of molecular factor crucial to counteract oxidative stress, the older cells are not able to adequately adapt themselves to external stress stimuli. Conclusions: During their life, endothelial cells impair the ability to defend themselves from oxidative stress stimuli. This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases. © 2015, Springer International Publishing Switzerland.

Estraneo A.,Scientific Institute of Telese Terme | Moretta P.,Scientific Institute of Telese Terme | Loreto V.,Scientific Institute of Telese Terme | Santoro L.,University of Naples Federico II | Trojano L.,The Second University of Naples
Archives of Physical Medicine and Rehabilitation | Year: 2014

Objective To report clinical conditions and neuropsychological functioning of patients with late recovery of responsiveness at least 5 years after injury. Design Patient series. Setting Patients discharged from an inpatient rehabilitation unit. Participants Patients (N=13) who recovered from a vegetative state 1 year after severe traumatic brain injury or 6 months after nontraumatic brain injury. Interventions Not applicable. Main Outcome Measures Coma Recovery Scale-Revised, Disability Rating Scale, and FIM. For patients who recovered full consciousness, neuropsychological tests specifically adapted for patients with very severe disabilities were used. Results After regaining responsiveness, 2 patients died because of severe clinical complications. Among the remaining 11 patients, 5 were still in a minimally conscious state at their last assessment, but 4 of them had recovered some complex behavioral responses to the environment (eg, they could follow simple commands, albeit inconsistently). Six patients had emerged from a minimally conscious state at the last evaluation. Severe functional disability was present in both patients who were conscious and patients who were minimally conscious. No patient was autonomous in common daily life activities or in transfers. All patients who were conscious showed variable cognitive impairments, and some of them also developed behavioral and psychological symptoms. However, such disturbances did not impede the patients' interaction with relatives and caregivers. Conclusions This study provides systematic data about the course of the disease in a cohort of patients that was previously considered as exceptional. Patients with late recovery show a variable degree of functional recovery, although they experience marked residual motor and cognitive disabilities. The present findings contribute to enhance the understanding of the course of the disease in patients with late recovery and might help clinicians optimize the levels of care and provide the patients' families with correct information. © 2014 by the American Congress of Rehabilitation Medicine.

Conti V.,The Second University of Naples | Corbi G.,University of Molise | Russomanno G.,The Second University of Naples | Simeon V.,The Second University of Naples | And 9 more authors.
Medicine and Science in Sports and Exercise | Year: 2012

PURPOSE: Exercise training is a nonpharmacological intervention that improves cardiovascular function and enhances endothelial homeostasis in patients with cardiovascular diseases. However, the amount of benefit achieved varies widely depending on the type and duration of exercise. Moreover, data about the long-term effects of physical activity are scarce. METHODS: In this study, endothelial cells, exposed or not to oxidative stress, were conditioned with sera from athletes regularly participating in sports classified as "aerobic" (triathlon), "mixed aerobic-anaerobic" (soccer), and "anaerobic" (sprint running). RESULTS: Functional and hemodynamic variables did not differ between groups of athletes, whereas there were dramatic changes in serum markers for oxidative stress. Lipid peroxidation assessed by the thiobarbituric acid reactive substances assay and catalase activity were the lowest and nitric oxide availability was the highest in sera of triathletes. Endothelial cells cultured in serum from triathletes (T-endothelial cells) had the highest survival, evaluated by viability assay, BrdU incorporation, and senescence-associated β galactosidase assays, and preserved the endothelial appearance before and after stress in contrast to the cells grown in sera from the other athletes. T-endothelial cells also had the highest catalase messenger RNA expression and, after stress, the highest catalase activity of all the endothelial cells. Moreover, poststress activity of Sirt1, a NAD-dependent deacetylase involved in cellular stress resistance and a key regulator of longevity, was significantly increased in T-endothelial cells. CONCLUSIONS: Different types of exercise training induced different molecular effects in terms of survival, morphology, and antioxidant system efficiency. The in vitro technique used herein may help to shed light on the molecular basis of effects of long-term physical activity in humans.

Conti V.,University of Salerno | Russomanno G.,University of Salerno | Corbi G.,University of Molise | Guerra G.,University of Molise | And 6 more authors.
Medicine and Science in Sports and Exercise | Year: 2013

Purpose: Moderate aerobic exercise reduces oxidative stress, whereas intense physical activity may produce the opposite result. At present, the effects of different exercise loads on oxidative stress markers and the response of human cells to different exercise volumes have not been fully elucidated. Methods: Human (Eahy-926) endothelial cells (EC), exposed or not exposed to oxidative stress, were conditioned with sera from two groups of triathletes practicing at different workloads. Results: Although no differences in functional and hemodynamic variables were observed between the two groups of triathletes, significant changes in some markers for oxidative stress were found in their sera. Thiobarbituric acid reactive substances and superoxide dismutase activity were similar, but triathletes practicing the sport at lower volume (T1) had higher serum nitric oxide and lower catalase activity than triathletes performing the training at greater load (T2). The EC conditioned with serum from T1 (T1-EC) showed higher survival and proliferation rates and lower senescence levels than the EC supplemented with T2 (T2-EC) serum both before and after oxidative stress induction. These effects depended on catalase as demonstrated via enzyme activity inhibition using 3-amino-1,2,4-triazole. After oxidative stress induction, Sirt1 activity, a regulator of the oxidative stress response, was significantly increased in the T1-EC but not in the T2-EC. Moreover, the T1-EC required less catalase activity than the T2-EC to counteract an equal amount of oxidative stress after H2O2 administration. Conclusion: This study demonstrates that the beneficial effects of aerobic exercise are eliminated when the training is performed at a greater workload. Moreover, we suggest an oxidative stress marker, serum catalase activity, as a valid tool to use in the supervision of changes to exercise volume. Copyright © 2013 by the American College of Sports Medicine.

Lymperopoulos A.,Nova Southeastern University | Lymperopoulos A.,Thomas Jefferson University | Rengo G.,Thomas Jefferson University | Rengo G.,Scientific Institute of Telese Terme | And 4 more authors.
Journal of Biological Chemistry | Year: 2010

Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell α2-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant (∼50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knockout (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac β-adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and β-adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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