Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly

Significance: The incidence of cardiovascular events (CVEs) increases with age, representing the main cause of death in an elderly population. Aging is associated with overproduction of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function, thus predisposing elderly patients to thrombotic complications. Recent Advances: There is increasing evidence to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, upregulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occurs during aging. This imbalance may predispose to thrombosis by enhancing platelet and clotting activation and eliciting endothelial dysfunction. Recently, gut-derived products, such as trimethylamine N-oxide (TMAO) and lipopolysaccharide, are emerging as novel atherosclerotic risk factors, and gut microbiota composition has been shown to change by aging, and may concur with the increased cardiovascular risk in the elderly. Critical Issues: Antioxidant treatment is ineffective in patients at risk or with cardiovascular disease. Further, anti-thrombotic treatment seems to work less in the elderly population. Future Directions: Interventional trials with antioxidants targeting enzymes implicated in aging-related atherothrombosis are warranted to explore whether modulation of redox status is effective in lowering CVEs in the elderly

Extra virgin olive oil use is associated with improved post-prandial blood glucose and LDL cholesterol in healthy subjects

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet and seems to account for the protective effect against cardiovascular disease. However, the underlying mechanism is still elusive

Hypercoagulation and antithrombotic treatment in coronavirus 2019. a new challenge

The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment

Un client web EPP per la Regione Toscana

L\u27Istituto di Informatica e Telematica del CNR di Pisa (IIT-CNR) gestisce il Registro del country code Top Level Domain .it (Registro .it). Nel corso del 2009, il Registro .it ha attivato un nuovo sistema di registrazione, denominato "sistema sincrono", basato sul protocollo di comunicazione EPP (Extensible Provisioning Protocol). Al fine di supportare la Regione Toscana nell\u27evoluzione dei propri sistemi di gestione dei domini, conseguentemente al passaggio dal vecchio sistema asincrono al nuovo sistema sincrono, lo IIT-CNR, sulla base di una convenzione tra i due enti, ha fornito il supporto tecnico per la progettazione e realizzazione di un\u27interfaccia client web EPP che disponesse delle funzionalit? necessarie alla registrazione e al mantenimento dei nomi a dominio nel .it in modalit? sincrona. Il client web ? stato implementato con un\u27applicazione J2EE da deployare su un\u27opportuna istanza dell\u27application server JBoss

Imbalance between nitric oxide generation and oxidative stress in patients with peripheral arterial disease: Effect of an antioxidant treatment

BackgroundNitric oxide (NO), a potent vasodilator produced by endothelial cells, is reduced in patients with peripheral arterial disease (PAD), but the mechanism has not been fully elucidated. Because NO is rapidly inactivated by superoxide anion, we speculated that enhanced oxidative stress could lower NO generation. The aim of our study was to investigate if an imbalance between oxidative stress and NO does exist in patients with PAD and if an increase of NO formation could be achieved by an antioxidant treatment.MethodsIn a first study, serum levels of nitrite and nitrate (NOx), markers of NO generation, and 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress and maximal walking distance (MWD), were measured in 40 PAD patients and 40 controls. In a second study, 10 PAD patients were randomly allocated in a crossover design to intravenous propionyl-L-carnitine (6 g/day) or placebo for 7 days, with a washout of 30 days between the two phases of the trial. Serum levels of NOx and 8-OHdG were measured before and after the study.ResultsCompared with controls, serum levels of 8-OHdG (mean ± SD) were significantly increased in PAD patients (4.4 ± 3.1 ng/mL vs 2.4 ± 1.2 ng/mL; P < .001), and serum levels of NOx were significantly decreased (11.6 ± 6 μM vs 17 ± 6.1 μM; P < .001). Levels of 8-OHdG and NOx were inversely correlated (r = −0.879; P < .001). Serum levels 8-OHdG were inversely correlated with MWD (r = −0.48, P = .002). The interventional trial showed no changes in the patients given placebo. Patients treated with propionyl-L-carnitine showed a significant increase of MWD from 101 ± 31 meters to 129 ± 35 meters (P = .007) and in NOx from 14.5 ± 4.5 μM to 17.1 ± 3.8 μM (P = .007). A significant decrease of 8-OHdG from 3.6 ± 1.1 ng/mL to 2.6 ± 1 ng/mL was also found (P = .005.)ConclusionsThis study suggests that in PAD patients, the reduction of NO generation could be dependent upon enhanced oxidative stress

Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants

Background & aims: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. Methods: Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. Results: Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p < 0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p < 0.001), Framingham cardiovascular risk score (p < 0.01) and lower prevalence of metabolic syndrome (p < 0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. Conclusions: We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype. (C) 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Soluble CD40 ligand predicts ischemic stroke and myocardial infarction in patients with nonvalvular atrial fibrillation

OBJECTIVE - Atrial fibrillation (AF) is associated with a high incidence of vascular disease that may be related to a prothrombotic and inflammatory state. Soluble CD40 ligand (sCD40L), which stems essentially from platelet activation, possesses inflammatory and prothrombotic properties. The aim of the study was to assess whether sCD40L is a predictor of stroke or myocardial infarction (MI) in patients with nonvalvular AF. METHODS AND RESULTS - Plasma levels of sCD40L were measured in 231 patients (177 [77%] had permanent or persistent AF, and 54 [23%] had paroxysmal AF). Patients were followed for a mean period of 27.8±8.8 months, and cardiovascular events such as fatal and nonfatal stroke and MI were recorded. AF population was divided in 2 groups according to sCD40L level above or below the median (4.76 ng/mL). The 2 patients' groups had similar distribution of cardiovascular risk factors, age, gender, medications, or serum C-reactive protein levels. During the follow-up period, vascular events occurred in 6 (2 nonfatal MI and 4 nonfatal ischemic strokes) of 116 patients with low levels of sCD40L (5.1%) and in 29 (11 fatal and 3 nonfatal MI; 3 fatal and 12 nonfatal ischemic strokes) of 115 patients with high levels (25.2%) (log-rank test: P<0.001). Using the COX proportional Hazards model, patients with sCD40L above the median were 4.63 times more likely to experience a vascular event (95% C.I.: 1.92 to 11.20). CONCLUSIONS - This study shows that enhanced soluble CD40L level is a predictor of vascular events in patients with nonvalvular AF, thus suggesting that enhanced platelet activation may play a role in its clinical progression. © 2007 American Heart Association, Inc

Extra virgin olive oil reduces gut permeability and metabolic endotoxemia in diabetic patients

Background: Extra virgin olive oil (EVOO) improves post-prandial glycemia, but the underlying mechanism has not been fully elucidated. We tested the hypothesis that EVOO improves post-prandial glycemia by reducing gut permeability-derived low-grade endotoxemia. Methods: Serum levels of lipopolysaccharides (LPS), zonulin, a marker of gut permeability, glucose, insulin and glucagon-like peptide 1 (GLP1) were measured in 20 patients with impaired fasting glucose (IFG) and 20 healthy subjects (HS) matched for sex and age. The same variables were measured in IFG patients (n = 20) and HS (n = 20) before and after a Mediterranean diet with 10 g EVOO added or not (n = 20) or in IFG patients (n = 20) before and after intake of 40 g chocolate with EVOO added or not. Results: Compared to HS, IFG had higher levels of LPS and zonulin. In HS, meal intake was associated with a significant increase of blood glucose, insulin, and GLP1 with no changes of blood LPS and zonulin. Two hours after a meal intake containing EVOO, IFG patients showed a less significant increase of blood glucose, a more marked increase of blood insulin and GLP1 and a significant reduction of LPS and zonulin compared to IFG patients not given EVOO. Correlation analysis showed that LPS directly correlated with blood glucose and zonulin and inversely with blood insulin. Similar findings were detected in IFG patients given a chocolate added or without EVOO. Conclusion: Addition of EVOO to a Mediterranean diet or chocolate improves gut permeability and low-grade endotoxemia

Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease