Glutathione infusion before primary percutaneous coronary intervention: A randomised controlled pilot study

Objective: In the setting of reperfused ST-elevation myocardial infarction (STEMI), increased production of reactive oxygen species (ROS) contributes to reperfusion injury. Among ROS, hydrogen peroxide (H2O2) showed toxic effects on human cardiomyocytes and may induce microcirculatory impairment. Glutathione (GSH) is a water-soluble tripeptide with a potent oxidant scavenging activity. We hypothesised that the infusion of GSH before acute reoxygenation might counteract the deleterious effects of increased H2O2 generation on myocardium. Methods: Fifty consecutive patients with STEMI, scheduled to undergo primary angioplasty, were randomly assigned, before intervention, to receive an infusion of GSH (2500 mg/25 mL over 10 min), followed by drug administration at the same doses at 24, 48 and 72 hours elapsing time or placebo. Peripheral blood samples were obtained before and at the end of the procedure, as well as after 5 days. H2O2 production, 8-iso-prostaglandin F2α (PGF2α) formation, H2O2 breakdown activity (HBA) and nitric oxide (NO) bioavailability were determined. Serum cardiactroponin T (cTpT) was measured at admission and up to 5 days. Results: Following acute reperfusion, a significant reduction of H2O2 production (p=0.0015) and 8-iso-PGF2α levels (p=0.0003), as well as a significant increase in HBA (p<0.0001)and NO bioavailability (p=0.035), was found in the GSH group as compared with placebo. In treated patients, attenuated production of H2O2 persisted up to 5 days from the index procedure (p=0.009) and these changes was linked to those of the cTpT levels (r=0.41, p=0.023). Conclusion: The prophylactic and prolonged infusion of GSH seems to determine a rapid onset and persistent blunting of H2O2 generation improving myocardial cell survival. Nevertheless, a larger trial, adequately powered for evaluation of clinical endpoints, is ongoing to confirm the current finding

Corticosteroid use, myocardial injury and in-hospital cardiovascular events in patients with community-acquired pneumonia

Background and purpose: Corticosteroids are often prescribed to community-acquired pneumonia (CAP) patients, but the relationship with major cardiovascular events (MACEs) is unclear. Experimental approach: 541 CAP patients were recruited (334 males, mean age 71.9 ± 16.2 years). High-sensitivity troponin T (hs-cTnT) was measured at admission, during the hospital stay and at discharge. MACE occurrence was registered during a long-term follow-up. Key results: Overall, 318 patients (59%) showed hs-cTnT elevation >99th percentile (>0.014 μg/L). Age, heart failure and the increasing quintiles of hs-cTnT (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.82-2.58, P < .001) predicted MACEs. Among patients with hs-cTnT >0.014 μg/L at admission, 102 patients (31%) were on corticosteroids and showed lower hs-cTnT increase (P = .021), (NADPH) oxidase-2 (Nox2) activation (P = .005) and incidence of MACEs than untreated ones (HR 0.64, 95% CI 0.41-0.97, P = .038); no effect of corticosteroids on MACEs was observed in CAP patients with normal troponin. In vitro study showed that glucocorticoids have an antioxidant effect via downregulation of Nox2 activity. Conclusion and implications: The study provides evidence that corticosteroid use is associated with lower increase of hs-cTnT and incidence of MACEs in CAP patients

DAMEWARE - Data Mining & Exploration Web Application Resource

Astronomy is undergoing through a methodological revolution triggered by an unprecedented wealth of complex and accurate data. DAMEWARE (DAta Mining & Exploration Web Application and REsource) is a general purpose, Web-based, Virtual Observatory compliant, distributed data mining framework specialized in massive data sets exploration with machine learning methods. We present the DAMEWARE (DAta Mining & Exploration Web Application REsource) which allows the scientific community to perform data mining and exploratory experiments on massive data sets, by using a simple web browser. DAMEWARE offers several tools which can be seen as working environments where to choose data analysis functionalities such as clustering, classification, regression, feature extraction etc., together with models and algorithms

Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2

Background. Neurodegenerative diseases (ND) as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α), serum H2O2, and LPS in patients with ND compared to controls. Methods. One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H2O2, and LPS in these two groups. Serum zonulin was used to assess gut permeability. Results. Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α, H2O2, and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.441; p<0.001), zonulin (Rs=0.411; p<0.001), serum H2O2 (Rs=0.329; p<0.001), and 8-iso-PGF2α (Rs=0.244; p=0.006). LPS significantly correlated with serum zonulin (Rs=0.818; p<0.001) and 8-iso-PGF2α (Rs=0.280; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX2-dp. LPS (SE, 0.165; standardized coefficient β, 0.459; p<0.001) and 8-iso-PGF2α (SE, 0.018; standardized coefficient β, 0.220; p=0.005) emerged as the only independent predictive variables associated with sNOX2-dp (R2=57%). Conclusion. This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation

The role of antioxidants supplementation in clinical practice. focus on cardiovascular risk factors

Oxidative stress may be defined as an imbalance between reactive oxygen species (ROS) and the antioxidant system to counteract or detoxify these potentially damaging molecules. This phenomenon is a common feature of many human disorders, such as cardiovascular disease. Many of the risk factors, including smoking, hypertension, hypercholesterolemia, diabetes, and obesity, are associated with an increased risk of developing cardiovascular disease, involving an elevated oxidative stress burden (either due to enhanced ROS production or decreased antioxidant protec-tion). There are many therapeutic options to treat oxidative stress-associated cardiovascular dis-eases. Numerous studies have focused on the utility of antioxidant supplementation. However, whether antioxidant supplementation has any preventive and/or therapeutic value in cardiovascular pathology is still a matter of debate. In this review, we provide a detailed description of oxidative stress biomarkers in several cardiovascular risk factors. We also discuss the clinical implications of the supplementation with several classes of antioxidants, and their potential role for protecting against cardiovascular risk factors

The DAME/VO-Neural Infrastructure: an Integrated Data Mining System Support for the Science Community

Astronomical data are gathered through a very large number of heterogeneous techniques and stored in very diversified and often incompatible data repositories. Moreover in the e-science environment, it is needed to integrate services across distributed, heterogeneous, dynamic "virtual organizations" formed by different resources within a single enterprise and/or external resource sharing and service provider relationships. The DAME/VONeural project, run jointly by the University Federico II, INAF (National Institute of Astrophysics) Astronomical Observatories of Napoli and the California Institute of Technology, aims at creating a single, sustainable, distributed e-infrastructure for data mining and exploration in massive data sets, to be offered to the astronomical (but not only) community as a web application. The framework makes use of distributed computing environments (e.g. S.Co.P.E.) and matches the international IVOA standards and requirements. The integration process is technically challenging due to the need of achieving a specific quality of service when running on top of different native platforms. In these terms, the result of the DAME/VO-Neural project effort will be a service-oriented architecture, obtained by using appropriate standards and incorporating Grid paradigms and restful Web services frameworks where needed, that will have as main target the integration of interdisciplinary distributed systems within and across organizational domains.Comment: 10 pages, Proceedings of the Final Workshop of the Grid Projects of the Italian National Operational Programme 2000-2006 Call 1575; Edited by Cometa Consortium, 2009, ISBN: 978-88-95892-02-

Interplay between Nox2 activity and platelet activation in patients with sepsis and septic shock. a prospective study

Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls (n=10, age 67.8±3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, p<0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, p<0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, p<0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, p<0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed. Conclusions. Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock

Diet supplementation, probiotics, and nutraceuticals in SARS-CoV-2 infection. A scoping review

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic

A web application for photometric redshift estimation

In the era of massive astronomical datasets, efficient identification of candidate quasars and the reconstruction of their three dimensional distribution in the Universe is a key requirement for constraining some of the main issues regarding the formation and evolution of QSOs. A method for the determination of photometric redshifts of QSOs based on multiwavelength photometry and on a combination of data mining techniques will be discussed. This procedure, specifically suited for accompanying the candidate selection method discussed in (D’Abrusco et al. 2008), makes use of specific tools developed under the EuroVO and NVO frameworks for data gathering, pre-processing and mining, while relying on the scaling capabilities of the computing grid. This method allowed us to obtain photometric redshifts with an increased accuracy (up to 30%) with respect to the literature

Proprotein convertase subtilisin kexin type 9 inhibitors reduce platelet activation modulating ox-LDL pathways

Background: Proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) lower LDL-cholesterol and slow atherosclerosis preventing cardiovascular events. While it is known that circulating PCSK9 enhances platelet activation (PA) and that PCSK9i reduce it, the underlying mechanism is not still clarified. Methods: In a multicenter before–after study in 80 heterozygous familial hypercholesterolemia (HeFH) patients on treatment with maximum tolerated statin dose ± ezetimibe, PA, soluble-NOX2-derived peptide (sNOX2-dp), and oxidized-LDL (ox-LDL) were measured before and after six months of PCSK9i treatment. In vitro study investigates the effects of plasma from HeFH patients before and after PCK9i on PA in washed platelets (wPLTs) from healthy subjects. Results: Compared to baseline, PCSK9i reduced the serum levels of LDL-c, ox-LDL, Thromboxane (Tx) B2, sNOX2-dp, and PCSK9 (p Conclusions: PCSK9i treatment reduces PA modulating NOX2 activity and in turn ox-LDL formation in HeFH patients