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High concentrations of free radicals are present in the blood of obese patients. Free radicals are associated with endothelial dysfunction, diabetes, and neoplastic transformation, all conditions that are closely related to obesity. The purpose of our study was to determine whether bariatric surgery modifies the production of free radicals in obese patients. In total, 20 patients with morbid obesity, who were candidates for laparoscopic sleeve gastrectomy (SG), and 18 controls were enrolled in the study. Oxidative stress was studied in obese subjects before and after sleeve gastrectomy. The evaluation of oxidative stress was carried out on blood samples using electron paramagnetic resonance, a refined spectroscopic technique used to identify and quantify the major free radicals, such as •OH, O2•, ONOO-, and NO. Oxidative stress was higher in subjects with morbid obesity prior to surgery, compared to the controls (CP• 9.9 ± 0.3 µM vs. 5.8 ± 0.2 µM). After SG, values decreased to levels comparable to those of controls (CP• 5.4 ± 0.2 µM). Further analysis identified O2• as the main free radical responsible for the oxidative stress. Obesity is associated with an increased blood concentration of free radicals. The normalization of free radicals after sleeve gastrectomy highlights another important benefit of this bariatric surgery technique.

Background and objectives: There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. Methods: EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. Results: The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). Conclusion: Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS. [ABSTRACT FROM AUTHOR]

Background:Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells. Methods:Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique. Results:Our results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2% respectively, p

Red blood cells (RBCs) are recognized to be important pathogenetic determinants in several human cardiovascular diseases (CVD). Undergoing to functional alterations when submitted to risk factors, RBCs modify their own intracellular signaling and the redox balance, shift their status from antioxidant defense to pro-oxidant agents, become a potent atherogenic stimulus playing a key role in the dysregulation of the vascular homeostasis favoring the developing and progression of CVD. Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality with a prevalence from two to five more likely in woman, mainly attributed to accelerated atherosclerosis. The purpose of this study was to correlate the RA disease activity and the RBCs functional characteristics. Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. The disease activity, measured as the number of swollen and painful joints (DAS-28), was correlated with 1) the expression of RBCs estrogen receptors, which modulate the RBC intracellular signaling, 2) the activation of the estrogen-linked kinase ERK1/2, which is a key regulator of RBC adhesion and survival, and 3) the levels of inflammatory-and oxidative stress-related biomarkers, such as the acutephase reactants, the antioxidant capacity of plasma, the reactive oxidizing species formation and 3-nitrotyrosine. All the biomarkers were evaluated in RA patients at baseline and 6 months after treatment with disease-modifying anti-rheumatic drugs (DMARDs). We found, for the first times, that in RA patients 1) the DAS-28 correlated with RBC ER-α expression, and did not correlate with total antioxidant capacity of plasma; 2) the RBC ER-α expression correlated with systemic inflammatory biomarkers and oxidative stress parameters, as well as ERK1/2 phosphorylation; and 3) the DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. These findings represent an important advance in the study of RA determinants favoring the developing of CVD, because strongly suggest that RBCs could also participate in the vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α. [ABSTRACT FROM AUTHOR]

Research has been conducted on the peroxynitrite. The reaction of peroxynitrite with human methemoglobin has been analyzed via the spectroscopic techniques and the results indicate that heme in this methemoglobin reacts bimolecularly with peroxynitrite in the absence of bicarbonate and is back-reduced by the reaction products.

Research has been conducted on the strong oxidant peroxynitrite that is involved in cell injury. The use of mass spectrometry in determining the modifications in oxyhemoglobin induced by peroxynitrite/CO (sub)2 is described.

A study was conduced on thiol function in S-nitroso targeting to red blood cells using spectrophotometry and electron paramagnetic resonance. The biochemical properties of two nitric oxide donors, the S-nitroso adduct of bovine serum albumin and the S-nitroso adduct of L-glutathione were examined. Results indicated that sulfhydryl groups have a regulatory function in NO targeting to plasma red blood cells.