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      Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases

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          Abstract

          Introduction: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. Methods: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. Results: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). Conclusion: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

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          Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study

          Elevated sputum eosinophil counts predict asthma exacerbations and responsiveness to inhaled corticosteroids but are impractical to measure in primary care. We investigated the relation between blood eosinophil count and prospective annual asthma outcomes for a large UK cohort.
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            Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment.

            Free radicals and other so-called 'reactive species' are constantly produced in the brain in vivo. Some arise by 'accidents of chemistry', an example of which may be the leakage of electrons from the mitochondrial electron transport chain to generate superoxide radical (O2*-). Others are generated for useful purposes, such as the role of nitric oxide in neurotransmission and the production of O2*- by activated microglia. Because of its high ATP demand, the brain consumes O2 rapidly, and is thus susceptible to interference with mitochondrial function, which can in turn lead to increased O2*- formation. The brain contains multiple antioxidant defences, of which the mitochondrial manganese-containing superoxide dismutase and reduced glutathione seem especially important. Iron is a powerful promoter of free radical damage, able to catalyse generation of highly reactive hydroxyl, alkoxyl and peroxyl radicals from hydrogen peroxide and lipid peroxides, respectively. Although most iron in the brain is stored in ferritin, 'catalytic' iron is readily mobilised from injured brain tissue. Increased levels of oxidative damage to DNA, lipids and proteins have been detected by a range of assays in post-mortem tissues from patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, and at least some of these changes may occur early in disease progression. The accumulation and precipitation of proteins that occur in these diseases may be aggravated by oxidative damage, and may in turn cause more oxidative damage by interfering with the function of the proteasome. Indeed, it has been shown that proteasomal inhibition increases levels of oxidative damage not only to proteins but also to other biomolecules. Hence, there are many attempts to develop antioxidants that can cross the blood-brain barrier and decrease oxidative damage. Natural antioxidants such as vitamin E (tocopherol), carotenoids and flavonoids do not readily enter the brain in the adult, and the lazaroid antioxidant tirilazad (U-74006F) appears to localise in the blood-brain barrier. Other antioxidants under development include modified spin traps and low molecular mass scavengers of O2*-. One possible source of lead compounds is the use of traditional remedies claimed to improve brain function. Little is known about the impact of dietary antioxidants upon the development and progression of neurodegenerative diseases, especially Alzheimer's disease. Several agents already in therapeutic use might exert some of their effects by antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone.
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              Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 June 2020
                June 2020
                : 21
                : 12
                : 4339
                Affiliations
                [1 ]Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; liliya.chamitava@ 123456univr.it (L.C.); lucia.cazzoletti@ 123456univr.it (L.C.); elisabetta.zanolin@ 123456univr.it (M.E.Z.)
                [2 ]Unit of Respiratory Medicine, Department of Medicine, University of Verona, 37134 Verona, Italy; marcello.ferrari@ 123456univr.it
                [3 ]Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; vgla@ 123456jhu.edu
                [4 ]Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan; anezarao@ 123456gmail.com
                [5 ]U.O. Mutagenesi e Prevenzione Oncologica, Ospedale Policlinico San Martino, 16132 Genova, Italy; paolo.degan@ 123456hsanmartino.it
                [6 ]Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy; agfois@ 123456uniss.it (A.G.F.); sara.solveig.fois@ 123456gmail.com (S.S.F.)
                [7 ]Unit of Respiratory Diseases, University Hospital Sassari (AOU), 07100 Sassari, Italy; elisabetta.zinellu@ 123456aousassari.it
                [8 ]Department of Medicine, Section of General Medicine and Atherothrombotic and Degenerative Diseases, University of Verona, 37134 Verona, Italy; annamaria.frattapasini@ 123456univr.it
                [9 ]Unit of Hygiene and Preventive, Environmental and Occupational Medicine, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy; morena.nicolis@ 123456univr.it
                [10 ]Unit of Occupational Medicine, Azienda Ospedaliero Universitaria di Verona, 37134 Verona, Italy; mario.olivieri@ 123456univr.it
                [11 ]Division of Respiratory Diseases, ERCS, S. Matteo, Hospital University of Pavia, 27100 Pavia, Italy; angelo.corsico@ 123456unipv.it
                [12 ]Department of Public Health and Pediatrics, University of Turin, 10126 Turin, Italy; roberto.bono@ 123456unito.it
                Author notes
                [* ]Correspondence: pirina@ 123456uniss.it
                Author information
                https://orcid.org/0000-0001-5330-572X
                https://orcid.org/0000-0001-7661-7785
                https://orcid.org/0000-0001-6105-0376
                https://orcid.org/0000-0002-2471-6594
                https://orcid.org/0000-0003-1457-8025
                Article
                ijms-21-04339
                10.3390/ijms21124339
                7353047
                32570774
                da12f843-1253-4d8a-a1b3-c7b7739d0954
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 May 2020
                : 16 June 2020
                Categories
                Article

                Molecular biology
                oxidative stress,inflammation,asthma,chronic bronchitis
                Molecular biology
                oxidative stress, inflammation, asthma, chronic bronchitis

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