Does influenza A infection increase oxidative damage?

Considerable data implicate oxidative damage in influenza pathogenesis. We examined temporal changes in oxidative damage using accurate biomarkers in an adult cohort with acute influenza infection and their relationships with clinical parameters. Clinical information and blood samples were collected during their acute illness and 3 months later. A fatigue questionnaire was administered 3 months following influenza infection. Thirty-five patients (mean age, 34 years) with polymerase chain reaction-confirmed influenza A infection were included; all patients returned for follow-up assessments. Adjusted levels of plasma F2-isoprostanes, total hydroxyeicosatetraenoic products (HETEs), 7beta-hydroxycholesterol and 7-ketocholesterol, serum gamma-glutamyltransferase, and high-sensitivity C-reactive protein (hsCRP) were increased during the acute illness compared with age-matched controls. Despite clinical recovery, levels of these biomarkers remained higher at month 3 compared with controls. A proportion of patients had persistent symptoms such as fatigue (23%), myalgia (14%), and arthralgia (11%) at month 3. Patients with significant fatigue had higher baseline levels of plasma F2-isoprostanes, F4-neuroprostanes, and total HETEs compared to those without fatigue. By contrast, patients with persistent arthralgia and myalgia had higher baseline levels of serum hsCRP compared to those without these symptoms. Our observations lead to the hypothesis that oxidative damage participates in the pathogenesis of influenza infection and postinfectious fatigue.published_or_final_versio

Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

published_or_final_versio

Association of mast cell-derived VEGF and proteases in dengue shock syndrome

Background: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls. Methodology/Principal Findings: The study was performed at Children\u27s Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. Conclusions: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity

The Annals: Welcoming the future of Medicine

10.47102/annals-acadmedsg.2021530Annals of the Academy of Medicine, Singapore5012877-87

Does radiotherapy increase oxidative stress? A study with nasopharyngeal cancer patients revealing anomalies in isoprostanes measurements

This study aimed to examine if exposure to ionizing radiation during clinical radiotherapy (RT) causes increased oxidative damage. Seven patients with nasopharyngeal cancer (NPC) who underwent RT took part in this controlled-trial study. Blood and urine samples were obtained for F 2-isoprostanes (F 2-IsoPs) measurement. Urinary F 2-IsoPs levels were elevated pre-treatment and remained high (but did not increase) during treatment, but decreased to the normal range after treatment. Plasma F 2-IsoPs decreased significantly after the start of treatment before rising midway through treatment. Levels decreased significantly to below baseline following treatment. However, the patients were observed to have substantially lower levels of plasma esterified arachidonic acid (AA) residues than controls. The data shows that NPC is associated with elevated F 2-isoprostanes in urine and in plasma after correction for decreased AA levels. RT did not increase these levels and, indeed, was associated with falls in F 2-IsoPs. The validity and usefulness of correction of plasma F 2-IsoPs for lowered AA levels is discussed. © 2010 Informa UK Ltd.link_to_subscribed_fulltex

Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels

Objective: There is considerable controversy about what constitutes optimal zinc intakes in patients with type 2 diabetes mellitus. Several studies suggest that higher zinc intakes improve vascular function and decrease oxidative damage. We aimed to assess the effects of zinc supplementation using a range of reliable biomarkers of oxidative damage and vascular function in patients with type 2 diabetes. Methods: Forty male type 2 diabetic patients were supplemented either with 240mg/day of zinc as zinc gluconate (n=20) or with placebo (n=20) for 3 months. Blood and spot urine samples were taken at baseline, days 3 and 7, months 1, 2 and 3 during supplementation and 1 month after cessation. Serum zinc, reliable biomarkers of oxidative damage (F 2-isoprostanes, neuroprostanes, cholesterol oxidation products, allantoin) as well as hydroxyeicosatetraenoic acid products and vascular-related indices (augmentation index, pulse wave velocity and aortic pressure) were measured. Results: Despite significantly higher levels of serum zinc in the treatment group, markers of oxidative damage, levels of hydroxyeicosatetraenoic acid products and vascular indices were unchanged by zinc supplementation during the four-month study period. Conclusion: Improving the zinc status in patients with type 2 diabetes with normal zinc levels did not have any impact on oxidative damage and vascular function, and such supplementation may not be generally beneficial in these individuals. © 2011 Elsevier Ireland Ltd.link_to_subscribed_fulltex

Decline in changing montreal cognitive assessment (MoCA) scores is associated withpost-stroke cognitive decline determined by a formal neuropsychological evaluation

© 2017 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objectives We aimed to examine changes in the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores within a one-year period after stroke/transient ischemic attack (TIA) in associating cognitive decline determined by a formal neuropsychological test battery. Methods Patients with ischemic stroke/TIA received MoCA and MMSE at baseline within 14 days after stroke/TIA, at 3 lusmn;6 months and 1-year follow-ups. The scores of MoCA and MMSE were considered to have declined if there were a reduction of -2 points in the respective scores measured across two time points. The decline in neuropsychological diagnosis transitional status was defined by a category transition from no cognitive impairment or any cognitive impairment to a more severe cognitive impairment or dementia. Results 275 patients with a mean age of 59.8 lusmn; 11.6 years, and education of 7.7 lusmn; 4.3 years completed all the assessments at baseline, 3 lusmn;6 months and 1-year follow-ups. A decline in MoCA scores from 3 lusmn;6 months to 1 year was associated with higher risk of decline in diagnosis transitional status (odd ratio = 3.21, p = 0.004) in the same time period whereas there was no association with a decline in MMSE scores. Conclusions The decline in MoCA scores from 3 lusmn;6 months to 1 year after stroke/TIA has three times higher risk for decline in the diagnosis transitional status. The decline of MoCA scores (reduction > 2points) is associated with the decline in neuropsychological diagnosis transitional status

Biomarkers of oxidative damage in cigarette smokers: Which biomarkers might reflect acute versus chronic oxidative stress?

Cigarette smoking predisposes to the development of multiple diseases involving oxidative damage. We measured a range of oxidative damage biomarkers to understand which differ between smokers and nonsmokers and if the levels of these biomarkers change further during the act of smoking itself. Despite overnight abstinence from smoking, smokers had higher levels of plasma total and esterified F 2-isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), F 4-neuroprostanes, 7-ketocholesterol, and 24- and 27-hydroxycholesterol. Levels of urinary F 2-isoprostanes, HETEs, and 8-hydroxy-2′-deoxyguanosine were also increased compared with age-matched nonsmokers. Several biomarkers (plasma free F 2-isoprostanes, allantoin, and 7β-hydroxycholesterol and urinary F 2-isoprostane metabolites) were not elevated. The smokers were then asked to smoke a cigarette; this acute smoking elevated plasma and urinary F 2- isoprostanes, plasma allantoin, and certain cholesterol oxidation products compared to presmoking levels, but not plasma HETEs or urinary 8-hydroxy-2′-deoxyguanosine. Smokers showed differences in plasma fatty acid composition. Our findings confirm that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking. Thus, different biomarkers do not measure identical aspects of oxidative stress. © 2011 Elsevier Inc.link_to_subscribed_fulltex