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Background: The purpose of this study was to investigate how 8-isoprostanes, used as a marker of airway oxidative stress, were related to sinus disease and asthma., Methods: We analyzed samples and data from two separate studies, one investigating sinonasal disease in asthma, the other investigating the effect of BMI on airway disease. We measured airway (nasal lavage) 8-isoprostanes and investigated the relationship with measures of sinus and asthma symptoms, asthma control and lung function., Results: The study of people with sinonasal disease and poorly controlled asthma included 48 obese, 31 overweight and 23 lean participants. In multivariate analysis, nasal lavage 8-isoprostane levels increased with increasing BMI (p < 0.01), and were higher in Caucasian than African American participants (p = 0.01). Sinus symptoms were inversely related to nasal 8-isoprostanes (p = 0.02) independent of BMI and Race. In the study investigating the effect of BMI on airway disease, we enrolled 13 controls with obesity and 21 people with obesity and asthma: 8-isoprostane levels were higher in obese controls than in obese people with asthma (p < 0.01), and levels were inversely related to sinus symptoms (p = 0.02) and asthma control (p < 0.01)., Interpretation: 8-isoprostanes in nasal lavage are increased in obesity, and increased in Caucasians compared with African Americans. However, levels are higher in obese controls than obese people with asthma, and appear inversely related to symptoms of airway disease., Clinical Implication: Airway 8-isoprostanes likely reflect complex oxidative signaling pathways, which are altered in obesity and those of different race, rather than being a simple marker of airway oxidative injury., Capsule Summary: Increased airway oxidative signaling (8-isoprostanes), may reflect normal physiology in the setting of obesity, as decreased levels are associated with disease activity in people with chronic sinonasal disease and asthma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The inflammatory events related to prostaglandins may play an important role in the progression of vessel stenosis. The aim of this study was to investigate the monocyte PTGES and 15-PGDH gene expression levels and the serum 13,14-dihyro-15-keto-PGF2α value involved in PGE2 metabolism in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520, miR-1297 and miR-34 were studied on the gene expression levels. A total of sixty subjects referred for coronary angiography including healthy controls (stenosis <5%), subjects with stent no restenosis) SNR, stenosis <5%) and subjects in stent restenosis (ISR, restenosis >70%) were participated in the study. The gene expression levels and the serum 13,14-dihyro-15-keto- PGF2α value were measured by RT-qPCR and ELISA techniques, respectively. Moreover, the effects of miRNAs on the gene expression levels were investigated by the monocyte transfection of miR/PEI complexes. The PTGES and 15-PGDH gene expression levels and serum 13,14-dihyro-15-keto- PGF2α value increased significantly (P <0.05). Based on the miR-520 and miR-34 expression levels, the miR/PEI transfection studies were confirmed significantly the gene expression changes. The monocyte PGE2 synthesis pathway is actively considered in the SNR and ISR patients and might be related to miR-34 and miR-520 functions., (Copyright © 2020. Published by Elsevier B.V.)

Background: A small number of studies have confirmed the presence of oxidative damage in patients with Duchenne muscular dystrophy (DMD). Nevertheless, it is unknown if there a relationship of circulating markers of oxidative stress with a muscle injury., Objective: We evaluated if oxidative damage and anti-oxidant markers are associated with muscle damage in DMD., Methods: This cross-sectional study included 24 patients with DMD classified in ambulatory and non-ambulatory. Markers of muscle damage (creatine kinase [CK]), oxidative damage (malondialdehyde [MDA], and 8-isoprostane), anti-oxidant function (Thiol and mRNA of NRF2 and NF-κB) and nitric oxide (NO) were quantified in circulation., Results: Total NO, MDA, and 8-isoprostane concentrations were significantly (p < 0.05) higher, and thiol concentration was lower in non-ambulatory than ambulatory patients. A significant correlation (p < 0.05) between muscle injury (evaluated by Vignos scale) with CK (r = -0.382), NO (r = 0.444), MDA (r = 0.503), 8-isoprostanes (r = 0.435) and thiol (r = -0.430) was observed., Conclusion: These findings suggest that non-ambulatory have high oxidative damage and low anti-oxidant function than ambulatory patients with DMD. Total nitric oxide and oxidative damage plasma markers increase, but the anti-oxidant marker thiol decreases with a muscle injury in boys with DMD. The findings of this study suggest that these markers could be considered as goods indicators of oxidative damage in longitudinal studies to evaluate the muscle injury during DMD progression. Additionally, these findings add new information about the pathophysiology of DMD., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia., Subjects and Methods: Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI., Results: The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD., Conclusion: Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.

Oxidative stress in the follicular fluid (FF) is thought to be responsible for the abnormal development of oocytes. In our study patients with polycystic ovarian syndrome (PCOS), endometriosis, and tubal infertility factor (TIF), and healthy women with a male factor of infertility, were prospectively enrolled. From each patient, a sample of individual FF was collected from a dominant follicle. Concentration levels of TAS, 8-IP, 8-OHdG, and AMH were determined. In women with PCOS, we found significantly lower values of oxidative stress markers in the FF. 8-IP and TAS levels were lower in the FF of women with endometriosis. In women with TIF, we also found significantly lower values of all tested markers in the FF, except for 8-OHdG and AMH. We wanted to see whether the biomarker measured in the FF in an individual diagnosis could predict a successfully obtained embryo from this particular follicle. The FF 8-OHdG result in PCOS patients stood out and proved to be a good predictive marker of matured and fertilized oocytes in these patients. Further research is needed to be able to apply the acquired knowledge in improving the outcome of IVF procedures.

Oxidative stress is a pathological condition characterized by an imbalance between body's antioxidant defenses and oxidizing agents, resulting in damage of endogenous molecules. These products can be used as markers of oxidative conditions; in particular, isoprostanes (IsoPs) come from the reaction of arachidonic acid with reactive oxygen species (ROS) and are currently defined as gold markers of oxidative stress in urine. Our main goal was the development of a reliable analytical method for the determination and quantification of the IsoPs in human urine by dispersive Liquid-Liquid Micro Extraction (dLLME) coupled with micro Solid Phase Extraction (μSPE) clean-up and HPLC-MS/MS analysis. The selected compounds are present in very small concentration in urine, furthermore, due to relevant matrix effect, they are challenging for ESI-MS/MS analysis. This approach provided selectivity and sensitivity for 8-isoprotaglandine F2α (8-iso-PGF2α), the "gold" OS marker, together with the main isomers. dLLME extraction allowed a significant enrichment factor and μSPE clean-up provided the removal of ion-suppressing compounds from the sample resulting in low matrix effect. The chromatographic separation was also challenging as the target compounds possess very similar chemical characteristics, so experimental conditions were carefully tuned. The reported method represents a useful tool for the detection of IsoPs in urine taking advantage of the combination of dLLME extraction and μSPE clean-up; overall recoveries were above 50 % and matrix effects were ≤15 %, with LOQs ranging between 0.020 and 0.060 ng mL -1 . The procedure is easy to use and rapid allowing the removal of interfering compounds and matrix effect maintaining a highly sensitive determination., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Isoprostanes are physiopathologic mediators of oxidative stress, resulting in lipid peroxidation. 8-isoprostane seems particularly useful for measuring oxidative stress damage. However, no reference range values are available for 8-isoprosante in exhaled breath condensate (EBC) of healthy adults, enabling its meaningful interpretation as a biomarker. We conducted this systematic review and meta-analysis according to the protocol following PROSPERO (CRD42020146623). After searching and analyzing the literature, we included 86 studies. After their qualitative synthesis and risk of bias assessment, 52 studies were included in meta-analysis. The latter focused on studies using immunological analytical methods and investigated how the concentrations of 8-isoprostane differ based on gender. We found that gender had no significant effect in 8-isoprostane concentration. Among other studied factors, such as individual characteristics and factors related to EBC collection, only the device used for EBC collection significantly affected measured 8-isoprostane concentrations. However, adjustment for the factors related to EBC collection, yielded uncertainty whether this effect is due to the device itself or to the other factors. Given this uncertainty, we estimated the reference range values of 8-isoprostane stratified by gender and EBC collection device. A better standardization of EBC collection seems necessary; as well more studies using chemical analytical methods to extend this investigation., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objective: To investigate the effectiveness of combining the 8-isoprostane and nitric oxide (NO) levels in exhaled breath condensate (EBC) with the clinical pulmonary infection score (CPIS) to assess ventilator-associated pneumonia (VAP) in patients on mechanical ventilation., Methods: Thirty-two patients with VAP served as the observation group and 32 patients without VAP served as the control group. The correlations of 8-isoprostane and NO levels in EBC with CPIS, chest X-ray score, oxygenation index, and lung injury score (LIS) were analyzed. The area under the curve (AUC) was compared with experimental data using the receiver operating characteristic curve (ROC) to predict VAP., Results: The 8-isoprostane and NO levels in EBC of VAP patients on mechanical ventilation were positively correlated with CPIS, chest X-ray score, and LIS, but negatively correlated with oxygenation index. The AUC of simplified CPIS combined with 8-isoprostane and NO levels in EBC for predicting VAP was 0.914, which suggests that this is a highly effective for making a diagnosis., Conclusions: The simplified CPIS combined with the 8-isoprostane and NO levels in EBC of patients on mechanical ventilation is effective for evaluating and diagnosing VAP. 8-Isoprostane and NO levels in EBC could be used as biomarkers to evaluate VAP.

Introduction: Prostaglandins are critical for the onset and progression of labor in mammals, and are formed by the metabolism of arachidonic acid. The products of arachidonic acid, 2-arachidonoylglycerol (2-AG), and anandamide (AEA) have a similar lipid back bone but differing polar head groups, meaning that identification of these products by immunoassay can be difficult., Materials and Methods: In the current study, we present the use of mass spectrometry as multiplex method of identifying the specific end products of arachidonic and anandamide metabolism by human derived amnion explants treated with either an infectious agent (LPS) or inflammatory mediator (IL-1β or TNF-α)., Results: Human amnion tissue explants treated with LPS, IL-1β, or TNF-α increased production of prostaglandin E 2 (PGE 2 ; p < 0.05) but decreased PGFM. Overall, PGE 2 production was greater compared to the other prostaglandins and prostamides irrespective of treatment., Conclusions: The findings of the current study are in keeping with the literature which describes amnion tissues as predominantly producing PGE 2 . The use of mass spectrometry for the differential identification of prostaglandins, prostamides, and other eicosanoids may help better elucidate mechanisms of preterm labor, and lead to new targets for the prediction of risk for preterm labor and/or birth., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hajizadeh Maleki, B, Tartibian, B, and Chehrazi, M. Effects of aerobic, resistance, and combined exercise on markers of male reproduction in healthy human subjects: a randomized controlled trial. J Strength Cond Res 33(4): 1130-1145, 2019-The effects of moderate intensity treadmill exercise training (MI), resistance training (RT), and combined treadmill + resistance training (CT) on markers of male reproductive function including seminal markers of oxidative stress and inflammation, and semen quality and sperm DNA integrity were evaluated in healthy human subjects. A total of 376 healthy sedentary male volunteers (aged 25-40) were screened and 282 were randomized into 4 treatment groups: MI (n = 71), RT (n = 71), CT (n = 71), and nonexercise (NON-EX, n = 70) groups for an experimental period of 24 weeks. After the intervention, compared with the NON-EX group, all 3 MI, RT, and CT exercise modalities showed significantly reduced body mass, fat percent, waist circumference, reactive oxygen species, interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α and improved maximal oxygen uptake (V[Combining Dot Above]O2max), progressive motility, sperm morphology, sperm concentration and sperm DNA integrity, as indicated by a decrease of percentage of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling-positive sperm cells (p ≤ 0.05). Body mass index, semen volume, number of spermatozoa, superoxide dismutase, catalase, total antioxidant capacity, malondialdehyde, and 8-isoprostane improved significantly in the MI and CT groups (p ≤ 0.05) but not significantly in the RT group (p > 0.05). In summary, all 3 MI, RT, and CT interventions attenuate seminal markers of inflammation and oxidative stress and improve body composition, semen quality parameters, and sperm DNA integrity in the studied population. In respect to all the aspects studied, those men who took part in MI intervention had the best results. Considering the seminological parameters, however, CT had a synergistic effect and was superior over the other interventions used.

Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols from Malus Pumila Miller cv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrial β-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward β-oxidation.

Oxidative stress contributes to dysfunctional immune responses and predisposes dairy cattle to several metabolic and inflammatory-based diseases. Although the negative effects of oxidative stress on transition cattle are well established, biomarkers that accurately measure oxidative damage to cellular macromolecules are not well defined in veterinary medicine. Measuring 15-F 2t -isoprostane, a lipid peroxidation product, is the gold standard biomarker for quantifying oxidative stress in human medicine. The aim of our study was to determine whether changes in 15-F 2t -isoprostane concentrations in plasma and milk could accurately reflect changes in oxidant status during different stages of lactation. Using liquid chromatography-tandem mass spectrometry, 15-F 2t -isoprostane concentrations were quantified in milk and plasma of 12 multiparous Holstein-Friesian cows that were assigned to 3 different sampling periods, including the periparturient period (1-2 d in milk; n = 4), mid lactation (80-84 d in milk; n = 4), and late lactation (183-215 d in milk; n = 4). Blood samples also were analyzed for indicators of oxidant status, inflammation, and negative energy balance. Our data revealed that 15-F 2t -isoprostane concentrations changed at different stages of lactation and coincided with changes in other gauges of oxidant status in both plasma and milk. Interestingly, milk 15-F 2t -isoprostane concentrations and other indices of oxidant status did not follow the same trends as plasma values at each stage of lactation. Indeed, during the periparturient period, systemic 15-F 2t -isoprostane increased significantly accompanied by an increase in the systemic oxidant status index. Milk 15-F 2t -isoprostane was significantly decreased during the periparturient period compared with other lactation stages in conjunction with a milk oxidant status index that trended lower during this period. The results from this study indicate that changes in 15-F 2t -isoprostane concentrations in both milk and plasma may be strong indicators of an alteration in redox status both systemically and within the mammary gland., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: In the field of nanoparticle exposure biomonitoring, oxidative stress biomarkers measured in exhaled breath condensate appear promising to detect early respiratory effects in workers handling nanomaterials. However, condensation is known for its poor efficiency in collecting non-volatiles in exhaled breath, leading to the low sensitivity of such measurements. Moreover, to be easily used in field studies on large groups of workers, the collection device must be disposable and convenient., Objectives: In this study, we have tested a totally disposable commercial device that allows for the easy dry collection of exhaled air after filtration on a patented filter. The suitability and efficiency of the SensAbues (SB) device for collecting 8-isoprostane were evaluated and compared to the RTube (RT)., Methods: Seven healthy volunteers performed two 15 min collections of exhaled breath, one with the SB and one with the RT. Blank devices were used to determine the background levels induced by each device. 8-isoprostane was measured in all samples using an EIA technique., Results: The levels of 8-isoprostane in the exhaled breath of volunteers after collection with the SB were significantly higher than those after collection with the RT. Moreover, the levels obtained in volunteers with the SB were significantly higher than background levels obtained in blank devices, which was not the case for the RT., Conclusions: This is the first study to report the ability of the SB device to collect and measure 8-isoprostane in exhaled breath. The proposed method offers better sensitivity than a classical collection with the RT device and should be further explored before future application in biomonitoring studies.

Objective: Airway oxidative stress and inflammation are likely to be involved in sleep disordered breathing (SDB) in children. We aimed to measure concentrations of 8-isoprostane (8-IsoP) in the exhaled breath condensate (EBC) and exhaled nitric oxide (FE NO ) in patients with SBD and healthy children, in order to assess the relationship between these two biomarkers, disease severity, and overnight changes., Methods: Patients with SDB (n = 46) and healthy controls (n = 20) aged 4.5-15.1 years (M/F: 36/30) underwent exhaled measurements. Patients with SDB underwent standard polysomnography to define primary snoring (PS: AHI < 1) and obstructive sleep apnea (OSA). Upon awakening the following morning, FE NO was measured and EBC was collected for the measurement of EBC 8-IsoP., Results: OSA patients yielded higher awakening levels of 8-IsoP in EBC than PS patients and control subjects. The 8-IsoP levels, though not FE NO , correlated with AHI (r = 0.40, p = 0.003) and SaO2 (r = -0.50, p = 0.001). Cut-off levels of 8-IsoP predicted OSA with a high AUC value (0.84, p = 0.000). Sensitivity and specificity for 8-IsoP levels above the percentile 50 (33.3 pg/mL) were 76.5% and 78.1%, respectively. 8-IsoP levels did not change from the evening to morning session, whereas morning FE NO levels rose significantly only in patients with mild OSA (p = 0.03)., Conclusion: Levels of 8-IsoP, though not FE NO , distinguish children with OSA from those with PS or healthy, correlate with disease severity and closely predict OSA in the whole sample., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Associations between outdoor air pollution and asthma in adults are still scarce, and the underlying biological mechanisms are poorly understood. Our aim was to study the associations between 1) long-term exposure to outdoor air pollution and current asthma, 2) exhaled 8-isoprostane (8-iso; a biomarker related to oxidative stress) and current asthma, and 3) outdoor air pollution and exhaled 8-iso.Cross-sectional analyses were conducted in 608 adults (39% with current asthma) from the first follow-up of the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Data on nitrogen dioxide, nitrogen oxides, particulate matter with a diameter ≤10 and ≤2.5 µm (PM 10 and PM 2.5 ), road traffic, and ozone (O 3 ) were from ESCAPE (European Study of Cohorts for Air Pollution Effects) and IFEN (French Institute for the Environment) assessments. Models took account of city and familial dependence.The risk of current asthma increased with traffic intensity (adjusted (a)OR 1.09 (95% CI 1.00-1.18) per 5000 vehicles per day), with O 3 exposure (aOR 2.04 (95% CI 1.27-3.29) per 10 µg·m -3 ) and with exhaled 8-iso concentration (aOR 1.50 (95% CI 1.06-2.12) per 1 pg·mL -1 ). Among participants without asthma, exhaled 8-iso concentration increased with PM 2.5 exposure (adjusted (a)β 0.23 (95% CI 0.005-0.46) per 5 µg·m -3 ), and decreased with O 3 and O 3-summer exposures (aβ -0.20 (95% CI -0.39- -0.01) and aβ -0.52 (95% CI -0.77- -0.26) per 10 µg·m -3 , respectively).Our results add new insights into a potential role of oxidative stress in the associations between outdoor air pollution and asthma in adults., Competing Interests: Conflict of interest: V. Siroux reports personal fees (speaker honorarium) from Teva, AstraZeneca and Novartis, outside the submitted work., (Copyright ©ERS 2018.)

Oxidative stress plays an important role in chronic respiratory diseases where the use of non-invasive ventilation seems to reduce the oxidative damage. Data on acute respiratory failure are still lacking. The aim of the study is to investigate the interplay between oxidative stress and acute respiratory failure, and the role of non-invasive ventilation in this setting. We enrolled 60 patients suffering from acute respiratory failure (PaO 2 /FiO 2 ratio <300): 30 consecutive patients treated with non-invasive ventilation and 30 consecutive patients treated with conventional oxygen therapy. Serum levels of soluble Nox2-derived peptide (sNOX2-dp), a marker of NADPH-oxidase activation, and 8-iso-PGF2α and H 2 O 2 , markers of oxidative stress, were evaluated at baseline and after 3 h of treatment. At baseline, higher values of sNOX2-dp, 8-iso-PGF2α and H 2 O 2 are associated with lower values of PaO 2 /FiO 2 ratio (p < 0.001). After 3 h, serum levels of sNOX2-dp, H 2 O 2 , and 8-iso-PGF2α significantly decrease in patients treated with non-invasive ventilation, but not in patients treated with conventional oxygen therapy. Delta changes of oxidative stress parameters correlate inversely with the delta changes of PaO 2 /FiO 2 (R = -0.623, p < 0.001 for sNOX2-dp; R = -0.428, p < 0.001 for H 2 O 2 ; R = -0.548, p < 0.001 for 8-iso-PGF2α). In the acute respiratory failure setting, treatment with non-invasive ventilation reduces the levels of oxidative stress in the first hours. This reduction is associated with an improvement of PaO 2 /FiO 2 ratio as well as in a reduction of NADPH-oxidase activity.

The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/antioxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F 2α (8-isoprostane), a marker of oxidative stress, in the exhaled breath condensate of 17 non-smoking patients with CF, in stable phase, and in 17 age-matched healthy subjects. The levels of GSH and total antioxidant capacity in patients with CF were significantly lower than in healthy subjects (0.66 ± 0.07 μM versus 1.30 ± 0.08 μM, p < 0.001, respectively for GSH; 0.157 ± 0.02 mM and 0.32 ± 0.01 mM, p < 0.05, respectively for antioxidant capacity). The concentration of 8-isoprostane was higher in CF than in healthy controls (26.5 ± 0.1 pg ml -1 versus 10.8 ± 0.1 pg ml -1 ; p < 0.05). A low concentration of antioxidant agents, particularly glutathione, and increased levels of 8-isoprostane in the exhaled breath suggest an altered oxidizing environment in the airways of patients with CF. This altered redox environment in the epithelial liquid surface may contribute to progressive lung disease.

Background: There is a need for easily measurable biomarkers that are able to identify different levels of asthma severity., Aim: To assess the association between peripheral blood cell counts, fractional nitric oxide in exhaled air (FeNO), urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and 8-isoprostane), and asthma severity in adult patients from the general population., Methods: In the Gene Environment Interactions in Respiratory Diseases study, 287 subjects with asthma (aged 20-64) were identified from the general population in Verona (Italy) (2008-2010). Self-reported asthma attacks, asthma-like symptoms and the use of hospital services in the past year were synthesized in a score of respiratory symptoms (SRS). The association of biomarkers with SRS and lung function measures (pre-bronchodilator FEV 1 % predicted and FEV 1 /FVC) was assessed using quasi-Poisson and Gaussian regression models, respectively., Results: Eosinophils (ratio of expected scores: RES[95%CI] = 1.19[1.09,1.30]), basophils (RES[95%CI] = 1.24[1.10,1.40]), lymphocytes (RES[95%CI] = 1.27[1.12,1.45]) and FeNO (RES[95%CI] = 1.18[1.02,1.37]) were positively associated with SRS. However, only eosinophils (RES[95%CI] = 1.15[1.02,1.30]) and lymphocytes (RES[95%CI] = 1.25[1.06,1.47]) showed an independent association. Furthermore, eosinophils (change in the expected outcome for 1-SD increase: CEO[95%CI] = -1.18[-2.09, -0.27]%), basophils (CEO[95%CI] = -1.24[-2.16, -0.33]%) and lymphocytes (CEO[95%CI] = -1.07[-1.99, -0.14]%) were individually, but not independently, associated with FEV 1 /FVC. Finally, neutrophils were negatively associated with FEV 1 % predicted (CEO[95%CI] = -2.22[-4.00, -0.44]%)., Conclusions: We identified a pattern of association between a set of biomarkers and asthma endotypes in adult patients from the general population, which could improve understanding of the heterogeneity and severity of the disease and could be useful in defining targeted therapeutic approaches.

Oxidative stress is a major factor explaining sperm dysfunction of spermatozoa surviving freezing and thawing and is also considered a major inducer of a special form of apoptosis, visible after thawing, in cryopreserved spermatozoa. To obtain further insights into the link between oxidative stress and the induction of apoptotic changes, stallion spermatozoa were induced to oxidative stress through redox cycling after exposure to 2-methyl-1,4-naphthoquinone (menadione), or hydroxyl radical formation after FeSO 4 exposure. Either exposure induced significant increases (p < 0.05) in two markers of lipid peroxidation: 8-iso-PGF 2α and 4-hydroxynonenal (4-HNE). While both treatments induced changes indicative of spermptosis (caspase-3 activation and decreased mitochondrial membrane potential) (p < 0.01), menadione induced sperm necrosis and a dramatic reduction in motility and thiol content in stallion spermatozoa. Thus, we provided evidence that oxidative stress underlies spermptosis, and thiol content is a key factor for stallion sperm function., (© 2017 Blackwell Verlag GmbH.)

Introduction: Type 1 diabetes is an insulin deficiency-based chronic disease. It leads to the development of hyperglycaemia, which plays a key role in the initiation and progression of tissue damage in patients with diabetes. This mostly results from oxidative stress, whose increased severity is observed in this group of patients. Increased levels of 8-isoprostanes are seen in many inflammatory diseases, including asthma, COPD and cystic fibrosis. These diseases demonstrated the usefulness of the exhaled breath condensate (EBC) for extracting material for markers of oxidative stress, including 8-isoprostanes. The purpose of this study was to assess the severity of oxidative stress measured with 8-isoprostane concentrations in the exhaled breath condensate in healthy subjects and in patients with type 1 diabetes with and without vascular complications., Material and Methods: 33 patients assigned to the control group, type 1 diabetes without complications group and type 1 diabetes group with advanced complications were included in the study. Retinopathy, nephropathy or neuropathy have been reported as a criterion distinguishing between complicated and uncomplicated diabetes. EBC was obtained for each subject. 8-isoprostane concentrations were determined in serum and EBC by ELISA., Results and Conclusions: Mean (± SD) blood levels of 8-isoprostane in patients with type 1 diabetes mellitus without complications and those with type 1 diabetes with advanced complications were significantly higher compared to the control group (178.17 [135.73] vs. 183.34 [200.41] vs. 47.13 [25.20] pg/ml; p < 0.05). The mean (± SD) concentration of 8-isoprostane in EBC was lower in diabetic patients with type 1 diabetes with advanced complications than in patients with type 1 diabetes without advanced complications and in the control group (8.32 [4.60] vs. 19.13 [22.35] vs. 28.17 [35.11] pg/ml; p < 0.05). Measurement of 8-isoprostanes in the EBC in patients with type 1 diabetes does not appear to be a good diagnostic tool for monitoring the activity of oxidative stress in these patients.

Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Significant controversy exists regarding the potential clinical benefit of normobaric hyperoxia (NBO) in patients with traumatic brain injury (TBI). This study consisted of two aims: 1) to assess whether NBO improves brain oxygenation and metabolism and 2) to determine whether this therapy may increase the risk of oxidative stress (OxS), using 8-iso-Prostaglandin F2α (PGF2α) as a biomarker. Thirty-one patients with a median admission Glasgow Coma Scale score of 4 (min: 3, max: 12) were monitored with cerebral microdialysis and brain tissue oxygen sensors and treated with fraction of inspired oxygen (FiO 2 ) of 1.0 for 4 h. Patients were divided into two groups according to the area monitored by the probes: normal injured brain and traumatic penumbra/traumatic core. NBO maintained for 4 h did not induce OxS in patients without preOxS at baseline, except in one case. However, for patients in whom OxS was detected at baseline, NBO induced a significant increase in 8-iso-PGF2α. The results of our study showed that NBO did not change energy metabolism in the whole group of patients. In the five patients with brain lactate concentration ([Lac] brain ) > 3.5 mmol/L at baseline, NBO induced a marked reduction in both [Lac] brain and lactate-to-pyruvate ratio. Although these differences were not statistically significant, together with the results of our previous study, they suggest that TBI patients would benefit from receiving NBO when they show indications of disturbed brain metabolism. These findings, in combination with increasing evidence that TBI metabolic crises are common without brain ischemia, open new possibilities for the use of this accessible therapeutic strategy in TBI patients.

This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO 2 , SiO 2, and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r=0.256, p=0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r=-0.272, p=0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the effect of calorie restriction and dietary antioxidant supplementation, separately or in combination, on the quality and quantity of sperm in male rats. Forty male rats were randomly allocated to four groups of 10 animals each, and fed for at least 86 days with an ad libitum diet (group 1), a restricted diet (group 2), an ad libitum diet and astaxanthin, vitamin E, and vitamin C supplements (group 3), or a restricted diet with astaxanthin, vitamin E, and vitamin C supplements (group 4). At the end of the study period, sperm count and motility were determined with a hemocytometer, and differences between the groups were analyzed by analysis of variance. In addition, total antioxidant capacity and 8-epi prostaglandin F2 alpha were measured at the beginning and end of the study period with an enzyme-linked immunosorbent assay method. After 86 days, a significantly higher sperm count was seen in group 4 compared to other groups. The percentage of immotile sperm was significantly decreased in groups 2, 3, and 4 compared to group 1. A significant increase in total antioxidant capacity was observed in group 3 (p = 0.02) and group 4 (p = 0.02) compared to groups 1 and 2. Antioxidant supplementation with or without calorie restriction had no significant effect on the serum isoprostane level in any group. Astaxanthinin, combined with vitamin E, vitamin C, and calorie restriction, was able to ameliorate, in part, infertility in male rats.

Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation. In turn, NF-κB up-regulates Twist2 expression, thereby fulfilling a positive feedback loop that activates the epithelial-mesenchymal transition program and enhances cancer stem cell (CSC)-like properties in BLBC. AKR1B1 expression promotes, whereas AKR1B1 knockdown inhibits, tumorigenicity and metastasis. Importantly, epalrestat, an AKR1B1 inhibitor that has been approved for the treatment of diabetic complications, significantly suppresses CSC properties, tumorigenicity, and metastasis of BLBC cells. Together, our study identifies AKR1B1 as a key modulator of tumor aggressiveness and suggests that pharmacologic inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC., (© 2017 Wu et al.)

Objectives: We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma., Design: A systematic review and meta-analysis of EBC 8-isoprostane., Methods: We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I 2 ., Results: We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane levels in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies were appropriate for inclusion in a random effects meta-analysis of mean difference. This found a statistically significant between-groups difference of 22 pg ml -1 . Confidence in the result is limited by the small number of studies and by substantial statistical heterogeneity (I 2  = 94)., Conclusion: The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It is essential to develop a robust and standardised methodology if the use of EBC 8-isoprostane in asthma is to be properly evaluated.

Nanoscale titanium dioxide (nanoTiO 2 ) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO 2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO 2 . This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C 6 -C 12 ) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 10 4 to 2.32 × 10 4 particles/cm 3 with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m 3 . All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO 2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO 2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.

The porcine corpus luteum (CL) displays delayed sensitivity to PGF-2α (luteolytic sensitivity, [LS]) until days 12 to 13 of cycle. The control of LS is unknown, but it is temporally associated with macrophage (which secrete tumor necrosis factor-α; TNF-α) infiltration into the CL. Other studies showed that TNF-α induces LS in vitro and that prostaglandins (PGs) may be involved in this mechanism. In experiment 1, PGF-2α and PGE secretion by luteal cells (LCs) was measured on days 4 to 14 of the estrous cycle, and the expression of PTGFS/AKR1B1 and PTGES/mPGES-1, determined by Western blot, before (day 7) vs after (day 13) the onset of LS. Results showed that the PGF-2α:PGE ratio increased significantly (P < 0.05) from day 4 to 13-14, and PTGFS/AKR1B1 and PTGES/mPGES-1 were significantly increased (P < 0.05) on day 13 (vs day 7). In experiment 2, LCs were collected from porcine CL at early (∼days 4-6) or mid (∼days 7-12) stages of the estrous cycle and cultured with 0, 0.1, 1, or 10 ng/mL TNF-α. Results showed that TNF-α significantly increased (P < 0.05) messenger RNA (mRNA) expression of cyclooxygenase (COX)-2 and mPGES-1 but not AKR1B1. TNF-α had no significant effects on AKR1B1 or mPGES protein abundance. TNF-α significantly increased (P < 0.05) PGE-2 but had no effect on PGF-2α secretion or on the PGF-2α:PGE2 ratio. In conclusion, although TNF-α increased COX2 and mPGES-1 mRNA, and PGE-2 secretion in vitro, it did not increase the PGF-2α:PGE2 ratio. Studies are currently directed toward exploring other pathways (eg, FP receptor signaling) by which TNF-α induces LS in the porcine CL., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background . The combination antiretroviral therapy (cART) increases the oxidative stress in HIV-infected people, which in turn favors the onset and aggravation of non-AIDS comorbidities, a common situation affecting these individuals. We aimed to evaluate the influence of cART initiation on oxidative stress parameters. This is a longitudinal study including 30 asymptomatic patients divided according to their CD4+ T cell count (G1: <500 cell/mL; G2: >500 cell/mL) before (M0) and after (M1) cART initiation. We analyzed total antioxidant capacity (TAC), fat-soluble vitamins, malondialdehyde, 8-isoprostane, and DNA damage. Results . Results showed a decrease in TAC, retinol, α -tocopherol, and some carotenoids, in addition to a significant increase in DNA damage at M1. These changes were more evident in G2 subjects. Moreover, there was a significant 8-isoprostane increase at M1 in individuals belonging to G1. Conclusion . The results indicate that cART interfered in the redox system, mainly by reducing the antioxidant defenses. In addition, patients who had CD4+ T counts higher than 500 cells/mm 3 showed more susceptibility to genotoxicity, while patients with less CD4+ T counts displayed more damage triggered by lipoperoxidation. Considering the early beginning of cART, its chronic use, and its capacity to alter the redox status, further long-term studies on larger cohorts are needed to define the best time to initiate therapy and to investigate new strategies to delay the development of non-AIDS diseases.

Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F 2 -isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3'-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF 2α and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF 2α in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF 2α , however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF 2α mass load was found to be strongly associated with that of trans-3'-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF 2α as a wastewater biomarker for the assessment of community public health.

Objectives: The aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress., Methods: We performed a randomized pilot study including 39 HIV-1-infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)-derived peptide (sNOX2-dp), a marker of NOX2 activation, and platelet prostaglandin F 2α (8-iso-PGF 2α ). Platelet activation was measured by soluble CD40L (sCD40L)., Results: At baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2-dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8-iso-PGF 2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups., Conclusions: ABC reduced platelet sNOX2-dp and 8-iso-PGF 2α in HIV-1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups., (© 2016 British HIV Association.)

Background: Helicobacter pylori (H. pylori) infection triggers both local inflammation, usually in gastric mucosa, and chronic systemic inflammation. It is assumed that this local and systemic inflammation is caused by extracellular products excreted by H. pylori. The aim of this study was to investigate the possible association between H. pylori infection and a local inflammatory response in the airway by using exhaled breath condensate technique., Materials and Methods: This study includes 41 H. pylori seropositive patients who have gastric symptoms and 27 healthy control subjects. Pulmonary function tests (PFT), chest X ray, and physical examination were performed in all patients and interleukin-6 (IL-6), 8-isoprostane and nitrotyrosine levels were measured in exhaled breath condensate., Results: Levels of IL-6 and 8-isoprostane in exhaled breath condensate (EBC) were significantly higher in H. pylori positive patients than control subjects (p < 0.05). Nitrotyrosine levels were also higher in H. pylori positive patients but the difference was not statistically significant. Both groups had similar leukocyte counts, C-reactive protein (CRP) levels and PFT parameters., Conclusion: H. pylori infection causes an asymptomatic airway inflammation which can be detected by exhaled breath condensate. The clinical importance of this inflammation remains unclear., (© 2016 John Wiley & Sons Ltd.)

The endocrine disruptor Bisphenol A (BPA) is ubiquitous in both aquatic and surface sediment environments because it is continuously released into sewage wastewater effluent. The measurement of BPA at wastewater treatment plants is rarely performed even though the United States Environmental Protection Agency (EPA) states that current levels of environmental BPA could be a threat to aquatic organisms. Therefore, the aims of this study were to measure BPA levels in sewage wastewater at different collection points over a 1-year period and to compare the levels of BPA to 8-isoprostane, a human derived fatty acid, found in sewage wastewater. We analyzed pre-treated sewage samples collected from three source points located in different communities in the metropolitan Detroit area provided by the Detroit Water and Sewerage Department. Human urine samples were also used in the study. BPA and 8-isoprostane were measured using ELISA kits from Detroit R&D, Inc. BPA levels from the same collection point oscillated more than 10-fold over 1 year. Also, BPA levels fluctuated differentially at each collection point. Highly fluctuating BPA values were confirmed by LC/MS/MS. The concentration of BPA in sewage wastewater was ~100-fold higher than the concentration of 8-isoprostane, while urinary concentration was ~20-fold higher. Thus, BPA levels discharged into the sewage network vary among communities, and differences are also observed within communities over time. The difference in BPA and 8-isoprostane levels suggest that most of the BPA discharged to sewage wastewater might be derived from industries rather than from human urine. Therefore, the continuous monitoring of BPA could account for a better regulation of BPA release into a sewage network.

Background: Oxidative stress has been implicated in numerous diseases, including arthritis, atherosclerosis, Alzheimer's disease, cancer, diabetes, hypertension, and inflammation. 8-iso-prostaglandin F2α, a member of the F2 isoprostane family, has been well-accepted as a valuable biomarker for the assessment of oxidative stress., Methods: We report the development and validation of an ultra-sensitive LC-MS/MS assay for urinary 8-iso-PGF2α measurements in pediatric population., Results: The assay was linear from 0.024 to 20nmol/l (R(2)=0.99). Recoveries were above 85% and matrix effects were below 5%. The variability was determined at nmol/l concentration: the intra-day variability (%CV) ranged from 3.9% to 4.5% (n=20); and the inter-day variability ranged from 4.3% to 5.7% (n=20). The accuracy of our laboratory developed test was evaluated with a clinical reference laboratory (n=39), and a correlation coefficient of 0.9257 was observed. Reference interval were established to be <0.5ng/mg creatinine in a group of pediatric population (2months-18years, n=123)., Conclusions: The precision of the assay will allow for accurate assessment of oxidative stress, and is acceptable for patient testing, particularly in pediatric population., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the levels of 8-isoprostane (8-IsoP) in the airways of competitive swimmers at baseline and after a swimming session according to their airway responsiveness., Methods: Twenty-three swimmers and six lifeguards had a baseline spirometry and bronchoprovocative challenges. During a second visit, swimmers performed a usual swimming session while lifeguards stayed in the same pool environment for the same time period. Forced expiratory volume in one second (FEV1) was measured before and 5 min after the end of the session. Exhaled breath condensate (EBC) was sampled before and 10 min after the session and EBC 8-IsoP levels were analysed by enzyme immunoassay. Change in EBC 8-IsoP from baseline to post-swimming session was calculated., Results: We observed no relationships between airway hyper-responsiveness and 8-IsoP values before or after swimming in swimmers. The levels of 8-IsoP were significantly higher after the training session (mean value 2.9, s = 0.5 pg mL(-1)) than at baseline (mean value 1.9, s = 0.4 pg mL(-1)) in swimmers only (p = .012). EBC 8-IsoP levels after the swimming session significantly correlated with the percent change in FEV1 after swimming., Conclusions: EBC 8-IsoP levels were increased after training in swimmers but not in lifeguards, suggesting that exercise-induced hyperpnoea in a chlorinated pool environment increases airways oxidative stress.

This study was to investigate whether working in conditions of elevated concentrations of mine gases (CO2, CO, CH4, DMS) and dust may result in oxidative stress. Coal miners (n=94) from the Velenje Coal mine who were arranged into control group and three groups according to a number of consecutive working days. 8-isoprostane as a biological marker of oxidative stress was measured in exhaled breath condensate (EBC). Miners who worked for three consecutive days had higher 8-isoprostane values in EBC compared to the control group. Gas/dust concentrations and exposure time of a single/two day shift seem too low to trigger immediate oxidative stress., (Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: A controlled human exposure study was conducted to investigate the impact of inhalational exposures to wood smoke PM2.5 on measured concentrations of airway and systemic inflammatory biomarkers., Methods: Mimicking wildland firefighter activities, 10 participants were exposed to three doses of wood smoke PM2.5 (filtered-air, 250 μg/m, and 500 μg/m) while exercising on a treadmill. Exhaled breath condensate (EBC) and blood plasma samples were obtained pre-, immediately post-, and 1-hour postexposure. 8-isoprostane, pH, and myeloperoxidase were measured in EBC, while H2O2, surfactant protein D, and pentraxin-3 (PTX3) were measured in both EBC and plasma., Results: Only pH, 8-isoprostane, and PTX3 displayed significant changes when comparing pre- and postexposures., Conclusions: Markers of inflammation and oxidative stress, including PTX3, pH, and 8-isoprostane in EBC and/or plasma, are sensitive to wood smoke inhalation, with further investigations warranted.

Background: The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation., Methods: Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit., Results: Both single high-dose FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma score (p<0.0001), PEF (p<0.0001), and FEV1 (p<0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p=0.001), and at the end of the six-day period in the FP group (p<0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p=0.012) and six days of P treatment (p=0.018) in children with asthma exacerbation., Conclusions: High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later., (Copyright © 2015 SEICAP. Published by Elsevier Espana. All rights reserved.)

Markers of oxidative stress and inflammation were analysed in the exhaled breath condensate (EBC) and urine samples of 14 workers (mean age 43  ±  7 years) exposed to iron oxide aerosol for an average of 10  ±  4 years and 14 controls (mean age 39  ±  4 years) by liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) after solid-phase extraction. Aerosol exposure in the workplace was measured by particle size spectrometers, a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS), and by aerosol concentration monitors, P-TRAK and DustTRAK DRX. Total aerosol concentrations in workplace locations varied greatly in both time and space. The median mass concentration was 0.083 mg m(-3) (IQR 0.063-0.133 mg m(-3)) and the median particle concentration was 66 800 particles cm(-3) (IQR 16,900-86,900 particles cm(-3)). In addition, more than 80% of particles were smaller than 100 nm in diameter. Markers of oxidative stress, malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C6-C12, in addition to markers of nucleic acid oxidation, including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), and of proteins, such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr) were analysed in EBC and urine by LC-ESI-MS/MS. Almost all markers of lipid, nucleic acid and protein oxidation were elevated in the EBC of workers comparing with control subjects. Elevated markers were MDA, HNE, HHE, C6-C10, 8-isoprostane, 8-OHdG, 8-OHG, 5-OHMeU, 3-ClTyr, 3-NOTyr, o-Tyr (all p  <  0.001), and C11 (p  <  0.05). Only aldehyde C12 and the pH of samples did not differ between groups. Markers in urine were not elevated. These findings suggest the adverse effects of nano iron oxide aerosol exposure and support the utility of oxidative stress biomarkers in EBC. The analysis of urine oxidative stress biomarkers does not support the presence of systemic oxidative stress in iron oxide pigment production workers.

Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, has detrimental effects on the structure and function of bovine corpus luteum (CL) in vivo. The objective was to investigate whether these effects were mediated directly by LPS or via LPS-induced release of PGF2α. Bovine ovaries with a mid-cycle CL were collected immediately after slaughter and isolated perfused for 240 min. After 60 min of equilibration, LPS (0.5 μg/ml) was added to the medium of five ovaries, whereas an additional six ovaries were not treated with LPS (control). After 210 min of perfusion, all ovaries were treated with 500 iu of hCG. In the effluent perfusate, concentrations of progesterone (P4) and PGF2α were measured every 10 and 30 min, respectively. Punch biopsies of the CL were collected every 60 min and used for RT-qPCR to evaluate mRNA expression of receptors for LPS (TLR2, -4) and LH (LHCGR); the cytokine TNFA; steroidogenic (STAR, HSD3B), angiogenic (VEGFA121, FGF2), and vasoactive (EDN1) factors; and factors of prostaglandin synthesis (PGES, PGFS, PTGFR) and apoptosis (CASP3, -8, -9). Treatment with LPS abolished the hCG-induced increase in P4 (P≤0.05); however, there was a tendency (P=0.10) for increased release of PGF2α at 70 min after LPS challenge. Furthermore, mRNA abundance of TLR2, TNFA, CASP3, CASP8, PGES, PGFS, and VEGFA121 increased (P≤0.05) after LPS treatment, whereas all other factors remained unchanged (P>0.05). In conclusion, reduced P4 responsiveness to hCG in LPS-treated ovaries in vitro was not due to reduced steroidogenesis, but was attributed to enhanced apoptosis. However, an impact of luteal PGF2α could not be excluded., (© 2016 Society for Reproduction and Fertility.)

Our recent investigation showed that hepcidin can reduce iron in the brain of iron-overloaded rat by down-regulating iron-transport proteins. It has also been demonstrated that iron is a major generator of reactive oxygen species. We therefore hypothesized that hepcidin could prevent iron accumulation and thus reduce iron-mediated oxidative stress in iron-overloaded rats. To test this hypothesis, we investigated the effects of pre-treatment of rats with recombinant-hepcidin-adenovirus (ad-hepcidin) on the contents of iron, dichlorofluorescein and 8-isoprostane in the brain. Hepcidin expression was detected by real-time PCR and immunofluorescence analysis. Iron contents were measured using Perl's staining as well as graphite furnace atomic absorption spectrophotometry. Dichlorofluorescein and 8-isoprostane were determined using a fluorescence spectrophotometer and an ELISA kit, respectively. We found that hepcidin contents in the cortex, hippocampus, striatum and substantia nigra of rats treated with ad-hepcidin are 3.50, 2.98, 2.93 and 4.07 fold of those of the control rats respectively. Also, we demonstrated that the increased iron as well as dichlorofluorescein and 8-isoprostane levels in all four brain regions, induced by injection of iron dextran, could be effectively prevented by pre-treatment of the rats with ad-hepcidin. We concluded that pre-treatment with ad-hepcidin could increase hepcidin expression and prevent the increase in iron and reduce reactive oxygen species in the brain of iron-overloaded rats., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Wood smoke, a well-known indoor and outdoor air pollutant, may cause adverse health effects through oxidative stress. In this study 8-isoprostane, a biomarker of oxidative stress, was measured in exhaled breath condensate (EBC) and urine before and after experimental exposure to wood smoke. The results were compared with measurements of other biomarkers of oxidative stress and inflammation. Thirteen subjects were exposed first to clean air and then, after 1 week, to wood smoke in an exposure chamber during 4-hour sessions. Exhaled breath condensate, exhaled nitric oxide, blood and urine were sampled before and at various intervals after exposure to wood smoke and clean air. Exhaled breath condensate was examined for 8-isoprostane and malondialdehyde (MDA), while exhaled air was examined for nitric oxide, serum for Clara cell protein (CC16) and urine for 8-isoprostane. 8-isoprostane in EBC did not increase after wood smoke exposure and its net change immediately after exposure was inversely correlated with net changes in MDA (r(s)= -0.57, p= 0.041) and serum CC16 (S-CC16) (r(p)= -0.64, p= 0.020) immediately after the exposure. No correlation was found between 8-isoprostane in urine and 8-isoprostane in EBC. In this study controlled wood smoke exposure in healthy subjects did not increase 8-isoprostane in EBC.

We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals.

Objective: To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes., Materials and Methods: The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL)., Results: (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]., Conclusion: The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Continued expansion of the nanotechnology industry has necessitated the self-assessment of manufacturing processes, specifically in regards to understanding the health related aspects following exposure to nanomaterials. There exists a growing concern over potential occupational exposure in the semiconductor industry where Al2O3, CeO2 and SiO2 nanoparticles are commonly featured as part of the chemical mechanical planarization (CMP) process. Chronic exposure to toxicants can result not only in acute cytotoxicity but also initiation of a chronic inflammatory state associated with diverse pathologies. In the current investigation, pristine nanoparticles and CMP slurry formulations of Al2O3, SiO2 and CeO2 were employed to assess their ability to induce cytotoxicity, inflammatory responses and reactive oxygen species in a mouse alveolar macrophage cell model. The pristine nanoparticles and slurries were not intrinsically cytotoxic and did not generate free radicals but were found to act as scavengers in the presence of an oxidant stimulant. Al2O3 and SiO2 nanoparticles increased levels of pro-inflammatory cytokines while pristine SiO2 nanoparticles induced generation of F2-Isoprostanes. In co-treatment studies, the pristine nanomaterials modulated the response to the inflammatory stimulant lipopolysaccharide. The studies have established that pristine nanoparticles and slurries do not impact the cells in a similar way indicating that they should not be used as slurry substitutes in toxicity evaluations. Further, we have defined how an alveolar cell line, which would likely be the first challenged upon nanomaterial aerosolization, responds to diverse mixtures of nanomaterials. Moreover, our findings reinforce the importance of using multiple analytic methods to define the redox state of the cell following exposure to commonly used industrial nanomaterials and toxicants., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Non-invasive monitoring of hormones using feces has become a vital tool for reproductive management and reliable pregnancy diagnosis in big cats. Previous studies described the PGF2α metabolite (PGFM) as an indicator of pregnancy in various feline species. The present study aimed to standardize pregnancy detection in big cats like the tiger (Panthera tigris), jaguar (Panthera onca) and lion (Panthera leo) using fecal samples. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LCMS) were performed to identify PGFM in feces. An EIA developed against 9α,11α-dihydroxy-15-oxo-prost-5-en-1-oic acid-BSA was used to assay PGFM in fecal samples of the Bengal tiger, Asiatic lion and jaguar. The PGFM levels increased after 9 weeks of pregnancy and remained elevated until parturition. All animals showed elevated levels of PGFM in the last trimester of pregnancy, thus making PGFM a reliable tool for pregnancy diagnosis during this period that can be useful in captive breeding programs in these species.

The use of sewage epidemiology to estimate the behavior of a large scale population has mainly been used to assess illicit drug use within a community. The systemic oxidative stress marker, 8-isoprostane, is a wildly accepted biomarker for various diseases such as diabetes, and cardiovascular and renal diseases. 8-Isoprostane is detected in urine and, as with illicit drugs, is excreted into urban sewer networks. Initially, we tested the hypothesis that differential 8-isoprostane levels are detected in wastewater of different communities and that 8-isoprostane values adjusted for the flow rate and population size will remain constant over a 2 months period. Sewage samples were collected from three sewage collection points supplied by different communities located in the Detroit metropolitan area and concentration of 8-isoprostane and synthetic plastic component, bisphenol A (BPA), were measured. Levels of 8-isoprostane were constant during the two measured months at each collection point in oppose to BPA levels. When the levels were compared among communities, 8-isoprostane levels in 24h flow and their concentrations per capita in each community varied by more than 5-fold among them. Considering the fact that 8-isoprostane is a biomarker of several diseases, we hypothesize that measurement of 8-isoprostane levels in sewage may serve as a risk assessment tool of oxidative stress-related diseases in a large scale population. Thus, sewage epidemiology can be utilized to obtain an early warning in a community to facilitate intervention for improvement of the community health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: During lung lobectomy, the operated lung is collapsed and hypoperfused; oxygen deprivation is accompanied by reactive hypoxic pulmonary vasoconstriction. After lung lobectomy, ischaemia present in the collapsed state is followed by expansion-reperfusion and lung injury attributed to the production of reactive oxygen species. The primary objective of this study was to investigate the time course of several markers of oxidative stress simultaneously in exhaled breath condensate and blood and to determine the relationship between oxidative stress and one-lung ventilation time in patients undergoing lung lobectomy., Methods: This single-centre, observational, prospective study included 28 patients with non-small-cell lung cancer who underwent lung lobectomy. We measured the levels of hydrogen peroxide, 8-iso-PGF2α, nitrites plus nitrates and pH in exhaled breath condensate (n = 25). The levels of 8-iso-PGF2α and nitrites plus nitrates were also measured in blood (n = 28). Blood samples and exhaled breath condensate samples were collected from all patients at five time points: preoperatively; during one-lung ventilation, immediately before resuming two-lung ventilation; immediately after resuming two-lung ventilation; 60 min after resuming two-lung ventilation and 180 min after resuming two-lung ventilation., Results: Both exhaled breath condensate and blood exhibited significant and simultaneous increases in oxidative-stress markers immediately before two-lung ventilation was resumed. However, all these values underwent larger increases immediately after resuming two-lung ventilation. In both exhaled breath condensate and blood, marker levels significantly and directly correlated with the duration of one-lung ventilation immediately before resuming two-lung ventilation and immediately after resuming two-lung ventilation. Although pH significantly decreased in exhaled breath condensate immediately after resuming two-lung ventilation, these pH values were inversely correlated with the duration of one-lung ventilation., Conclusions: During lung lobectomy, the operated lung is collapsed and oxidative injury occurs, with the levels of markers of oxidative stress increasing simultaneously in exhaled breath condensate and blood during one-lung ventilation. These increases were larger after resuming two-lung ventilation. Increases immediately before resuming two-lung ventilation and immediately after resuming two-lung ventilation were directly correlated with the duration of one-lung ventilation., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A reliable oxidative stress biomarker, 8-iso-prostaglandin F2α (8-iso-PGF2α), was for the first time quantitatively analysed in wastewater using an analytical method consisting of liquid chromatography-high resolution mass spectrometry coupled to immunoaffinity clean-up (IAC-LC-HRMS). Factors influencing the method's robustness were investigated, including analyte stability in sewage and enzymatic deconjugation with β-glucuronidase. The IAC-LC-HRMS method was linear over the range of 0.1-100ng/mL with correlation coefficient (R(2)) of 0.999. The quantification limits were sufficiently low to detect 8-iso-PGF2α in sewage (method quantification limit of 0.3ng/L) and precision, expressed as relative standard deviation was less than 7% and the accuracy expressed as relative recovery was in the 103-113% range. As a result, the application of the method to 24-h composite wastewater samples from Oslo showed 8-iso-PGF2α concentrations of 18.9-23.3ng/L for 8 days in March 2015. This study demonstrates a standard method to analyse 8-iso-PGF2α in sewage that will contribute to the further investigation of the potential use of 8-iso-PGF2α as a sewage biomarker for assessing the status of community health., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Previous studies have indicated that OxS (oxidative stress) may appear as a possible reason for poor ART outcome. Our aim was to study OxS levels in both partners of couples seeking Assisted reproduction Technology (ART)., Methods: Altogether 79 couples were recruited. Oxidative DNA damage (8-OHdG) and lipid peroxidation (8-EPI) were measured, and clinical background and ART outcomes were recorded., Results: Both OxS markers accurately reflected clinical conditions with prominent negative effects attributable to genital tract infections, endometriosis, uterine myoma and smoking. Furthermore, the level of OxS was also affected by partner's state of health. The highest 8-EPI levels were detected in both partners when biochemically detectable pregnancies did not develop into clinically detectable pregnancies (in women, 97,8 ± 16,7 vs 72.9 ± 22,9, p = 0.007; in men, 89.6 ± 20,4 vs 72,1 ± 22,6, p = 0.049)., Conclusions: To conclude, high grade systemix OxS in both partners may negatively affect the maintenance and outcome of pregnancy. Applying the detection of OxS in ART patients may select patients with higher success rate and/or those who require antioxidant therapy. This would lead to improvement of ART outcome as well as natural fertility.