Interrelationship between renin-angiotensin-aldosterone system and oxidative stress in chronic heart failure patients with or without renal impairment.

We investigated oxidative stress and RAAS biomarkers, as well as their association, in chronic heart failure (CHF) patients on optimized medical therapy, stratified by disease severity or by renal function. Since vitamin D has been shown to attenuate RAAS activation and oxidative stress, we further evaluated the relationship between vitamin D, RAAS and oxidative stress in CHF patients with or without renal impairment. Sixty CHF outpatients were included and stratified by disease severity or by renal function. We quantified urinary hydrogen peroxide, plasma and urinary isoprostanes, plasma total antioxidant status, urinary angiotensinogen (intrarenal RAAS activation biomarker) and plasma angiotensinogen, plasma renin and aldosterone concentration, serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin peptides, and serum total 25-hydroxyvitamin D (S-total 25(OH)D). Severe CHF patients had higher urinary isoprostanes (p = 0.002) and lower S-total 25(OH)D (p = 0.006) compared to mild-to-moderate patients, but no differences were observed for other redox or RAAS biomarkers. Patients with impaired renal function (iRF) had higher urinary angiotensinogen (p = 0.003) and lower S-total 25(OH)D (p = 0.028) compared to those with normal renal function (nRF), while no differences were observed for the remaining RAAS and redox parameters. Several positive correlations between oxidative stress and RAAS biomarkers were detected in iRF patients, while in patients with nRF these correlations were primarily inverse. In CHF-iRF patients, S-25(OD)D was inversely associated with urinary isoprostanes, which in turn were positively associated with plasma angiotensinogen and serum ACE. In conclusion, CHF patients with renal function impairment have increased intrarenal RAAS activation and lower vitamin D values and might benefit from the combination of RAAS blockers with vitamin D and/or antioxidants.

Urinary markers of oxidative stress respond to infection and late-life in wild chimpanzees.

Oxidative stress (OS) plays a marked role in aging and results from a variety of stressors, making it a powerful measure of health and a way to examine costs associated with life history investments within and across species. However, few urinary OS markers have been examined under field conditions, particularly in primates, and their utility to non-invasively monitor the costs of acute stressors versus the long-term damage associated with aging is poorly understood. In this study, we examined variation in 5 urinary markers of oxidative damage and protection under 5 validation paradigms for 37 wild, chimpanzees living in the Kibale National Park, Uganda. We used 924 urine samples to examine responses to acute immune challenge (respiratory illness or severe wounding), as well as mixed-longitudinal and intra-individual variation with age. DNA damage (8-OHdG) correlated positively with all other markers of damage (F-isoprostanes, MDA-TBARS, and neopterin) but did not correlate with protection (total antioxidant capacity). Within individuals, all markers of damage responded to at least one if not both types of acute infection. While OS is expected to increase with age, this was not generally true in chimpanzees. However, significant changes in oxidative damage were detected within past-prime individuals and those close to death. Our results indicate that OS can be measured using field-collected urine and integrates short- and long-term aspects of health. They further suggest that more data are needed from long-lived, wild animals to illuminate if common age-related increases in inflammation and OS damage are typical or recently aberrant in humans.

Measurement of Enzymatic and Nonenzymatic Polyunsaturated Fatty Acid Oxidation Products in Plasma and Urine of Macular Degeneration Using LC-QTOF-MS/MS.

Oxidized polyunsaturated fatty acids (PUFA) are associated to pathogenesis of diseases including cardiovascular and neurodegeneration. The novel products are not only biomarkers but also lipid mediators in gene regulation and signaling pathways. Herein, simultaneous quantitation of 28 products derived from nonenzymatic and enzymatic oxidation of PUFA i.e. 5-, 15-F2t -isoprostanes, 7-, 17-F2t -dihomo-isoprostanes, 7-, 17-F2t -dihomo-isofurans, 5-, 8-, 18-F3t -isoprostanes, 4-, 10-, 13-, 14-, 20-F4t -neuroprostanes, 5-, 8-, 9-, 11-,12-, 15-, 20-HETE, 4-, 7-, 11-, 14-, 17-HDHA, RvE1, and NPD1 using LC-(ESI)-QTOF-MS/MS was developed. These products were measurable in a single sample and the analytical time was relative short (~15 min). Furthermore, we showed that the use of internal standards is a requisite to normalize matrix effects and preparation loss for the quantitation. Validation assays indicated the method to be robust for plasma and mid-stream urine sample analysis in particular from those of age-related macular degeneration subjects, where the accuracy of quantitation displayed good repeatability.

The Buckwheat Iminosugar d-Fagomine Attenuates Sucrose-Induced Steatosis and Hypertension in Rats.

SCOPE: This study examines the long-term functional effects of d-fagomine on sucrose-induced factors of metabolic dysfunctions and explores possible molecular mechanisms behind its action. METHODS AND RESULTS: Wistar Kyoto rats are fed a 35% sucrose solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The following are recorded: body weight; energy intake; glucose tolerance; plasma leptin concentration and lipid profile; populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F2t isoprostanes (F2 -IsoPs); perigonadal fat deposition; and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. d-Fagomine reduces sucrose-induced hypertension, urine uric acid and F2 -IsoPs (markers of oxidative stress), steatosis, and liver DAGs, without significantly affecting perigonadal fat deposition, and impaired glucose tolerance. It also promotes excretion of enterobacteriales generated by the dietary intervention. CONCLUSION: d-fagomine counteracts sucrose-induced steatosis and hypertension, presumably by reducing the postprandial levels of fructose in the liver.

Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2α during pregnancy in Puerto Rico.

BACKGROUND: Lower socioeconomic status (SES) and psychosocial stress during pregnancy have been associated with adverse birth outcomes. While hypothalamic-pituitary-axis activation is thought to be the primary driver, oxidative stress may also be involved mechanistically. We used data from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (N=476) to examine associations between self-reported psychosocial stress measures, SES indicators, and urinary oxidative stress biomarker concentrations, hypothesizing that women with lower SES and increased psychosocial stress would have elevated oxidative stress biomarkers. METHODS: Maternal age, education, marital status, insurance status, alcohol use and smoking status were obtained via self-reported questionnaires and were used as indicators of SES. Perceived stress, depression, negative life experiences, neighborhood perceptions, and social support were self-reported in questionnaires administered during pregnancy. Responses were grouped into tertiles for analysis, where the highest tertile corresponded to highest level of psychosocial stress. Urinary concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its primary metabolite were measured at three study visits (median 18, 24, 28 weeks gestation) and averaged to reflect oxidative stress across pregnancy. Linear models were used to examine associations between SES indicators, tertiles of psychosocial stress and oxidative stress biomarkers. RESULTS: Average levels of 8-iso-PGF2α and the 8-iso-PGF2α metabolite were higher among pregnant women who were younger, who had public compared to private insurance, and who were unemployed compared to employed. However, no associations were observed between psychosocial stress measures and biomarker concentrations in adjusted analyses. CONCLUSIONS: Psychosocial stress during pregnancy, as indicated by self-reported questionnaire measures, was not associated with biomarkers of oxidative stress in the PROTECT study. However, results suggest that these biomarkers are elevated among women of lower SES, which is typically associated with stress. Notably, compared to other populations, self-reported psychosocial stress measures were lower in PROTECT compared to other populations.

Assessment of lipid peroxidation and artificial neural network models in early Alzheimer Disease diagnosis.

OBJECTIVE: Lipid peroxidation constitutes a molecular mechanism involved in early Alzheimer Disease (AD) stages, and artificial neural network (ANN) analysis is a promising non-linear regression model, characterized by its high flexibility and utility in clinical diagnosis. ANN simulates neuron learning procedures and it could provide good diagnostic performances in this complex and heterogeneous disease compared with linear regression analysis. DESIGN AND METHODS: In our study, a new set of lipid peroxidation compounds were determined in urine and plasma samples from patients diagnosed with early Alzheimer Disease (n = 70) and healthy controls (n = 26) by means of ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Then, a model based on ANN was developed to classify groups of participants. RESULTS: The diagnostic performances obtained using an ANN model for each biological matrix were compared with the corresponding linear regression model based on partial least squares (PLS), and with the non-linear (radial and polynomial) support vector machine (SVM) models. Better accuracy, in terms of receiver operating characteristic-area under curve (ROC-AUC), was obtained for the ANN models (ROC-AUC 0.882 in plasma and 0.839 in urine) than for PLS and SVM models. CONCLUSION: Lipid peroxidation and ANN constitute a useful approach to establish a reliable diagnosis when the prognosis is complex, multidimensional and non-linear.

Does the Coexistence of Chronic Obstructive Pulmonary Disease and Atrial Fibrillation Affect Nox2 Activity and Urinary Isoprostanes Excretion?

Chronic obstructive pulmonary disease (COPD) and atrial fibrillation (AF) are characterized by increased oxidative stress, but the impact of the coexistence of COPD and AF on systemic oxidative stress is unclear. We performed a cross-sectional study including 157 outpatients to investigate the Nox2-related oxidative stress in patients with AF and COPD. COPD was defined by an FEV1/FVC <0.70. Oxidative stress was measured by sNox2-dp, a marker of Nox2 activation, and urinary isoprostanes. We divided patients into four groups: Group 0: hypertension (n = 49, controls); Group 1: COPD (n = 42); Group 2: AF (n = 33); and Group 3: COPD and AF (n = 33). Mean age was 68.3 ± 11.0 years, and 46.5% were women. Patients with COPD or AF showed increased levels of sNox2-dp as compared with group 0; sNox2-dp further increased in patients with COPD + AF. In these patients, sNox2-dp was higher than in those with COPD (p < 0.001) or AF (p = 0.003). At multivariable logistic regression analysis, chronic kidney disease, COPD, and AF were associated with sNox2-dp above median. Similar results were observed for urinary isoprostanes. We hypothesize that the coexistence of COPD in AF patients may be associated with an increased systemic oxidative stress by the upregulation of Nox2. Antioxid. Redox Signal. 31, 786-790.

Wood dust and urinary 15-F2t isoprostane in Italian industry workers.

Wood dust is one of the most common occupational exposures, with about 3.6 million of workers in the wood industry in Europe. Wood particles can deposit in the nose and the respiratory tract and cause adverse health effects. Occupational exposure to wood dust has been associated with malignant tumors of the nasal cavity and paranasal sinuses. The induction of oxidative stress and the generation of reactive oxygen species through activation of inflammatory cells could have a role in the carcinogenicity of respirable wood dust. Therefore, we conducted a cross-sectional study to evaluate the prevalence of urinary 15-F2t isoprostane (15-F2t-IsoP), a biomarker of oxidative stress and peroxidation of lipids, in 123 wood workers compared to 57 unexposed controls living in Tuscany region, Italy. 15-F2t-IsoP generation was measured by ELISA. The main result of the present study showed that a statistically significant excess of this biomarker occurred in the workers exposed to 1.48 mg/m3 of airborne wood dust with respect to the unexposed controls. The overall mean ratio (MR) between the workers exposed to wood dust and the controls was 1.36, 95% Confidence Interval (C.I.) 1.18-1.57, after correction for age and smoking habits. A significant increment of 15-F2t-IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F2t-IsoP was significantly associated with co-exposure to organic solvents, i.e., MR of 1.41, 95% C.I. 1.17-1.70, after adjustment for age and smoking habits. A 41% excess was observed in long-term wood workers, 95% C.I. 1.14-1.75. Multivariate regression analysis showed that the level of 15-F2t-IsoP was linearly correlated to the length of exposure, regression coefficient (ß) = 0.244 ±â€¯0.002 (SE). The overall increment by exposure group persisted after stratification for smoking habits. For instance, in smokers, a 53% excess was detected in the wood workers as compared to the controls, 95% C.I. 1.23-1.91. Our data support the hypothesis that oxidative stress and lipid peroxidation can have a role in the toxicity of wood dust F2-IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens.

Quantitative metabolic profiling of urinary eicosanoids for clinical phenotyping.

The eicosanoids are a family of lipid mediators of pain and inflammation involved in multiple pathologies, including asthma, hypertension, cancer, atherosclerosis, and neurodegenerative diseases. These signaling mediators act locally, but are rapidly metabolized and transported to the systemic circulation as a mixture of primary and secondary metabolites. Accordingly, urine has become a useful readily accessible biofluid for monitoring the endogenous synthesis of these molecules. Herein, we present the validation of a rapid, repeatable, and precise method for the extraction and quantification of 32 eicosanoid urinary metabolites by LC-MS/MS. For 12 out of 17 deconjugated glucuronide eicosanoids, there was no improvement in recovered signal. These metabolites cover the major synthetic pathways, including prostaglandins, leukotrienes, and isoprostanes. The method linearity was >0.99 for all metabolites analyzed, the limit of detection ranged from 0.05-5 ng/ml, and the average extraction recoveries were >90%. All analytes were stable for at least three freeze/thaw cycles. The method was formatted for large-scale analysis of clinical cohorts, and the long-term repeatability was demonstrated over 15 months of acquisition, evidencing high precision (CV <15%, except for tetranorPGEM and 2,3-dinor-11ß-PGF2α, which were <30%). The presented method is suitable for focused mechanistic studies as well as large-scale clinical and epidemiological studies that require repeatable methods capable of producing data that can be concatenated across multiple cohorts.

Adrenic acid non-enzymatic peroxidation products in biofluids of moderate preterm infants.

Oxidative stress plays an essential role in processes of signaling and damage to biomolecules during early perinatal life. Isoprostanoids and isofuranoids from the free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs) are widely recognized as reliable biomarkers of oxidative stress. However, their quantification is not straightforward due to high structural similarity of the compounds formed. In this work, a semiquantitative method for the analysis of adrenic acid (AdA, C22:4 n-6) non-enzymatic peroxidation products (i.e. dihomo-isoprostanes and dihomo-isofurans) was developed. The proposed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was applied to the analysis of blood plasma and urine from preterm infants providing information about AdA peroxidation.

Effects of Cyclic Fatty Acid Monomers from Heated Vegetable Oil on Markers of Inflammation and Oxidative Stress in Male Wistar Rats.

This study assesses the effects of cyclic fatty acid monomers (CFAM) from heated vegetable oils on oxidative stress and inflammation. Wistar rats were fed either of these four diets for 28 days: canola oil (CO), canola oil and 0.5% CFAM (CC), soybean oil (SO), and soybean oil and 0.5% CFAM (SC). Markers of oxidative stress and inflammation were determined by micro liquid chromatography tandem mass spectrometry (micro-LC-MS/MS) and enzyme-linked immunosorbent assay (ELISA) kits, respectively. Analysis of variance (ANOVA) for a 2 × 2 factorial design was performed to determine the CFAM and oil effects and interactions between these two factors at P ≤ 0.05. For significant interactions, a post hoc multiple comparison test was performed, i.e., Tukey HSD (honest significant difference) test. CFAM induced higher plasma levels of 15-F2t-IsoP (CC, 396 ± 43 ng/mL, SC, 465 ± 75 ng/mL vs CO, 261 ± 23 ng/mL and SO, 288 ± 35 ng/mL, P < 0.05). Rats fed the SC diet had higher plasma 2,3-dinor-15-F2t-IsoP (SC, 145 ± 9 ng/mL vs CC, 84 ± 8 ng/mL, CO, 12 ± 1 ng/mL, and SO, 12 ± 1 ng/mL, P < 0.05), urinary 2,3-dinor-15-F2t-IsoP (SC, 117 ± 12 ng/mL vs CC, 67 ± 13 ng/mL, CO, 15 ± 2 ng/mL, and SO, 18 ± 4 ng/mL, P < 0.05), and plasma IL-6 (SC, 57 ± 10 pg/mL vs CC, 48 ± 11 pg/mL, CO, 46 ± 9 pg/mL, and SO, 44 ± 4 pg/mL, P < 0.05) than the other three diet groups. These results indicate that CFAM increased the levels of markers of oxidative stress, and those effects are exacerbated by a CFAM-high-linoleic acid diet.

Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers.

Lipid peroxidation plays an important role in Alzheimer Disease, so corresponding metabolites found in urine samples could be potential biomarkers. The aim of this work is to develop a reliable ultra-performance liquid chromatography-tandem mass spectrometry analytical method to determine a new set of lipid peroxidation compounds in urine samples. Excellent sensitivity was achieved with limits of detection between 0.08 and 17 nmol L-1, which renders this method suitable to monitor analytes concentrations in real samples. The method's precision was satisfactory with coefficients of variation around 5-17% (intra-day) and 8-19% (inter-day). The accuracy of the method was assessed by analysis of spiked urine samples obtaining recoveries between 70% and 120% for most of the analytes. The utility of the described method was tested by analyzing urine samples from patients early diagnosed with mild cognitive impairment or mild dementia Alzheimer Disease following the clinical standard criteria. As preliminary results, some analytes (17(RS)-10-epi-SC-Δ15-11-dihomo-IsoF, PGE2) and total parameters (Neuroprostanes, Isoprostanes, Isofurans) show differences between the control and the clinical groups. So, these analytes could be potential early Alzheimer Disease biomarkers assessing the patients' pro-oxidant condition.

Antihypertensive Effect of γ-Aminobutyric Acid-Enriched Brown Rice on Spontaneously Hypertensive Rats.

'Haiibuki' is a giant embryo rice cultivar that contains abundant γ-aminobutyric acid (GABA) compared with conventional rice cultivars. Here, we performed a functional evaluation of 'GABA-enriched brown rice' (GEBR) prepared by modifying the 'Haiibuki' cultivar to contain more GABA. Study 1: Spontaneously hypertensive rats were divided into three groups [control (cornstarch), normal brown rice, and GEBR] and fed an orally administered diet for 4 wk. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group as compared with the other groups. Study 2: Rats were divided into two groups and fed ad libitum for 12 wk. The two groups were control (commercial feed with 5% cornstarch) and GEBR (commercial feed with 5% GEBR). Body weight, blood pressure, food consumption, and water intake were measured during the study period, and blood chemistry was analyzed after the study. Plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and urinary isoprostane were measured 12 and 10 wk after the start of the study, respectively. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group. The 8-OHdG and isoprostane levels were significantly lower in the GEBR group than in the control group, demonstrating an oxidative stress-reducing effect. Therefore, GEBR exhibited a blood pressure elevation-inhibitory effect under the conditions of this study. The antioxidative action may occur secondarily to the antihypertensive action of GABA, suggesting that the long-term ad libitum ingestion of GEBR prevents hypertension. A reduction in oxidative stress could reduce the chances of complications in cardiovascular diseases.

GC-MS Analysis of Lipid Oxidation Products in Blood, Urine, and Tissue Samples.

Oxidant stress has been identified as important in the pathology of many diseases. Oxidation products of polyunsaturated fatty acids collectively termed isoprostanes, neuroprostanes, and isofurans are considered the most reliable measures of in vivo lipid oxidation, and they are widely used to assess oxidant stress in various diseases. Here we describe the measurement of these lipid oxidation products using gas chromatography mass spectrometry with electron capture negative ionization.

Oxidative Stress and Breast Cancer Risk in Premenopausal Women.

BACKGROUND: Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause. METHODS: We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression. RESULTS: After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (≥2.94 ng/mgCr) to <25th percentile (1.01 ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9 kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30 kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9 kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases). CONCLUSIONS: Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.

Urinary Isoprostane Levels and Age-Related Macular Degeneration.

Purpose: Oxidative stress, characterized by an excessive production of reactive oxygen intermediates has been suggested to play a role in the pathogenesis of age-related macular degeneration (AMD). We examined the association of urinary F2-isoprostanes (F2-IsoPs), a marker of lipid peroxidation and the most reliable marker of oxidative damage with AMD. Methods: We included 238 adults with AMD and 390 age- and sex-matched controls without AMD who participated in a population-based cross-sectional study in Singapore (Singapore Chinese Eye Study, 2009-2011). AMD was graded from retinal photographs using the Wisconsin Age-Related Maculopathy Grading System. Urinary-free F2-IsoPs (pmol/mmol of creatinine) were measured by gas chromatography mass spectrometry (GC-MS). The association between F2-IsoPs and AMD was examined using unconditional logistic regression models adjusted for potential confounders including smoking, body mass index (BMI), blood pressure, total and high-density lipoprotein cholesterol, and history of cardiovascular disease. Results: Higher levels of F2-IsoPs were associated with AMD independent of potential confounders. Compared to quartile 1 (Q1) of F2-IsoPs, the multivariable odds ratio (95% confidence interval) of AMD in quartiles 2, 3, and 4 were 2.05 (1.26-3.32), 1.80 (1.10-2.94), and 1.76 (1.06-2.94), respectively. In subgroup analyses comparing Q4 to Q1, this association was stronger in women, those with BMI less than 25 kg/m2 and those with hypertension, but no significant interaction was found (P interaction > 0.1 for each strata). Conclusions: Higher levels of urinary F2-IsoPs levels were associated with AMD independent of potential confounders in Chinese adults.

Relationship Between Alternative Resuscitation Strategies, Host Response and Injury Biomarkers, and Outcome in Septic Shock: Analysis of the Protocol-Based Care for Early Septic Shock Study.

OBJECTIVES: The Protocol-based Care for Early Septic Shock trial found no differences across alternative resuscitation strategies in all-cause mortality. A separate aim was to determine whether differences in resuscitation strategies affected trajectories of biomarkers of key pathways associated with downstream clinical outcomes of sepsis and whether there were differences in survival across treatment arms for patients with different baseline biomarker profiles. DESIGN: Secondary analysis of a large randomized clinical trial. SETTING: Thirty-one U.S. hospitals. PATIENTS: Six hundred twenty-eight patients with septic shock. INTERVENTIONS: Two resuscitation protocols versus usual care. MEASUREMENTS AND MAIN RESULTS: We measured a panel of biomarkers representing four pathophysiologic domains: "inflammation" (tumor necrosis factor, interleukin-6, and -10); "coagulation" (D-dimers, thrombin-antithrombin complex); "oxidative stress" (urine isoprostane); and "tissue hypoxia" (lactate) at 0, 6, 24, and 72 hours after treatment. We analyzed whether alternative resuscitation strategies affected biomarker trajectories over 72 hours and whether effects on 90-day hospital mortality varied by baseline (time 0) biomarker profiles-both using regression models with interaction terms for treatment arms. For all baseline biomarkers, higher concentrations were associated with increased risk of death by 90 days. However, there was no significant effect of treatment assignment on subsequent biomarker trajectories. We did find evidence for heterogeneity of treatment effect of protocol-based care on mortality for patients with different baseline [interleukin-6] and [interleukin-6] × [interleukin-10] profiles, whereas patients with the lowest quartiles fared better with protocol-based care (odds ratios, 0.32 [0.13-075]; p = 0.01 and 0.32 [0.14-0.73]; p = 0.01, respectively). CONCLUSIONS: In patients with septic shock, alterations in inflammation, coagulation, oxidative stress, and tissue hypoxia are common and associated with adverse outcomes but are not influenced by protocol-based resuscitation compared with usual care. However, contrary to expectation, protocol-based resuscitation appeared to be superior in patients with lower concentrations of inflammatory biomarkers. The mechanisms responsible for this effect are unclear.

Fermented goat milk improves antioxidant status and protects from oxidative damage to biomolecules during anemia recovery.

BACKGROUND: Iron deficiency anemia (IDA) is one of the most common nutritional problems in the world, and it is accepted that reactive oxygen species (ROS) production is altered during IDA. The aim of this study was to assess the influence of fermented goat and cow milks on enzymatic antioxidant activities and gene expression, and their role in protecting from oxidative damage during anemia recovery. RESULTS: After feeding the fermented milks-based diets (cow or goat), a significant elevation of some antioxidant endogenous enzymes was found, together with an increase in total antioxidant status (TAS), and a decrease in 8-hydroxy-2'-deoxyguanosine (8-OHdG) was recorded in animals consuming fermented goat milk-based diet. In contrast, DNA strand breaks, hydroperoxides, 15-F2t-isoprostanes and protein carbonyl groups were lower in some tissues in animals fed fermented goat milk-based diet, revealing an improvement in both systemic and cellular antioxidant activity of plasma and tissues due to fermented goat milk consumption. CONCLUSION: Fermented goat milk consumption induces a protective increase in TAS together with lower oxidative damage biomarkers, revealing that the milk protects main cell bioconstituents (lipids, protein, DNA, prostaglandins) from evoked oxidative damage during anemia recovery. © 2016 Society of Chemical Industry.

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment.

BACKGROUND: Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. METHODS: Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. RESULTS: In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. CONCLUSIONS: Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products.