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1.
BMJ Paediatr Open ; 8(1)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735834

RESUMO

BACKGROUND: There is limited evidence regarding the optimal time to commence parenteral nutrition (PN) in term and late preterm infants. DESIGN: Single-centre, non-blinded, exploratory randomised controlled trial. SETTING: A level-3 neonatal unit in a stand-alone paediatric hospital. PATIENTS: Infants born ≥34 weeks of gestation and ≤28 days, who needed PN. Eligible infants were randomised on day 1 or day 2 of admission. INTERVENTIONS: Early (day 1 or day 2 of admission, N=30) or late (day 6 of admission, N=30) PN. MAIN OUTCOME MEASURES: Plasma phenylalanine and F2-isoprostane levels on day 4 and day 8 of admission. Secondary outcomes were amino-acid and fatty-acid profiles on day 4 and day 8, and clinical outcomes. RESULTS: The postnatal age at randomisation was similar between the groups (2.3 (SD 0.8) vs 2.3 (0.7) days, p=0.90). On day 4, phenylalanine levels in early-PN infants were higher than in late-PN (mean (SD) 62.9 (26.7) vs 45.5 (15.3) µmol/L; baseline-adjusted percentage difference 25.8% (95% CI 11.6% to 39.9%), p<0.001). There was no significant difference in phenylalanine levels between the two groups on day 8. There was no significant difference between the groups for F2-isoprostane levels on day 4 (early-PN mean (SD) 389 (176) vs late-PN 419 (291) pg/mL; baseline-adjusted percentage difference: -4.4% (95% CI -21.5% to 12.8%) p=0.62) and day 8 (mean (SD) 305 (125) vs 354 (113) pg/mL; adjusted mean percentage difference -16.1 (95% CI -34.1 to 1.9) p=0.09).Postnatal growth restriction for weight was less severe in the early-PN group (change in weight z-score from baseline to discharge: -0.6 (0.6) vs -1.0 (0.6); p=0.02). The incidence of hyperglycaemia was greater in the early-PN group (20/30 (66.7%) vs 11/30 (36.7%), p=0.02). CONCLUSIONS: The timing of the commencement of PN did not seem to affect the degree of oxidative stress in critically ill term and late preterm infants. The effect of transiently high plasma phenylalanine with early PN on clinical outcomes requires further investigation. TRIAL REGISTRATION NUMBER: ACTRN12620000324910.


Assuntos
Recém-Nascido Prematuro , Nutrição Parenteral , Fenilalanina , Humanos , Recém-Nascido Prematuro/sangue , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido , Nutrição Parenteral/métodos , Masculino , Feminino , Fenilalanina/sangue , Fatores de Tempo , F2-Isoprostanos/sangue , Idade Gestacional
2.
Eur J Pediatr ; 183(7): 3085-3094, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38658398

RESUMO

As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5-6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n = 40) and a control group (CG, n = 17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p < 0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r = - 0.29, p = 0.043 and r = - 0.31, p = 0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found.  Conclusion: Antioxidant-rich food in kindergarten is warranted due to its potential health-protective effect. Additionally, we present original data on the average levels of urinary and serum OSBs in healthy 5-6-year-old children.  Trial registration: The study was registered at ClinicalTrials.gov, on February 5, 2020 ( https://clinicaltrials.gov/ct2/show/NCT04252105 ). What is Known: • Kindergartens are recognized as promising environments for public health measures. • A diet rich in antioxidants can reduce OSBs and, consequently, the risk of developing NCDs. What is New: • Antioxidant-rich kindergarten diet can ensure a protective intake of dTAC in children. • Original data on serum oxidative stress biomarkers (d-ROMs, PAT, and OSI) and urinary oxidative stress biomarkers (MDA, 8-OHdG, and F2 isoprostanes) in healthy 5-6-year-old children.


Assuntos
Antioxidantes , Biomarcadores , Estresse Oxidativo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Pré-Escolar , Antioxidantes/análise , Antioxidantes/administração & dosagem , Masculino , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Criança , Malondialdeído/sangue , Malondialdeído/urina , 8-Hidroxi-2'-Desoxiguanosina/urina , 8-Hidroxi-2'-Desoxiguanosina/sangue , Refeições , F2-Isoprostanos/urina , F2-Isoprostanos/sangue
3.
J Int Soc Sports Nutr ; 18(1): 58, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419082

RESUMO

BACKGROUND: Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial. METHOD: In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (VO2peak: 58.5 ± 6.2 ml·kg- 1·min- 1, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO2peak followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day- 1) and a placebo. Free F2-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO2peak and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected. RESULTS: Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F2-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml- 1) compared to placebo (44.7 ± 16.9 pg·ml- 1 p = 0.03). CONCLUSION: These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.


Assuntos
Antioxidantes/farmacologia , Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Mitocôndrias Musculares/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Substâncias para Melhoria do Desempenho/farmacologia , Ubiquinona/análogos & derivados , Adulto , Antioxidantes/metabolismo , Estudos Cross-Over , Método Duplo-Cego , F2-Isoprostanos/sangue , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Compostos Organofosforados/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio , Substâncias para Melhoria do Desempenho/metabolismo , Esforço Físico/efeitos dos fármacos , Esforço Físico/fisiologia , Placebos/metabolismo , Placebos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fenômenos Fisiológicos da Nutrição Esportiva/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Esportiva/fisiologia , Fatores de Tempo , Ubiquinona/metabolismo , Ubiquinona/farmacologia
4.
Nutrients ; 13(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207221

RESUMO

F2-IsoProstanes (F2-IsoPs) are major biomarkers of oxidative stress and are associated with type 2 diabetes (T2D). Further, plasma levels of F2-IsoPs may be modified by dairy products. The aim is to investigate the effect of high dairy product (HD) consumption compared to an adequate dairy product (AD) consumption on the level of F2-IsoPs among hyperinsulinemic subjects. In this crossover study, participants were randomized in two groups: HD (≥4 servings/day), or AD (≤2 servings/day) for six weeks. Fasting blood glucose and insulin were measured. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Six isomers of F2-IsoPs were quantified by HPLC-MS/MS. Twenty-seven subjects with hyperinsulinemia (mean age; 55 ± 13 years, BMI; 31.4 ± 3.3 kg/m2) were included. Fasting glucose, insulin and HOMA-IR were unchanged after HD or AD intervention. After HD intake, the total level of F2-IsoPs (p = 0.03), 5-F2t-IsoP (p = 0.002), and 8-F2t-IsoP (p = 0.004) decreased compared to AD. The 15-F2t-IsoP tended to be positively correlated with fasting blood glucose (r = 0.39, p = 0.08). Generally, F2-IsoPs levels were higher among men compared to women regardless of the dairy intake. Overall, intake of HD decreased plasma levels of F2-IsoPs compared to AD without modifying glycemic parameters.


Assuntos
Laticínios , F2-Isoprostanos/sangue , Hiperinsulinismo/metabolismo , Sobrepeso , Adulto , Idoso , Biomarcadores/sangue , Glicemia , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Diabetes Mellitus Tipo 2 , Ingestão de Alimentos , Jejum , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Espectrometria de Massas em Tandem
5.
J Sports Sci ; 39(6): 673-682, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33172351

RESUMO

Measuring alterations in redox homoeostasis in athletes can provide insights into their responses to training such as adaptations or fatigued states. However, redox monitoring is impractical in athletes given the time burden of venepuncture and subsequent laboratory assays. The ability of point-of-care tests (POC): 1) Free Oxygen Radical Test (FORT) and 2) Free Oxygen Radical Defence (FORD), to reliably measure whole blood oxidative stress between days and after exercise is unknown as well as their relationship with laboratory measures (F2-isoprostanes, total antioxidant capacity; TAC). Participants completed two trials performed on separate days comprising blood sampling at rest (n=22) and after treadmill-running (n=14). Between-day CVs for FORT (4.6%) and FORD (4.8%) were acceptable at rest. There was no difference in the between-day magnitude of change in any biomarker from pre- to post-exercise (p>0.05), yet the within-trial change in FORD was variable (trial one: +4.5%, p=0.15; trial two: +6.3%, p<0.05). TAC and FORD were significantly correlated pre- and post-exercise (r=~0.53, p<0.05), whereas F2-isoprostanes and FORT had a significant correlation pre-exercise only (r=0.45, p=0.03). Overall, the POC tests are reliable and could be used for baseline longitudinal redox monitoring. More data is required on POC tests for assessing redox perturbations induced by exercise.


Assuntos
Exercício Físico/fisiologia , Radicais Livres/sangue , Estresse Oxidativo/fisiologia , Testes Imediatos , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Teste de Esforço , F2-Isoprostanos/sangue , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
6.
Int J Sports Med ; 42(5): 441-447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33124012

RESUMO

Glutathione is the most abundant cellular antioxidant and regulates redox homeostasis. Healthy individuals with certain antioxidant inadequacies/deficiencies exhibit impairments in physiological functions. The aim was to investigate whether low levels of dietary cysteine intake are associated with a) lower erythrocyte glutathione, b) increased plasma F2-isoprostanes, and c) impaired muscle function. Towards this aim, we recorded the dietary intake of the three amino acids that synthesize glutathione (i. e., glutamic acid, cysteine, and glycine) in forty-one healthy individuals, and subsequently measured erythrocyte glutathione levels. Maximal isometric strength and fatigue index were also assessed using an electronic handgrip dynamometer. Our findings indicate that dietary cysteine intake was positively correlated with glutathione levels (r=0.765, p<0.001). In addition, glutathione levels were negatively correlated with F2-isoprostanes (r=- 0.311, p=0.048). An interesting finding was that glutathione levels and cysteine intake were positively correlated with maximal handgrip strength (r=0.416, p=0.007 and r=0.343, p=0.028, respectively). In conclusion, glutathione concentration is associated with cysteine intake, while adequate cysteine levels were important for optimal redox status and muscle function. This highlights the importance of proper nutritional intake and biochemical screening with the goal of personalized nutrition.


Assuntos
Cisteína/administração & dosagem , Glutationa/sangue , Força da Mão , Músculo Esquelético/fisiologia , Adulto , Ingestão de Alimentos , Eritrócitos/metabolismo , F2-Isoprostanos/sangue , Feminino , Humanos , Contração Isométrica , Masculino , Fadiga Muscular , Estresse Oxidativo , Adulto Jovem
7.
Med Arch ; 74(3): 199-204, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32801436

RESUMO

INTRODUCTION: Cardiovascular disease (CAD) associated with death and disability remains a serious medical problem. In some patients the initial clinical coronary artery disease presentation is stable angina pectoris. AIM: The aim of the study was to evaluate the effect of EECP therapy with or without trimetazidine (TMZ) in patients with refractory angina via modulating peripheral monocyte expression of Toll like receptor2 (TLR2) and its downstream signaling. METHODS: This is a double-blind randomized prospective study in which 88 stable refractory angina patients allocated into two groups, Enhanced External Counter Pulsation (EECP) group: included 44 patients with stable refractory angina, and were treated with EECP-Therapy. TMZ-EECP group: included 44 patients with stable refractory angina, we gave TMZ 35 mg twice daily in addition to EECP-Therapy. RESULTS: TLR2 expression in peripheral monocyte investigated by flow cytometry and 8-iso-prostaglandin F2ß (8-iso-PGF2 ß), interleukin1ß (IL-1ß), heat shock protein 60 (HSP60) and monocytes chemoattractant protein-1(MCP-1) were also measured before the EECP-therapy and before giving TMZ to patients, and after 35 hours of EECP treatment (7 consecutive weeks). Inhibition in TLR2 expression in peripheral monocyte was observed among the EECP group (P<0.05). Inflammatory cytokine MCP-1 was remarkably decreased in both study groups but (heat shock protein 60 (HSP60), MCP-1 and interleukin-1ß (IL-1ß)) significantly decreased levels were observed among the TMZ-EECP group (P<0.05). Also, the oxidative stress biomarker 8-iso-prostaglandin F2ß (8-iso-PGF2ß) was decreased in both study groups but significantly decreased levels were observed among the TMZ-EECP group (P<0.05). TMZ and EECP therapy in patients with stable refractory angina remarkably decreased the inflammatory markers HSP60, MCP-1 and IL-1ß in serum levels also the decreased levels were found in serum levels of oxidative stress marker 8-iso-PGF2ß serum level. CONCLUSION: EECP-therapy decreased the expression of TLR2 on peripheral monocytes in patients with chronic stable refractory angina which yield improvement in the quality of patients' life by decreasing the frequency of angina episodes, decreasing the Short-acting nitrate use and change the exercise tolerance and distance.


Assuntos
Angina Pectoris/sangue , Angina Pectoris/terapia , Contrapulsação , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Chaperonina 60/sangue , Quimiocina CCL2/sangue , Terapia Combinada , Método Duplo-Cego , F2-Isoprostanos/sangue , Feminino , Humanos , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/sangue , Monócitos/metabolismo , Satisfação do Paciente , Estudos Prospectivos , Receptor 2 Toll-Like/sangue
8.
Fertil Steril ; 114(3): 646-652, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682516

RESUMO

OBJECTIVE: To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimüllerian hormone (AMH), an indicator of ovarian reserve, in a population-based cohort of women of black and white ethnicities. DESIGN: Cross-sectional analysis. SETTING: Not applicable. PATIENTS: The CARDIA Women's Study, a population-based cohort. Black (n = 398) and white (n = 432) late reproductive-aged women (mean age 40 ± 3.6 years) without histories of gynecologic surgery. MAIN OUTCOME MEASURES: Log-transformed serum AMH concentrations. RESULTS: Linear regression models evaluated whether plasma F2-isoprostanes were associated with log-transformed AMH after adjustment for age, race, smoking, body mass index, and oral contraceptive pill use. Higher levels of F2-isoprostanes were associated with lower AMH levels (ß -0.048 per standard deviation, 95% confidence interval -0.087, -0.01). The observed associations were stronger at younger ages (P=.04 for interaction between levels of age and F2-isoprostanes). Indicators of other steps in the oxidative stress pathway (superoxide dismutase, paraoxonase activity, oxidized low-density lipoprotein cholesterol, and carotenoids) were not associated with AMH, although lower phospholipase A2 activity (ß 0.036 per standard deviation, 95% confidence interval 0.001, 0.071) was associated with lower AMH across all ages. CONCLUSION: In a population-based cohort, higher levels of F2-isoprostanes were associated with lower ovarian reserve, particularly at younger ages.


Assuntos
Hormônio Antimülleriano/sangue , F2-Isoprostanos/sangue , Reserva Ovariana , Adulto , Negro ou Afro-Americano , Fatores Etários , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Estresse Oxidativo , Estados Unidos , População Branca
9.
Biomarkers ; 25(4): 315-321, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32274952

RESUMO

Prognostication after cardiac arrest (CA) represents a challenging issue, and several biomarkers have been proposed in the attempt to predict outcome. Among these, F2-isoprostanes stand out as potential biomarkers for early prognostication, providing information on the magnitude of global oxidative injury after return of spontaneous circulation (ROSC). We performed a topical review searching PubMed and Scopus databases to identify studies evaluating the modifications of F2-isoprostanes in the early period after CA, and a meta-analysis of studies providing curves of F2-isoprostanes plasma levels seeking to describe the biomarker's kinetics after CA. Evidence suggests that plasma levels of F2-isoprostanes increase in the early post-resuscitation period and seem well correlated with the burden of ischaemia-reperfusion injury. Our meta-analysis shows a possible increase as early as 5 minutes after ROSC, which persists at 2 hours and is attenuated at 4 hours. Clinical studies are warranted to evaluate the utility of this biomarker for prognostication purposes in CA survivors.


Assuntos
Biomarcadores/sangue , F2-Isoprostanos/sangue , Parada Cardíaca Extra-Hospitalar/sangue , Traumatismo por Reperfusão/sangue , Reanimação Cardiopulmonar , Diagnóstico Precoce , Humanos , Parada Cardíaca Extra-Hospitalar/patologia , Estresse Oxidativo/genética , Prognóstico , Traumatismo por Reperfusão/patologia
10.
World J Biol Psychiatry ; 21(8): 642-650, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32081046

RESUMO

Objectives: Attenuation of brain-derived neurotrophic factor (BDNF) availability and increased dipeptidyl peptidase-4 (DPP4) activity have both been reported to link to the pathogenesis of depression. The aim of this study was to test the correlation between depressive symptoms and plasma DPP4 activity to BDNF ratio (DBR).Methods: We evaluated DPP4 activity, BDNF, oxidative stress parameters and inflammatory markers and calculated DBR in a cross-sectional sample of 1640 non-diabetic participants.Results: DPP4 activity was negatively related to BDNF in participants with and without depressive symptoms (r= -0.351 and r= -0.404, p<.001). Nitrotyrosine and 8-iso-PGF2a mediated 18.4 and 12.6% of the total effect of DPP4 activity on BDNF, respectively. 8-iso-PGF2a, nitrotyrosine, C-reactive protein, interleukin-6 and PHQ-9 score progressively increased across DBR quartiles. Participants whose DBRs were in the highest quartile had 2.64-fold increased odds (OR = 3.03) of depressive symptoms. The depressive symptoms risk increased more with lower levels of BDNF and higher levels of DPP4 activity (p<.05).Conclusions: Our data suggested inverse correlation between DPP4 activity and BDNF through the oxidative stress mediator. The positive relationship between DBR and depressive symptoms risk raises feasibility of identifying DBR as a novel biological marker or even a possible therapeutic target for depression.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Depressão/sangue , Depressão/psicologia , Dipeptidil Peptidase 4/sangue , Glucose/metabolismo , Idoso , Estudos Transversais , F2-Isoprostanos/sangue , Humanos , Inflamação/sangue , Pessoa de Meia-Idade , Estresse Oxidativo , Tirosina/análogos & derivados , Tirosina/sangue
11.
Clin Genitourin Cancer ; 18(2): e174-e179, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31899150

RESUMO

INTRODUCTION: Oxidative stress has been found to be associated with the progression of prostate cancer (PCa); however, human studies which identify differential roles of each oxidation pathway in PCa progression are lacking. We aimed to identify which oxidative stress markers, specifically lipid and global oxidation and glycation, are associated with PCa progression. PATIENTS AND METHODS: We recruited 3 groups of patients from a urologic clinic at the University of Cincinnati Medical Center: men with PCa who had undergone prostatectomy, men with PCa under watchful waiting, and men with benign prostatic hyperplasia (BPH). We used the most commonly used lipid oxidation marker, F2-isoprostanes; global oxidation markers, fluorescent oxidation products (FlOPs); and the commonly used marker for advanced glycation end products, carboxymethyllysine. These biomarkers were measured in plasma samples at baseline entry. Plasma prostate-specific antigen (PSA) was measured at enrollment and follow-up visits. RESULTS: Compared with men with BPH, men with PCa who had undergone prostatectomy had 26% (P = .01) higher levels of F2-isoprostanes and 20% (P = .08) higher levels of carboxymethyllysine. All the oxidation markers were similar when comparing men under watchful waiting with men with BPH. When examining the associations between baseline oxidation markers and follow-up PSAs, we found that different oxidation markers had differential patterns associated with PSA elevation. F2-isoprostanes were positively associated with PSA elevation among men with PCa; FlOP_320 was positively associated with PSA elevation among both men with PCa and men with BPH, whereas among men with PCa under watchful waiting, FlOP_360 and FlOP_400 had opposite trends of associations with PSA elevation. CONCLUSIONS: Our study suggested that high levels of lipid oxidation were associated with PCa progression, whereas different global oxidation markers had different patterns associated with PCa progression. Large-scale clinical studies are needed to confirm our associations. Our study provides a comprehensive view of the relationship between biomarkers and PCa progression.


Assuntos
F2-Isoprostanos/sangue , Calicreínas/sangue , Lisina/análogos & derivados , Estresse Oxidativo , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Seguimentos , Humanos , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Próstata/cirurgia , Prostatectomia/estatística & dados numéricos , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Medição de Risco/métodos , Conduta Expectante/estatística & dados numéricos
12.
Anesthesiology ; 132(3): 551-561, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31770146

RESUMO

BACKGROUND: Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. METHODS: In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. RESULTS: Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). CONCLUSIONS: Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Delírio do Despertar/patologia , Delírio do Despertar/psicologia , Estresse Oxidativo , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/psicologia , Idoso , Idoso de 80 Anos ou mais , Barreira Hematoencefálica , Estudos de Coortes , F2-Isoprostanos/sangue , Feminino , Furanos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas S100/sangue , Ubiquitina Tiolesterase/sangue
13.
Biol Res Nurs ; 21(5): 458-465, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31315444

RESUMO

PURPOSE: The purpose of this study was to explore the influence of oxidative stress (F2-isoprostanes) and inflammatory (interleukin [IL]-8) biomarkers on symptom trajectories during the first 18 months of childhood leukemia treatment. METHOD: A repeated-measures design was used to evaluate symptoms experienced by 218 children during treatment. A symptom cluster (fatigue, pain, and nausea) was explored over four time periods: initiation of post-induction therapy, 4 and 8 months into post-induction therapy, and the beginning of maintenance therapy (12 months postinduction). F2-isoprostanes and IL-8 were evaluated in cerebrospinal fluid (CSF) samples collected at baseline (diagnosis) and then at the four time periods. The longitudinal relationships of these biomarkers with the symptom cluster were examined using the longitudinal parallel process. RESULTS: Pain and fatigue levels were highest during the post-induction phases of treatment and decreased slightly during maintenance therapy, while nausea scores were relatively stable. Even in the later phases of treatment, children continued to experience symptoms. CSF levels of the biomarkers increased during the post-induction phases of treatment. Early increases in the biomarkers were associated with more severe symptoms during the same period; patients who had increased biomarkers over time also experienced more severe symptoms over time. CONCLUSIONS: Findings reveal that children experienced symptoms throughout the course of leukemia treatment and support hypothesized longitudinal relationships of oxidative stress and inflammatory biomarkers with symptom severity. Activation of the biomarker pathways during treatment may explain underlying mechanisms of symptom experiences and identify which children are at risk for severe symptoms.


Assuntos
F2-Isoprostanos/sangue , Leucemia/tratamento farmacológico , Estresse Oxidativo/imunologia , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Fadiga/etiologia , Feminino , Humanos , Leucemia/imunologia , Estudos Longitudinais , Masculino , Náusea/etiologia , Dor/etiologia , Síndrome
14.
Free Radic Res ; 53(4): 377-386, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31117841

RESUMO

Oxidative stress has been identified as a process which is detrimental to brain health, and associated with age-related cognitive declines. Few studies to-date have examined the relationship between in vivo oxidative stress biomarkers and cognitive performance within healthy elderly populations. The current study investigated the relationship between reaction time and oxidative stress, as measured by blood plasma concentrations of F2-isoprostanes using a sample of 251 healthy, non-demented, elderly volunteers (Male; 111: Female 140) aged 60-75 years from the Australian Research Council Longevity Intervention (ARCLI) study cohort. A Jensen Box was used in conjunction with the Hick paradigm in order to differentiate simple from choice reaction time (two, four and eight-choice conditions) as well as movement (MT) and decision times (DT). MT, but not DT, was found to be significantly slower for participants in the high F2-isoprostane group compared to the low F2-isoprostane group, across all stimulus choices. F2-isoprostanes, age and Wechsler Abbreviated Scale of Intelligence (WASI) full scale intelligence quotient (IQ) were found to be significant predictors of average MT in the sample as a whole. These findings provide preliminary evidence to suggest that higher levels of oxidative stress may be associated with impaired psychomotor speed in the healthy elderly population.


Assuntos
Biomarcadores/sangue , F2-Isoprostanos/sangue , Inteligência/fisiologia , Estresse Oxidativo , Desempenho Psicomotor/fisiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
15.
Artigo em Inglês | MEDLINE | ID: mdl-31126516

RESUMO

INTRODUCTION: Pregnancy and physical activity are associated with oxidative stress and immune changes. We hypothesized that pregnant women physically more active in early pregnancy will display a better oxidative stress management and inflammatory response later in pregnancy compared with less active pregnant women. MATERIAL AND METHODS: Maternal physical activity using accelerometry monitors for 1 week and cardiorespiratory fitness (VO2 at anaerobic threshold) were assessed at 14-18 weeks in 58 pregnant women. Plasma and erythrocytes membrane samples were obtained from maternal blood samples at 14-18 and 34-37 weeks of pregnancy. Pro-inflammatory prostaglandin (PG) F2α and oxidative stress-derived F2-isoprostanes were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: Higher physical activity levels at 14-18 weeks measured by mean counts per minute, >30 min/d of moderate to vigorous activity or >6500 steps/d at 14-18 weeks of pregnancy were associated with lower levels of total plasmatic PGF2α later in pregnancy. Concentrations of 5 F2-isomers in erythrocyte membranes in late pregnancy were significantly higher in the third (17.5-19.5 mL kg-1 min-1) and/or fourth (19.6-27.7 mL kg-1 min-1) quartiles of cardio-respiratory fitness compared to the first quartile (13.9-15.9 mL kg-1 min-1). CONCLUSIONS: Overall, higher cardio-respiratory fitness in early pregnancy is associated with enhanced erythrocyte membranes oxidation at 34-37 weeks reflecting a higher oxygen transfer capacity. Also, the most active women experienced lower circulating levels of pro-inflammatory PGF2α in plasma at 34-37 weeks, a marker associated with adverse antenatal inflammation-associated conditions. These results support the practice of physical activity by pregnant women.


Assuntos
Dinoprosta/sangue , F2-Isoprostanos/sangue , Estresse Oxidativo/genética , Aptidão Física , Adulto , Biomarcadores/sangue , Peso Corporal/genética , Peso Corporal/fisiologia , Cromatografia Líquida de Alta Pressão , Eritrócitos/metabolismo , Exercício Físico , F2-Isoprostanos/genética , Feminino , Humanos , Isomerismo , Gravidez , Espectrometria de Massas em Tandem
16.
J Acad Nutr Diet ; 119(7): 1160-1167, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30928321

RESUMO

BACKGROUND: Thiamin is a required coenzyme in energy production reactions that fuel myocardial contraction. Therefore, thiamin deficiency (TD) may aggravate cardiac dysfunction in patients with systolic heart failure (HF). OBJECTIVE: To determine the prevalence of TD in ambulatory participants with HF as well as the relationships between thiamin status and HF severity, dietary thiamin intake, diuretic use, and circulating neurohormones. DESIGN: A cross-sectional study comparing the prevalence of TD in ambulatory patients with HF with that of controls. Demographic, anthropometric, nutrition, medication use, and heart function data were collected from direct interviewing, questionnaires, and medical records. Blood samples were obtained to measure levels of neurohormones and assess TD. PARTICIPANTS/SETTING: Fifty age-matched control participants without HF and 100 outpatients with HF and reduced left ventricular function were recruited from clinics at St Michael's Hospital, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada, between September 2009 and February 2011. MAIN OUTCOME MEASURES: To assess TD, erythrocyte thiamin pyrophosphate (TPP) was measured using high-performance liquid chromatography. TD was defined as TPP<6.07 µg/dL (180 nmol/L). STATISTICAL ANALYSES PERFORMED: Prevalence rates were analyzed using χ2 test. Nonparametric statistics (Jonckheere-Terpstra, Kruskal-Wallis, Spearman's correlation) were used to assess TPP levels in relation to HF severity, medication use and plasma concentrations of F2-isoprostanes, norepinephrine, and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: There was no significant difference in the prevalence of TD in outpatients with HF (6%) and controls (6%) (P=0.99). No relationship was found between heart function, thiamin intake, use or dose of diuretics, and TD. A positive relationship was observed between erythrocyte TPP and F2-isoprostane levels (rs=0.22, P=0.03) but not between erythrocyte TPP and norepinephrine (P=0.45) and NT-proBNP (P=0.58). CONCLUSION: The prevalence of TD was low in ambulatory HF participants suggesting that, unlike hospitalized patients, ambulatory patients may be at a low risk for TD.


Assuntos
Insuficiência Cardíaca/sangue , Deficiência de Tiamina/epidemiologia , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Fator Natriurético Atrial/sangue , Estudos Transversais , F2-Isoprostanos/sangue , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Ontário/epidemiologia , Prevalência , Precursores de Proteínas/sangue , Deficiência de Tiamina/etiologia
17.
Biomarkers ; 24(4): 394-400, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30907677

RESUMO

Purpose: Oxidative stress (OS) has been implicated in the pathogenesis of metabolic syndrome (MetS). The acute change in OS biomarkers due to exercise, known as exercise-induced OS (EIOS), is postulated to be a more appropriate marker of OS compared to spot OS measures. These studies objectives were to investigate EIOS in participants with MetS and compare the associations between EIOS, spot OS measures and MetS severity. Methods: Sixty-three participants with MetS had MetS severity assessed using the MetS Z-score. Participants undertook a cardiorespiratory fitness test ( V O2peak) to volitional exhaustion (∼8-12 minutes). Plasma OS (total F2-isoprostanes (IsoP), protein carbonyls (PCs)) and antioxidant (glutathione peroxidase (GPx), total antioxidant status (TAS)) biomarkers were measured from samples obtained before and five minutes post- V O2peak test. Wilcoxon's signed-rank tests were used to determine changes in OS markers. Results: There were no significant (p > 0.05) changes in OS or antioxidant biomarkers from pre- to post-exercise (median (interquartile range): IsoP -15.5 (-71.8 to 47.8) pg/mL; PC -0.01 (-0.16 to 0.13) nmol/mg protein; GPx 0.76 (-4.94 to 9.82) U/L, TAS 0.03 (0.00-0.05) mmol/L). Conclusions: A V O2peak test to exhaustion failed to induce OS in participants with MetS. There were no associations between MetS severity and spot OS or EIOS biomarkers.


Assuntos
Aptidão Cardiorrespiratória , Glutationa Peroxidase/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Esforço Físico , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Estudos Transversais , Teste de Esforço/métodos , F2-Isoprostanos/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo , Carbonilação Proteica , Índice de Gravidade de Doença
18.
Exp Biol Med (Maywood) ; 244(3): 272-278, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30727766

RESUMO

IMPACT STATEMENT: We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.


Assuntos
F2-Isoprostanos/sangue , Hemorragia/fisiopatologia , Pressão Negativa da Região Corporal Inferior/métodos , Estresse Oxidativo/fisiologia , Adulto , Feminino , Voluntários Saudáveis , Hemorragia/sangue , Humanos , Masculino
19.
Artigo em Inglês | MEDLINE | ID: mdl-30103922

RESUMO

BACKGROUND: Diabetes and pregnancy are both associated with oxidative stress, characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation of arachidonic acid, a n - 6 polyunsaturated fatty acid (PUFA). We hypothesized that pregnant women with pre-existing diabetes will be characterized by elevated levels of specific F2-isoPs isomers and altered PUFA composition in plasma early pregnancy when compared to normoglycemic controls. METHODS: Plasma samples from 23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort). Six F2-isoprostanes isomers were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in plasmatic phospholipids were measured by gas chromatography coupled to a flame ionization detector. RESULTS: F2-isoprostanes, specifically the 8-iso-15(R)-PGF2α levels, were 67% higher in diabetic than normoglycemic pregnancies (p = 0.026). The total n - 6 PUFA and arachidonic acid level did not differ between study groups. In contrast, total n - 3 level was 32% lower in diabetic pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre-existing diabetes than in controls (p = 0.042). CONCLUSIONS: Pre-existing diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when compared to other pathologies of pregnancy, such as preeclampsia, as previously assessed in the same cohort.


Assuntos
Diabetes Mellitus/sangue , F2-Isoprostanos/análise , Ácidos Graxos/análise , Primeiro Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/sangue , Adulto , Cromatografia Líquida de Alta Pressão/métodos , F2-Isoprostanos/sangue , Ácidos Graxos/sangue , Feminino , Idade Gestacional , Humanos , Linoleoil-CoA Desaturase/metabolismo , Estresse Oxidativo , Fosfolipídeos/química , Gravidez , Espectrometria de Massas em Tandem/métodos
20.
Oxid Med Cell Longev ; 2018: 7608108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050660

RESUMO

This research paper is aimed at evaluating the predictive role of a default panel of oxidative stress (OS) biomarkers for the early identification of infants at high risk of HIE and their validation through the correlation with MRI findings. A multicenter prospective observational study was performed between March 2012 and April 2015 in two European tertiary NICUs. Eighty-four term infants at risk for HIE (pH < 7, BE < -13 mmol/L, and 5' Apgar < 5) were enrolled. Three were excluded for chromosomal abnormalities and one due to lack of blood samples. The final population was divided according to the severity of perinatal hypoxia into 2 groups: mild/moderate HIE and severe HIE. Advanced oxidation protein products (AOPP), non-protein-bound iron (NPBI), and F2-isoprostanes (F2-IsoPs) were measured in blood samples at P1 (4-6 hours), P2 (24-72 hours), and P3 (5 days), in both groups. MRIs were scored for the severity of brain injury, using a modified Barkovich score. The mean GA was 39.8 weeks (SD 1.4) and the mean birth weight 3538 grams (SD 660); 37 were females and 43 males. Significantly lower 5' Apgar score, pH, and BE and higher Thompson score were found in group II compared to group I at birth. Group II showed significantly higher AOPP and NPBI levels than group I (mean (SD) AOPP: 15.7 (15.5) versus 34.1 (39.2), p = 0.033; NPBI 1.1 (2.5) versus 3.9 (4.4), p = 0.013) soon after birth (P1). No differences were observed in OS biomarker levels between the two groups at P2 and P3. A regression model, including adjustment for hypothermia treatment, gender, and time after birth, showed that AOPP levels and male gender were both risk factors for higher brain damage scores (AOPP: OR 3.6, 95% CI (1.1-12.2) and gender: OR 5.6, 95% CI (1.2-25.7), resp.). Newborns with severe asphyxia showed higher OS than those with mild asphyxia at birth. AOPP are significantly associated with the severity of brain injury assessed by MRI, especially in males.


Assuntos
Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Estresse Oxidativo/fisiologia , Produtos da Oxidação Avançada de Proteínas/sangue , Biomarcadores/metabolismo , Lesões Encefálicas/sangue , Lesões Encefálicas/metabolismo , F2-Isoprostanos/sangue , Feminino , Humanos , Hipóxia-Isquemia Encefálica/sangue , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos
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