Systemic oxidative stress in children with cystic fibrosis with bacterial infection including Pseudomonas Aeruginosa.

INTRODUCTION: Oxidative stress (OS) occurs in cystic fibrosis (CF). OBJECTIVE: The objective of this work is to evaluate the influence of bacterial infection on biomarkers of OS (catalase [CAT], glutathione peroxidade [GPx], reduced glutathione [GSH]), markers of oxidative damage (protein carbonyls [PC], thiobarbituric acid reactive substances [TBARS]), together with the nutritional status and lung function in children with CF. METHODS: Cross-sectional study including CF group (CFG, n = 55) and control group (CG, n = 31), median age: 3.89 and 4.62 years, respectively. CFG was distributed into CFG negative bacteriology (CFGB-, n = 27) or CFG positive bacteriology (CFGB+, n = 28), and CFG negative Pseudomonas aeruginosa (CFGPa-, n = 36) or CFG positive Pseudomonas aeruginosa (CFGPa+, n = 19). RESULTS: Compared with CG, CFG (P = .034) and CFGB+ (P = .042) had lower body mass index-for-age z-score; forced expiratory volume in the first second was lower in CFGB+ and CFGPa+ (both P < .001). After adjusting for confounders and compared with CG: CFG showed higher TBARS (P ≤ .001) and PC (P = .048), and lower CAT (P = .004) and GPx (P = .003); the increase in PC levels was observed in CFGB+ (P = .011) and CFGPa+ (P = .001) but not in CFGB- (P = .510) and CFGPa- (P = .460). CONCLUSIONS: These results indicate a systemic OS in children with CF. The presence of bacterial infection particularly Pseudomonas aeruginosa seems to be determinant to exacerbate the oxidative damage to proteins, in which PC may be a useful biomarker of OS in CF.

Relationship between urinary nitrate concentrations and cognitive function in older adults: findings from the NHANES survey.

This study evaluated the association of urinary nitrate concentrations with cognition in older subjects enrolled in the NHANES study. We also explored whether associations between urinary nitrate and cognition were modified by cardiovascular risk, vitamin D status and vitamin C intake. Two NHANES cycles were merged (2011-2012 and 2013-2014) and a total of 1,015 adults aged 60-80 (69.4 ± 0.3) years were included. Cognition was assessed using the Word List Learning, Word List Recall, Animal Fluency and the Digit Symbol Substitution tests. Urinary nitrate was analysed using electrospray tandem mass spectrometry. Urinary nitrate concentrations were not associated with cognitive performance on any of the cognitive tests. Associations were also not significant in subjects at greater risk for cognitive impairment (i.e. high cardiovascular risk and non-optimal vitamin D status). Longitudinal analyses are needed to explore the associations of urinary nitrate concentrations with dietary nitrate intake and cognitive function.

C-reactive protein/albumin ratio is associated with lung function among children/adolescents with cystic fibrosis: a three-year longitudinal study

ABSTRACT BACKGROUND: Chronic lung infections, inflammation and depletion of nutritional status are considered to be prognostic indicators of morbidity in patients with cystic fibrosis. The aim of this study was to investigate the association between inflammatory markers and lung function, nutritional status and morbidity among children/adolescents with cystic fibrosis. DESIGN AND SETTINGS: Prospective three-year longitudinal study conducted in an outpatient clinic in southern Brazil. METHODS: Children/adolescents aged 1-15 years with cystic fibrosis were enrolled. Nutritional status was determined from weight-to-length and body mass index-to-age z-scores and was classified as acceptable, at risk or nutritional failure. Tumor necrosis factor-α, interleukin-1β, myeloperoxidase, C-reactive protein and C-reactive protein/albumin ratio were analyzed. Lung function was evaluated based on the forced expiratory volume in the first second and morbidity according to the number of hospitalizations for pulmonary exacerbation and infections by Pseudomonas aeruginosa. Lung function, nutritional status and morbidity were the outcomes. Odds ratios and 95% confidence intervals were to evaluate the effect of baseline inflammatory markers on the clinical outcomes after three years of follow-up and p-values < 0.05 were considered significant. RESULTS: We evaluated 38 children/adolescents with cystic fibrosis: 55% female; median age (with interquartile range), 3.75 years (2.71-7.00). Children/adolescents with high C-reactive protein/albumin ratio at baseline had odds of 18 (P = 0.018) of presenting forced expiratory volume in the first second ≤ 70% after three years. The other inflammatory markers were not associated with the outcomes. CONCLUSION: C-reactive protein/albumin ratio was associated with forced expiratory volume in the first second ≤ 70% after three years.

C-reactive protein/albumin ratio is associated with lung function among children/adolescents with cystic fibrosis: a three-year longitudinal study.

BACKGROUND: Chronic lung infections, inflammation and depletion of nutritional status are considered to be prognostic indicators of morbidity in patients with cystic fibrosis. The aim of this study was to investigate the association between inflammatory markers and lung function, nutritional status and morbidity among children/adolescents with cystic fibrosis. DESIGN AND SETTINGS: Prospective three-year longitudinal study conducted in an outpatient clinic in southern Brazil. METHODS: Children/adolescents aged 1-15 years with cystic fibrosis were enrolled. Nutritional status was determined from weight-to-length and body mass index-to-age z-scores and was classified as acceptable, at risk or nutritional failure. Tumor necrosis factor-α, interleukin-1ß, myeloperoxidase, C-reactive protein and C-reactive protein/albumin ratio were analyzed. Lung function was evaluated based on the forced expiratory volume in the first second and morbidity according to the number of hospitalizations for pulmonary exacerbation and infections by Pseudomonas aeruginosa. Lung function, nutritional status and morbidity were the outcomes. Odds ratios and 95% confidence intervals were to evaluate the effect of baseline inflammatory markers on the clinical outcomes after three years of follow-up and p-values < 0.05 were considered significant. RESULTS: We evaluated 38 children/adolescents with cystic fibrosis: 55% female; median age (with interquartile range), 3.75 years (2.71-7.00). Children/adolescents with high C-reactive protein/albumin ratio at baseline had odds of 18 (P = 0.018) of presenting forced expiratory volume in the first second ≤ 70% after three years. The other inflammatory markers were not associated with the outcomes. CONCLUSION: C-reactive protein/albumin ratio was associated with forced expiratory volume in the first second ≤ 70% after three years.

Influence of inflammatory response, infection, and pulmonary function in cystic fibrosis.

AIMS: Recurrent infections and activation of the inflammatory response affect the prognosis of cystic fibrosis (CF). We investigated the relationship between inflammatory response, infection, and pulmonary function in CF. MAIN METHODS: A clinical-cross-sectional study was conducted with 86 subjects: control group (CG, n=31, the same age and sex of the CF group), and CF group (CFG, n=55, age: 1-16 years), further distributed into CFG negative or positive bacteriology (CFGB(-)/CFGB(+)), and CFG negative or positive Pseudomonas aeruginosa (CFGPa(-)/CFGPa(+)). Using the Wald test, multiple linear regression (95% confidence interval) was performed between CG and CFG, and between CG and each of the CF subgroups (CFGB(-)/CFGB(+) and CFGPa(-)/CFGPa(+)). The inflammatory markers evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities, interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential leukocyte counts. KEY FINDINGS: After adjusting for sex and age, CFG compared to CG revealed an increase of MPO, IL-1ß (P<0.001 in all subgroups), and CRP: CFG (P=0.002), CFGB(-) (P=0.007), CFGB(+) (P=0.009), CFGPa(-) (P=0.004) and CFGPa(+) (P=0.020). NOx (P=0.001, P<0.001), leukocytes (P=0.002, P=0.001), and neutrophils (P=0.003, P<0.001) were increased in CFGB(+) and CFGPa(+), respectively. A negative correlation between FEV1 and leukocytes (P=0.008) and FEV1 and neutrophils (P=0.031) resulted in CFG. SIGNIFICANCE: The inflammatory response characterized by the increase of MPO, IL-1ß, and CRP is determinant for CF. Also leukocytosis due to neutrophilia determines the pulmonary function deficiency in this disease.

Systemic oxidative stress in children and teenagers with Down syndrome.

AIMS: The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome. MAIN METHODS: The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n=20) compared to healthy controls (n=18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically. KEY FINDINGS: Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls. SIGNIFICANCE: The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.