ascorbic-acid and Cystic-Fibrosis

Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain an oxidant-antioxidant balance. Current literature suggests a relationship between oxidative status and lung function.. To synthesize existing knowledge of the effect of antioxidants such as vitamin C, vitamin E, ß-carotene, selenium and glutathione in cystic fibrosis lung disease.. The Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and PubMed were searched using detailed search strategies. We contacted authors of included studies and checked reference lists of these studies for additional, potentially relevant studies.Last search of Cystic Fibrosis Trials Register: 29 August 2013.. Randomized controlled studies and quasi-randomized controlled studies of people with cystic fibrosis comparing antioxidants as listed above (individually or in combination) in more than a single administration to placebo or standard care.. Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted trial investigators to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress, inflammation, nutritional status, days on antibiotics and adverse events during supplementation. If meta-analysed, studies were subgrouped according to method of administration and the duration of supplementation.. One quasi-randomized and nine randomized controlled studies were included, with a total of 436 participants. Eight studies analyzed oral supplementation with antioxidants and two inhaled supplements.One study (n = 46) of an oral combined supplement demonstrated a significant difference in forced expiratory volume at one second expressed as per cent predicted after two weeks in favour of the control group, mean difference -4.30 (95% confidence interval -5.64 to -2.96); however a further study (n = 41) of oral supplementation with glutathione showed a significant improvement in this outcome and in forced vital capacity after six months from the treatment start, mean difference 17.40 (95% confidence interval 13.69 to 21.11) and 14.80 (95% confidence interval 9.66 to 19.94) respectively. The combined supplement study also indicated a significant improvement in quality of life favouring control, mean difference -0.06 points on the quality of well-being scale (95% confidence interval -0.12 to -0.01). Based on one study (n = 41) of oral glutathione supplementation in children, the supplements had a positive effect on the nutritional status (body mass index %) of the patients, mean difference 17.20 (95% confidence interval 12.17 to 22.23). In two studies (n = 83) that supplemented vitamin E, there was an improvement after two months in the blood levels of vitamin E, mean difference 11.78 μM/L (95% confidence interval 10.14 to 13.42).Based on one of the two studies of inhaled glutathione supplementation, there was an improvement in the forced expiratory volume at one second expressed as per cent predicted after three and six months (n = 153), mean difference 2.57 (95% confidence interval 2.24 to 2.90) and 0.97 (95% confidence interval 0.65 to 1.29) respectively. Only one of the studies reported quality of life data that could be analysed, but data showed no significant differences between treatment and control.None of the 10 included studies was judged to be free of bias.. There appears to be conflicting evidence regarding the clinical effectiveness of antioxidant supplementation in cystic fibrosis. Based on the available evidence, glutathione (administered either orally or by inhalation) appears to improve lung function in some cases and decrease oxidative stress; however, due to the very intensive antibiotic treatment and other treatments that cystic fibrosis patients receive, the beneficial effect of antioxidants is very difficult to assess in patients with chronic infection without a very large population sample and a long-term (at least six months) study period. Further studies, especially in very young patients, examining clinically relevant outcomes, dose levels, timing and the elucidation of clear biological pathways by which oxidative stress is involved in cystic fibrosis, are necessary before a firm conclusion regarding effects of antioxidants supplementation can be drawn.

Topics: Administration, Inhalation; Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Child; Cystic Fibrosis; Humans; Micronutrients; Oxidative Stress; Quality of Life; Randomized Controlled Trials as Topic; Selenium; Vitamin E; Vitamins

Cystic fibrosis is one of the most common autosomal recessive genetic disorders in caucasians of Northern European descent, affecting approximately 30 000 children and adults living in the United States, today. Complications of this chronic disease result in deterioration of lung function and development of pancreatic abnormalities requiring pharmacological therapy and may include patients seeking complementary and alternative option for treatment. Health care professionals should be knowledgeable of these therapies to effectively provide education and drug therapy management. This article offers an overview of the most common complementary therapies in cystic fibrosis such as vitamin A, vitamin C, vitamin E, zinc, omega 3 fatty acids, docosahexaenoic acid (DHA), garlic, ginseng, and curcumin.

Topics: Antioxidants; Ascorbic Acid; Curcumin; Cystic Fibrosis; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-3; Garlic; Humans; Panax; Phytotherapy; Vitamin A; Vitamin E; Zinc

Airway infection leads to progressive damage of the lungs in cystic fibrosis (CF), partly due to oxidative stress. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) may help maintain an oxidant-antioxidant balance. Current literature suggests a relationship between oxidative status and lung function.. To synthesize existing knowledge of the effect of vitamin C, vitamin E, ß-carotene and selenium in CF lung disease.. The Cochrane CF and Genetic Disorders Group CF Trials Register, PubMed, CINAHL and AMED were searched using detailed search strategies. We contacted authors of included studies and checked reference lists of these studies for additional, potentially relevant studies.Last search of CF Trials Register: 09 September 2010.. Randomized controlled trials and quasi-randomized controlled trials of people with CF with explicitly stated diagnostic criteria, comparing vitamin E, vitamin C, ß-carotene and selenium (individually or in combination) to placebo or standard care.. Two authors independently selected trials, extracted data and assessed risk of bias. We contacted trialists to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress, inflammation, body mass index, days on antibiotics and adverse events during supplementation. If meta-analysed, studies were subgrouped according to combined or single antioxidant supplementation.. Four randomized controlled trials and one quasi-randomized controlled trial were included; only three trials (87 participants) presented data suitable for analysis. Based on two trials, there was no significant improvement in lung function; one trial indicated significant improvement in quality of life favouring control, mean difference -0.06 points on the quality of well-being scale (95% confidence interval -0.12 to -0.01). Based on two trials, selenium-dependent glutathione peroxidase enzyme significantly improved in favour of combined supplementation, mean difference 1.60 units per gram of haemoglobin (95% CI 0.30 to 2.90) and selenium supplementation, mean difference 10.20 units per gram of haemoglobin (95% CI 2.22 to 18.18). All plasma antioxidant levels, except vitamin C, significantly improved with supplementation.. There appears to be conflicting evidence regarding the clinical effectiveness of antioxidant supplementation in CF. Based on the evidence, antioxidants appear to decrease quality of life and oxidative stress; however, few trials contributed data towards analysis. Further trials examining clinically important outcomes and elucidation of a clear biological pathway of oxidative stress in CF are necessary before a firm conclusion regarding effects of antioxidants supplementation can be drawn.

Topics: Adult; Antioxidants; Ascorbic Acid; Child; Cystic Fibrosis; Humans; Micronutrients; Oxidative Stress; Quality of Life; Randomized Controlled Trials as Topic; Selenium; Vitamin E; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Breast Feeding; Child, Preschool; Cystic Fibrosis; Female; Humans; Hypervitaminosis A; Infant; Infant, Newborn; Male; Rickets; Vitamin A; Vitamin A Deficiency; Vitamin B Complex; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Adult; Ascorbic Acid; Avitaminosis; Child; Cystic Fibrosis; Dietary Supplements; Humans; Vitamin A Deficiency; Vitamin E Deficiency; Vitamin K Deficiency; Vitamins

Topics: Administration, Inhalation; Ascorbic Acid; beta Carotene; Cystic Fibrosis; Humans; Lung Diseases; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Sulfhydryl Compounds; Trachea

Vitamin supplements are routinely prescribed in cystic fibrosis, but published recommendations vary widely and there is little consistency in clinical practice. A review of the literature confirms that, while supplementation of the water-soluble vitamins (including B12 and folate) is unnecessary in uncomplicated cystic fibrosis, deficiency of the fat-soluble vitamins can lead to clinical problems. Supplements of these vitamins should be ensured for all patients with cystic fibrosis, while sparing them the unnecessary inconvenience of taking other vitamin supplements except where these are specifically indicated.

Topics: Ascorbic Acid; Cystic Fibrosis; Humans; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin E; Vitamins

Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplementation with anti-oxidants is potentially beneficial for CF patients.. The effect of 4 weeks of oral N-acetylcysteine (NAC) treatment (2400 mg/day divided into two doses) on biochemical parameters of oxidative stress was investigated in an open-label, controlled, randomized trial on 21 patients; 11 patients in the NAC group and 10 in the control group. Biochemical parameters of oxidative burden and plasma levels of antioxidants were assessed at the end of the study and compared to the baseline values in the two groups.. A significant increase in the plasma levels of the antioxidant ascorbic acid (p=0.037) and a significant decrease in the levels of the oxidized form of ascorbic acid (dehydroascorbate) (p=0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change significantly compared to baseline in either of the groups. A better lung function was observed in the NAC treated group with a mean (SD) change compared to baseline of FEV1% predicted of 2.11 (4.6), while a decrease was observed in the control group (change -1.4 (4.6)), though not statistically significant.. Treatment with N-acetylcysteine 1200 mg×2/day for 30 days significantly decreased the level of oxidized vitamin C and increased the level of vitamin C (primary end-points) and a not statistically significant improvement of lung function was observed in this group of patients.

Topics: Acetylcysteine; Administration, Oral; Adult; Antioxidants; Ascorbic Acid; Chronic Disease; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Female; Forced Expiratory Volume; Humans; Inflammation; Lung; Male; Middle Aged; Oxidative Stress; Pseudomonas Infections; Reactive Oxygen Species; Treatment Outcome

Oxidative stress, as measured by 8-iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations.. We examined changes in plasma 8-iso-PGF(2)(alpha), antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation.. Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 micro g vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg beta-carotene, 90 micro g Se, and 500 micro g vitamin A)]. Plasma concentrations of 8-iso-PGF(2)(alpha), vitamins E and C, beta-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation.. Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (+/- SEM) changes (Delta) in vitamin E were 10.6 +/- 1.5 and -1.9 +/- 0.9 micro mol/L, respectively (P < 0.001), (Delta)beta-carotene were 0.1 +/- 0.04 and -0.01 +/- 0.02 micro mol/L, respectively (P = 0.007), (Delta)selenium were 0.51 +/- 0.10 and -0.09 +/- 0.04 micro mol/L, respectively (P < 0.001), and (Delta)glutathione peroxidase activity were 1.3 +/- 0.3 and -0.3 +/- 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha), (Delta)vitamin C, (Delta)fatty acid composition, (Delta)superoxide dismutase activity, (Delta)lung function, or (Delta)white cell count. Within group B, (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity (r = 0.586, P = 0.005), (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Delta8-iso-PGF(2)(alpha) (r = 0.538, P = 0.010).. Whereas increased beta-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated.

Topics: Antioxidants; Ascorbic Acid; Child; Cystic Fibrosis; Diet Records; Dinoprostone; Double-Blind Method; Fatty Acids; Female; Humans; Isoprostanes; Male; Oxidative Stress; Respiratory Function Tests; Selenomethionine; Vitamin A; Vitamin E

Many cystic fibrosis (CF) patients have increased circulating levels of oxidation products and/or decreased antioxidant status. This study investigated whether treatment of pulmonary exacerbations decreased oxidative stress in CF patients. Seventeen adult patients were studied at the beginning and end of treatment with intravenous antibiotics. Plasma concentrations of the antioxidants ascorbic acid, alpha-tocopherol, uric acid and total reduced thiols, together with plasma retinol, lipid hydroperoxides, malondialdehyde and protein carbonyl levels were determined. Median (interquartile range) pretreatment and post-treatment levels were compared using the Wilcoxon signed rank test. Clinical resolution was reflected by improved spirometry. Significant increases were observed in plasma ascorbic acid (pre 30.4 (15.7-38.6) microM, post 35.2 (27.3-49.6) microM), alpha-tocopherol (pre 19.7 (13.6-25.2) microM, post 25.2 (19.3-31.6) microM) and retinol (pre 1.9 (1.5-2.5) microM, post 2.7 (1.7-3.5) microM). No change in plasma total reduced thiols occurred following treatment (pre 409 (366-420) microM, post 392 (366-423) microM), whereas uric acid fell with treatment (pre 307 (274-394) microM, post 260 (216-317) microM). Neither plasma protein carbonyls or malondialdehyde levels altered with treatment (protein carbonyls pre 0.47 (0.28-1.27), post 0.67 (0.42-0.83) nM x mg protein(-1); malondialdehyde pre 0.75 (0.53-1.18), post 0.84 (0.65-1.15) microM). Lipid hydroperoxides levels did decrease following treatment (53 (18-85) versus 17 (10-55) nM). This study demonstrated that treatment of infective exacerbations resulted in increased plasma levels of some antioxidant vitamins. No immediate change in plasma protein oxidation was observed, but lipid oxidation was decreased.

Topics: Adult; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Bacterial Infections; Biomarkers; Cystic Fibrosis; Female; Humans; Injections, Intravenous; Male; Prognosis; Recurrence; Sputum; Statistics, Nonparametric; Treatment Outcome; Vitamin E

The aim of this study was to determine the efficacy of oral beta-carotene supplementation for the correction of an oxidant-antioxidant imbalance in cystic fibrosis (CF). We studied 24-patients with cystic fibrosis and 14 healthy controls. 13 CF-patients were allocated to a CF-supplementation group, which received 1 mg beta-carotene/kg BW/d up to a body weight (BW) of 50 kg, patients with a BW greater 50 kg received 50 mg beta-carotene/d for 12 weeks. For the following 12 weeks all patients of the CF-supplementation group were treated with 10 mg beta-carotene/d. Placebos with starch were applied to 11 CF-patients. Baseline plasma beta-carotene concentrations of CF patients (mean +/- SD, 0.08 +/- 0.04 mumol/l) were significantly lower than those of age-matched controls (o.3 +/- 0.1 mumol/l) (p < 0.001). beta-carotene concentrations of the CF-supplementation group increased rapidly and reached a value of 0.6 mumol/l after 12 weeks of supplementation. Normal values were measured for plasma ascorbate and alpha-tocopherol. Plasma retinol concentrations were in the lower normal range and did not increase during supplementation. Total antioxidative capacity in plasma of the CF-supplementation group increased after 12 weeks of supplementation at an extent of 12%. Positive influence was indicated by a decrease of plasma malondialdehyde. Thus oral beta-carotene supplementation is effective in normalizing status of beta-carotene and malondialdehyde in CF patients.

Topics: Adolescent; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Child; Cystic Fibrosis; Humans; Lipid Peroxidation; Lycopene; Malondialdehyde; Vitamin A; Vitamin E

Patients with cystic fibrosis (CF) may be more susceptible to oxidative cell injury than normal healthy children due to both the impaired absorption of antioxidant nutrients and the increased oxidative stress caused by chronic pulmonary infections. The purpose of this study was to examine whether markers of oxidative damage to lipids (malondialdehyde-like substances and lipid hydroperoxides) and proteins (protein carbonyls) were present in the plasma of CF patients. Mean values (+/- SD) of thiobarbituric acid-reactive substances were significantly higher in patients (6.93 +/- 1.47 mumol/L; n = 25) than in controls (5.84 +/- 0.59 mumol/L; n = 10). FFA hydroperoxides were not detected in control subjects (the detection limit of the assay was 0.02 mumol/L), but in 11 of the 33 CF patients studied they were found in a range of 0.03-0.34 mumol/L. Plasma protein carbonyl concentrations did not differ significantly between the two groups (p = 0.076), although a much wider distribution was observed in the CF patients (range 0.17-5.64 nmol/mg protein) than in the control group (range 0.24-1.55 nmol/mg protein). No correlation was found between thiobarbituric acid-reactive substances and FFA hydroperoxides or between either of these markers and protein carbonyl content. Concentrations of plasma vitamin E, vitamin C, and protein sulfhydryls were within the normal ranges in both control subjects and CF patients. The concentration of uric acid was significantly reduced (p < 0.01) in the CF group (204 +/- 96.99 mumol/L) compared with that in control subjects (352 +/- 81.11 mumol/L), but reduction in plasma levels of this antioxidant did not correlate with increased markers of free radical damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Ascorbic Acid; Biomarkers; Blood Proteins; Child; Child, Preschool; Cystic Fibrosis; Fatty Acids, Nonesterified; Female; Humans; Lipid Peroxides; Male; Malondialdehyde; Oxidative Stress; Reference Values; Thiobarbituric Acid Reactive Substances; Vitamin E

Two CFTR-dependent β-adrenergic sweat rate tests applying intradermal drug injections were reported to better define diagnosis and efficacy of CFTR-directed therapies. The aim of this work was to develop and test a needle-free image-based test and to provide an accurate analysis of the responses.. The modified method was conducted by applying two successive iontophoresis sessions using the Macroduct device. Efficiency of drug delivery was tested by evaporimetry. Cholinergically stimulated sweating was evoked by pilocarpine iontophoresis. β-adrenergically stimulated sweating was obtained by iontophoresis of isoproterenol and aminophylline in the presence of atropine and ascorbic acid. A nonlinear mixed-effects (NLME) approach was applied to model volumes of sweat and subject-specific effects displaying inter- and intra-subject variability.. Iontophoresis provided successful transdermal delivery of all drugs, including almost neutral isoproterenol and aminophylline. Pilocarpine was used at a concentration ∼130-times lower than that used in the classical Gibson and Cooke sweat test. Addition of ascorbic acid lowered the pH of the solution, made it stable, prevented isoproterenol degradation and promoted drug iontophoresis. Maximal secretory capacity and kinetic rate of β-adrenergic responses were blunted in CF. A cutoff of 5.2 minutes for ET50, the time to reach the half maximal secretion, discriminated CF from controls with a 100% sensitivity and specificity. Heterozygous showed an apparently reduced kinetic rate and a preserved secretory capacity.. We tested a safe, well-tolerated needle-free image-based sweat test potentially applicable in children. Modelling responses by NLME allowed evaluating metrics of CFTR-dependent effects reflecting secretory capacity and kinetic rate.

Topics: Adrenergic Agents; Aminophylline; Ascorbic Acid; Child; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Iontophoresis; Isoproterenol; Pilocarpine; Sweat

Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration.. Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (. The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.

Topics: Adult; alpha-Tocopherol; Ascorbic Acid; Cystic Fibrosis; gamma-Tocopherol; Humans; Tocopherols; Vitamin E; Vitamins

Defective airway mucus clearance is a defining characteristic of cystic fibrosis lung disease, and improvements to current mucolytic strategies are needed. Novel approaches targeting a range of contributing mechanisms are in various stages of preclinical and clinical development. ARINA-1 is a new nebulized product comprised of ascorbic acid, glutathione, and bicarbonate. Using microoptical coherence tomography, we tested the effect of ARINA-1 on central features of mucociliary clearance in F508del/F508del primary human bronchial epithelial cells to assess its potential as a mucoactive therapy in cystic fibrosis. We found that ARINA-1 significantly augmented mucociliary transport rates, both alone and with CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy, whereas airway hydration and ciliary beating were largely unchanged compared with PBS vehicle control. Analysis of mucus reflectivity and particle-tracking microrheology indicated that ARINA-1 restores mucus clearance by principally reducing mucus layer viscosity. The combination of bicarbonate and glutathione elicited increases in mucociliary transport rate comparable to those seen with ARINA-1, indicating the importance of this interaction to the impact of ARINA-1 on mucus transport; this effect was not recapitulated with bicarbonate alone or bicarbonate combined with ascorbic acid. Assessment of CFTR chloride transport revealed an increase in CFTR-mediated chloride secretion in response to ARINA-1 in CFBE41o

Topics: Ascorbic Acid; Bicarbonates; Cells, Cultured; Cystic Fibrosis; Epithelial Cells; Glutathione; Humans; Ion Transport; Mucociliary Clearance

The purpose of this work is the evaluation of the nutritional status of patients with cystic fibrosis (CF), based on the level of vitamin C in urine and vitamins A and E in serum, using the fast, selective and fully automated micellar electrokinetic capillary chromatographic (MEKC) and microemulsion electrokinetic capillary chromatographic (MEEKC) methods. The optimization of parameters affecting the electrophoretic separation provided adequate separation of the analytes of interest in the short time of 8 min (MEKC) and 20 min (MEEKC). The developed methods were practical applications to evaluate the levels of vitamins A, C and E in real samples from 28 children suffering from cystic fibrosis and from 10 healthy volunteers. Based on the mean concentration values obtained in the two groups, it can be seen that the levels of each vitamin were lower in patients with CF than in healthy volunteers. In the case of vitamin E, these differences in both groups were statistically significant, while the disproportion of concentrations of vitamins A and C in both the studied groups were not so relevant. On the other hand, a principal component analysis (PCA) confirmed that in some patients with CF the concentration of vitamin A was significantly lower than in the control group. Thus, the future evaluation of the status of fat-soluble vitamins in the longer term for the evaluation of the nutritional status of patients with CF should be continued. The presented CE methods can become useful tools for the evaluation of the nutritional status of patients with CF.

Topics: Adolescent; Ascorbic Acid; Case-Control Studies; Child; Child, Preschool; Chromatography, Micellar Electrokinetic Capillary; Cystic Fibrosis; Female; Humans; Infant; Male; Nutritional Status; Vitamin A; Vitamin E

A series of N-methylthio-β-lactams with antibacterial activity were thoroughly evaluated as antioxidants. We found that only the presence of a polyphenolic moiety anchored to the β-lactam ring ensured an adequate antioxidant potency. New compounds, efficiently combining in one structure antioxidant and antibacterial activity, may provide a promising basis for the development of new leads useful in adverse clinical conditions such as in cystic fibrosis patients, in whom colonization by MRSA and epithelial damage by chronic pulmonary oxidative stress take place.

Topics: Anti-Bacterial Agents; Antioxidants; Azetidines; Cystic Fibrosis; Dose-Response Relationship, Drug; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Monobactams; Structure-Activity Relationship; Sulfides

In cystic fibrosis (CF) children, we investigated the predictive impact of glutathione S-transferases (GST) activity and genotypes P1, M1 and T1, and antioxidant levels on stage-severity of Pseudomonas aeruginosa lung infection.. GST activity was determined in whole blood by spectrophotometry, and GST genotypes by multiplex PCR RFLP for 36 CF and 9 control children. Levels of glutathione in erythrocyte and vitamins A, E and C in plasma were measured by HPLC.. No difference in GST activity and no relationship between GST activity and antioxidant levels were observed in CF children as compared to controls. However, GST activity was lower in CF children with severe clinical status and infection, and the frequency of GSTP1 wild type genotype AA, prevalent in uninfected CF children (75%), decreased in infected ones (33%).. GST activity and genotype could play an important role in modulating P. aeruginosa lung infection in CF patients.

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cystic Fibrosis; Erythrocytes; Female; Genotype; Glutathione; Glutathione Transferase; Humans; Male; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Pseudomonas aeruginosa; Pseudomonas Infections; Vitamin A; Vitamin E; Young Adult

Previous work in our laboratory has shown that glutathione (GSH) availability is linked to cellular supply of ascorbic acid, through the action of gamma-glutamyltransferase (GGT). This enzyme activity is expressed in bronchial epithelia, and is also secreted in epithelial lining fluid. We verified thus the possibility that GGT-mediated metabolism of glutathione may favour the supply of ascorbic acid to bronchial cells. Using human BEAS-2B cells transfected with GGT cDNA, as well as WT cells exposed to ELF-like GGT concentrations, we observed that indeed much higher (5-10 fold) levels of ascorbic acid are accumulated in the presence of GSH and active GGT. The data suggest that administration of aerosolized GSH to CF patients may as well concur to sustain the vitamin C status of bronchial epithelia.

Topics: Antioxidants; Ascorbic Acid; Bronchi; Cells, Cultured; Chromatography, High Pressure Liquid; Cystic Fibrosis; Ephrins; Epithelial Cells; gamma-Glutamyltransferase; Glutathione; Humans; Respiratory Mucosa; Signal Transduction; Spectrophotometry

Vitamin C (l-ascorbate) is present in the respiratory lining fluid of human lungs, and local deficits occur during oxidative stress. Here we report a unique function of vitamin C on the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), a cAMP-dependent Cl channel that regulates epithelial surface fluid secretion. Vitamin C (100 microM) induced the openings of CFTR Cl channels by increasing its average open probability from 0 to 0.21 +/- 0.08, without a detectable increase in intracellular cAMP levels. Exposure of the apical airway surface to vitamin C stimulated the transepithelial Cl secretion to 68% of forskolin-stimulated currents. The average half-maximal stimulatory constant was 36.5 +/- 2.9 microM, which corresponds to physiological concentrations. When vitamin C was instilled into the nasal epithelium of human subjects, it effectively activated Cl transport in vivo. In CF epithelia, previous treatment of the underlying trafficking defect with trimethylamine oxide or expression of WT CFTR restored the activation of Cl transport by vitamin C. Sodium dependency and phloretin sensitivity, as well as the expression of transcripts for sodium-dependent vitamin C transporter (SVCT)-1 and SVCT2, support a model in which an apical vitamin C transporter is central for relaying the effect of vitamin C to CFTR. We conclude that cellular vitamin C is a biological regulator of CFTR-mediated Cl secretion in epithelia. The pool of vitamin C in the respiratory tract represents a potential nutraceutical and pharmaceutical target for the complementary treatment of sticky airway secretions by enhancing epithelial fluid secretion.

Topics: Animals; Ascorbic Acid; Base Sequence; Cell Line; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA, Complementary; Gene Expression; Humans; In Vitro Techniques; Ion Transport; Mice; Mice, Inbred CFTR; Molecular Sequence Data; Mutation; Organic Anion Transporters, Sodium-Dependent; Respiratory System; Sodium-Coupled Vitamin C Transporters; Symporters

The aim of the study was to assess the antioxidant status in cystic fibrosis (CF) patients compared to healthy controls. In order to determine the influence of nutrition on the level of the antioxidants, nutrient intake was also monitored in both groups at the time of the antioxidant assessment.. The authors measured the serum malondialdehyde levels in children with CF, n = 21; 9 females and 12 males, mean age: 8.71 years (6-12 years) and compared these values to the levels found in age-matched healthy control subjects, n = 24; 13 females and 11 males, mean age: 8.33 years (6-12 years). In order to assess the antioxidant status, catalase and superoxide dismutase activities in washed erythrocytes, glutathione peroxidase activity of heparinized whole blood and serum ascorbic acid, alpha-tocopherol and retinol levels were measured. Total antioxidant status (TAS) was also tested. The patients with CF received vitamin supplementation in doses prescribed in international guidelines (alpha-tocopherol: <10 years 100 mg daily, >10 years 200 mg daily, retinol: 2.5 mg daily, ascorbic acid: 100-200 mg daily).. Plasma levels of malondialdehyde were significantly higher (p < 0.05), superoxide dismutase activities were significantly lower (p < 0.05) in patients with cystic fibrosis. There were no significant differences in catalase, glutathione peroxidase activities and TAS levels between CF patients and control group. Plasma ascorbic acid, alpha-tocopherol and retinol levels were within normal limits in both groups.. On the basis of the present results this regime failed to provide sufficient antioxidant protection. Therefore, the authors suggest that the daily dose of these antioxidants should be either increased or to administer in parenteral route to patients with severe form of the disease.

Topics: Antioxidants; Ascorbic Acid; Catalase; Child; Cystic Fibrosis; Female; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Malondialdehyde; Nutritional Status; Superoxide Dismutase; Vitamin A; Vitamin E

Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L, all indexes of inflammation were relatively high, whereas those with concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

Topics: Adolescent; Adult; Ascorbic Acid; beta Carotene; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; Cytokines; Dose-Response Relationship, Drug; Female; Humans; Infant; Inflammation; Interleukin-6; Leukocyte Elastase; Lipid Peroxidation; Lung Diseases; Male; Malondialdehyde; Nutritional Status; Orosomucoid; Seasons; Tumor Necrosis Factor-alpha; Vitamin E

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Cystic Fibrosis; Humans; Scurvy; Thiobarbituric Acid Reactive Substances

The aim of this study was to determine whether a relationship exists between the circulating concentration of antioxidants, or markers of oxidative stress, and pulmonary function in cystic fibrosis patients. Plasma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidation) and protein carbonyls (protein oxidation). Antioxidant status was determined from the plasma concentrations of alpha-tocopherol, ascorbic acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow (FEF25-75) were measured in 25 of the subjects by spirometry, and expressed as percentage predicted for normal height, weight and age. Lung function decreased significantly with age and was associated with decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl concentrations. The reduction in pulmonary function correlated with elevated plasma malondialdehyde, but not with lipid hydroperoxide or protein carbonyl concentrations. Patients with severe lung dysfunction (FEV1 < 50% predicted) had higher plasma concentrations of lipid hydroperoxides than those with mild-to-moderate lung dysfunction (FEV1 > 50% pred). This study provides evidence that cystic fibrosis patients have inadequate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative lung injury contributes to the decline in pulmonary function in these patients.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Child; Child, Preschool; Cystic Fibrosis; Free Radicals; Humans; Lung; Lung Diseases; Oxidative Stress; Respiratory Function Tests; Sulfhydryl Compounds; Uric Acid; Vitamin E

Plasma antioxidant status and total radical-trapping antioxidant potential (TRAP) of children (n = 24) with cystic fibrosis (CF) were compared with those of children (n = 21) without the disease. Children with CF were found to have elevated plasma concentrations of ascorbic acid (94.6 +/- 58.2 mumol/L), with respect to normal children (65.6 +/- 18.8 mumol/L). Plasma uric acid (330.8 +/- 84 versus 198.0 +/- 31 mumol/L p < 0.01) and sulfhydryl group (518 +/- 43 versus 363 +/- 31 mumol/L p < 0.01) concentrations were also elevated in CF. Vitamin E levels (16.9 +/- 1.8 versus 18.4 +/- 1.3 mumol/L) were at the low end of the normal range. Despite an overall increased antioxidant array, CF patients had a reduced TRAP capacity (488 +/- 34 versus 580 +/- 79 mumol/L, p < 0.05). TRAP measurements in CF patients showed a strong negative correlation (r = 0.80, p < 0.001) with high ascorbic acid concentration, suggesting a prooxidant effect of ascorbic acid. Oral administration of ascorbic acid to adults was found to diminish TRAP activity. Concentrations of ascorbic acid similar to those seen in CF patients were attained in ascorbate-supplemented individuals, with substantial decreases in TRAP capacity. These studies suggest that high plasma ascorbic acid levels in children with CF may have a prooxidant effect. This appears to reduce the extracellular antioxidant defense of these children and may increase susceptibility to oxidative stress.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Child; Child, Preschool; Cystic Fibrosis; Free Radicals; Humans; Lipid Peroxidation; Sulfhydryl Compounds; Uric Acid; Vitamin E

Topics: Adult; Ascorbic Acid; Cystic Fibrosis; Electrolytes; Humans; Reference Values; Saliva; Submandibular Gland

The water-soluble (B1, B2, B6, C, folic acid) and fat-soluble vitamin (A, carotene, E, and D) status of 36 patients with cystic fibrosis was assessed and compared with a control group of 21 age-matched normal children. Twenty-seven of the patients were receiving vitamin supplements (except folic acid and vitamin E) at the time of investigation. Vitamin B1, B2, and B6 status was adequate in all patients, and there was little evidence of folic acid deficiency. Vitamin C stores might not have been adequate in some of these patients, despite daily supplements with 50 mg of the vitamin. Steatorrhoea, often severe, was present in most of them. Serum carotene and vitamin E concentrations were low in over 90% of patients and were related to the severity of steatorrhoea. Vitamin A was low in over 40% of the patients despite daily vitamin supplements of 4000 IU and correlated with the serum retinol-binding protein level. Serum 25-OH cholecalciferol was low in some patients whether or not they were receiving a daily supplement of 400 IU vitamin D. In a short-term supplementation trial with water-miscible preparations of vitamin A and E in 14 patients, the serum levels of both vitamins responded well to 2 weeks of treatment with 50 mg vitamin E and 4000 IU vitamin A. Except for serum vitamin A, which was lowest in patients with the poorest clinical grading, the other vitamins were not influenced by the clinical grade of the patients.

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Cystic Fibrosis; Female; Folic Acid; Humans; Infant; Male; Riboflavin; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin E; Vitamins

Topics: Adolescent; Animals; Anti-Bacterial Agents; Ascorbic Acid; Child; Cystic Fibrosis; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Erythromycin; Female; Humans; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sulfamethoxazole; Trimethoprim

Topics: Ascorbic Acid; Child; Chromatography; Cystic Fibrosis; Humans; Hydro-Lyases; Phenylacetates; Tyrosine