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Category Archives: Cystic Fibrosis

Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Recommendation

Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: RecommendationThis may be due both to an enormously pronounced lung inflammation in CF lungs, which leads to the continuous generation of free radicals by PMNs and consequently to profound oxidative protein damage and an insufficient protective effect of known antioxidants. Based on the correlation between the level of protein carbonyls, neutrophil granulocyte count, and lung function, the carbony-lation state of pulmonary proteins may be used as a marker of disease and help to explore pathophysiology of oxidative stress.
The pattern of the proteins that were carbonylated in the lavages was displayed by two-dimensional electrophoresis and Western blotting. The distribution of oxidized proteins on two-dimensional gels was different in the groups of patients with different carbonyl levels.

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Conclusion

It has been suggested that recurring oxidative lung injury can contribute to the decline in pulmonary function in these patients.- In our findings, there was also a weak positive correlation between protein carbonyls and the age of the CF patients (n = 51; rs = 0.32; p = 0.02) but not between age and pulmonary function (n = 51; rs = — 0.22; p = 0.12). This may reflect a decreasing antioxidative capacity with age or declining activity of the proteasome.” Previously it was demonstrated that the formation of myeloperoxidase-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF may contribute to bronchial injury and respiratory fail-ure. tadanafil

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Discussion

Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: DiscussionIn addition to the overall degree and pattern of protein oxidation, surfactant protein A (SP-A) was investigated as an example of a lung-specific protein. We demonstrated that SP-A was readily oxidized, as it was found heavily labeled even in CF patients with a very low degree of oxidation (n = 3; mean overall BALF carbonyls, 18 pmol/mL) [Fig 5]. In all samples with higher degrees of oxidation (n = 5; mean overall BALF carbonyls, 9,050 pmol/mL), SP-A was undetectable or present only at extremely low amounts.
CF patients had significantly higher level of oxidative stress than control subjects, as assessed by protein oxidation from the content of protein carbonyls in their BALF. The highest levels were found in patients with pathologic pulmonary function or with highly elevated neutrophil counts. Compared to control subjects without lung disease, CF patients with normal lung function, defined as FEV1 > 80% of predicted, also had significantly higher protein carbonyl levels.

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Results Oxidation of BALF Proteins

The overall degree of protein oxidation in BALF was significantly higher in CF patients than in healthy subjects (Fig 1). CF patients with pathologic FEV1 (< 80% of predicted) had considerably higher levels of protein carbonyls (median, 3,033 pmol/mL BALF; 15.6 pmol/^g protein) compared to either CF patients with normal pulmonary function values (FEV1 > 80% of predicted; 612 pmol/mL; 6.9 pmol/ ^g; p < 0.01) or healthy control subjects (0 pmol/ mL, p < 0.001) [Fig 1].

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Biochemical Methods

Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Biochemical MethodsThe content of protein carbonyls was assessed as a measure of oxidative stress by the sensitive dot-blot assay as described. The lower limit of the detection was 2 pmol of carbonyls per microgram of protein. The assay was calibrated by dilutions of different proportions of oxidized and reduced bovine serum albumin (BSA) [Paesel-Lorei; Hanau, Germany]. BSA was oxidized in vitro by the Fenton reaction and completely reduced by NaBH4. The concentration of protein carbonyls in these BSA mixtures was quantified in a colorimetric assay.
Two-dimensional sodium dodecylsulfate-polyacrylamide gel electrophoresis was performed on two-dimensional gels (Nu-PAGE; Invitrogen; Carlsbad, CA) with modification for protein carbonyl identification. canadian healthcare mall

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis: Methods

A more relevant measure of oxidative stress in the lungs may be derived from assessments of samples containing epithelial lining fluid of the distal airways including the alveoli as obtained by BAL. Such measurements have been reported only in young CF patients.
The goal of this study was to investigate protein oxidation in CF patients with a wide range of endobronchial inflammation in relation to their lung function and degree of pulmonary inflammation. We hypothesized that the level of protein oxidation may be increased even in the presence of normal pulmonary function tests. Our findings demonstrated a close relation between the degree of protein oxidation, neutrophil granulocyte (PMN) count in BAL fluid (BALF), and lung function of the subjects, suggesting a causal relationship among these variables, BALF, which was available as a cell-free supernatant, was analyzed from 55 patients with CF. These patients had participated in the Bronchoalveolar Lavage for the Evaluation of Antiinflammatory Treatment study and the Glutathione study in the Munich, Cologne, and Berlin study centers.1112 The clinical characteristics of the patients are given in Table 1. canadian health care mall

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Oxidative Changes of Bronchoalveolar Proteins in Cystic Fibrosis

Oxidative Changes of Bronchoalveolar Proteins in Cystic FibrosisConvincing evidence suggests that oxidative stress and reactive oxygen species (ROS) play an important role in the etiology and progression of a number of human diseases. The normal, noninflamed lung is well adapted to the relatively high ambient oxygen concentration, but the extremely high generation of ROS during inflammation overwhelms the protective mechanisms of the lung, and it becomes a particularly vulnerable target during inflammatory processes. Generation of oxidative species is a principal contributor to inflammatory injury, and failure to control inflammation may lead to continuing inflammation and organ dysfunction progressing to organ failure. comments

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The Effect of High Doses of Inhaled Salbutamol and Ipratropium Bromide in Patients With Stable Cystic Fibrosis: Finally

The Effect of High Doses of Inhaled Salbutamol and Ipratropium Bromide in Patients With Stable Cystic Fibrosis: FinallyEaston and coworkers compared the bronchodilating effects of albuterol and IB given by aerosol either alone or in sequence. They administered 120 \Lg of IB and 800 jig of albuterol over a 30-min period. When used alone, both bronchodilators significantly increased airflow and relieved hyperinflation, and there was no significant difference between the two drugs. After the improvement with the initial bronchodilator, the subsequent effect of a second inhaled bronchodilator was not greater than that of placebo. Our results in a group of young patients with chronic lung disease due to CF are similar to the results presented by Easton and coworkers. We did not find any beneficial bronchodilator effect of multidrug therapy when high doses were used. Although the patients did not have side effects with the doses administered, it is possible that in some patients, regular doses of p-adrenergic combined with anticholinergic agents may be a better therapeutic approach to avoid side effects.

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The Effect of High Doses of Inhaled Salbutamol and Ipratropium Bromide in Patients With Stable Cystic Fibrosis: Conclusion

Hordvik and coworkers found that bronchodilator responsiveness in CF decreases during acute pulmonary exacerbations. Our patients were in stable condition, with no history of admission to hospital for the previous 3 months, and no pulmonary exacerbation up to 4 weeks prior to the study. Fattishal studied the response to bronchodilators in CF patients in a longitudinal and cross-sectional manner by using pulmonary function data over an 8-year period. A proportion of patients (40 percent) presented a positive response to inhaled adrenergic agents; however, there was a lack of consistent response. Zinman and coworkers found a mean of 8 percent increase in FEVX after isoeth-arine (p2-sympathomimetic) in a group of 12 CF patients, but also found an increase in the degree of non-homogeneous lung emptying after the inhalation of the drug. Van Haren et al recently found, in a group of 20 adult CF patients, that both inhalation of terbu-taline and IB caused dose-related bronchodilation.
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The Effect of High Doses of Inhaled Salbutamol and Ipratropium Bromide in Patients With Stable Cystic Fibrosis: Discussion

The Effect of High Doses of Inhaled Salbutamol and Ipratropium Bromide in Patients With Stable Cystic Fibrosis: DiscussionThe efficacy of bronchodilator therapy in patients with CF has been discussed previously by several authors. Zach et al showed that in a proportion of CF patients, increased bronchial smooth muscle tone mechanically compensated for structural damage; therefore, inhaled bronchodilators may induce airway compression during forced expiratory maneuvers. Our subjects were selected because they had a positive response to bronchodilators in the past, and during the protocol the individual improvement in FEVj from baseline was variable but at least 8 percent. Eggleston and coworkers studied the response to inhaled S in two groups of CF patients classified according to their response to inhaled methacholine. Among those who responded to methacholine, daily peak expiratory flow rate (PEFR) measurements improved significantly more with albuterol than with placebo.

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