scholarly journals Local and Systemic Alterations of the L-Arginine/Nitric Oxide Pathway in Sputum, Blood, and Urine of Pediatric Cystic Fibrosis Patients and Effects of Antibiotic Treatment

2020 ◽  
Vol 9 (12) ◽  
pp. 3802
Author(s):  
Beatrice Hanusch ◽  
Folke Brinkmann ◽  
Sebene Mayorandan ◽  
Kristine Chobanyan-Jürgens ◽  
Anna Wiemers ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Antibiotic Therapy ◽  
Acute Exacerbation ◽  
Antibiotic Treatment ◽  
Asymmetric Dimethylarginine ◽  
Lower Plasma ◽  
Lung Functions ◽  
Before And After ◽  
Lung Impairment

Alterations in the L-arginine (Arg)/nitric oxide (NO) pathway have been reported in cystic fibrosis (CF; OMIM 219700) as the result of various factors including systemic and local inflammatory activity in the airways. The aim of the present study was to evaluate the Arg/NO metabolism in pediatric CF patients with special emphasis on lung impairment and antibiotic treatment. Seventy CF patients and 78 healthy controls were included in the study. CF patients (43% male, median age 11.8 years) showed moderately impaired lung functions (FEV1 90.5 ± 19.1% (mean ± SD); 21 (30%) had a chronic Pseudomonas aeruginosa (PSA) infection, and 24 (33%) had an acute exacerbation). Plasma, urinary, and sputum concentrations of the main Arg/NO metabolites, nitrate, nitrite, Arg, homoarginine (hArg), and asymmetric dimethylarginine (ADMA) were determined in pediatric CF patients and in healthy age-matched controls. Clinical parameters in CF patients included lung function and infection with PSA. Additionally, the Arg/NO pathway in sputum samples of five CF patients was analyzed before and after routine antibiotic therapy. CF patients with low fractionally exhaled NO (FENO) showed lower plasma Arg and nitrate concentrations. During acute exacerbation, sputum Arg and hArg levels were high and dropped after antibiotic treatment: Arg: pre-antibiotics: 4.14 nmol/25 mg sputum vs. post-antibiotics: 2.33 nmol/25 mg sputum, p = 0.008; hArg: pre-antibiotics: 0.042 nmol/25 mg sputum vs. post-antibiotics: 0.029 nmol/25 mg sputum, p = 0.035. The activated Arg/NO metabolism in stable CF patients may be a result of chronic inflammation. PSA infection did not play a major role regarding these differences. Exacerbation increased and antibiotic therapy decreased sputum Arg concentrations.

scholarly journals Antibiotic therapy and fat digestion and absorption in cystic fibrosis.

2011 ◽  
Vol 58 (3) ◽  
Author(s):  
Aleksandra Lisowska ◽  
Andrzej Pogorzelski ◽  
Grzegorz Oracz ◽  
Wojciech Skorupa ◽  
Szczepan Cofta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Therapy ◽  
Pancreatic Insufficiency ◽  
Bacterial Load ◽  
Mass Gain ◽  
Exocrine Pancreatic Insufficiency ◽  
Oral Drug ◽  
Lipid Digestion ◽  
Fat Digestion ◽  
Before And After

Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to result in reduced bacterial load of the intestine and significant body mass gain. The effect was suggested to be linked to the improvement of intestinal digestion and absorption. Therefore, we aimed to assess the influence of routinely applied antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion and absorption, before and after antibiotic therapy. Sixteen subjects were treated intravenously with ceftazidime and amikacin, eight patients orally with ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to reflect digestion and absorption of lipids. The values are expressed as means (medians). The values of CPDR before and after antibiotic therapy did not differ in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327] or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167]. In conclusion, antibiotic therapy applied routinely in the course of pulmonary exacerbation in CF patients does not seem to result in an improvement of fat digestion and absorption.

scholarly journals Changes of Proteases, Antiproteases, and Pathogens in Cystic Fibrosis Patients’ Upper and Lower Airways after IV-Antibiotic Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Ulrike Müller ◽  
Julia Hentschel ◽  
Wibke K. Janhsen ◽  
Kerstin Hünniger ◽  
Uta-Christina Hipler ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Therapy ◽  
Proteolytic Enzymes ◽  
Before And After ◽  
Lower Airways ◽  
Time Changes ◽  
First Time ◽  
Antibiotic Courses ◽  
Sinonasal Symptoms ◽  
Multiplex Bead

Background. In cystic fibrosis (CF) the upper (UAW) and lower airways (LAW) are reservoirs for pathogens likePseudomonas aeruginosa. The consecutive hosts’ release of proteolytic enzymes contributes to inflammation and progressive pulmonary destruction. Objectives were to assess dynamics of protease : antiprotease ratios and pathogens in CF-UAW and LAW sampled by nasal lavage (NL) and sputum before and after intravenous- (IV-) antibiotic therapy.Methods. From 19 IV-antibiotic courses of 17 CF patients NL (10 mL/nostril) and sputum were collected before and after treatment. Microbiological colonization and concentrations of NE/SLPI/CTSS (ELISA) and MMP-9/TIMP-1 (multiplex bead array) were determined. Additionally, changes of sinonasal symptoms were assessed (SNOT-20).Results. IV-antibiotic treatment had more pronounced effects on inflammatory markers in LAW, whereas trends to decrease were also found in UAW. Ratios of MMP-9/TIMP-1 were higher in sputum, and ratios of NE/SLPI were higher in NL. Remarkably, NE/SLPI ratio was 10-fold higher in NL compared to healthy controls. SNOT-20 scores decreased significantly during therapy(P=0.001).Conclusion. For the first time, changes in microbiological patterns in UAW and LAW after IV-antibiotic treatments were assessed, together with changes of protease/antiprotease imbalances. Delayed responses of proteases and antiproteases to IV-antibiotic therapy were found in UAW compared to LAW.

Early Diagnosis and Management of Cerebritis in a Child

PEDIATRICS ◽  
1980 ◽  
Vol 65 (3) ◽  
pp. 484-486
Author(s):  
Thomas E. Liston ◽  
Jerry J. Tomasovic ◽  
Edwin A. Stevens
Keyword(s):  
Cerebrospinal Fluid ◽  
Early Diagnosis ◽  
Antibiotic Therapy ◽  
Computerized Tomography ◽  
Antibiotic Treatment ◽  
Therapeutic Response ◽  
Intracranial Lesion ◽  
Infectious Process ◽  
Before And After ◽  
Cerebrospinal Fluid Protein

A 3½-year-old boy with primary staphylococcal septicemia presented with elevated cerebrospinal fluid protein and pleocytosis. Serial computerized tomography examinations revealed the development of an intracranial lesion suggestive of an early infectious process. All cultures of cerebrospinal fluid taken before and after antibiotic treatment revealed no growth. Although no focal neurological findings evolved, both clinical and radiologic abnormalities resolved with antibiotic therapy. Computerized tomography can provide a means to diagnose cerebritis and to evaluate therapeutic response.

scholarly journals Sildenafil improves vascular endothelial function in patients with cystic fibrosis

2018 ◽  
Vol 315 (5) ◽  
pp. H1486-H1494 ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Gábor Csányi ◽  
Kathleen T. McKie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Endothelial Function ◽  
Protein Expression ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Systemic Complications ◽  
Acute Dose ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Before And After

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.

scholarly journals Hydrogen peroxide and nitric oxide in exhaled air of children with cystic fibrosis during antibiotic treatment

2000 ◽  
Vol 16 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Q. Jobsis ◽  
H.C. Raatgeep ◽  
S.l Schellekens ◽  
A Kroesbergen ◽  
W.C.j Hop ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Hydrogen Peroxide ◽  
Antibiotic Treatment ◽  
Exhaled Air

scholarly journals Pseudomonas aeruginosacross-colonization and persistence in patients with cystic fibrosis. Use of a DNA probe

1989 ◽  
Vol 102 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Christiane Wolz ◽  
Gerd Kiosz ◽  
John W. Ogle ◽  
Michael L. Vasil ◽  
Urs Schaad ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Antibiotic Therapy ◽  
Summer Camp ◽  
Dna Probe ◽  
The Other ◽  
Sibling Pairs ◽  
Long Period ◽  
Strain Change ◽  
Before And After ◽  
Different Strains

SUMMARYTo investigate cross-colonization with and persistence ofPseudomonas aeruginosain cystic fibrosis (CF). 181 isolates from 76 CF patients were typed using aP. aeruginosa-specific DNA probe. Whereas sibling pairs predominantly harboured genotypically identicalP. aeruginosastrains, all of the other patients harboured different strains. Seventy-nine per cent (22/31) of the infected CF patients harboured the same strains at the beginning and the end of a summer camp. A change of strains was seen in 10% (3/31) of the patients at the end of the camp. Forty-six per cent (6/13) of the patients who were apparently initially uninfected, acquiredP. aeruginosaby the end of the period. Genotyping proved that strain change or acquisition was due to cross-colonization in four of nine cases. Very littleP. aeruginosawas isolated from the inanimate environment. Persistence ofP. aeruginosaafter a temporary loss due to antibiotic therapy was seen in 12/16 paired patient strains before and after antibiotic therapy. Thus, suppression followed a flare-up seemed to occur in these patients rather than eradication and a new infection. When 35 patients were followed over a period of 6 months, 7 (20%) changed the strain in their sputum. Only one of 43 patients harboured two differentP. aeruginosastrains simultaneously over a long period.

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