Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azithromycin (AZM) is a new macrolide antibiotic with a high intracellular/extracellular concentration ratio. Immunomodulatory and antiinflammatory properties have been reported with other macrolides, especially erythromycin. The aim of the present study was to evaluate the effect of AZM on the production of proinflammatory mediators by alveolar macrophages (AM) up to 4 weeks after a 3-day course of AZM (500 mg, once a day). Nineteen non-smoking healthy male subjects were investigated with bronchoscopy and bronchoalveolar lavage. Group 1 received no treatment. Groups 2, 3, and 4 were bronchoscoped 1, 7 and 30 days, respectively, after AZM administration. AZM concentrations were simultaneously measured in plasma and in AM extracts. In serum, AZM levels were higher in group 2 (32.8 +/- 14.2 micrograms/l), at the lower limit of detection in group 3 (2.8 +/- 1.7 micrograms/l), and no longer detectable in group 4. In AM extracts, the highest concentrations were measured in group 2 (51.6 +/- 28.3 ng/microliter) and in group 3 (31.8 +/- 17.2 ng/microliter), and were detected up to 30 days after treatment in group 4 (2.9 +/- 2.3 ng/microliter). There was no significant differences between groups for blood or BAL proinflammatory cytokines levels (TNF-alpha, IL-1 beta, IL-6), and for superoxide generation by AM. We conclude that a 3-day course of AZM 500 mg/day in healthy subjects does not alter the proinflammatory cytokine profile in blood and in AM despite the prolonged tissue impregnation by this drug.
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PMID:Function of human alveolar macrophages after a 3-day course of azithromycin in healthy volunteers. 1010 42

A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphate-buffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C(max)/MIC) and percent time that the serum concentration exceeded the MIC (%T > MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, beta-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.
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PMID:Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia. 1569 15

Patients with cystic fibrosis (CF) experience declining pulmonary function related to chronic airway inflammation, which results from epithelial and immune cell secretion of proinflammatory mediators that promote neutrophil influx into the airways. This inflammatory response may be disproportionate to the inciting infectious stimulus, resulting in an overly exuberant influx of neutrophils. The neutrophils release proteases, including neutrophil elastase, that eventually overwhelm the antiprotease capacity of the lung and cleave structural proteins, leading to bronchiectasis. This deleterious inflammatory process in patients with CF has become a potential therapeutic target, though the development of effective antiinflammatory therapies has been limited by the lack of sensitive outcome measures. Historically, indirect measures of lung disease, such as spirometry, have been used to assess the effect of antiinflammatory drugs. BAL remains the primary method of interrogating the inflammatory status of the airway, but the procedure is invasive and may eventually be supplanted by induced sputum. Anatomic imaging with high-resolution CT scanning is used clinically, but has unknown utility, and functional imaging, using positron emission tomography, appears promising but is still investigational. Despite the paucity of outcome measures, clinical trials of antiinflammatory agents, including corticosteroids and ibuprofen, have demonstrated benefits, though their use has been limited by adverse effects. Azithromycin is increasingly used as an immunomodulatory agent, although its mechanism of action remains unclear. Strategies for modulating the airway inflammation in patients with CF are currently under development and may offer new therapeutic options for these patients.
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PMID:Airway inflammation in cystic fibrosis. 1825 15