Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.25.1 (deoxyribonuclease)
1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The problem of evaluating the long-term effects of recombinant human deoxyribonuclease (rhDNase) on forced expiratory volume in one second (FEV1) in cystic fibrosis (CF) patients was considered. A two-stage mixed effects model, incorporating relevant predictive variables, captured the diverse patterns of decline of FEV1 for patients with different demographic characteristics. Based on the results of modeling the dropout process, it is clear that the probability of early dropout was closely related to patient's responsiveness to rhDNase treatment. Failure to consider the existence of informative censoring severely biased the estimates of the rate of decline and affected the interpretation of the results.
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PMID:Statistical analysis of the long-term effects of recombinant human deoxyribonuclease on pulmonary function in cystic fibrosis patients. 1095 12

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or complicated respiratory syncytial virus bronchiolitis in infancy.
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PMID:DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis. 1171 80

Inhaled recombinant human deoxyribonuclease (rhDNase) delivered by nebulizer improves pulmonary function and reduces the rate of pulmonary exacerbations in cystic fibrosis subjects. Standard jet nebulizers are relatively inefficient and require a delivery time of 10-20 min. We conducted an open-label, proof-of-concept study to evaluate whether bolus inhalation of rhDNase with a more efficient delivery system was safe and effective in cystic fibrosis subjects. The AERx system used for this study aerosolized 1.35 mg of rhDNase in three inhalations at a single sitting. The predicted AERx lung dose was approximately 0.68 mg, a dose consistent with lung doses of rhDNase given by jet nebulizer. In our 16 subjects with cystic fibrosis, a mean relative increase in FEV(1) of 7.8% (p < or = 0.001) was observed after 15 days of bolus delivery of rhDNase with the AERx system. The safety profile of rhDNase given as a bolus was similar to that observed with traditional nebulizer delivery. This study demonstrated that bolus inhalation of rhDNase was feasible, reasonably well-tolerated, and associated with improvement in pulmonary function in this small group of cystic fibrosis subjects.
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PMID:Bolus inhalation of rhDNase with the AERx system in subjects with cystic fibrosis. 1282 11

Poor clearance of airway secretions contributes to the pulmonary disease in cystic fibrosis (CF). Bronchodilator therapy might benefit in CF, but the efficacy is controversial. Effects of mucolytic agents have not been demonstrated conclusively. Only, efficacy of recombinant human deoxyribonuclease (rhDNase) is established with a rapid onset of benefit.
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PMID:[Inhaled bronchodilators and mucolytic agents in cystic fibrosis]. 1467 35

Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis (CF), but its long-term effect on airway inflammation remains unknown. In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease. A total of 105 patients with CF (> or =5 years of age) having normal lung function were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a normal percentage of neutrophils in BAL fluid at baseline were not randomized and served as the control group. The percentage of neutrophils in the pooled BAL sample was similar in both randomized groups at baseline. A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that in patients with CF, an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment.
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PMID:Effect of treatment with dornase alpha on airway inflammation in patients with cystic fibrosis. 1468 61

Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). Alternate-day rhDNase and hypertonic saline (HS) represent potential cheaper alternative therapies. However, not all patients improve on treatment. To assess response, many CF centers have developed formal n-of-1 trials of treatment to find out who benefits. Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year. There are no data correlating individual response at a shorter time period with 3-month response. We assessed whether individual responses to daily rhDNase, alternate-day rhDNase, and HS could be predicted from lung function response at 6 weeks, thus shortening the n-of-1 trial, or from baseline patient characteristics, therefore avoiding the need for an n-of-1 trial. In a randomized crossover trial, 48 CF children were allocated consecutively to 12 weeks of once-daily 2.5-mg rhDNase, alternate-day 2.5-mg rhDNase, and twice-daily 5 ml of 7% HS. Forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) were measured at baseline and then at 6 and 12 weeks into each treatment period. Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months. There was some evidence that response to HS was worse in patients with lower baseline lung function. However, there was no association between response to alternate-day or daily rhDNase and baseline characteristics. In conclusion, response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months. For daily and alternate-day rhDNase, at least, the drug needs to be administered for at most 6 weeks initially to assess long-term response to treatment. Response to treatment could not be reliably predicted from baseline characteristics.
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PMID:Predicting response to rhDNase and hypertonic saline in children with cystic fibrosis. 1502 26

In patients with cystic fibrosis (CF), the poor clearance of airway secretions promotes recurrent cycles of pulmonary infection and inflammation. In recent years, novel drugs have been developed to alter the properties of the secretions in an attempt to aid chest physiotherapy in improving airway clearance. Once-daily nebulised recombinant human deoxyribonuclease (rhDNase; dornase alfa; Pulmozyme) is the most widely used mucoactive therapy in patients with CF. It has been shown to reduce the viscoelasticity of sputum from patients with CF and enhance the clearance of secretions. Clinical trials have shown rhDNase to be a well tolerated treatment that improves pulmonary function and reduces respiratory exacerbations. However, the response to treatment is heterogeneous and only a proportion of patients with CF actually benefit from the treatment. At present, we are unable to predict which patients will benefit from rhDNase. Many CF centers have developed formal n-of-1 trials of treatment to find out who benefits and to justify prescribing the agent. rhDNase is an expensive therapy and is mainly used in patients over the age of 5 years with moderate to severe lung disease. However, studies have shown that rhDNase may be useful in patients with milder lung disease. Comparisons with another mucoactive drug, hypertonic saline, have shown rhDNase to be more effective. Recently, it has been shown that giving rhDNase on an alternate-day basis, rather than daily, is equally effective, potentially reducing costs and treatment time.
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PMID:The use of human deoxyribonuclease (rhDNase) in the management of cystic fibrosis. 1598 99

The present study focused on patients with cystic fibrosis (CF), who were on maintenance therapy with recombinant human deoxyribonuclease (rhDNase), with the aim of comparing efficacy and possible side effects of nebulisation of rhDNase when taken before bedtime with efficacy and side effects when taken after waking up. A randomised, double-blind, double-dummy, crossover study group was used. The inclusion criteria were as follows: 1) CF, 2) stable clinical condition and 3) rhDNase maintenance therapy. Patients in group I inhaled rhDNase before bedtime and a placebo after waking up in weeks 1-2. The protocol was reversed during weeks 3-4. Group II patients performed the reverse of this sequence. Patients continued with their daily routine sputum expectoration. The primary end-point was classified as the maximal instantaneous forced flow when 25% of the forced vital capacity remained to be exhaled (MEF(25%)). Pulmonary functions tests were performed on days 0, 7, 14, 21 and 28. At 1, 2, 3 and 4 weeks arterial oxygen saturation and cough frequency were measured during the night. A total of 24 patients completed the study. The mean (range) age of the patients was 13 (6-19) yrs. MEF(25%), taken to be the primary end-point, did not show a significant difference between nebulisation of rhDNase before bedtime compared with when taken after waking up. Nocturnal cough, oxygen saturation, and other secondary end-points were not significantly different between the two study periods. In conclusion, the present study found that it is equally effective and safe to nebulise recombinant human deoxyribonuclease before bedtime compared with when performed after waking up in children with cystic fibrosis, who are on maintenance treatment with recombinant human deoxyribonuclease.
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PMID:Recombinant human DNase nebulisation in children with cystic fibrosis: before bedtime or after waking up? 1759 73

Cystic fibrosis is characterised by chronic bronchopulmonary sepsis. Various therapeutic modalities attempt to enhance the clearance of airway secretions. Dornase alfa (recombinant human deoxyribonuclease) reduces the viscoelasticity of sputum from patients with cystic fibrosis by depolymerising extracellular DNA. The drug is administered as an aerosol using a jet nebuliser at a dosage of 2.5mg once daily. It improves pulmonary function and reduces the risk of respiratory exacerbations requiring parenteral antibacterials. Various clinical trials have demonstrated a heterogeneous response to dornase alfa and have been unable to predict which groups of patients benefit from treatment. Patient selection is further complicated because some individuals do not exhibit improvements in lung function, but benefit in terms of a decrease in infective exacerbations. All patients with cystic fibrosis who produce purulent sputum are potential candidates for dornase alfa therapy. We suggest that compliant patients be considered for treatment with dornase alfa, irrespective of disease severity, but should be closely monitored and be assessed at regular intervals to monitor treatment response.
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PMID:Dornase alfa. 1803 Nov 6

Pseudomonas aeruginosa is an opportunistic pathogen that occupies a wide variety of environmental niches. Extracellular DNA is ubiquitous in various environments and is a rich source of carbon, nitrogen and phosphate. Here we show that P. aeruginosa is capable of using DNA as a nutrient source. Under phosphate-limiting conditions, or when DNA is supplied as a source of phosphate, expression of PA3909 is induced. PA3909 encodes an extracellular deoxyribonuclease (DNase), which is required for degradation of DNA and utilization of DNA as a source of carbon, nitrogen and phosphate. Stabilization of PA3909 by the addition of excess Mg(2+) and Ca(2+) was required for DNase activity in culture supernatants. Extracellular DNase activity was seen in multiple P. aeruginosa strains and isolates from cystic fibrosis patients. The primary Xcp type II secretion system but not the Hxc type II secretion system is required for DNase activity and the ability to use DNA as a source of nutrients. This study identifies an extracellular DNase produced by P. aeruginosa that enables degradation of extracellular DNA into an accessible source of carbon, nitrogen and phosphate. DNase production by P. aeruginosa also has important implications for virulence and biofilm formation.
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PMID:Pseudomonas aeruginosa produces an extracellular deoxyribonuclease that is required for utilization of DNA as a nutrient source. 2037 Aug 19


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