Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.21.1 (DNase)
 7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By improving pulmonary function in patients with cystic fibrosis (CF), recombinant human deoxyribonuclease (rhDNase) may affect resting energy expenditure (REE). To examine this hypothesis, we measured REE by indirect calorimetry in seven patients with CF before (day 0) and 2 weeks after (day 15) administration of aerosolized rhDNase. Baseline REE was higher in all patients than predicted for age, sex, and weight (mean +/- SEM 128 +/- 4.9%; range, 116-147%). After 2 weeks of aerosolized rhDNase, mean forced vital capacity (FVC) (in % of predicted values) improved significantly from 54.1 +/- 2.2 to 66.3 +/- 4.2% (mean improvement, 12.3%; 95% CI, 2.8, 21; P < 0.05) and REE decreased by 11.0% (95% CI 3.2, 17.5; P < 0.05). In addition, the larger the improvement in FVC in response to rhDNase the greater the decrease in energy expenditure (r - 0.88). The REE decreased in all patients who had an increase in FVC and remained unchanged in two patients who had no change in FVC. We conclude that patients with CF whose lung function improve in response to aerosolized rhDNase have an acute and proportionate reduction in their resting energy expenditure.
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PMID:Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis. 780 Apr 31

As most of the morbidity seen in cystic fibrosis (CF) is related to pulmonary complications, new therapies are being developed that seek to ameliorate these debilitating sequelae. Recently, there has been intense effort into the development of new aerosol-based therapies for CF. This review summarizes much of this recent investigation, with particular emphasis on therapies described in the literature within the past year. Agents that act on the airway epithelium to alter ionic fluxes, namely amiloride and uridine 5'-triphosphate, are outlined. The effects of tobramycin delivered via nebulizer in a cohort of stable CF patients is reported. Recombinant human DNase and distearoyl phosphatidylglycerol liposomes, agents that alter the adhesiveness of CF mucus, are outlined as possible strategies for CF treatment. Finally, antiprotease therapy is considered as a possible addition to the CF armamentarium.
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PMID:Inhalation-based therapies in the treatment of cystic fibrosis. 806 31

Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis. High levels of DNA in the sputum make the sputum viscous and difficult to expectorate. Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to reduce the viscoelasticity of the sputum from CF patients. We have done a phase II double-blind randomised placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for 10 days. All patients had forced vital capacity (FVC) above 40% predicted and were clinically stable. Patients were followed up for 42 days from the start of drug/placebo administration. All 71 randomised patients, aged 16-55, completed every aspect of the study and baseline characteristics were similar in the two groups. Baseline forced expiratory volume in one second (FEV1) was 46% of predicted for patients randomised to rhDNase, and 48% for those randomised to placebo; and baseline FVC was 76% of predicted for both groups. The mean percentage change in FEV1 from baseline was a 13.3% rise on rhDNase and a 0.2% fall on placebo (p < 0.001). FVC rose 7.2% in the rhDNase group and 2.3% in the placebo group (not significant). There were no life-threatening adverse events and no anaphylactic reactions. There was no significant difference in side-effects between the groups. This study confirms that short-term administration of rhDNase in stable patients with cystic fibrosis is safe and improves lung function.
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PMID:Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis. 810 60

Respiratory disease in cystic fibrosis (CF) patients is characterized by purulent secretions in the airways, recurrent respiratory infections and progressive deterioration of lung function. Sputum from CF patients has a high concentration of DNA which is released by dead leukocytes. DNA is a contributor to the viscoelastic properties of sputum. Recombinant human DNase has been shown to decrease the viscoelastic properties of respiratory secretions of patients with CF in vitro. This article outlines the phase 1, 2 and 3 trial of rhDNase that have been performed in the UK and in the US. The largest of these trials, the phase 3 trial, involved 968 patients over a 24 week period. There was improvement in FEV1 by 6% in the patients receiving rhDNase. Compared to placebo controlled patients, patients given aerosolized rhDNase spent 1.2-1.4 less days in hospital and had 2.4-2.7 fewer days of antibiotic treatment. There was no evidence of an asthmatic response. There was an increased incidence of voice alteration in the rhDNase groups (16% and 12% compared to 7%). An antibody response was seen in up to 5% in the rhDNase patients over the 24 week period, although this appeared to be without any clinical effect. In conclusion, the clinical trials of aerosolized rhDNase show that it appears safe, improves spirometry, and reduces the need for antibiotic treatment for acute exacerbations of the pulmonary disease of CF.
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PMID:Clinical trials of recombinant human DNase in cystic fibrosis patients. 812 6

Obstruction of airways by viscous sputum causes lung damage in patients with cystic fibrosis (CF). Sputum samples from CF patients were shown to contain filamentous actin. Human plasma gelsolin, a protein that severs actin filaments, rapidly decreased the viscosity of CF sputum samples in vitro. Gc globulin and deoxyribonuclease I, proteins that sequester monomeric actin but do not sever actin filaments, were less efficient than gelsolin in diminishing sputum viscosity. These results suggest that gelsolin may have therapeutic potential as a mucolytic agent in CF patients.
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PMID:Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. 831 Feb 95

Cystic fibrosis, an autosomal recessive disorder, is the most common genetic disease of Caucasians. One in 25 Caucasians are carriers of the gene. The gene is found far less commonly in other races. There are over 230 different alleles of the gene, located on the 7th chromosome. The gene encodes for a membrane protein that functions as an ion channel. The survival of cystic fibrosis patients has been gradually increasing, with a mean survival in 1990 of 28 years. If the current trend of improved survival continues, it is estimated that half of cystic fibrosis patients will be over 18 years old by 1996. Disease is found in many organs including the lungs, sinuses, pancreas, gastrointestinal tract, hepatobiliary system, sweat glands and reproductive tract. The majority of patients die of pulmonary disease. The airways become chronically colonized with bacteria that cannot be eradicated, leading to bronchitis, bronchiectasis, and finally, pulmonary fibrosis with respiratory failure. The pulmonary disease may be complicated by massive hemoptysis and pneumothorax. Patient survival rates have increased because of antibiotic therapy and improved nutrition with pancreatic enzyme replacements. New treatments for the pulmonary disease are under clinical trial and include antiproteases, amiloride, a sodium channel blocker, and DNase. The insertion of the normal cystic fibrosis allele into an animal model using a modified adenovirus with effective transcription suggests that gene therapy may be possible in the future, but safety and technical problems have to be addressed.
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PMID:Cystic fibrosis. 842 40

Cystic fibrosis (CF) is the commonest lethal hereditary disease in Caucasians. The disease involves a gene mutation located at the long arm of chromosome 7, and more than 300 mutations have been identified. CF is a systemic illness affecting the upper respiratory tract and airways, sweat and salivary glands, pancreas, gastrointestinal tract, liver and male reproductive system. The course is highly variable depending on the specific molecular abnormalities in the mutant gene. The current approach to therapy now involves the use of: (i) chest physiotherapy; (ii) bronchodilators when there is evidence of airways hyperreactivity; (iii) oral and intravenous antibiotics for acute pulmonary exacerbations and aerosolised antibiotics for prevention; (iv) recombinant human deoxyribonuclease I (dornase alfa) to promote airways clearance; (v) amiloride to improve sputum viscosity; (vi) pancreatic enzyme replacement therapy along with nutritional support and supplements; (vi) vitamins; and (vii) ursodeoxycholic acid in selected patients. The use of antiprotease and anti-inflammatory agents has been shown to be useful in preventing the damage secondary to chronic lung infection. In patients with severely impaired lung function, lung transplantations have been performed with good results. Finally, it seems probable that lung disease in CF patients will be ameliorated or prevented in the future with early gene therapy, using vectors such as recombinant adenoviruses, adeno-associated virus, lipofection or retrovirus. However, this require extensive basic and clinical research.
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PMID:Drug management of noninfective complications of cystic fibrosis. 853 51

We tested the hypothesis that recombinant human deoxyribonuclease 1 (rhDNase) reduces airflow obstruction and improves mucociliary clearance in patients with cystic fibrosis (CF), and that improvements seen in FEV1 and FVC after rhDNase treatment are independent of chest physical therapy (CPT). CF patients inhaled placebo (10 patients) or 2.5 mg rhDNAse aerosol (10 patients) twice a day for six consecutive days. Compared with baseline, there were no statistically significant differences between the two study groups by Day 6 for indices of airflow obstruction obtained from gamma-camera images of the right lung following inhalation of 99mTc aerosol, or for mucociliary clearance or the rate of clearance of the radioaerosol, quantified over a 6-h period. By Day 6, FEV1 and FVC were significantly higher in the rhDNase-treated group than in the placebo group, increasing by an average of 9.4 +/- 3.5% and 12.7 +/- 2.6%, respectively, as compared with a decrease of 1.8 +/- 1.7% and an increase of 0.4 +/- 1.1%, respectively (p < 0.05). There was no significant change in the FEV1/FVC ratio on Day 6 (0.68 +/- 0.05) compared with baseline (0.70 +/- 0.05) in the rhDNase group. On Day 6, FEV1 and FVC decreased after CPT in both study groups, but the decreases were not significant. Our results indicate that aerosolized rhDNase improves FEV1 and FVC independent of CPT. We were unable to demonstrate that rhDNase reduces airflow obstruction or improves mucociliary clearance.
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PMID:Effect of rhDNase on airflow obstruction and mucociliary clearance in cystic fibrosis. 856 29

Treatment with either rhDNase or high-frequency oscillation has been shown to be effective in improving the physical and transport properties of airway secretions in cystic fibrosis (CF). The objects of this in vitro study was to examine whether combined treatment with oscillation and rhDNase results in greater change of CF sputum spinnability than either treatment by itself. Aliquots of sputum (0.4 g) from eight CF patients were subjected to the following protocols for 15 minutes and then followed for a total of 30 minutes: 1) incubation with 0.04 ml DNase 50 micrograms rhDNase/normal saline (10% dilution) at 37 degrees C to achieve 5 micrograms DNase/g of sputum final concentration; 2) airflow oscillation at 27 Hz similar to the airflow magnitude produced by a commercial high-frequency chest compression (HFCC) device; 3) negative control with no treatment; 4) positive (dilution) control, incubating with 10% saline by volume; 5) combination of DNase and oscillation, and 6) combination of saline and oscillation. For each protocol, sputum spinnability (in mm, mean +/- SD) was measured by means of a filancemeter at baseline, 15, and 30 minutes. Treatment with DNase decreased spinnability significantly more than either saline or oscillation at 15 and 30 minutes (P < 0.02 and P < 0.04, respectively). Incubation with saline or oscillation of CF sputum for 15 and 30 minutes decreased spinnability significantly compared with control. The combination of DNase and oscillation decreased spinnability significantly more than treatment with DNase alone (3.74 +/- 0.45 vs. 6.54 +/- 0.73 at 15 minutes, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of combined treatment with rhDNase and airflow oscillations on spinnability of cystic fibrosis sputum in vitro. 857 Mar 6

Cystic fibrosis (CF) is a disease with a high morbidity and mortality from pulmonary disease. Sputum from CF patients contains high levels of deoxyribonucleic acid (DNA), which contribute to its viscoelasticity. Recombinant deoxyribonuclease (rhDNase) has been developed and in vitro studies have showed reduction in the viscoelasticity of CF sputum. This article reviews the in vivo clinical trials conducted to determine the safety and efficacy of this treatment. Phase 1 studies showed preliminary safety data and some evidence of clinical benefit. The two Phase 2 short-term studies showed improvement in pulmonary function and important safety data. The Phase 3 study, which included 968 patients, showed improvement in forced expiratory volume in one second (FEV1) of 5.8% and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation of infection was reduced by 28% with once daily and 37% with twice daily treatment, compared to placebo. The drug was safe and there was some improvement in quality of life data. Longer-term open labelled studies, the results of intermittent administration, administration to severely ill patients, and the use of different delivery systems are reviewed. In conclusion, recombinant deoxyribonuclease is a new treatment which has been shown to benefit patients with cystic fibrosis when used in conjunction with conventional treatment.
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PMID:DNase trials in cystic fibrosis. 858 38


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