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Gulnaz Vafina, Elmira Zainutdinova, Emil Bulatov, Maria N Filimonova
One of the approaches to effective airway cleansing is the degradation of DNA into smaller fragments. For this purpose Pulmozyme® is used with high efficacy because it contains recombinant DNase I as its active component. The aim of the study was to comparatively analyze DNase activity of Pulmozyme® and the nuclease from gram-negative bacteria Serratia marcescens , because at optimal conditions the catalytic efficiency of the nuclease is much higher than the efficiency of DNase I. Highly polymerized DNA and purulent-mucous sputum were used as substrates...
2018: Frontiers in Pharmacology
Wilbur de Kruijf, Carsten Ehrhardt
Oral inhalation offers the opportunity of targeting drugs locally to different regions of the respiratory tract or alternatively, using the high surface area of the alveoli for systemic delivery. Pulmozyme and the inhaled insulins (i.e. Exubera and Afrezza) are examples of the scope of pulmonary drug delivery of biopharmaceuticals-albeit with strikingly different commercial success. Particularly, the failure of Exubera and the subsequent overreactions (e.g. the unsubstantiated lung cancer fear), lastingly stunned the field of systemically inhaled protein and peptide drugs...
October 2017: Current Opinion in Pharmacology
Saqib Walayat, Nooreen Hussain, Jaymon Patel, Faiz Hussain, Preeti Patel, Sonu Dhillon, Bhagat Aulakh, Subramanyam Chittivelu
Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein...
2017: International Medical Case Reports Journal
Melissa Pastoressa, Truong Ma, Nicholas Panno, Michael Firstenberg
Successful treatment of traumatic hemothoraces is imperative to reduce morbidity and mortality among patients. Treatment modalities range from more conservative to invasive measures, including antibiotic therapy, thoracostomy tube placement, video-assisted thoracoscopic surgery, or thoracotomy. Various studies have documented success in using fibrinolytics such as tissue plasminogen activator (tPA) in conjunction with deoxyribonuclease administered through a chest tube to resolve a hemothorax. The optimal dose and frequency of fibrinolytic therapy have not yet been determined although most studies report administering therapy two times a day for 3 days...
April 2017: International Journal of Critical Illness and Injury Science
Melissa Scala, Deborah Hoy, Maria Bautista, Judith Jones Palafoutas, Kabir Abubakar
OBJECTIVE: Evaluate the feasibility, safety, and efficacy of adjunctive treatment with dornase alfa in preterm patients with ventilator-associated pulmonary infection (VAPI) compared to standard care. WORKING HYPOTHESIS: We hypothesize that therapy with dornase alfa will be safe and well tolerated in the preterm population with no worsening of symptoms, oxygen requirement, or need for respiratory support. STUDY DESIGN: Prospective, randomized, blinded, pilot study comparing adjunctive treatment with dornase alfa to sham therapy...
June 2017: Pediatric Pulmonology
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino-Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
Gregg A Duncan, James Jung, Andrea Joseph, Abigail L Thaxton, Natalie E West, Michael P Boyle, Justin Hanes, Jung Soo Suk
The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1...
November 3, 2016: JCI Insight
Veronica Chorro-Mari, Nanna Christiansen
AIM: Due to national changes to the commissioning process of high cost nebulisers (HCN) for Cystic Fibrosis (CF) patients, CF centres have to repatriate the prescribing of the HCN to the tertiary care centres.1 The following nebulisers will no longer be prescribed by primary care: Cayston® (Aztreonam); Colomycin®, Pomixin®, Clobreathe® (Colistimethate); Pulmozyme® (Dornase alfa); Tobi®, Tobi Podhaler ®, Bramitob® (Tobramycin).This abstract explains how the Royal London Hospital (RLH) Paediatric Pharmacy recruited over 100 paediatric (CF) patients smoothly within a period of 4 months and set up a homecare system to avoid patients and families having to travel large distances to obtain their medication...
September 2016: Archives of Disease in Childhood
Mieke Boon, Mark Jorissen, Martine Jaspers, Patrick Augustijns, François L Vermeulen, Marijke Proesmans, Kris De Boeck
INTRODUCTION: Nebulized drugs are used in the treatment of cystic fibrosis (CF) lung disease, asthma, and COPD, and increasingly also in other chronic lung diseases. Their use in CF is reasonably evidence based, but this is not so for use in other orphan diseases. Potential side effects often have not been studied. Therefore, we evaluated the influence of nebulized drugs on ciliary activity in an in vitro model. METHODS: We constructed an in vitro nebulization model to examine the effect of drugs on ciliary activity...
August 2016: Journal of Aerosol Medicine and Pulmonary Drug Delivery
Iain Simpson, James Blakemore
This Industry Update covers the period from 1 January through 31 January, 2015, and is based on information sourced from company press releases, scientific literature, patents and various news websites. This month saw drugs from Shire and Janssen win fast track approval status from the US FDA which reduces the target time for the Agency to take action from 10 to 6 months. Sanofi and Regeneron also heard that they have won fast track approval for alirocumab a PCSK9 inhibitor for cholesterol lowering following their purchase of a 'Priority Review Voucher' from BioMarin...
April 2015: Therapeutic Delivery
Robert Bucki, Katrina Cruz, Katarzyna Pogoda, Ashley Eggert, LiKang Chin, Marianne Ferrin, Giovanna Imbesi, Denis Hadjiliadis, Paul A Janmey
BACKGROUND: DNase (Pulmozyme) effectiveness in cystic fibrosis treatment is in some cases limited by its inability to access DNA trapped within bundles in highly viscous fluids that also contain actin. Dissociating DNA-containing bundles using actin depolymerizing agents and polyanions has potential to increase DNase efficacy. METHODS: Fluorescence measurements of YOYO-1 and a rheological creep-recovery test quantified DNA content and viscoelasticity in 150 sputum samples from adult CF patients and their susceptibility to fluidization by DNase1, alone and in combination with gelsolin and poly-aspartate (p-Asp)...
September 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Don B Sanders, Zhanhai Li, Alan S Brody
RATIONALE: Abnormalities on chest computed tomography (CT) in children with cystic fibrosis (CF) have been shown to correlate with short-term measures of lung disease. Chest CT scores offer promise as a potential surrogate end point in CF; however, there is limited information available on the ability of chest CT scores to predict future morbidity. OBJECTIVES: Determine whether chest CT scores are associated with the rate of pulmonary exacerbations over the next 10 years...
January 2015: Annals of the American Thoracic Society
Rossella Grande, Laura Nistico, Karthik Sambanthamoorthy, Mark Longwell, Antonio Iannitelli, Luigina Cellini, Antonio Di Stefano, Luanne Hall Stoodley, Paul Stoodley
Extracellular DNA (eDNA) is an important component of the extracellular polymeric substance matrix and is important in the establishment and persistence of Staphylococcus aureus UAMS-1 biofilms. The aim of the study was to determine the temporal expression of genes involved in early biofilm formation and eDNA production. We used qPCR to investigate expression of agrB, which is associated with secreted virulence factors and biofilm dispersal, cidA, which is associated with biofilm adherence and genomic DNA release, and alsS, which is associated with cell lysis, eDNA release and acid tolerance...
April 2014: Pathogens and Disease
Samya Z Nasr, Will Chou, Kathleen F Villa, Eunice Chang, Michael S Broder
OBJECTIVE: To investigate adherence to dornase alfa therapy among commercially-insured patients with cystic fibrosis (CF) and to examine the impact of adherence on health and economic outcomes. METHODS: This retrospective cohort analysis included CF patients with ≥1 dornase alfa (Pulmozyme) pharmacy claim between 1 October 2006 and 30 September 2008 and with continuous enrollment in the health insurance plan at least 1 year before and 1 year after their index dornase alfa claim...
2013: Journal of Medical Economics
Jessica Nutik Zitter, Pierre Maldjian, Michael Brimacombe, Kevin P Fennelly
BACKGROUND: Lobar or segmental collapse of the lung in mechanically ventilated patients is a common occurrence in the intensive care unit. Management is labor and time intensive and not highly effective. METHODS: We conducted a randomized, placebo-controlled, double-blind pilot study to determine whether nebulized Dornase alfa improves radiologic and clinical outcomes in ventilated patients with lobar atelectasis. Drug or placebo was administered twice daily until extubation, death, or transfer...
April 2013: Journal of Critical Care
Goetz Parsiegla, Christophe Noguere, Lydia Santell, Robert A Lazarus, Yves Bourne
Recombinant human DNase I (Pulmozyme, dornase alfa) is used for the treatment of cystic fibrosis where it improves lung function and reduces the number of exacerbations. The physiological mechanism of action is thought to involve the reduction of the viscoelasticity of cystic fibrosis sputum by hydrolyzing high concentrations of DNA into low-molecular mass fragments. Here we describe the 1.95 Å resolution crystal structure of recombinant human DNase I (rhDNase I) in complex with magnesium and phosphate ions, both bound in the active site...
December 21, 2012: Biochemistry
Jeffrey S Wagener, Oren Kupfer
PURPOSE OF REVIEW: Dornase alfa (Pulmozyme) is one of the most commonly used medications to treat the lung disease of cystic fibrosis (CF). As other respiratory medications have entered the clinical market, understanding the proper use and indication for dornase alfa is increasingly important. In addition, dornase alfa is being used to treat other medical conditions. This review covers recent publications and expanding indications. RECENT FINDINGS: Understanding dornase alfa's mechanism of action and impact on the pathophysiology of CF leads to an improved understanding of optimal therapy, ways to improve adherence and use with other medications...
November 2012: Current Opinion in Pulmonary Medicine
Aaron Shaw, Daniela Bischof, Aparna Jasti, Aaron Ernstberger, Troy Hawkins, Kenneth Cornetta
In the production of lentiviral vector for clinical studies the purity of the final product is of vital importance. To remove plasmid and producer cell line DNA, investigators have incubated the vector product with Benzonase, a bacterially derived DNase. As an alternative we investigated the use of Pulmozyme, a U.S. Food and Drug Administration-approved human DNase for the treatment of cystic fibrosis, by comparing the efficiency of DNA removal from lentiviral vector preparations. A green fluorescent protein-expressing lentiviral vector was prepared by transient calcium phosphate transfection of HEK 293T cells and DNA removal was compared when treating vector after harvest or immediately after transfection...
February 2012: Human Gene Therapy Methods
Tatiana Rozov, Viviane Ziebell de Oliveira, Maria Angélica Santana, Fabíola Villac Adde, Rita Heloisa Mendes, Ilma Aparecida Paschoal, Francisco J Caldeira Reis, Laurinda Yoko Shinzato Higa, Antonio Carlos de Castro Toledo, Márcia Pahl et al.
SUMMARY BACKGROUND: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. PATIENTS AND METHODS: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T(0)), and at 3 (T(1)), 6 (T(2)), 9 (T(3)), and 12 (T(4)) months of follow-up...
September 2010: Pediatric Pulmonology
Anne Marie McLaughlin, Emmet McGrath, Rupert Barry, Jim J Egan, Charles G Gallagher
INTRODUCTION: Recombinant human deoxyribonuclease (rhDNase) reduces sputum viscosity and improves pulmonary function in cystic fibrosis (CF). OBJECTIVE: The objective of this study was to describe our experience in which rhDNase (Pulmozyme; Roche, Basel, Switzerland) was administered by bronchoscopic instillation into atelectatic lobes in five adults with CF. CONCLUSION: We found this method successful in treating lobar atelectasis, which was resistant to conventional therapy with antibiotics and physiotherapy...
April 2008: Clinical Respiratory Journal
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