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Search results for: Recombinant Human DNase Proteins

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#34015562   2021/05/11 To Up

Recombinant human DNase I for the treatment of cancer-associated thrombosis: A pre-clinical study.

Cancer patients are more likely to develop thrombosis, and this co-morbidity is related to the worse prognosis of the disease. The increased formation of neutrophil extracellular traps (NETs) has been proposed as one of the mechanisms to explain cancer-associated thrombosis. In vivo, degradation of NETs with recombinant human DNase I (rhDNase I) prevents thrombus formation in mouse models. In this work, we evaluated the effect of two different chronic treatments with rhDNase I in a murine NET-dependent prothrombotic state in breast cancer model. Medium-term treatment (2.5 mg/kg rhDNase I for eight consecutive days) did not interfere with the primary growth of 4T1 tumors. On the other hand, it effectively prevented thrombus formation in the inferior vena cava stenosis model. Remarkably, medium-term treatment with rhDNase I showed minor impact in the tail-bleeding model. Different from the medium-term, the long-term treatment with rhDNase I (2.5 mg/kg for 18 successive days) drastically reduced the overall survival. Remarkably, the concomitant use of Ertapenem, a carbapenem antibiotic, and rhDNase I significantly attenuated the mortality observed in the long-term treatment. Our results suggest the therapeutic potential of rhDNase I to treat cancer-associated thrombosis, although its chronic use should be carefully evaluated and potentially harmful.
Carolina B S Várady, Ana Carolina Oliveira, Robson Q Monteiro, Tainá Gomes

1826 related Products with: Recombinant human DNase I for the treatment of cancer-associated thrombosis: A pre-clinical study.

20 ug10

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#33735508   2021/03/18 To Up

Dornase alfa for cystic fibrosis.

Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.
Connie Yang, Mark Montgomery

2457 related Products with: Dornase alfa for cystic fibrosis.

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#33686652   2021/03/09 To Up

Timing of dornase alfa inhalation for cystic fibrosis.

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review.
Ruth Dentice, Mark Elkins

1694 related Products with: Timing of dornase alfa inhalation for cystic fibrosis.

250 ml 100ul10 100 ul200 mg2000 rxn100 ug25 g 5 G0.1 mg0.1 mg

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#33547099   2021/02/05 To Up

Successful drainage of complex haemoserous malignant pleural effusion with a single modified low-dose intrapleural alteplase and dornase alfa.

Patients with symptomatic complex malignant pleural effusion (MPE) are frequently unfit for decortication and have a poorer prognosis. Septations can develop in MPE, which may lead to failure of complete drainage and pleural infection. Intrapleural fibrinolytic therapy (IPFT) is an alternative treatment. The use of IPFT in patients with anaemia and high risk for intrapleural bleeding is not well established. We report a successful drainage of complex haemoserous MPE with a single modified low-dose of intrapleural 5 mg of alteplase and 5 mg of dornase alfa in a patient with pre-existing anaemia with no significant risk of intrapleural bleeding.
Boon Hau Ng, Nur Husna Mohd Aminudin, Mona Zaria Nasaruddin, Jamalul Azizi Abdul Rahaman

1931 related Products with: Successful drainage of complex haemoserous malignant pleural effusion with a single modified low-dose intrapleural alteplase and dornase alfa.

100 G1 mg5mg1 g100ug100 ul96 wells (1 kit)1000 TESTS/0.65ml0.1mg100ug

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#33435568   2021/01/08 To Up

Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development.

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 () would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.
Anjali Trivedi, Meraj A Khan, Geetanjali Bade, Anjana Talwar

1153 related Products with: Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development.

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#33397211   2021/01/05 To Up

Inspiration and Exasperation: The Challenges of Inhaled Biologics.

The delivery of biotherapeutic molecules (antibodies, proteins, peptides) and nucleic acids via the respiratory route has presented challenges for regulatory approval, due in part to a lack of understanding of the expected pathology, mechanisms of toxicity, and immunogenicity induced by the inhalation route. Although the first inhaled biotherapeutic was approved some time ago (Dornase Alfa, Pulmozyme; Genetech, 1993), no other inhaled biotherapeutics have been marketed for the treatment of human disease other than the inhaled insulins (Exubera; Pfizer, 2006 and Afrezza; Mannkind Corporation, 2014). As a result, scientific knowledge within the toxicologic pathology community is fragmented with precious little publicly available data. Therefore, one of the aims of this special edition was to generate a collection of manuscripts that pathologists and toxicologists could refer in order to understand the pathology, mechanisms of toxicity, immunogenicity, and challenges associated with the development of inhaled biotherapeutics.
Peter Hall, John L Vahle, Karyn Colman

1926 related Products with: Inspiration and Exasperation: The Challenges of Inhaled Biologics.

200ul125 mg500 Units2.5 mg1000 tests100ug10 mg100ul100 mg 100ul

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#33264072   // To Up

Polysulfated Hyaluronan GlycoMira-1111 Inhibits Elastase and Improves Rheology in Cystic Fibrosis Sputum.

Cystic fibrosis (CF) lung disease is marked by high concentrations of neutrophil elastase (NE) and DNA polymers; both factors contribute to airway disease. Although inhaled recombinant human dornase alfa reduces the frequency of CF pulmonary exacerbations, it also increases free NE activity in the sputum. There are no approved anti-NE therapies for patients with CF. We investigated whether synthetic, low-molecular weight polysulfated hyaluronan GlycoMira-1111 (GM-1111) would be effective as an anti-NE drug using CF sputum. Anti-NE activity of GM-1111 was tested in CF sputum in the presence or absence of dornase alfa and/or hypertonic saline using a spectrophotometric assay specific for human NE and was compared with unfractionated heparin. We tested whether GM-1111 disaggregated DNA from CF sputum (using gel electrophoresis analysis) or modified CF sputum viscoelastic properties (using a dynamic rheometer). GM-1111 and unfractionated heparin had near equivalent anti-NE activity in CF sputum in the presence of dornase alfa. Both GM-1111 and unfractionated heparin retained anti-NE activity in hypertonic saline but with decreased activity. GM-1111 increased the release of soluble DNA in CF sputum, resulting in improved depolymerization efficacy of dornase alfa. GM-1111 decreased CF sputum elasticity. GM-1111 inhibited NE activity, enhanced DNA depolymerization by deoxyribonuclease, and decreased viscoelastic properties of CF sputum, similar to effects reported previously for unfractionated heparin. Unlike heparins, GM-1111 is synthetic, with minimal anticoagulant activity, and is not derived from animal products. These key attributes provide advantages over unfractionated heparin as a potential therapeutic for CF.
Apparao B Kummarapurugu, Shuo Zheng, Abigail Pulsipher, Justin R Savage, Jonathan Ma, Bruce K Rubin, Thomas P Kennedy, Judith A Voynow

2603 related Products with: Polysulfated Hyaluronan GlycoMira-1111 Inhibits Elastase and Improves Rheology in Cystic Fibrosis Sputum.

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#33259904   2020/11/28 To Up

PEGylation of recombinant human deoxyribonuclease I decreases its transport across lung epithelial cells and uptake by macrophages.

Conjugation to high molecular weight (MW ≥ 20 kDa) polyethylene glycol (PEG) was previously shown to largely prolong the lung residence time of recombinant human deoxyribonuclease I (rhDNase) and improve its therapeutic efficacy following pulmonary delivery in mice. In this paper, we investigated the mechanisms promoting the extended lung retention of PEG-rhDNase conjugates using cell culture models and lung biological media. Uptake by alveolar macrophages was also assessed in vivo. Transport experiments showed that PEGylation reduced the uptake and transport of rhDNase across monolayers of Calu-3 cells cultured at an air-liquid interface. PEGylation also decreased the uptake of rhDNase by macrophages in vitro whatever the PEG size as well as in vivo 4 h following intratracheal instillation in mice. However, the reverse was observed in vivo at 24 h due to the higher availability of PEGylated rhDNase in lung airways at 24 h compared with rhDNase, which is cleared faster. The uptake of rhDNase by macrophages was dependent on energy, time, and concentration and occurred at rates indicative of adsorptive endocytosis. The diffusion of PEGylated rhDNase in porcine tracheal mucus and cystic fibrosis sputa was slower compared with that of rhDNase. Nevertheless, no significant binding of PEGylated rhDNase to both media was observed. In conclusion, decreased transport across lung epithelial cells and uptake by macrophages appear to contribute to the longer retention of PEGylated rhDNase in the lungs.
Sohaib Mahri, Eléonore Hardy, Tobias Wilms, Herlinde De Keersmaecker, Kevin Braeckmans, Stefaan De Smedt, Cynthia Bosquillon, Rita Vanbever

2747 related Products with: PEGylation of recombinant human deoxyribonuclease I decreases its transport across lung epithelial cells and uptake by macrophages.

1 mg10 ug2 1.00 flask10 520 10 100 50 105.00 ug

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#33169591   2020/11/10 To Up

Cryptococcal empyema treated with tube thoracostomy and intrapleural fibrinolysis.

A 55-year old woman with a history of relapsed T-cell ALL presented with right pleuritic chest pain and decreased breath sounds over the right hemithorax. Imaging of the chest showed loculated effusions. Tube thoracostomy was performed with intrapleural application of alteplase and dornase alpha over a 3-day period. Repeat imaging demonstrated a marked decrease in the volume of the effusion. In most prior published cases of pleural cryptococcosis, surgical drainage was required in addition to prolonged antifungal agents. More than 50% of patients with cryptococcal infection have severe underlying disease or immunodeficiency state making them high risk for surgery. This is the first case to our knowledge of cryptococcal empyema successfully treated with tube thoracostomy and intrapleural fibrinolysis.
Akshay Kohli, Ashutosh Sachdeva, Edward M Pickering

1452 related Products with: Cryptococcal empyema treated with tube thoracostomy and intrapleural fibrinolysis.

500 Vials/Unit0.1 mg25 mg50 ul100 per bag, 10 bags per1096T100 μg100ul100 5/100 Packing /sleeve/bo

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#33095650   // To Up

Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.

Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress (e.g., by the release of reactive oxygen species and myeloperoxidase during NETs formation in the airways) would increase mucus viscoelasticity. We collected human airway mucus from endotracheal tubes of healthy patients admitted for elective surgery and coincubated these samples with NETs from phorbol 12-myristate 13-acetate-stimulated neutrophils. Unstimulated neutrophils served as controls, and blocking experiments were performed with dornase alfa for extracellular DNA and the free radical scavenger dimethylthiourea for oxidation. Compared with controls, the coincubation of mucus with NETs resulted in ) significantly increased mucus viscoelasticity (macrorheology) and ) significantly decreased mesh pore size of the mucus and decreased movement of muco-inert nanoparticles through the mucus (microrheology), but ) NETs did not cause visible changes in the microstructure of the mucus by scanning EM. Incubation with either dornase alfa or dimethylthiourea attenuated the observed changes in macrorheology and microrheology. This suggests that the release of NETs may contribute to airway mucus obstruction by increasing mucus viscoelasticity and that this effect is not solely due to the release of DNA but may in part be due to oxidative stress.
Rosalie S Linssen, Guihong Chai, Jonathan Ma, Apparao B Kummarapurugu, Job B M van Woensel, Reinout A Bem, Logan Kaler, Gregg A Duncan, Lei Zhou, Bruce K Rubin, Qingguo Xu

1221 related Products with: Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.

50μl1 ml 5 G100ul1 mL96T 5 G100 ug1.00 ml5mg25 mg1 g

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