scholarly journals Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection

2020 ◽  
Vol 37 ◽  
pp. 100756
Author(s):  
H.K. Okur ◽  
K. Yalcin ◽  
C. Tastan ◽  
S. Demir ◽  
B. Yurtsever ◽  
...  
2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.


2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.


1998 ◽  
Vol 51 (3) ◽  
pp. 231-237 ◽  
Author(s):  
T. Gilchrist ◽  
M.A. Glasby ◽  
D.M. Healy ◽  
G. Kelly ◽  
D.V. Lenihan ◽  
...  

PEDIATRICS ◽  
1958 ◽  
Vol 21 (1) ◽  
pp. 21-21

This is a preliminary report of a new approach to treatment of sickle-cell disease based on the knowledge that the sickling phenomenon resides in a defect in the hemoglobin which, when deoxygenated, undergoes molecular rearrangement with consequent alteration of the shape of the erythrocyte. The sickle-cell phenomenon is not seen in fully oxygenated blood. It seemed reasonable to the authors to employ carbonic anhydrase inhibitor to control reduction of hemoglobin in sickle-cell disease to such an extent as to prevent the occurrence of sickling. The carbonic anhydrase inhibitor employed was acetazolamide (Diamox®). Experiments were conducted in vitro and also in vivo in a single Negro baby 8 months of age. Before treatment the patient's blood contained 18.7% sickled cells. One hour after 2 mg of acetazolamide per kilogram the percentage of sickled cells was reduced to 11.8%; 1 hour after 7 mg of acetazolamide per kilogram the percentage of sickled cells was reduced to 7.5%. At the time of this preliminary report the patient had been treated with acetazolamide for 29 days with an increase in the hemoglobin from 7.1 to 9.4 gm/100 ml. In a preliminary period of observation of 41 days before treatment the hemoglobin had declined during two separate episodes of hemolysis. The theory of the suggested mode of treatment is discussed. A detailed account of the clinical observations is to be the subject of a further report.


2011 ◽  
Vol 20 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Wei-Qiang Tan ◽  
Zheng-Jun Gao ◽  
Jing-Hong Xu ◽  
Hang-Ping Yao

Oncotarget ◽  
2018 ◽  
Vol 9 (18) ◽  
pp. 14160-14174 ◽  
Author(s):  
Giovani M. Favero ◽  
Jessica L. Paz ◽  
Andréia H. Otake ◽  
Durvanei A. Maria ◽  
Elia G. Caldini ◽  
...  

Author(s):  
E. J. Kollar

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.


Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.


Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.


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