scholarly journals Retraction: Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia

2022 ◽  
Vol 17 (5) ◽  
pp. 958
Keyword(s):  
Nafamostat Mesylate

scholarly journals Filter lifetimes of different hemodiafiltration membrane materials in dogs: reevaluation of the optimal anticoagulant dosage

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiroko Yuzawa ◽  
Yousuke Hirose ◽  
Tomonori Kimura ◽  
Keisuke Shinozaki ◽  
Moe Oguchi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Activated Partial Thromboplastin Time ◽  
Target Range ◽  
Membrane Material ◽  
Actual Clinical Practice ◽  
Membrane Materials ◽  
Filter Membrane ◽  
Hemorrhagic Complications ◽  
Materials Used ◽  
Nafamostat Mesylate

Abstract Background In continuous renal replacement therapy (CRRT), administration of anticoagulants is necessary for achieving a certain level of filter lifetime. Generally, anticoagulant doses are controlled to keep activated partial thromboplastin time and other indicators within a certain target range, regardless of the membrane materials used for the filter. However, in actual clinical practice, the filter lifetime varies significantly depending on the membrane material used. The objective of this study was to demonstrate that the minimum anticoagulant dose necessary for prolonging the filter lifetime while reducing the risk of hemorrhagic complications varies depending on the type of membrane. Methods In three beagles, hemodiafiltration was performed with hemofilters using polysulfone (PS), polymethylmethacrylate (PMMA), and AN69ST membranes separately. The minimum dose of nafamostat mesylate (NM) that would allow for 6 h of hemodiafiltration (required dose) was investigated for each membrane material. Results The NM doses required for 6 h of hemodiafiltration were 2 mg/kg/h for the PS membrane, 6 mg/kg/h for the PMMA membrane, and 6 mg/kg/h for the AN69ST membrane. Conclusion For hemodiafiltration performed in beagles, the required NM dose varied for each filter membrane material. Using the optimal anticoagulant dose for each membrane material would allow for safer CRRT performance.

scholarly journals The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 629 ◽  
Author(s):  
Mizuki Yamamoto ◽  
Maki Kiso ◽  
Yuko Sakai-Tagawa ◽  
Kiyoko Iwatsuki-Horimoto ◽  
Masaki Imai ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Assay System ◽  
Dependent Manner ◽  
Cell Type ◽  
S Protein ◽  
Candidate Drug ◽  
A Cell ◽  
Transmembrane Serine Protease ◽  
Nafamostat Mesylate

Although infection by SARS-CoV-2, the causative agent of coronavirus pneumonia disease (COVID-19), is spreading rapidly worldwide, no drug has been shown to be sufficiently effective for treating COVID-19. We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. Furthermore, nafamostat mesylate blocked SARS-CoV-2 infection of Calu-3 cells with an effective concentration (EC)50 around 10 nM, which is below its average blood concentration after intravenous administration through continuous infusion. On the other hand, a significantly higher dose (EC50 around 30 μM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates. Together, our study shows that nafamostat mesylate potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and also inhibits SARS-CoV-2 infection in vitro in a cell-type-dependent manner. These findings, together with accumulated clinical data regarding nafamostat’s safety, make it a likely candidate drug to treat COVID-19.

scholarly journals AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Takahiro Hirayama ◽  
Nobuyuki Nosaka ◽  
Yasumasa Okawa ◽  
Soichiro Ushio ◽  
Yoshihisa Kitamura ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Anticoagulant Therapy ◽  
Nafamostat Mesylate

Active Inhibitory Effect of Nafamostat Mesylate against the Elevation of Plasma Myeloperoxidase during Hemodialysis

Nephron ◽  
1997 ◽  
Vol 75 (4) ◽  
pp. 420-425 ◽  
Author(s):  
Kazuto Inose ◽  
Kumeo Ono ◽  
Akiyasu Tsutida ◽  
Masayuki Onai ◽  
Minoru Komai ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Nafamostat Mesylate

scholarly journals Synergistic inhibition of two host factors that facilitate entry of Severe Acute Respiratory Syndrome Coronavirus 2

2021 ◽  
Author(s):  
Alex J.B. Kreutzberger ◽  
Anwesha Sanyal ◽  
Ravi Ojha ◽  
Jesse Pyle ◽  
Olli Vapalahti ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Kinase Inhibitor ◽  
Fold Increase ◽  
Cell Types ◽  
Late Endosomes ◽  
Combined Use ◽  
Proteolytic Cleavages ◽  
Different Cell Types ◽  
Nafamostat Mesylate

Repurposing FDA-approved inhibitors able to prevent infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could provide a rapid path to establish new therapeutic options to mitigate the effects of coronavirus disease 2019 (COVID-19). Proteolytic cleavages of the spike S protein of SARS-CoV-2, mediated by the host cell proteases cathepsin and TMPRSS2, alone or in combination, are key early activation steps required for efficient infection. The PIKfyve kinase inhibitor apilimod interferes with late endosomal viral traffic, and through an ill-defined mechanism prevents in vitro infection through late endosomes mediated by cathepsin. Similarly, inhibition of TMPRSS2 protease activity by camostat mesylate or nafamostat mesylate prevents infection mediated by the TMPRSS2-dependent and cathepsin-independent pathway. Here, we combined the use of apilimod with camostat mesylate or nafamostat mesylate and found an unexpected ~5-10 fold increase in their effectiveness to prevent SARS-CoV-2 infection in different cell types. Comparable synergism was observed using both, a chimeric vesicular stomatitis virus (VSV) containing S of SARS-CoV-2 (VSV-SARS-CoV-2) and SARS-CoV-2 virus. The substantial ~5 fold or more decrease of half maximal effective concentrations (EC50 values) suggests a plausible treatment strategy based on the combined use of these inhibitors.

Sign in / Sign up

Export Citation Format

Share Document