Ramatroban, an orally bioavailable immunomodulator and antithrombotic agent for treatment of COVID-19 disease: A Case Report

Abstract SARS-CoV-2 pneumonia and COVID-19 disease are characterized by a maladaptive immune response and prothrombotic state. The Spike protein of SARS-CoV-2 virus unleashes a storm of lipid mediators with very high levels of thromboxane B2 and prostaglandin D2 in the bronchoalveolar lavage fluid. DPr2 receptors for prostaglandin D2 and TPr receptors for thromboxane A2 have been proposed as therapeutic targets in COVID-19 in order to decrease viral load and inhibit platelet dependent thrombosis, respectively. Ramatroban is an oral, dual receptor antagonist of the DPr2 and TPr receptors with established safety profile, having been used in Japan for the treatment of allergic rhinitis for over 20 years. We report two patients, an 88-year-old woman and a 31-year-old man, both with COVID-19 pneumonia who were successfully treated in ambulatory setting with oral ramatroban, leading to rapid improvement in oxygen saturation from about 80–82% to about 90–95% over 24–48 hours followed by gradual recovery from the disease. The mechanism of action of ramatroban and its efficacy reported here supports clinical trials on this drug as a potential treatment for COVID-19.

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Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

10.21203/rs.3.rs-30944/v1 ◽

2020 ◽

Author(s):

Qiancheng Luo ◽

Rui Liu ◽

Guorong Liu ◽

Min Hang ◽

Guo Chen ◽

...

Keyword(s):

Inflammatory Response ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Surface Expression ◽

Pulmonary Injury ◽

Protective Mechanisms ◽

Tnf Α ◽

G Protein Coupled ◽

Very High ◽

Masson Staining

Abstract BackgroundSepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist antiplatelet drug.MethodsIn our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using mouse models.ResultsTdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β, IL-6, and TNF-α. Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 ༈GPR17༉induced by CLP. Conclusion: Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

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A Case Series of Pulmonary Mucormycosis Caused by Rhizopus Microsporus

Austin Journal of Microbiology ◽

10.26420/austinjmicrobiol.2021.1033 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Mei Y ◽

◽

Sun P ◽

Wang Z ◽

Huang X ◽

...

Keyword(s):

Amphotericin B ◽

Bronchoalveolar Lavage Fluid ◽

Case Series ◽

Lavage Fluid ◽

Rhizopus Microsporus ◽

Fatal Disease ◽

Ionization Time ◽

Pulmonary Mucormycosis ◽

History Of ◽

Very High

Mucormycosis is a relatively uncommon but intractable fungal infectious disease. The mortality is very high when it occurs. In this study, we reported a continuous cases of pulmonary mucormycosis in three patients who suffered from chronic kidney disease, history of renal transplantation and multiple myeloma in April 2017, respectively. Cultures were obtained from several specimens (pathological tissue, bronchoalveolar lavage fluid and sputum) and all identified as Rhizopus microsporus by Matrix-Assisted Laser Desorption Ionization Time- Of-Flight (MALDI-TOF) mass spectrometry and ITS DNA sequencing methods. In addition, they all showed susceptibility to amphotericin B and posaconazole. Unfortunately, even through the three patients all treated with amphotericin B and posaconazole, one man still died eventually. Clinicians should keep an eye on patients who are at high risk of acquiring this fatal disease and make early intervention strategies to reduce terrible outcomes.

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Sulfidopeptide leukotrienes mediate acrolein-induced bronchial hyperresponsiveness

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1838 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1838-1845 ◽

Cited By ~ 18

Author(s):

G. D. Leikauf ◽

C. A. Doupnik ◽

L. M. Leming ◽

H. E. Wey

Keyword(s):

Receptor Antagonist ◽

Guinea Pigs ◽

Bronchoalveolar Lavage Fluid ◽

Bronchial Hyperresponsiveness ◽

Lavage Fluid ◽

Lipid Mediators ◽

Leukotriene Receptor Antagonist ◽

Bronchial Responsiveness ◽

Lipoxygenase Inhibitors ◽

Leukotriene Receptor

The sulfidopeptide leukotrienes are bronchoconstrictive lipid mediators thought to have an important role in the pathophysiology of asthma. The objective of this study was to determine if treatment with a leukotriene receptor antagonist and 5-lipoxygenase inhibitors could diminish acrolein-induced bronchial hyperresponsiveness and to determine whether leukotriene (LT) C4 generation is augmented by acrolein exposure. Guinea pigs (groups of 6–7) were exposed to 1.3 ppm acrolein for 2 h and bronchial responsiveness to intravenous acetylcholine determined twice before, and once 1, 2, 6, and 24 h after exposure. Immediately after acrolein exposure (5 min) specific total airway resistance (sRt) increased from 0.86 +/- 0.01 to 1.29 +/- 0.07 ml.cmH2O.ml-1.s. Within 1 h after exposure, the effective dose of acetylcholine sufficient to double sRt (ED200) decreased from 114.0 +/- 6.6 to 58.5 +/- 6.5 micrograms.kg-1.min-1. Bronchial hyperresponsiveness became maximal at 2 h with ED200 = 44.7 +/- 4.2 and persisted for up to 24 h after exposure (24 h ED200 = 60.2 +/- 11.6 micrograms.kg-1.min). A LTC4/LTD4 receptor antagonist, L-649,923 (10 mg/kg iv), and two putative inhibitors of 5-lipoxygenase, L-651,392 (10 mg/kg po) and U-60,257 (5 mg/kg i.v.), diminished the immediate bronchoconstriction and markedly inhibited bronchial hyperresponsiveness. Analysis of bronchoalveolar lavage fluid obtained from guinea pigs after acrolein exposure revealed a significant increase in immunoreactive LTC4 concentrations (control LTC4 = 8.8 +/- 0.3, n = 7; exposed LTC4 = 15.9 +/- 2.4 pg/ml, n = 6). Treatment with L-651,392 inhibited this response (acrolein exposed = 9.4 +/- 2.4 pg/ml, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

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