To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoVinfected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect needs to be further assessed in a prospective clinical trial.
Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Diagnosis and Treatment for 2019 Novel Coronavirus Diseases released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings:17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.006) and case severity (p=0.021) in critical and severe patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.014, HR=0.37, 95%CI[0.155-0.833]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation:Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding:National Science and Technology Major Project.
Objective-To investigate the gross arrangement of the principal muscular bundles of the two atria, and to suggest how it may contribute to contraction and spread of atrial excitation. Design-A prospective analysis based on anatomical examination of adult human hearts. Setting-A national heart and lung institute and a tertiary referral centre for cardiac disease. Material-9 normal postmortem human hearts. Methods-Dissection of atrial muscles with macrophotography. Results-The atrial walls consist of circumferential and longitudinal muscular bundles, the former being arranged at the base of the atria with the latter predominating in the parietal walls. The muscular bundles in the right atrium are larger than those in the left. The main muscles forming the right atrial wall are the terminal crest and terminal pectinate muscles. The terminal crest, the most obvious muscle, is arranged longitudinally with its pectinate muscles connecting to the musculature of the atrioventricular vestibule. No structure resembling the terminal crest is seen in the left atrium. Instead the left atrial wall is composed of intermingled series of muscles, chief of these being the interatrial band and the septoatrial bundle. The former is arranged circumferentially at the atrial base, while the latter is mainly longitudinal. The wall of the right atrium is not of uniform thickness because of the presence of the terminal crest and its pectinate muscles on its internal surface. By contrast, the left atrial wall is much more uniform and its average thickness is greater than that of the right atrium. The rim of the oval fossa is the most important muscular structure on the septal surface and is formed by the infolded atrial walls. The other principal muscles of the atria attach to it, so that the rim provides mechanical support for overall movement of the atrial walls. Comparison of the gross arrangement of the atrial musculature with earlier echocardiographic measurements showed that this arrangement of the muscle explains movement of the atrioventricular ring and overall atrial contraction, and provides a suitable substrate for preferential conduction. Conclusion-The anatomical features of the atrial musculature explain the known facts concerning atrial contraction and preferential conduction. (Br HeartJ7 1995;73:559-565)
RBM5 is one member of a group of structurally related genes that includes RBM6 and RBM10. RBM10 maps to Xp11.23, and one allele is inactivated as a result of X chromosome inactivation. Both RBM5 and RBM6 map to 3p21.3, a tumor suppressor region that experiences loss of heterozygosity in the majority of lung cancers. Overexpression of RBM5, which encodes an RNA-binding protein involved in the regulation of alternative splicing and retards ascites associated tumor growth in immunocompromised mice, a phenomenon that may be related to an associated ability to modulate apoptosis. As part of our quest to gain a better understanding of how the proapoptotic activity of RBM5 might contribute to tumor suppressor function, we reviewed all the literature relating to RBM5 expression, with a focus on lung cancer. On the basis of the existing data, we suggest that-to more thoroughly assess the potential involvement of RBM5 as a lung cancer regulatory protein-more research is required regarding (a) the expression of not only full-length RBM5 but all of the alternate variants associated with the locus, in relation to histologic subtype and smoking history, and (b) the mutation status of various genes within the transforming growth factor-alpha signaling pathway, which may function to either directly or indirectly regulate RBM5 activity in RBM5-retaining lung cancers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.