scholarly journals Umifenovir and coronavirus infections: a review of research results and clinical practice

2020 ◽  
Vol 92 (11) ◽  
pp. 91-97
Author(s):  
I. A. Leneva ◽  
N. Y. Pshenichnaya ◽  
V. A. Bulgakova
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Antiviral Therapy ◽  
Respiratory Infections ◽  
Clinical Investigation ◽  
Meta Analysis ◽  
Antiviral Agent ◽  
Antiviral Drugs ◽  
Virus Elimination

Coronaviruses are known to cause acute respiratory infections. Antiviral therapy, including for COVID-19, is based on clinical practice, experimental data and trial results. The purpose of this review is to: provide and systematize actual preclinical data, clinical trials results and clinical practice for antiviral agent umifenovir (Arbidol). Databases Scopus, Web of Science, RSCI and medRxiv were used for publication searching from 2004. A meta-analysis of clinical trials results was performed. Umifenovir is antiviral agent, it belongs to fusion inhibitors, interacts with SARS-CoV-2 spike protein. Umifenovir the impede the trimerization of spike glycoprotein and inhibit host cell adhesion, at the level of the coronaviruses S-protein of interaction with ACE2 receptor. Preclinical studies in vitro and on animals show umifenovir activity against a number of coronaviruses, including SARS-CoV, MERS-CoV, SARS-CoV-2, and others. Umifenovir, in combination with other antiviral drugs, symptomatic or traditional medicine, was used in China to treat patients with COVID-19, resulting in reduced mortality, virus elimination, the frequency of more severe course and complications in middle severity. However, antiviral therapy for the treatment of severe patients, with ARDS, did not lead to improved outcomes. In comparative clinical studies, umifenovir showed similar effectiveness with other antiviral drugs, and lower frequency of adverse reactions. Therapy with umifenovir, led to an increase percentage of patients with negative results of PCR tests on days 714 (I2=69.8%, RR 0.48, 95% CI 0.190.76; p=0.001). The efficacy and safety of antivirals against SARS-CoV-2 still requires clinical investigation. Moderate forms of COVID-19 could be effectively treated by antivirals, but severe forms of COVID-19, characterized by pulmonary immunopathology, require different approaches to treatment.

scholarly journals Antiviral therapy: current concepts and practices.

1992 ◽  
Vol 5 (2) ◽  
pp. 146-182 ◽  
Author(s):  
B Bean
Keyword(s):  
Antiviral Therapy ◽  
Respiratory Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Virus Infections ◽  
Immunodeficiency Virus ◽  
Viral Respiratory Infections ◽  
Toxic Drugs ◽  
Viral Respiratory

Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

scholarly journals Could Azithromycin Be Part of Pseudomonas aeruginosa Acute Pneumonia Treatment?

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne-Gaëlle Leroy ◽  
Jocelyne Caillon ◽  
Nathalie Caroff ◽  
Alexis Broquet ◽  
Stéphane Corvec ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Trials ◽  
Respiratory Infections ◽  
Direct Interaction ◽  
Membered Ring ◽  
Careful Examination ◽  
Major Interest ◽  
Acute Pneumonia

Azithromycin (AZM) is a 15-membered-ring macrolide that presents a broad-spectrum antimicrobial activity against Gram-positive bacteria and atypical microorganisms but suffers from a poor diffusion across the outer-membrane of Gram-negative bacilli, including Pseudomonas aeruginosa (PA). However, AZM has demonstrated clinical benefits in patients suffering from chronic PA respiratory infections, especially cystic fibrosis patients. Since the rise of multidrug-resistant PA has led to a growing need for new therapeutic options, this macrolide has been proposed as an adjunctive therapy. Clinical trials assessing AZM in PA acute pneumonia are scarce. However, a careful examination of the available literature provides good rationales for its use in that context. In fact, 14- and 15-membered-ring macrolides have demonstrated immunomodulatory and immunosuppressive effects that could be of major interest in the management of acute illness. Furthermore, growing evidence supports a downregulation of PA virulence dependent on direct interaction with the ribosomes, and based on the modulation of several key regulators from the Quorum Sensing network. First highlighted in vitro, these interesting properties of AZM have subsequently been confirmed in the animal models. In this review, we systematically analyzed the literature regarding AZM immunomodulatory and anti-PA effects. In vitro and in vivo studies, as well as clinical trials were reviewed, looking for rationales for AZM use in PA acute pneumonia.

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

scholarly journals Cardioprotective Properties Of Xenon

2020 ◽  
Vol 9 (2) ◽  
pp. 264-272
Author(s):  
A. I. Shpichko ◽  
O. A. Grebenchikov ◽  
I. V. Molchanov ◽  
A. K. Shabanov ◽  
N. P. Shpichko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Randomized Clinical Trials ◽  
Protective Action ◽  
Experimental Studies ◽  
Molecular Targets ◽  
Cardiac Complications ◽  
Ischemia And Reperfusion

Abstract The review presents the main aspects of the cardioprotective properties of the xenon inhalation anesthetic. Based on the analysis of publications, the article discusses modern views on the mechanisms of the protective action of xenon, realized using pre- and post-conditioning mechanisms, shows major molecular targets and their effects. The article presents the results of experimental studies in vivo and in vitro, which showed the protective effect of xenon on the myocardium and the results of recent randomized clinical trials. The analysis of studies demonstrates the ability of xenon to increase myocardial resistance to ischemia and reperfusion and opens up good prospects for its use in clinical practice in patients with a high risk of cardiac complications.

Book review: Deadly medicines and organized crime

2016 ◽  
Vol 2 (2) ◽  
pp. 138-139
Author(s):  
Shankar PR ◽  
Alshakka MAM
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Pharmaceutical Industry ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Organized Crime ◽  
Healthcare Professionals ◽  
Meta Analysis ◽  
Degree Of Control

Clinical trials have attracted negative attention recently. The degree of control of the pharmaceutical industry over the design, conduct and analysis of clinical trials has been criticized. Healthcare professionals increasingly rely on data obtained from clinical trials and from meta-analysis and systematic reviews. The process of publishing clinical trials and framing clinical practice guidelines is being increasingly influenced by the pharmaceutical industry.

Longevidade de dentes tratados endodonticamente e restaurados com pinos metálicos e de fibra de vidro: uma revisão integrativa da literatura

2021 ◽  
Vol 12 (1) ◽  
pp. 61
Author(s):  
Viviane Figueiredo ◽  
José Luiz Costa Neto ◽  
Julia Guedes Alcoforado Souza ◽  
Kamila Azoubel Barreto
Keyword(s):  
Clinical Trials ◽  
Clinical Study ◽  
Failure Mode ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Dental Restoration ◽  
Supporting Evidence ◽  
Endodontically Treated Teeth

OBJECTIVE: Review the literature in an integrative way, regarding a clinical longevity of endodontically treated teeth restored with fiberglass and metallic pins and with fixed crowns, based survival factors and failure mode. METHODOLOGY: A search was carried out in the Lilacs and Pubmed databases, with the following descriptors: dental restoration (dental restoration; restauración dental), dental pins (dental pins; pins dentales), clinical study (clinical study; estudio clínico). The inclusion criteria were: articles that addressed the variables of clinical longevity, survival rate and failure mode of metallic pins and fiberglass, in Portuguese, English and Spanish, published between 2010 and 2020, such as clinical trials with or without randomization and systematic reviews with or without meta-analysis. And, the exclusion criteria were: narrative literature reviews, clinical cases, in vitro and silico studies , letters to the editor and opinion articles. RESULTS: Combining the search methods, 06 articles were identified, of which 04 articles were randomized clinical trials and 02 articles were systematic reviews. The included studies show a high level of scientific evidence. FINAL CONSIDERATIONS: The present integrative literature review, regarding the clinical longevity of teeth endodontically treated and restored with metal and fiberglass pins, observed that the clinical results are still conflicting in relation to the factors of survival and failure mode. And that, the remaining coronary structure seems to be more important for the success of the rehabilitation than the material of the pin, however the supporting evidence is limited.

scholarly journals Viral Determinants of Resistance to Treatment in Patients with Hepatitis C

2007 ◽  
Vol 20 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Anette Wohnsland ◽  
Wolf Peter Hofmann ◽  
Christoph Sarrazin
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Phase 1 ◽  
Treatment Success ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Immune Defense ◽  
Phenotypic Resistance

SUMMARY Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-α) in combination with the nucleoside analogue ribavirin leads to a sustained virologic response in approximately half of the patients. IFN-α is classified as an indirect treatment, as it interacts with the host's immune response. The mechanism of action of ribavirin is still unknown. The benefit of triple therapy by adding other antiviral agents, e.g., amantadine, is controversial. Currently, new direct antiviral drugs (HCV protease/polymerase inhibitors) are being evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy has been attributed to amino acid variations within distinct regions of the HCV polyprotein. While sensitivity to IFN-α-based antiviral therapy in vivo is clearly correlated with the number of mutations within the HCV NS5A protein, the underlying functional mechanisms for this association are unknown. In turn, in vitro, several mechanisms to circumvent the host immune defense or to block treatment-induced antiviral activities have been described for different HCV proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now is entering a new era in which the development of resistance may become the most important parameter for treatment success or failure.

scholarly journals Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Vascularized Composite Allotransplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Heyes ◽  
Andrew Iarocci ◽  
Yourka Tchoukalova ◽  
David G. Lott
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Graft Survival ◽  
Human Populations ◽  
Extensive Literature ◽  
Solid Organ ◽  
Preclinical Studies ◽  
Skin Allograft ◽  
Transplant Tolerance

This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.

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