-
Journal of Traditional Chinese Medicine... Oct 2018To assess the efficacy and safety in 105 patients with seasonal Influenza in Beijing, the mixture prepared with Chinese medicines follows the treatment regimen of... (Randomized Controlled Trial)
Randomized Controlled Trial
Mixture prepared with Chinese medicines in terms of releasing exterior cold and clearing interior heat: its efficacy and safety in patients with seasonal influenza-a randomized controlled trial.
OBJECTIVE
To assess the efficacy and safety in 105 patients with seasonal Influenza in Beijing, the mixture prepared with Chinese medicines follows the treatment regimen of releasing exterior cold and clearing interior heat.
METHODS
Total 330 patients with seasonal influenza were enrolled and randomly and averagely divided into the Chinese herbal medicine, the western medicine and the Chinese patent medicine group. They were treated with Chinese medicine Oseltamivir Phosphate Capsules and the Scattering Wind and Resolving Toxins Capsules. The main efficacy indicators were the antifebrile onset time and recovery time of body temperature. The efficacy and safety of the mixture was scientifically evaluated. Comparisons of several variables were analyzed.
RESULTS
Median antifebrile onset time of the Chinese herbal medicine group was significantly shorter than the western medicine group (P < 0.05) and the Chinese patent medicine group (P < 0.05). The median antifebrile recovery time of the Chinese herbal medicine group was significantly shorter than the Chinese patent medicine group (P < 0.05). The groups evaluated by TCM symptom pattern effect, both the Chinese herbal medicine group and Western Medicine group were better than the Chinese patent medicine group (P < 0.05). The disappearance rate of main symptoms and some minor symptom patterns of the Chinese herbal medicine group were higher than the other 2 groups.
CONCLUSION
The mixture of releasing exterior cold and clearing interior heat could significantly shorten the fever time with safety.
Topics: Adult; Body Temperature; Drugs, Chinese Herbal; Female; Fever; Humans; Influenza, Human; Male; Middle Aged; Phytotherapy; Seasons; Treatment Outcome
PubMed: 32185992
DOI: No ID Found -
Antiviral Research May 2016The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June,...
The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses.
Topics: Amantadine; Antibody-Dependent Enhancement; Antiviral Agents; Coronavirus Infections; Drug Resistance, Viral; Enzyme Inhibitors; Humans; Influenza, Human; Neuraminidase; Orthomyxoviridae; Oseltamivir; Picornaviridae Infections; Respiratory Tract Infections; Rimantadine; Severe Acute Respiratory Syndrome; Texas; Virus Replication
PubMed: 26872862
DOI: 10.1016/j.antiviral.2016.01.012 -
Viruses Jun 2018Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal...
Influenza A virus (IAV) causes seasonal epidemics and occasional but devastating pandemics, which are major public health concerns. Because the effectiveness of seasonal vaccines is highly variable and the currently available drugs are limited in their efficacy because of the emergence of drug resistance, there is an urgent need to develop novel antivirals. In this study, we characterized a recombinant IAV-carrying luciferase (Gluc) gene and determined its potential as a tool for evaluating therapeutics. We demonstrated that this recombinant IAV is replication-competent in tissue culture and pathogenic in mice, although it is slightly attenuated compared to the parental virus. Luciferase expression correlated well with virus propagation both in vitro and in vivo, providing a simple measure for viral replication in tissue culture and in mouse lungs. To demonstrate the utility of this virus, ribavirin and oseltamivir phosphate were used to treat the IAV-infected cells and mice, and we observed the dose-dependent inhibition of viral replication by a luciferase assay. Moreover, the decreased luciferase expression in the infected lungs could predict the protective efficacy of antiviral interventions as early as day 2 post virus challenge. In summary, this study provides a new and quantitative approach to evaluate antivirals against IAV.
Topics: Animals; Antiviral Agents; Dogs; Drug Evaluation, Preclinical; Genes, Reporter; HEK293 Cells; Humans; Influenza A virus; Luciferases; Lung; Madin Darby Canine Kidney Cells; Mice; Orthomyxoviridae Infections; Staining and Labeling; Treatment Outcome
PubMed: 29899269
DOI: 10.3390/v10060325 -
Minerva Medica Jul 2023
PubMed: 37486204
DOI: 10.23736/S0026-4806.23.08816-X -
Scientific Reports Mar 2019The pandemic 2009 influenza A H1N1 virus is associated with significant mortality. Targeting S1PR1, which is known to modulate the immune response, provides protection...
The pandemic 2009 influenza A H1N1 virus is associated with significant mortality. Targeting S1PR1, which is known to modulate the immune response, provides protection against pathogenic influenza virus. The functional role and molecular mechanism of S1PR1 were analysed by generating inducible endothelial cell-specific S1PR1 knockout mice and assessing the therapeutic efficacy of the selective S1PR1 agonist CYM5442 against acute lung injury (ALI) induced by the 2009 influenza A H1N1 virus. Immune-mediated pulmonary injury is aggravated by the absence of endothelial S1PR1 and alleviated by treatment with CYM-5442, suggesting a protective function of S1PR1 signaling during H1N1 infection. S1PR1 signaling does not affect viral clearance in mice infected with influenza. Mechanistically, the MAPK and NF-kB signaling pathways are involved in the ALI mediated by S1PR1 in infected mice. Combined administration of the S1PR1 agonist CYM-5442 and the antiviral drug oseltamivir provides maximum protection from ALI. Our current study provides insight into the molecular mechanism of S1PR1 mediating the ALI induced by H1N1 infection and indicates that the combination of S1PR1 agonist with antiviral drug could potentially be used as a therapeutic remedy for future H1N1 virus pandemics.
Topics: Administration, Intranasal; Animals; Antiviral Agents; Blotting, Western; Female; Fluorescent Antibody Technique; Indans; Influenza A Virus, H1N1 Subtype; Lung; Male; Mice; Mice, Knockout; Orthomyxoviridae Infections; Oseltamivir; Oxadiazoles; Real-Time Polymerase Chain Reaction; Sphingosine-1-Phosphate Receptors
PubMed: 30918324
DOI: 10.1038/s41598-019-41760-7 -
Drug Design, Development and Therapy 2015Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of...
Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma.
Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%-25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%-50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31(+) endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer.
Topics: Absorbable Implants; Angiogenesis Inhibitors; Animals; Antigens, CD; Cadherins; Carcinoma; Cell Line, Tumor; Chemistry, Pharmaceutical; Drug Carriers; Drug Implants; Interleukin Receptor Common gamma Subunit; Liver Neoplasms; Lung Neoplasms; Mice, Inbred NOD; Mice, Knockout; Neovascularization, Pathologic; Oseltamivir; Pancreatic Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Polyethylene Glycols; Solubility; Time Factors; Xenograft Model Antitumor Assays
PubMed: 26309402
DOI: 10.2147/DDDT.S90170 -
Journal of Virology Dec 2018Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations...
Screening of chemical libraries with 2,000 synthetic compounds identified salinomycin as a hit against influenza A and B viruses, with 50% effective concentrations ranging from 0.4 to 4.3 μM in cells. This compound is a carboxylic polyether ionophore that exchanges monovalent ions for protons across lipid bilayer membranes. Monitoring the time course of viral infection showed that salinomycin blocked nuclear migration of viral nuclear protein (NP), the most abundant component of the viral ribonucleoprotein (vRNP) complex. It caused cytoplasmic accumulation of NP, particularly within perinuclear endosomes, during virus entry. This was primarily associated with failure to acidify the endosomal-lysosomal compartments. Similar to the case with amantadine (AMT), proton channel activity of viral matrix protein 2 (M2) was blocked by salinomycin. Using purified retroviral Gag-based virus-like particles (VLPs) with M2, it was proved that salinomycin directly affects the kinetics of a proton influx into the particles but in a manner different from that of AMT. Notably, oral administration of salinomycin together with the neuraminidase inhibitor oseltamivir phosphate (OSV-P) led to enhanced antiviral effect over that with either compound used alone in influenza A virus-infected mouse models. These results provide a new paradigm for developing antivirals and their combination therapy that control both host and viral factors. Influenza virus is a main cause of viral respiratory infection in humans as well as animals, occasionally with high mortality. Circulation of influenza viruses resistant to the matrix protein 2 (M2) inhibitor, amantadine, is highly prevalent. Moreover, the frequency of detection of viruses resistant to the neuraminidase inhibitors, including oseltamivir phosphate (OSV-P) or zanamivir, is also increasing. These issues highlight the need for discovery of new antiviral agents with different mechanisms. Salinomycin as the monovalent cation-proton antiporter exhibited consistent inhibitory effects against influenza A and B viruses. It plays multifunctional roles by blocking endosomal acidification and by inactivating the proton transport function of M2, the key steps for influenza virus uncoating. Notably, salinomycin resulted in marked therapeutic effects in influenza virus-infected mice when combined with OSV-P, suggesting that its chemical derivatives could be developed as an adjuvant antiviral therapy to treat influenza infections resistant or less sensitive to existing drugs.
Topics: Administration, Oral; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Endosomes; Gene Expression Regulation, Neoplastic; Influenza A virus; Mice; Nucleocapsid Proteins; Orthomyxoviridae Infections; Oseltamivir; Protein Transport; Pyrans; RNA-Binding Proteins; Viral Core Proteins; Viral Matrix Proteins; Virus Internalization
PubMed: 30282713
DOI: 10.1128/JVI.01441-18 -
Evidence-based Complementary and... 2015Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used...
The inhibitory effect of kakkonto, Japanese traditional (kampo) medicine, on brain penetration of oseltamivir carboxylate in mice with reduced blood-brain barrier function.
Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression.
PubMed: 25788966
DOI: 10.1155/2015/917670 -
Cells Mar 2024Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by...
Functional Selectivity of Cannabinoid Type 1 G Protein-Coupled Receptor Agonists in Transactivating Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition Metastatic Phenotype.
Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by cannabinoids, particularly in cancer and cancer metastasis. GPCRs can have more than one active state, a phenomenon called either 'biased agonism', 'functional selectivity', or 'ligand-directed signaling'. However, there are increasing arrays of cannabinoid allosteric ligands with different degrees of modulation, called 'biased modulation', that can vary dramatically in a probe- and pathway-specific manner, not from simple differences in orthosteric ligand efficacy or stimulus-response coupling. Here, emerging evidence proposes the involvement of CB1 GPCRs in a novel biased GPCR signaling paradigm involving the crosstalk between neuraminidase-1 (Neu-1) and matrix metalloproteinase-9 (MMP-9) in the activation of glycosylated receptors through the modification of the receptor glycosylation state. The study findings highlighted the role of CB1 agonists AM-404, Aravnil, and Olvanil in significantly inducing Neu-1 sialidase activity in a dose-dependent fashion in RAW-Blue, PANC-1, and SW-620 cells. This approach was further substantiated by findings that the neuromedin B receptor inhibitor, BIM-23127, MMP-9 inhibitor, MMP9i, and Neu-1 inhibitor, oseltamivir phosphate, could specifically block CB1 agonist-induced Neu-1 sialidase activity. Additionally, we found that CB1 receptors exist in a multimeric receptor complex with Neu-1 in naïve, unstimulated RAW-Blue, PANC-1, and SW-620 cells. This complex implies a molecular link that regulates the interaction and signaling mechanism among these molecules present on the cell surface. Moreover, the study results demonstrate that CB1 agonists induce NFκB-dependent secretory alkaline phosphatase (SEAP) activity in influencing the expression of epithelial-mesenchymal markers, E-cadherin, and vimentin in SW-620 cells, albeit the impact on E-cadherin expression is less pronounced compared to vimentin. In essence, this innovative research begins to elucidate an entirely new molecular mechanism involving a GPCR signaling paradigm in which cannabinoids, as epigenetic stimuli, may traverse to influence gene expression and contribute to cancer and cancer metastasis.
Topics: Cannabinoid Receptor Agonists; Matrix Metalloproteinase 9; Vimentin; Ligands; Glycosylation; Neuraminidase; Receptors, G-Protein-Coupled; Cannabinoids; Epithelial-Mesenchymal Transition; Cadherins; Neoplasms
PubMed: 38534324
DOI: 10.3390/cells13060480 -
International Medical Case Reports... 2017A few reports have described ocular complications of influenza A infection, such as impaired ocular movement, parasympathetic ocular nerve, keratitis, macular lesion,...
BACKGROUND
A few reports have described ocular complications of influenza A infection, such as impaired ocular movement, parasympathetic ocular nerve, keratitis, macular lesion, and frosted branch angiitis. We encountered a rare case of acute anterior uveitis and optic neuritis associated with influenza A infection.
CASE PRESENTATION
A 70-year-old man presented with symptoms of upper respiratory tract infection. A rapid diagnostic test showed a positive result for influenza A. At the same time, he developed ocular symptoms including blurred vision with optic disk edema and hemorrhage in the left eye, and bilateral red eyes. Multiplex polymerase chain reaction performed on aqueous humor sample detected no viral infection. Visual field testing with a Goldmann perimeter showed central and paracentral scotomas in the left eye. In addition to antiviral agent (oseltamivir phosphate 75 mg), the patient was prescribed topical prednisolone acetate ophthalmic suspension eye drops every 5 hours and high-dose intravenous methylprednisolone 1,000 mg daily for 3 days. Two months later, his best-corrected visual acuity improved to 20/50 with regression of visual field defects in his left eye.
CONCLUSION
We report a case of bilateral acute anterior uveitis and unilateral optic neuritis concomitant with influenza A infection. Topical and systemic corticosteroids were effective to resolve acute anterior uveitis and neuritis. Analysis of aqueous humor sample suggested that acute anterior uveitis and optic neuritis in this case were not caused by influenza A virus infection per se but by autoimmune mechanism.
PubMed: 28115874
DOI: 10.2147/IMCRJ.S113217