scholarly journals Protective Effects of Astodrimer Sodium 1% Nasal Spray Formulation against SARS-CoV-2 Nasal Challenge in K18-hACE2 Mice

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1656
Author(s):  
Jeremy R. A. Paull ◽  
Carolyn A. Luscombe ◽  
Alex Castellarnau ◽  
Graham P. Heery ◽  
Michael D. Bobardt ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Nasal Spray ◽  
Viral Genome ◽  
Infectious Virus ◽  
Virus Transmission ◽  
Protective Effects ◽  
Viral Shedding ◽  
Nasal Secretions ◽  
Spray Formulation ◽  
The Brain

Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1β, TNFα and TGFβ and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19.

scholarly journals Total viral genome copies and virus–Ig complexes after infection with influenza virus in the nasal secretions of immunized mice

2004 ◽  
Vol 85 (8) ◽  
pp. 2339-2346 ◽  
Author(s):  
Tomoki Yoshikawa ◽  
Keiko Matsuo ◽  
Kazutoshi Matsuo ◽  
Yujiro Suzuki ◽  
Akio Nomoto ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Viral Genome ◽  
Infectious Virus ◽  
Influenza Viruses ◽  
Dependent Manner ◽  
Virus Elimination ◽  
Virus Particles ◽  
Wide Range ◽  
Nasal Secretions ◽  
Kinetics Of

The kinetics of infectious virus (p.f.u.), total virus and virus–Ig complex formation following influenza A/PR8 (H1N1) viral infection was examined in the nasal secretions of naive mice and mice immunized with A/PR8, A/Yamagata (H1N1), A/Guizhou (H3N2) and B/Ibaraki influenza viruses. The total number of virus particles and the number within virus–Ig complexes, captured in advance using an anti-mouse Ig-coated plate, were determined on the basis of viral genome copy number using quantitative RT-PCR. The kinetics of infectious and total virus particle formation, the latter of which increased by 103–104-fold above infectious virus numbers, showed that virus elimination from the nasal area was earlier in A/PR8, A/Yamagata and A/Guizhou-X virus-immunized mice, in decreasing order, compared with naive mice. Early virus elimination correlated with the level of A/PR8 virus-reactive antibodies in immunized mice. Virus elimination coincided with the appearance of virus–Ig complexes shortly after infection. This result suggested that antibodies led to the formation of immune complexes in a dose-dependent manner together with a reduction in number of infectious virus particles. The fact that a large number of virus particles was observed in immune complexes for a wide range antibody levels made it difficult to detect slight differences in virus number within the immune complexes, depending on antibody level. These results suggested that the formation of virus–Ig complexes in virus-immunized mice shortly after infection is involved in early virus elimination, which is determined by the strength of protective immunity against challenge viruses.

scholarly journals Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model

2021 ◽  
Author(s):  
Jorge Errecalde ◽  
Adrian Lifschitz ◽  
Graciela Vecchioli ◽  
Laura Ceballos ◽  
Francisco Errecalde ◽  
...  
Keyword(s):  
Nasal Spray ◽  
Pig Model ◽  
Spray Formulation

Rescue of functional replication origins from embedded configurations in a plasmid carrying the adenovirus genome

1984 ◽  
Vol 4 (2) ◽  
pp. 302-309
Author(s):  
D Hanahan ◽  
Y Gluzman
Keyword(s):  
Viral Genome ◽  
Infectious Virus ◽  
Adenovirus Type ◽  
Small Fragment ◽  
Origin Of Replication ◽  
Wild Type ◽  
Base Pairs ◽  
Bacterial Plasmid ◽  
Dna Fragment ◽  
Adenovirus Type 5

A variant of the adenovirus type 5 genome which lacks EcoRI sites has been cloned in a bacterial plasmid after the addition of EcoRI oligonucleotide linkers to its ends. Closed circular forms of the recombinant viral genome were not infectious upon their introduction into permissive eucaryotic cells. The linear genome released by digestion of the 39-kilobase recombinant plasmid (pXAd) with EcoRI produced infectious virus at about 5% of the level of wild-type controls. The viruses which arose were indistinguishable from the parental strain, and the normal termini of the viral genome had been restored. Marker rescue experiments demonstrate that provision of a DNA fragment with a normal viral end improves infectivity. When a small fragment carrying a wild-type left end (the 0 to 2.6% ClaI-B fragment) was ligated to ClaI-linearized pXAd, virus was produced with efficiencies comparable to a similar reconstitution of the two ClaI fragments of the wild-type genome. These viruses stably carry the left-end fragment at both ends, leaving the normal right end embedded in 950 base pairs of DNA. The embedded right origin is inactive. The consensus of the analyses reported here is that a free end is a necessary configuration for the sequences which make up the adenovirus origin of replication.

scholarly journals EFFICACY AND SAFETY OF NASAL SPRAY PREVALIN IN THE TREATMENT OF ALLERGIC RHINITIS PATIENTS

2012 ◽  
Vol 9 (5) ◽  
pp. 55-59
Author(s):  
A A Tsyvkina ◽  
L V Luss ◽  
S V Tsarev ◽  
N V Shartanova
Keyword(s):  
Allergic Rhinitis ◽  
Nasal Cavity ◽  
Nasal Spray ◽  
Clinical Effect ◽  
Clinical Symptoms ◽  
Efficacy And Safety ◽  
Nasal Breathing ◽  
Results Of Treatment ◽  
Functional Methods ◽  
Positive Clinical Effect

Background. To study of efficacy, tolerability and safety of nasal spray Prevalin in the treatment of allergic rhinitis patients. Methods. 30 patients with allergic rhinitis in the age of18 till 45 years were observed. Prevalin was given as one insufflation into each nasal cavity 3 times a day for 21 days. Results of treatment were assessed by the dynamics of clinical symptoms and the results of functional methods . Results. The positive clinical effect was observed in 22 patients (73,3%), using Prevalin. Clinical effect was characterized by the restoration of nasal breathing, reduce swelling of the nasal mucosa. We did not establish a good result of treatment in 8 patients. Conclusion. The study demonstrated clinical efficacy and safety of spray Prevalin.

scholarly journals Baicalein, Baicalin, and Wogonin: Protective Effects against Ischemia-Induced Neurodegeneration in the Brain and Retina

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Li Pan ◽  
Kin-Sang Cho ◽  
Irvin Yi ◽  
Chi-Ho To ◽  
Dong Feng Chen ◽  
...  
Keyword(s):  
Time Window ◽  
Therapeutic Potential ◽  
Vascular Dysfunction ◽  
Pathological Condition ◽  
Vascular Occlusion ◽  
Protective Effects ◽  
Scutellaria Baicalensis Georgi ◽  
Retinal Vascular Occlusion ◽  
Low Cytotoxicity ◽  
The Brain

Ischemia is a common pathological condition present in many neurodegenerative diseases, including ischemic stroke, retinal vascular occlusion, diabetic retinopathy, and glaucoma, threatening the sight and lives of millions of people globally. Ischemia can trigger excessive oxidative stress, inflammation, and vascular dysfunction, leading to the disruption of tissue homeostasis and, ultimately, cell death. Current therapies are very limited and have a narrow time window for effective treatment. Thus, there is an urgent need to develop more effective therapeutic options for ischemia-induced neural injuries. With emerging reports on the pharmacological properties of natural flavonoids, these compounds present potent antioxidative, anti-inflammatory, and antiapoptotic agents for the treatment of ischemic insults. Three major active flavonoids, baicalein, baicalin, and wogonin, have been extracted from Scutellaria baicalensis Georgi (S. baicalensis); all of which are reported to have low cytotoxicity. They have been demonstrated to exert promising pharmacological capabilities in preventing cell and tissue damage. This review focuses on the therapeutic potentials of these flavonoids against ischemia-induced neurotoxicity and damage in the brain and retina. The bioactivity and bioavailability of baicalein, baicalin, and wogonin are also discussed. It is with hope that the therapeutic potential of these flavonoids can be utilized and developed as natural treatments for ischemia-induced injuries of the central nervous system (CNS).

scholarly journals Infectious SARS-CoV-2 is emitted in aerosols

2021 ◽  
Author(s):  
Seth A. Hawks ◽  
Aaron J. Prussin ◽  
Sarah C. Kuchinsky ◽  
Jin Pan ◽  
Linsey C. Marr ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Infectious Virus ◽  
Emission Rate ◽  
Clinical Signs ◽  
Respiratory Viruses ◽  
Post Inoculation ◽  
Viral Shedding ◽  
Contact Transmission ◽  
Respiratory Droplets ◽  
Kinetics Of

Respiratory viruses such as SARS-CoV-2 are transmitted in respiratory droplets and aerosols, which are released during talking, breathing, coughing, and sneezing. Non-contact transmission of SARS-CoV-2 has been demonstrated, suggesting transmission in aerosols. Here we demonstrate that golden Syrian hamsters emit infectious SARS-CoV-2 in aerosols, prior to and concurrent with the onset of mild clinical signs of disease. The emission rate is 25 infectious virions/hour on days 1 and 2 post-inoculation, with viral RNA levels 200-fold higher than infectious virus in aerosols. Female hamsters have delayed kinetics of viral shedding in aerosols compared to male hamsters. The majority of virus is contained within aerosols <8 microns in size. Thus, we provide direct evidence that, in hamsters, SARS-CoV-2 is an airborne virus.

Vilazodone Hydrochloride Multi-Dose Nasal Spray Solution for the Treatment of Depression: Design, Optimization, and Evaluation

2021 ◽  
Vol 16 ◽  
Author(s):  
Praful Giradkar ◽  
Deepa H. Patel
Keyword(s):  
Nasal Spray ◽  
Benzalkonium Chloride ◽  
Research Work ◽  
Tween 80 ◽  
Oral Route ◽  
Sodium Carboxymethylcellulose ◽  
Intranasal Route ◽  
Spray Solution ◽  
Treatment Of Depression ◽  
The Brain

Introduction: The aim of present research work was to prepare, optimized, and evaluate the multi-dose nasal spray solution for delivery of vilazodone hydrochloride to the brain by the intranasal route in order to overcome the drawback associated with the oral route for the treatment of depression. Background: Depression is a mental disorder associated with abnormalities in neuronal transport in the brain primarily serotonin, norepinephrine, and dopamine that adversely affects a person's lifestyle, sleep pattern, work, eating habits, and general health. Vilazodone hydrochloride acts by enhancing the serotonergic activity in the brain by inhibiting serotonin (5-HT) reuptake. Materials/ Methods: The excipients used to formulate vilazodone hydrochloride multi-dose nasal spray solution were sulphobutylether-β-cyclodextrin sodium (solubilizer), sodium carboxymethylcellulose (viscosity builder), tween 80 (surface tension modifier), glycerol (humectant), benzalkonium chloride (preservative), and purified water (vehicle). The simple conventional mixing technique was used for the preparation of the multi-dose nasal spray solution. The solution was prepared in two parts, in the first part sulphobutylether-β-cyclodextrin sodium and drug substance dissolved in purified water under stirring followed by the addition of glycerol and benzalkonium chloride solution. In the second part, tween 80 dissolved in warm water followed by the addition of sodium carboxymethylcellulose under stirring, finally both parts mixed and the required volume was adjusted with purified water. The central composite design was used for the optimization of the formulation. The solution was evaluated for physicochemical properties, selective toxicity, and experimental kinetics. Results: The prepared vilazodone hydrochloride multi-dose nasal spray solution was shown viscosity (40.5 ± 1.65 mPa.s), droplet size distribution (span) (1.88 ± 0.55 µm), spray area (288 ± 1.25 mm2), ovality (1.10 ± 1.35), dripping speed (0.25 cm /30 sec), visual appearance (clear free from particulate matter), pH (6.35 ± 0.10), shot weight (100.6 ± 0.32 mg), density (1.03 ± 0.20 g/ml), % drug content (101.8 ± 0.15 %), displacement value for in-vitro mucoadhesion (3.47 ± 0.25 cm), average flux (Jss) for permeability (241.06 ± 1.45 μg/cm2/hrs), permeability coefficient (48.21 ±1.46 cm/hrs), enhancement ratio (1.73), local toxicity study shows no epithelium cell damage, isotonicity (386.58 mOsmol / kg). Plasma Cmax (24.56 ±3.98 ng/ml), Tmax (1.0 hrs), and AUC 0-12 (82.68 ±10.22 ng.h/ml). Brian tissue Cmax (22.95 ±4.22), Tmax (1.0 hrs) and AUC 0-12 (77.82 ±6.25 ng.h/ml). Nasal bioavailability (251.74 ±45.12% ) and, drug targeting index 1.54 Conclusion: The present research work results showed that the prepared multi-dose nasal spray solution of vilazodone hydrochloride was suitable for the delivery of the drug to the brain by the intranasal route and might be beneficial to overcome drawbacks associated with the oral route of administration for the treatment of depression.

scholarly journals A COVID-19 Hotspot Area: Activities and Epidemiological Findings

2020 ◽  
Vol 8 (11) ◽  
pp. 1711 ◽  
Author(s):  
Francesca Cito ◽  
Laura Amato ◽  
Alessandra Di Giuseppe ◽  
Maria Luisa Danzetta ◽  
Simona Iannetti ◽  
...  
Keyword(s):  
Muscle Pain ◽  
Virus Transmission ◽  
P Value ◽  
Epidemiological Investigation ◽  
Blood Samples ◽  
Viral Shedding ◽  
Abruzzo Region ◽  
The Difference ◽  
The Village ◽  
Emergency Measures

By late March 2020, Villa Caldari, a small village of the municipality of Ortona (Abruzzo region), was registering an incidence rate of COVID-19 cases ten times greater than the overall municipality and was declared a hotspot area. Twenty-two days later, epidemiological investigation and sampling were performed, to evaluate SARS-CoV-2 circulation and the presence of SARS-CoV-2 antibodies. Overall, 681 nasopharyngeal swabs and 667 blood samples were collected. Only one resident of the village resulted in being positive for RNA viral shedding, while 73 were positive for SARS-CoV-2 antibodies. The overall seroprevalence was 10.9%. The difference between the seroprevalence of infection in asymptomatic and symptomatic individuals was significant (χ2 = 14.50 p-value = 0.0001). Amongst the residents positive for antibodies, fatigue and/or muscle pain, fever and anosmia were the most experienced symptoms, whose most frequent onset was observed during the first two weeks of March. Familial and habit-related clusters were highlighted. Nevertheless, the investigations showed a low SARS-CoV-2 circulation in the village at the time of the sampling, demonstrating virus transmission could be limited when strict emergency measures are followed. Given the favorable results, the emergency measures were then lifted.

scholarly journals Reversal of age-associated oxidative stress in mice by PFT, a novel kefir product

2020 ◽  
Vol 34 ◽  
pp. 205873842095014
Author(s):  
Mamdooh Ghoneum ◽  
Shaymaa Abdulmalek ◽  
Deyu Pan
Keyword(s):  
Oxidative Stress ◽  
Low Density Lipoprotein ◽  
Redox Homeostasis ◽  
Density Lipoprotein ◽  
Antioxidant Enzyme Activities ◽  
Protective Effects ◽  
Oxidative Stress Biomarkers ◽  
Age Related ◽  
Total Antioxidant ◽  
The Brain

Introduction: Oxidative stress is a key contributor to aging and age-related diseases. In the present study, we examine the protective effects of PFT, a novel kefir product, against age-associated oxidative stress using aged (10-month-old) mice. Methods: Mice were treated with PFT orally at a daily dose of 2 mg/kg body weight over 6 weeks, and antioxidant status, protein oxidation, and lipid peroxidation were studied in the brain, liver, and blood. Results: PFT supplementation significantly reduced the oxidative stress biomarkers malondialdehyde (MDA) and nitric oxide; reversed the reductions in glutathione (GSH) levels, total antioxidant capacity (TAC), and anti-hydroxyl radical (AHR) content; enhanced the antioxidant enzyme activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD); inhibited the liver enzyme levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT); significantly reduced triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels; and significantly elevated high density lipoprotein (HDL) levels. Interestingly, PFT supplementation reversed the oxidative changes associated with aging, thus bringing levels to within the limits of the young control mice in the brain, liver, and blood. We also note that PFT affects the redox homeostasis of young mice and that it is corrected post-treatment with PFT. Conclusion: Our findings show the effectiveness of dietary PFT supplementation in modulating age-associated oxidative stress in mice and motivate further studies of PFT’s effects in reducing age-associated disorders where free radicals and oxidative stress are the major cause.

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