scholarly journals In-vitro virucidal activity of hypothiocyanite and hypothiocyanite/lactoferrin mix against SARS-CoV-2

2020 ◽  
Author(s):  
Luca Cegolon ◽  
Mattia Mirandola ◽  
Claudio Salaris ◽  
Maria Vittoria Salvati ◽  
Cristiano Salata ◽  
...  
Keyword(s):  
Upper Airway ◽  
In Vitro Study ◽  
Alveolar Type ◽  
Virucidal Activity ◽  
Human Immune System ◽  
Pharmacological Interventions ◽  
Protection Measures ◽  
Viral Spread

ABSTRACTSARS-CoV-2 replicates efficiently in the upper airway during prodromal stage with resulting viral shedding into the environment from patients with active disease as well as from asymptomatic individuals. So far, virus spread has been exclusively contained by non-pharmacological interventions (social distancing, face masks, hand washing and several measures limiting business activities or movement of individuals)1,2. There is a need to find pharmacological interventions to mitigate the viral spread, supporting yet limiting the existing health protection measures while an effective and safe vaccine will hopefully become available. Hypothiocyanite and lactoferrin as part of the innate human immune system were shown to have a large spectrum of cidal activity against bacteria, fungi and viruses2,3. To test their virucidal activity against SARS-CoV-2 we conducted an in-vitro study. Here we show a dose-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by the presence of lactoferrin. The two substances are devoid of any cytotoxicity and may be administered combined by aerosol to exploit their antiviral activity at the port of entry (mouth, nasal cavity, conjunctiva) or exit (mouth, through emission of respiratory droplets) of SARS-CoV-2 in the human body. Furthermore, aerosol with hypothiocyanite and lactoferrin combined could also have a therapeutic effect in the lower respiratory tract, at the level of gas exchange units of the lung, preventing the devastating infection of alveolar type II cells where ACE2 is highly expressed. An in-vivo validation of in-vitro results is urgently required.

scholarly journals Hypothiocyanite and Hypothiocyanite/Lactoferrin Mixture Exhibit Virucidal Activity In Vitro against SARS-CoV-2

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 233
Author(s):  
Luca Cegolon ◽  
Mattia Mirandola ◽  
Claudio Salaris ◽  
Maria Vittoria Salvati ◽  
Giuseppe Mastrangelo ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Innate Immune ◽  
European Medicines Agency ◽  
Virucidal Activity ◽  
Pharmacological Interventions ◽  
Prodromal Stage ◽  
Upper Airways ◽  
Viral Shedding ◽  
Asymptomatic Individuals

SARS-CoV-2 replicates efficiently in the upper airways during the prodromal stage, resulting in environmental viral shedding from patients with active COVID-19 as well as from asymptomatic individuals. There is a need to find pharmacological interventions to mitigate the spread of COVID-19. Hypothiocyanite and lactoferrin are molecules of the innate immune system with a large spectrum cidal activity. The Food and Drug Administration and the European Medicines Agency designated the hypothiocyanite and lactoferrin combination as an orphan drug. We report an in vitro study showing that micromolar concentrations of hypothiocyanite exhibit dose- and time-dependent virucidal activity against SARS-CoV-2 and that the latter is slightly enhanced by the simultaneous presence of lactoferrin.

Effects of TSH and calcitriol on bone metabolism: in vivo and in vitro study

2014 ◽  
Author(s):  
Ivo Dumic-Cule ◽  
Dunja Rogic ◽  
Damir Jezek ◽  
Lovorka Grgurevic ◽  
Slobodan Vukicevic
Keyword(s):  
Bone Metabolism ◽  
In Vitro Study ◽  
Vitro Study

scholarly journals 64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elodie A. Pérès ◽  
Jérôme Toutain ◽  
Louis-Paul Paty ◽  
Didier Divoux ◽  
Méziane Ibazizène ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Vitro Study ◽  
Tumor Location ◽  
Preclinical Study ◽  
Significant Rise ◽  
Lower Oxygen ◽  
Cu Complexes ◽  
Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

scholarly journals 5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

2021 ◽  
Vol 22 (3) ◽  
pp. 1083
Author(s):  
Sukkum Ngullie Chang ◽  
Se Ho Kim ◽  
Debasish Kumar Dey ◽  
Seon Min Park ◽  
Omaima Nasif ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Elevated Serum ◽  
In Vitro Study ◽  
Biological Properties ◽  
Autophagic Flux ◽  
Serum Aminotransferase ◽  
Ccl4 Treatment

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

scholarly journals Effect of cannulation site on emboli travel during cardiac surgery

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Mira Puthettu ◽  
Stijn Vandenberghe ◽  
Stefanos Demertzis
Keyword(s):  
Cardiac Surgery ◽  
In Vitro Study ◽  
Blood Stream ◽  
Air Bubbles ◽  
Arterial Tree ◽  
Air Bubble ◽  
Cannulation Site ◽  
The Brain

Abstract Background During cardiac surgery, micro-air emboli regularly enter the blood stream and can cause cognitive impairment or stroke. It is not clearly understood whether the most threatening air emboli are generated by the heart-lung machine (HLM) or by the blood-air contact when opening the heart. We performed an in vitro study to assess, for the two sources, air emboli distribution in the arterial tree, especially in the brain region, during cardiac surgery with different cannulation sites. Methods A model of the arterial tree was 3D printed and included in a hydraulic circuit, divided such that flow going to the brain was separated from the rest of the circuit. Air micro-emboli were injected either in the HLM (“ECC Bubbles”) or in the mock left ventricle (“Heart Bubbles”) to simulate the two sources. Emboli distribution was measured with an ultrasonic bubble counter. Five repetitions were performed for each combination of injection site and cannulation site, where air bubble counts and volumes were recorded. Air bubbles were separated in three categories based on size. Results For both injection sites, it was possible to identify statistically significant differences between cannulation sites. For ECC Bubbles, axillary cannulation led to a higher amount of air bubbles in the brain with medium-sized bubbles. For Heart Bubbles, aortic cannulation showed a significantly bigger embolic load in the brain with large bubbles. Conclusions These preliminary in vitro findings showed that air embolic load in the brain may be dependent on the cannulation site, which deserves further in vivo exploration.

Inhibition of Cyclosporin A-Induced Gingival Overgrowth by Azithromycin Through Phagocytosis: An In Vivo and In Vitro Study

2004 ◽  
Vol 75 (3) ◽  
pp. 380-387 ◽  
Author(s):  
Jeong-Won Paik ◽  
Chang-Sung Kim ◽  
Kyoo-Sung Cho ◽  
Jung-Kiu Chai ◽  
Chong-Kwan Kim ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
In Vitro Study ◽  
Vitro Study ◽  
Gingival Overgrowth

Atelocollagen Sponge as a Stem Cell Implantation Scaffold for the Treatment of Scarred Vocal Folds

2010 ◽  
Vol 119 (11) ◽  
pp. 805-810 ◽  
Author(s):  
Satoshi Ohno ◽  
Shigeru Hirano ◽  
Ichiro Tateya ◽  
Shin-Ichi Kanemaru ◽  
Hiroo Umeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stromal Cells ◽  
Fluorescent Protein ◽  
In Vitro Study ◽  
Vocal Folds ◽  
Green Fluorescent ◽  
Cell Implantation

Objectives: Treatment of vocal fold scarring remains a therapeutic challenge. Our group previously reported the efficacy of treating injured vocal folds by implantation of bone marrow—derived stromal cells containing mesenchymal stem cells. Appropriate scaffolding is necessary for the stem cell implant to achieve optimal results. Terudermis is an atelocollagen sponge derived from calf dermis. It has large pores that permit cellular entry and is degraded in vivo. These characteristics suggest that this material may be a good candidate for use as scaffolding for implantation of cells. The present in vitro study investigated the feasibility of using Terudermis as such a scaffold. Methods: Bone marrow—derived stromal cells were obtained from GFP (green fluorescent protein) mouse femurs. The cells were seeded into Terudermis and incubated for 5 days. Their survival, proliferation, and expression of extracellular matrix were examined. Results: Bone marrow—derived stromal cells adhered to Terudermis and underwent significant proliferation. Immunohistochemical examination demonstrated that adherent cells were positive for expression of vimentin, desmin, fibronectin, and fsp1 and negative for beta III tubulin. These findings indicate that these cells were mesodermal cells and attached to the atelocollagen fibers biologically. Conclusions: The data suggest that Terudermis may have potential as stem cell implantation scaffolding for the treatment of scarred vocal folds.

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