SARS-CoV-2 vs. SARS-CoV-1 management: antibiotics and inflammasome modulators potential.

The coronavirus SARS-CoV-2 at the origin of COVID-19 shares more than 70% genetic similarity with SARS-CoV-1 that was at the origin of 2003 SARS. Infection-associated symptoms are very similar between SARS and COVID-19 diseases and are the same as community-acquired pneumonia symptoms. Antibiotics were empirically given to SARS patients in the early stages of the pathology whereas a different strategy has been decided in the management of COVID-19 pandemic with a worldwide shutdown. The cytokine storm, both identified in SARS and COVID-19 severe cases, is generated through inflammasome activation, which opens therapeutic perspectives to counteract the pathogenic inflammation. As corticoids have numerous side effects that limit their use, focusing on anti-inflammasome agents could represent a safer alternative for patients with severe COVID-19.

A marine-sourced fucoidan solution inhibits Toll-like-receptor-3-induced cytokine release by human bronchial epithelial cells.

Fucoidans are sulfated polysaccharides from brown algae, known to have immunomodulatory activity. Their effects on the response of airway epithelial cells to Toll-like receptor 3 (TLR3) stimulation have not been characterized. Our objective was to evaluate the effects of a marine-sourced fucoidan solution (MFS) on the TLR3-induced expression and/or production of cytokines and prostaglandin by human primary bronchial epithelial cells as a model of the airway epithelium. The cells were incubated with MFS in the presence or absence of Poly(I:C) (a TLR3 agonist that mimics viral RNA). Cytokine expression and production were assessed using RT-qPCR and ELISA. The expression of cyclooxygenase-2 and the production of prostaglandin E2 were also measured. Relative to control, exposure to MFS was associated with lower Poly(I:C)-induced mRNA expression of various cytokines and chemokines, and lower COX-2 production. The MFS inhibited the production of some cytokines (IL-1α, IL-1ß, TNFα, and IL-6), chemokines (CCL5, CCL22, CXCL1, CXCL5 and CXCL8) and prostaglandin E2 but did not alter the production of IL-12/25, CCL2 and CCL20. At clinically relevant concentrations, the MFS inhibited the TLR3-mediated production of inflammatory mediators by human primary bronchial epithelial cells - suggesting that locally applied MFS might help to reduce airway inflammation in viral infections.

[Wiedemann-Beckwith syndrome: a new approach for reduction glossoplasty using Ultracision(®)]. / Syndrome de Wiedemann-Beckwith - glossectomie de réduction par Ultracision(®) : une approche novatrice.

INTRODUCTION: A reduction glossectomy may be complicated by tongue and mouth floor edema and extend the recovery time for a normal tongue function. We performed reduction glossectomy using Ultracision(®), an ultrasonic vibrating device, so as to limit these complications. TECHNICAL NOTE: We performed a keyhole glossoplasty under general anesthesia. The initial tongue incision was performed with a cold scalpel, then the glossectomy was continued with Ultracision(®) only. We also used CURVED SHEARS(®). We evaluated our preliminary results with 3 patients presenting with Wiedemann-Beckwith syndrome. CONCLUSION: Ultracision(®) is a useful tool for intra-oral surgery, and should soon be more frequently used. It is an alternative to electrocautery for this type of surgery.

Severe ocular infections with contact lens: role of multipurpose solutions.

PURPOSE: To determine whether multipurpose solutions, widely used for contact lens disinfections, could be at the origin of ocular pathologies (contact lens intolerance and ocular infections). METHODS: An observational cohort study (questionnaire analysis) was carried out to estimate the number of contact lens wearers, type of infection, and type of lens care regimen used by patients. Besides, multipurpose solutions cytotoxicity (necrosis and apoptosis) was evaluated on a conjunctival cell line using cytofluorometry. RESULTS: In the general population, 59% of contact lens wearers use multipurpose solutions whereas 35% use oxidative products. Of the questioned contact lens wearers with ocular infections, 80% used multipurpose solutions. Multipurpose solutions are therefore not efficient enough against microorganisms, and cannot be considered as disinfectant solutions but only as preservatives. However, preservatives are known to be toxic to ocular surface, so apoptosis induced by multipurpose solutions could lead to ocular surface diseases. Our cytofluorometry study allowed us to demonstrate that contact lens multipurpose solutions containing preservatives are cytotoxic through caspase 3 induction, chromatin condensation and P2X7 cell-death receptor activation, in contrast with unpreserved sterile saline solutions that were found inert. CONCLUSIONS: Multipurpose solutions seem to be preservative but not disinfecting solutions. They are not adapted to the final rinse of contact lenses because of apoptosis induction. It could explain part of lens intolerance.

[Oxidative stress modulation using polyphenol-rich blueberries: application on a human retinal cell model]. / Modulation du stress oxydant par la myrtille riche en polyphénols sur un modèle de cellules humaines de rétine.

INTRODUCTION: The retina is located in a highly oxygenated environment and is therefore particularly susceptible to oxidative damage. Blueberries have a high antioxidant potential since they are rich in anthocyans. The aim of this study was to investigate the cytoprotective role of blueberries on human retinal cells. MATERIALS AND METHODS: Blueberry extract was incubated at 0.05% and 0.1% for 15 minutes or 24 hours on a human retinal cell line. Then oxidative stress was induced by 150 microM tert-butylhydroperoxide (tBHP) for 1 hour. Intracellular metabolism, reactive oxygen species, superoxide anion, and mitochondrial apoptosis were evaluated using Alamar blue, DCFDA, dihydroethidium, and nonylacridine orange dyes, respectively. Tests were performed using cytofluorometry adapted to microplates. RESULTS: Blueberry protected cells against tBHP-induced cytotoxicity. It increased cell viability, decreased oxidative stress and mitochondrial apoptosis. After a 24-hour preincubation time, blueberry totally inhibited tBHP-induced cytotoxicity. CONCLUSION: Blueberry seems to be a potent antioxidant and could be easily added to food complements to prevent or limit ocular pathologies induced by oxidative stress.

Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

[Role of conditioning medium cytotoxicity. An example with an intraocular lens preloaded in injector]. / Rôle de la cytotoxicité du milieu de transport d'implants: cas de lentilles intraoculaires conditionnées en injecteur.

INTRODUCTION: Following material vigilance cases encountered with the hydrophilic acrylic intraocular lens, ACR6D SE preloaded in the Premier shooter, we studied the cytotoxicity of the intraocular lens and its conditioning to identify the cytotoxic element. We proposed medical device modification to improve its biocompatibility. MATERIALS AND METHODS: Biocompatibility-cytotoxicity assays were carried out according to ISO 10993-5 recommendations. Tests were performed on the SRA 01/04 human lens epithelial cell line. Neutral red, Hoechst 33342, and YO-PRO-1 fluorescent probes were used to assess membrane integrity, total DNA, and membrane fluidity, respectively. Materials samples were prepared in culture medium according to the ISO 10993-5 elution procedure. Pure saline solutions and conditioning liquids were tested directly on cells. RESULTS: The intraocular lens and injector were not cytotoxic. Conditioning liquids induced membrane fluidity perturbation characteristic of apoptosis. Tests performed on new versions of the medical device identified a better adapted conditioning liquid. CONCLUSION: The results suggest that the cytotoxicity of the conditioning liquid could explain the postoperative complication rate. When we changed the conditioning liquid with sterile irrigating solution (i.e., rich divalent cation marine solution), we eliminated cellular stress. Fluorescent probes are well adapted to assess medical device biocompatibility-cytotoxicity.

Age-dependent effects on redox status, oxidative stress, mitochondrial activity and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon cells.

The age-related difference in fluoroquinolone-induced tendon toxicity was investigated. In vitro tendon cells from juvenile and young adult rabbits, respectively, were incubated with quinolone (nalidixic acid, NA) or fluoroquinolone (ofloxacin, OFX or pefloxacin, PEF) at 0.01 microM to 1 mM for 72 h. Redox status, glutathione (GSH), reactive oxygen species (ROS), and mitochondrial activity were assessed using intracellular fluorescent probes. Fluorescence signal was detected on living adherent tenocytes in microplates using cold-light cytofluorometry. Tendon toxicity differed significantly between the two cell groups and the difference was greatest with highest dose (1 mM). For 72 h, significant (p < 0.001) differences between immature and young adult primary tenocytes were observed for redox status decrease, GSH decrease, and ROS production increase. Mitochondrial activity remained unaltered in immature tenocytes. We confirm two groups of intrinsic tendon toxicity (OFX/NA vs. PEF) associated to oxidative stress (GSH decrease). Our in vitro experimental model confirms the clinical observations of age dependent tenotoxicity. First group (NA, OFX) showed greater intrinsic tenotoxicity for young adult than immature tenocytes, second group (PEF) was highly toxic for immature and young adult cells. The three quinolones do not altered mitochondrial activity in immature tenocytes whereas alteration was observed in young adult tenocytes.