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Antiviral and Anti-Inflammatory Activities of Fluoxetine in a SARS-CoV-2 Infection Mouse Model
- D. Péricat, S. A. Leon-Icaza, M. Sánchez-Rico, C. Mühle, I. Zoicas, F. Schumacher, R. Planès, R. Mazars, G. Gros, A. Carpinteiro, K. A. Becker, J. Izopet, N. Strub-Wourgaft, P. Sjö, O. Neyrolles, B. Kleuser, F. Limosin, E. Gulbins, J. Kornhuber, E. Meunier, N. Hoertel, C. Cougoule
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S119-S120
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Introduction
The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19.
ObjectivesThe aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.
MethodsWe evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5.
ResultsFluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects (Figure 3).
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ConclusionsOur findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.
Disclosure of InterestNone Declared
Effects of marine protected areas on recruitment processes with special reference to Mediterranean littoral ecosystems
- S. PLANES, R. GALZIN, A. GARCIA RUBIES, R. GOÑI, J.-G. HARMELIN, L. LE DIRÉACH, P. LENFANT, A. QUETGLAS
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- Journal:
- Environmental Conservation / Volume 27 / Issue 2 / June 2000
- Published online by Cambridge University Press:
- 10 May 2002, pp. 126-143
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Although site-attached fish can be expected to increase in abundance in marine protected areas (MPAs), there is little known about recruitment effects. The present work reviews concepts and field evidence for enhancement of recruitment of species in MPAs, focusing geographically on the Mediterranean littoral because of its long history of intensive fishery exploitation, but drawing on evidence from studies on recruitment processes in general on MPAs both in the Mediterranean and elsewhere. We considered recruitment as the process of a fish being added to the local population. The general questions of interest are whether the increase in biomass of species protected in MPAs has an effect on recruitment in the MPAs or in neighbouring areas, and, on competition and predation effects on new recruits. A flow diagram of the effects of MPA status on recruitment is developed and employed to identify the relevant processes. The diagram incorporates three levels of factors: (1) characteristics of MPAs (location, size, habitat type, oceanography and level of protection); (2) life stages of species protected in MPAs relevant to recruitment (eggs, larvae, settlers and juveniles); and (3) fundamental processes of dispersal/movement, predation and competition. From this conceptual diagram, the following main components of the recruitment process were identified and used to structure the review: (1) relationship between the ecology of pelagic stages and the design, location and oceanographic regime of MPAs; (2) effects of protection in MPAs from fishery exploitation of nursery habitats on settlement success; and (3) effects of protection on survival of settlers and juveniles from competition and predation. We found an exceptionally low number of studies specifically addressing recruitment processes in MPAs. This was particularly the case in what concerns the relationship between larval ecology and the characteristics and oceanographic regime of MPAs. The effectiveness of MPAs in promoting recruitment mainly depends on the locations and on sizes of the MPAs in relation to the reproductive biology and larval ecology of the species concerned. The locations and sizes of MPAs in turn depend on MPA objectives, whether the purpose is to protect entire life cycles, the juveniles, or to increase egg production and larval export. The assessment of the relationship between the protection of nursery habitats and settlement success indicates that the magnitude of the effects of protection depends on whether the recruitment of the species involved is restricted to a narrowly-defined set of environmental conditions or, on the contrary, can occur in diverse environments, including areas beyond the influence of the MPAs. Thus, the locations of MPAs determine the habitats which are protected and, consequently, the species, the settlement of which will be favoured. For Mediterranean shallow-water species, the near-shore zone encompasses most of the essential nursery habitats for protection. Recruitment studies conducted in MPAs in the north-western Mediterranean have showed no differences in survival of newly-settled littoral fish between MPAs and the areas outside of them. Conversely, for older recruits, mortality was found to be higher inside MPAs, probably due to the increased abundance and size of large predators. This study highlights the almost total absence of studies addressing even the most elementary questions of recruitment in the specific context of MPAs.
Spatio-temporal variability in growth of juvenile sparid fishes from the Mediterranean littoral zone
- S. Planes, E. Macpherson, F. Biagi, A. Garcia-Rubies, J. Harmelin, M. Harmelin-Vivien, J.-Y. Jouvenel, L. Tunesi, L. Vigliola, R. Galzin
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- Journal:
- Journal of the Marine Biological Association of the United Kingdom / Volume 79 / Issue 1 / February 1999
- Published online by Cambridge University Press:
- 04 April 2001, pp. 137-143
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Populations of three species of juvenile Sparidae (Diplodus puntazzo, Diplodus sargus and Diplodus vulgaris) were sampled at different spatial scales in the north-western Mediterranean Sea over two years to follow growth after settlement. Length–frequency distributions were collected each week for periods of six months following the arrival of off-shore larvae in inshore habitats. Data were collected by underwater visual census along permanent transects.
Growth rate measured as the slope of the linear relationship between mean size and time varied between species. Diplodus puntazzo (0.160 mm d−1) and D. vulgaris (0.202 mm d−1), which are settling in winter experienced slower growth than D. sargus (0.567 mm d−1) which settles in summer. It is concluded that the difference was in part due to water temperature. Analysis of growth rate within each species also revealed significant differences among sites probably related to the currents and the water mass temperatures.
3 - Report Group 3 – Photochemistry in the sea-surface microlayer
- Edited by Peter S. Liss, University of East Anglia, Robert A. Duce, Texas A & M University
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- Book:
- The Sea Surface and Global Change
- Published online:
- 24 September 2009
- Print publication:
- 20 March 1997, pp 71-92
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Summary
Introduction
Due to the enrichment of chemicals and biota within the sea-surface microlayer, there is the widely held presumption that the surface microlayer could act as a highly efficient and selective microreactor, effectively concentrating and transforming materials brought to the interface from the atmosphere and oceans by physical processes. Rapid photochemical, chemical, and biological reactions within the microlayer could produce a variety of interesting feedbacks. For example, photochemical reactions might destroy (or produce) surface-active species, thereby altering surface wave damping and gas exchange rates. Elevated levels of highly reactive intermediates produced within this zone could present a ‘reaction barrier’ to the transport of some chemicals and trace gases across the air–sea interface, thus affecting their flux to the atmosphere or ocean. Further, reactions occurring within the microlayer potentially could enhance (or deplete) the surface concentrations of certain gases relative to those of bulk seawater, chemically modify compounds during their transport across the interface, alter the redox state, speciation and biological availability of trace metals deposited by the atmosphere to the interface, as well as influence the types and distributions of microlayer materials introduced to the atmosphere by bubble injection and to the deep ocean by particle settling.
Although these processes are very intriguing and potentially of great importance, in many instances evidence supporting the existence of them is lacking.