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      Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish

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          Abstract

          Anesthetic failure is common in dental inflammation processes, even when modern agents, such as articaine, are used. Nanostructured lipid carriers (NLC) are systems with the potential to improve anesthetic efficacy, in which active excipients can provide desirable properties, such as anti-inflammatory. Coupling factorial design (FD) for in vitro formulation development with in vivo zebrafish tests, six different NLC formulations, composed of synthetic (cetyl palmitate/triglycerides) or natural (avocado butter/olive oil/copaiba oil) lipids were evaluated for loading articaine. The formulations selected by FD were physicochemically characterized, tested for shelf stability and in vitro release kinetics and had their in vivo effect (anti-inflammatory and anesthetic effect) screened in zebrafish. The optimized NLC formulation composed of avocado butter, copaiba oil, Tween 80 and 2% articaine showed adequate physicochemical properties (size = 217.7 ± 0.8 nm, PDI = 0.174 ± 0.004, zeta potential = − 40.2 ± 1.1 mV, %EE = 70.6 ± 1.8) and exhibited anti-inflammatory activity. The anesthetic effect on touch reaction and heart rate of zebrafish was improved to 100 and 60%, respectively, in comparison to free articaine. The combined FD/zebrafish approach was very effective to reveal the best articaine-in-NLC formulation, aiming the control of pain at inflamed tissues.

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          Neutrophil recruitment and function in health and inflammation.

          Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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            Phytochemistry: ibuprofen-like activity in extra-virgin olive oil.

            Newly pressed extra-virgin olive oil contains oleocanthal--a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. We show here that this similar perception seems to be an indicator of a shared pharmacological activity, with oleocanthal acting as a natural anti-inflammatory compound that has a potency and profile strikingly similar to that of ibuprofen. Although structurally dissimilar, both these molecules inhibit the same cyclooxygenase enzymes in the prostaglandin-biosynthesis pathway.
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              A transgenic zebrafish model of neutrophilic inflammation.

              We have established an in vivo model for genetic analysis of the inflammatory response by generating a transgenic zebrafish line that expresses GFP under the neutrophil-specific myeloperoxidase promoter. We show that inflammation is induced after transection of the tail of zebrafish larvae and that this inflammation subsequently resolves over a similar time course to mammalian systems. Quantitative data can be generated from this model by counting of fluorescent cells or by digital image analysis. In addition, we show that the resolution of experimentally induced inflammation can be inhibited by the addition of a pancaspase inhibitor, zVD.fmk, demonstrating that experimental manipulation of the resolution of inflammation is possible in this model.
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                Author and article information

                Contributors
                cfeijoo@unab.cl
                depaula@unicamp.br
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                12 November 2020
                12 November 2020
                2020
                : 10
                : 19733
                Affiliations
                [1 ]GRID grid.411087.b, ISNI 0000 0001 0723 2494, Department of Biochemistry and Tissue Biology, Institute of Biology, , University of Campinas-UNICAMP, ; Rua Monteiro Lobato, 255, Cid. Universitária Zeferino Vaz, Campinas, São Paulo, 13083862 Brazil
                [2 ]GRID grid.412848.3, ISNI 0000 0001 2156 804X, Laboratory of Fish Immunology, Department of Biological Sciences, Faculty of Life Sciences, , Andres Bello University, ; 8370146 Santiago, Chile
                [3 ]GRID grid.411087.b, ISNI 0000 0001 0723 2494, Department of Analytical Chemistry, Institute of Chemistry, , UNICAMP, ; Campinas, São Paulo, Brazil
                Article
                76751
                10.1038/s41598-020-76751-6
                7665027
                33184457
                d4e7be6e-31cc-46b4-94d3-fd0e1bc093a6
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 August 2020
                : 2 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001807, Fundação de Amparo à Pesquisa do Estado de São Paulo;
                Award ID: 17/15174-5
                Award ID: 14/25372-0
                Award ID: 14/14457
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Funded by: FundRef http://dx.doi.org/10.13039/501100002848, Comisión Nacional de Investigación Científica y Tecnológica;
                Award ID: 21151452
                Award Recipient :
                Funded by: INCT-Bioanalítica
                Funded by: FundRef http://dx.doi.org/10.13039/501100002850, Fondo Nacional de Desarrollo Científico y Tecnológico;
                Award ID: 1171199
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                dentistry,drug delivery
                Uncategorized
                dentistry, drug delivery

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