Dexamethasone

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Dexamethasone

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Dexamethasone
© 2020 PFPC

COVID-19

Recently, dexamethasone, a fluorinated steroid about 30 times more as active as cortisione, was approved for treatment in COVID-19. Considering what is known about the pathophysiology of COVID-19, this could turn out to be disastrous decision, if not applied appropriately.
"Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only...Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies." (Theoharides & Conti, 2020)
Theoharides TC, Conti P - "Dexamethasone for COVID-19? Not so fast" J Biol Regul Homeost Agents 34(3) (2020) doi: 10.23812/20-EDITORIAL_1-5. Epub ahead of print. PMID: 32551464
https://pubmed.ncbi.nlm.nih.gov/32551464/

Selvaraj V, Dapaah-Afriyie K, Finn A, Flanigan TP - "Short-Term Dexamethasone in Sars-CoV-2 Patients" R I Med J (2013) 103(6):39-43 (2020) PMID: 32570995.
https://pubmed.ncbi.nlm.nih.gov/32570995/

Malone R, Tomera KM, Egbujiobi L, Kittah JR - "Famotidine and Celecoxib COVID-19 Treatment Without and With Dexamethasone; Retrospective Comparison of Sequential Continuous Cohorts" (2021)
https://www.researchsquare.com/article/rs-526394/v1
"The effects of added dexamethasone on laboratory biomarkers, and particularly on neutrophil count, lymphocyte count, and neutrophil to lymphocyte ratio raise concerns about the long-term effects of dexamethasone treatment with or without famcox during acute COVID-19 on the incidence and severity of chronic COVID (“long COVID” or PASC)."


Fluoride

Dexamethasone enhances fluoride effects on bone (Takada et al, 1996).

Takada J, Chevalley T, Baylink DJ, Lau KH. - "Dexamethasone enhances the osteogenic effects of fluoride in human TE85 osteosarcoma cells in vitro" Calcif Tissue Int. 1996 May;58(5):355-61. doi: 10.1007/BF02509385. PMID: 8661971.
https://pubmed.ncbi.nlm.nih.gov/8661971/

Inkielewicz-Stepniak I, Radomski MW, Wozniak M - "Fisetin prevents fluoride- and dexamethasone-induced oxidative damage in osteoblast and hippocampal cells" Food Chem Toxicol 50(3-4):583-9 (2012) doi: 10.1016/j.fct.2011.12.015. Epub 2011 Dec 17. PMID: 22198064.
https://pubmed.ncbi.nlm.nih.gov/22198064/

(Dexamethasone contains 4.84% fluorine per molecule).


Gq/11

Dexamethasone increases G q/11 expression (Cheung et al, 2002; Mitchell et al, 1997).

Cheung R, Mitchell J - “Mechanisms of regulation of G(11)alpha protein by dexamethasone in osteoblastic UMR 106-01 cells” Am J Physiol Endocrinol Metab 282(1):E24-30 (2002)

Mitchell J, Bansal A - "Dexamethasone increases G alpha q-11 expression and hormone-stimulated phospholipase C activity in UMR-106-01 cells" Am J Physiol 273(3 Pt 1):E528-35 (1997)

Wie J, Kim J, Ha K, Zhang YH, Jeon JH, So I - " Dexamethasone activates transient receptor potential canonical 4 (TRPC4) channels via Rasd1 small GTPase pathway" Pflugers Arch 467(10):2081-91. (2015) doi: 10.1007/s00424-014-1666-0. Epub 2014 Dec 14. PMID: 25502319
https://link.springer.com/article/10.10 ... 014-1666-0


Thyroid

Maes M, Vandewoude M, Schotte C, Martin M, Blockx P - "Suppressive effects of dexamethasone on hypothalamic-pituitary-thyroid axis function in depressed patients" J Affect Disord 20(1):55-61 (1990)

Fluorinated steroid analogues (dexamethasone) increase rT3 levels and reduce T3 and fT3 levels (Kjellman et al, 1993; Maes et al, 1990; Reinhardt et al, 1999) -> PFPC, 2003)
admin
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Posts: 5797
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DEX and thyroid hormones

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Ahmed RG - " Gestational dexamethasone alters fetal neuroendocrine axis" Toxicol Lett 258:46-54 (2016)` doi: 10.1016/j.toxlet.2016.05.020. Epub 2016 May 21. PMID: 27220267.
https://pubmed.ncbi.nlm.nih.gov/27220267/

Carbone DL, Zuloaga DG, Lacagnina AF, McGivern RF, Handa RJ - "Exposure to dexamethasone during late gestation causes female-specific decreases in core body temperature and prepro-thyrotropin-releasing hormone expression in the paraventricular nucleus of the hypothalamus in rats" Physiol Behav (2012)108:6-12. doi: 10.1016/j.physbeh.2012.07.010. Epub 2012 Aug 2. PMID: 22884559; PMCID: PMC3513498
https://pubmed.ncbi.nlm.nih.gov/22884559/

Buimer M, van Wassenaer AG, Kok JH - "Postnatal administration of dexamethasone for weaning off the ventilator affects thyroid function" Neonatology. 94(3):164-9 (2008) doi: 10.1159/000143395. Epub 2008 Jul 9. PMID: 18612213
https://pubmed.ncbi.nlm.nih.gov/18612213/
(increase in rT3)

Forhead AJ, Jellyman JK, Gardner DS, Giussani DA, Kaptein E, Visser TJ, Fowden AL - "Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus" Endocrinology 148(2):800-5 (2007) doi: 10.1210/en.2006-1194. Epub 2006 Nov 16. PMID: 17110425.
(increase in rT3)

Verhoelst CH, Darras VM, Roelens SA, Artykbaeva GM, Van der Geyten S - "Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain" J Endocrinol 183(1):235-41 (2004). doi: 10.1677/joe.1.05743. PMID: 15525590
https://pubmed.ncbi.nlm.nih.gov/15525590/
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