However, higher doses of dexamethasone override the export capacity of P-glycoprotein and enter the brain to produce central activation of GRs. In conjunction with the suppression of endogenous corticosteroids by dexamethasone, this results in skewed ratios of activation of peripheral versus central GRs as well as skewed ratios of activation of GRs versus MRs when compared to non-synthetic corticosteroids. These differences can have significant clinical relevance. Chemistry
Dexamethasone is a synthetic pregnane corticosteroid and derivative of cortisol (hydrocortisone) and is also known as 1-dehydro-9α-fluoro-16α-methylhydrocortisone or as 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The molecular and crystal structure of dexamethasone has been determined by X-ray crystallography. It is a stereoisomer of betamethasone, the two compounds differing only in the spatial configuration of the methyl group at position 16 (see steroid nomenclature). Synthesis
To synthesize dexamethasone, 16β-methylprednisolone acetate is dehydrated to the 9,11-dehydro derivative. This is then reacted with a source of hypobromite, such as basic N-bromosuccinimide, to form the 9α-bromo-11β-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone. History
Dexamethasone was first synthesized by Philip Showalter Hench in 1957. It was introduced for medical use in 1958.On 16 June 2020, the RECOVERY Trial announced preliminary results stating that dexamethasone improves survival rates of hospitalized patients with COVID-19 receiving oxygen or on a ventilator. Benefits were only observed in patients requiring respiratory support; those who did not require breathing support saw a worse survival rate than the control group, although the difference may have been due to chance.
Noma—a gangrenous disease still widespread among malnourished children living on the borders of the Sahara desert—can cause ankylosis of the maxilla and mandible, impairing the ability to speak and eat. Fibrodysplasia Ossificans Progressiva is a rare bone disease in which muscle, tendons and ligaments turn to bone. This leads to progressive ankylosis of almost all joints. Society and culture
In 2014, Liliana Cernecca, a six-year-old girl at the time, was only able to open her mouth a couple millimeters after one of her jaw joints fused. She underwent surgery to correct her jaw ankylosis during which her jaw was operated on and unlocked. Fossil record
Evidence for ankylosis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Ankylosis has been reported in dinosaur fossils from several species, including Allosaurus fragilis, Becklespinax altispinax, Poekilopleuron bucklandii, and Tyrannosaurus rex (including the Stan specimen). References


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