In the fruit fly Drosophila melanogaster, where a fly possessing two X chromosomes is a female and a fly possessing a single X chromosome is a sterile male, a loss of an X chromosome early in embryonic development can result in sexual mosaics, or gynandromorphs. Likewise, a loss of the Y chromosome can result in XY/X mosaic males.An example of this is one of the milder forms of Klinefelter syndrome, called 46,XY/47,XXY mosaic wherein some of the patients cells contain XY chromosomes, and some contain XXY chromosomes. The 46/47 annotation indicates that the XY cells have the normal number of 46 total chromosomes, and the XXY cells have a total of 47 chromosomes. Also monosomies can present with some form of mosaicism. The only non-lethal full monosomy occurring in humans is the one causing Turners syndrome. Around 30% of Turners syndrome cases demonstrate mosaicism, while complete monosomy (45, X) occurs in about 50–60% of cases. Mosaicism need not necessarily be deleterious, though. Revertant somatic mosaicism is a rare recombination event with a spontaneous correction of a mutant, pathogenic allele. In revertant mosaicism, the healthy tissue formed by mitotic recombination can outcompete the original, surrounding mutant cells in tissues such as blood and epithelia that regenerate often. In the skin disorder ichthyosis with confetti, normal skin spots appear early in life and increase in number and size over time.Other endogenous factors can also lead to mosaicism, including mobile elements, DNA polymerase slippage, and unbalanced chromosomal segregation. Exogenous factors include nicotine and UV radiation.
Interactions and contraindications
Elvitegravir is metabolised via the liver enzyme CYP3A. Substances that induce this enzyme can reduce elvitegravir concentrations in the body, potentially triggering the development of resistant virus strains. Consequently, co-administration of strong CYP3A inducers is contraindicated; examples are rifampicin, the anticonvulsants carbamazepine, phenobarbital and phenytoin, as well as St Johns wort.Glucuronidation of elvitegravir is facilitated by the enzymes UGT1A1 and 3, resulting in increased blood plasma levels when taken together with strong UGT1A inhibitors such as ritonavir and other HIV protease inhibitors. (But ritonavir also increases elvitegravir levels by inhibiting CYP3A.) Furthermore, elvitegravir is a weak to medium inducer of CYP1A2, CYP2C19, CYP2C9, CYP3A, and a number of UGTs; the clinical relevance of these findings is however unclear. Pharmacology
Mechanism of action
Elvitegravir inhibits the enzyme integrase of HIV-1, and of HIV-2 to a lesser extent. The virus needs this enzyme to integrate its genetic code into the hosts DNA. Pharmacokinetics
The drug is taken by mouth. When taken together with ritonavir and a meal, it reaches highest blood plasma concentrations after four hours. Bioavailability is better with fatty meals. In the bloodstream, 98–99% of the substance are bound to plasma proteins. It is metabolized mainly by CYP3A oxidation, and secondly by UGT1A1 and 3 glucuronidation. Nearly 95% are excreted via the feces, and the rest via urine. Plasma half-life when combined with ritonavir is 8.7 to 13.7 hours. References
External links
"Elvitegravir". Drug Information Portal. U.S. National Library of Medicine.