A 2004 review of studies of dioxin and endometriosis concluded that "the human data supporting the dioxin-endometriosis association are scanty and conflicting", and a 2009 follow-up review also found that there was "insufficient evidence" in support of a link between dioxin exposure and developing endometriosis. A 2008 review concluded that more work was needed, stating that "although preliminary work suggests a potential involvement of exposure to dioxins in the pathogenesis of endometriosis, much work remains to clearly define cause and effect and to understand the potential mechanism of toxicity". Pathophysiology
While the exact cause of endometriosis remains unknown, many theories have been presented to better understand and explain its development. These concepts do not necessarily exclude each other. The pathophysiology of endometriosis is likely to be multifactorial and to involve an interplay between several factors. Formation
The main theories for the formation of the ectopic endometrium-like tissue include retrograde menstruation, Müllerianosis, coelomic metaplasia, vascular dissemination of stem cells, and surgical transplantation were postulated as early as 1870. Each is further described below. Retrograde menstruation theory
The theory of retrograde menstruation (also called the implantation theory or transplantation theory) is the most commonly accepted theory for the dissemination and transformation of ectopic endometrium into endometriosis. It suggests that during a womans menstrual flow, some of the endometrial debris flow backward through the Fallopian tubes and into the peritoneal cavity, attaching itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as or transform into endometriosis.
Penciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally (by mouth) it is more often used as a topical treatment. It is the active ingredient in the cold sore medications Denavir (NDC 0135-0315-52), Vectavir and Fenivir. Famciclovir is a prodrug of penciclovir with improved oral bioavailability. Penciclovir was approved for medical use in 1996. Medical use
In herpes labialis, the duration of healing, pain and detectable virus is reduced by up to one day, compared with the total duration of 2–3 weeks of disease presentation. Mechanism of action
Penciclovir is inactive in its initial form. Within a virally infected cell a viral thymidine kinase adds a phosphate group to the penciclovir molecule; this is the rate-limiting step in the activation of penciclovir. Cellular (human) kinases then add two more phosphate groups, producing the active penciclovir triphosphate. This activated form inhibits viral DNA polymerase, thus impairing the ability of the virus to replicate within the cell. The selectivity of penciclovir may be attributed to two factors. First, cellular thymidine kinases phosphorylate the parent form significantly less rapidly than does the viral thymidine kinase, so the active triphosphate is present at much higher concentrations in virally infected cells than in uninfected cells. Second, the activated drug binds to viral DNA polymerase with a much higher affinity than to human DNA polymerases. As a result, penciclovir exhibits negligible cytotoxicity to healthy cells.