However, it has been shown to have comparable affinity with calcitriol for the vitamin D receptor (VDR), while being less than 1% as active as the calcitriol in regulating calcium metabolism. The vitamin D receptor belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kidney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes. In mouse studies, topical calcipotriol administration to the ear and dorsal skin led to a dose-dependent increase in the production of the epithelial cell-derived cytokine TSLP by keratinocytes, and triggered atopic dermatitis at high concentrations. This upregulation of TSLP production due to calcipotriol application is thought to be mediated through the coactivation of vitamin D receptor/RXRα and vitamin D receptor/RXRβ heterodimers. As psoriasis is typically thought to be partially driven by Th1/Th17 inflammatory cytokines, calcipotriol treatment at appropriate concentrations may alleviate psoriasis symptoms by repressing Th1/Th17 inflammation through TSLP production, which is linked to a Th2 response. However, it is important to note that this has not yet been confirmed. Pharmacokinetics
After application and systemic uptake, calcipotriol undergoes rapid hepatic metabolism. Calcipotriol is metabolized to MC1046 (the α,β−unsaturated ketone analog), which is subsequently metabolized to its primary metabolite, the saturated ketone analog MC1080.
An imperforate hymen is a congenital disorder where a hymen without an opening completely obstructs the vagina. It is caused by a failure of the hymen to perforate during fetal development. It is most often diagnosed in adolescent girls when menstrual blood accumulates in the vagina and sometimes also in the uterus. It is treated by surgical incision of the hymen. Signs and symptoms
Affected newborns may present with acute urinary retention. In adolescent females, the most common symptoms of an imperforate hymen are cyclic pelvic pain and amenorrhea; other symptoms associated with hematocolpos include urinary retention, constipation, low back pain, nausea, and diarrhea. Other vaginal anomalies can have similar symptoms to an imperforate hymen. Vaginal atresia and a transverse vaginal septum require differentiation. A strong urge to defecate has been observed in a few women. Complications
If untreated or unrecognized before puberty, an imperforate hymen can lead to peritonitis or endometriosis due to retrograde bleeding. Additionally, it can lead to mucometrocolpos (dilatation of the vaginal canal and uterus due to mucus buildup) or hematometrocolpos (dilatation due to buildup of menstrual fluid). Mucometrocolpos and hematocolpos can in turn cause urinary retention, constipation, and urinary tract infection. Pathophysiology
An imperforate hymen is formed during fetal development when the sinovaginal bulbs fail to canalize with the rest of the vagina. Although some instances of familial occurrence have been reported, the conditions occurrence is mostly sporadic, and no genetic markers or mutations have been linked to its cause.