Ciclosporin (cyclosporine) is an immunosuppressive drug first approved for use in organ transplantation to prevent rejection. Ciclosporin is also known to be used for the treatment of psoriasis, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease, among other indications. While it is recommended that all medications that are not absolutely necessary should be avoided during pregnancy, this may not be an option for many women whose quality of life is significantly impacted without treatment, or for those who must continue immunosuppressive therapy to avoid organ rejection. The purpose of this review is to provide a comprehensive report from the literature of ciclosporin exposure during pregnancy. PubMed, MEDLINE and the Cochrane Database of Systematic Reviews were searched for English-language articles published from 1970 to 2012 that included reports of pregnant women treated at any time during pregnancy with ciclosporin. On an initial search, it was evident that much of the available information is limited to pregnancy after transplant, which suggests that ciclosporin use during pregnancy appears to be associated with premature delivery and low birthweight infants. Comorbidities such as hypertension, pre-eclampsia and gestational diabetes mellitus are also reported at higher incidences than the general population. Medical literature concerning women with autoimmune disorders exposed to ciclosporin during pregnancy are currently limited to case reports and registry data, and, as such, it is difficult to determine if any risks associated with ciclosporin therapy during pregnancy are due to exposure to the drug alone or to pre-existing maternal comorbidities. The literature suggests that ciclosporin therapy during pregnancy should be carefully considered by the treating physician, but may be a safe alternative for patients with autoimmune disease refractory to conventional treatment. Continued monitoring of this patient population remains a key component to understanding the risk factors associated with ciclosporin exposure during pregnancy.

The major alteration in photoaged skin is the deposition of massive amounts of abnormal elastic material, termed solar elastosis. In previous work, it has been shown that solar elastosis is accompanied by increased abundance of elastin and fibrillin mRNAs and upregulation of elastin promoter activity. Using a transgenic mouse line, which expresses the human elastin promoter, linked to a chloramphenicol acetyltransferase reporter gene, in a tissue-specific and developmentally regulated manner, we investigated the effects of ultraviolet A radiation and ultraviolet B radiation on human elastin promoter activity in vivo and in vitro. Irradiation of mice with a single dose of ultraviolet B radiation (491.4 mJ/cm2) resulted in an increase up to 8.5-fold in promoter activity, whereas a more modest increase of 1.8-fold was measured with ultraviolet A radiation (38.2 J/cm2). In addition, in vitro studies revealed over a thirtyfold increase in elastin promoter activity in response to ultraviolet B radiation (5.5 mJ/cm2), whereas no change was measured in response to ultraviolet A radiation (2.2 J/cm2). These results confirm the role of ultraviolet B radiation in elastin promoter activation in photoaging, and identify ultraviolet A radiation as a contributing factor. This system should serve as a useful in vivo and in vitro model to study cutaneous photoaging, and for testing compounds that may protect against cutaneous photodamage.

Glucocorticoids exert their action on gene expression through activation of cytoplasmic glucocorticoid receptors (GRs) that bind to glucocorticoid response elements (GREs). The consensus GRE consists of two half sites (underlined), AGAACANNNTGTTCT. We have recently cloned the entire human elastin gene. Nucleotide sequencing of the promoter region disclosed the presence of three putative GREs with the downstream half-site sequence TGTTCC that has homology with the consensus GRE, although the upstream half site showed no homology. To examine the functionality of these putative GREs in binding to the GRs, we performed gel mobility shift and supershift assays with synthetic oligomers containing the putative GREs and a recombinant GR protein, expressed in a baculovirus system. All three GREs identified in the elastin promoter bound the receptor. A chimeric oligonucleotide containing the upstream consensus GRE half site and the downstream elastin promoter GRE half site was capable of binding the receptor, and this binding could be competed with the elastin promoter GRE. Nonconservative substitution of single nucleotides (positions 1-6) in the elastin GRE indicated that mutations in the positions 1-3 and 6 had relatively little effect, but substitutions in positions 4 and 5 rendered the oligomer less effective in competing for the binding. These observations suggest that the downstream half site of GREs in the human elastin promoter is sufficient for receptor binding and certain nucleotides are critical for the efficient binding. The results also imply that the three GREs within the human elastin promoter are active and mediate the glucocorticoid-induced up-regulation of human elastin promoter activity.

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