Anti-Müllerian hormone levels before and after uterine artery embolization

Objective: To determine the effects of uterine artery embolization (UAE) on ovarian reserve as measured by Anti-Müllerian hormone (AMH) levels.

Material and methods: Non-randomized, observational study of 89 women 23–40 years of age who received UAE. Control hormone levels were measured prior to UAE and the first post-embolization measurement was taken at various times post-procedure (mean?=?190?±?229 days).

Results: Historical work verified by our earlier work has shown that AMH levels decline with age. Regression analysis allows us to determine whether UAE contributes to a greater decline in AMH values over that naturally occurring with aging. The effect of the procedure was found to contribute no deleterious effect to the natural decline in AMH levels. In addition, multiple blood draws were obtained from 32 patients up to 47 months post-UAE. Regression studies with these patients as their own controls showed no long-term diminishment of ovarian reserve due to the UAE procedure.

Conclusions: Earlier reported data are consistent with larger sample size. UAE does not affect ovarian reserve in women <40 as evidenced by no significant change in AMH levels after embolization. Women who are of reproductive age and have uterine fibroids can consider UAE without concern for adverse effects on their fertility.     

Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24

Background  Psoriasis is a Th17/Th1‐mediated skin disease that often responds to antitumour necrosis factor (TNF)‐α therapies, such as etanercept. Objectives  To better define mechanisms by which etanercept improves psoriasis and to gain insight into disease pathogenesis. Methods  We investigated the early biochemical and cellular effects of etanercept on skin lesions in responder patients prior to substantial clinical improvement (≤ 4 weeks). Results  By 1 week, etanercept acutely suppressed gene expression of the interleukin (IL)‐20 subfamily of cytokines (IL‐19, IL‐20, IL‐24), which were found to be predominantly epidermis‐derived and which are implicated in stimulating epidermal hyperplasia. Additionally, by 1 week of therapy, suppression of other keratinocyte‐derived products (chemokines, antimicrobial proteins) occurred, while suppression of epidermal regenerative hyperplasia occurred within 1–3 weeks. Th17 elements (IL‐23p19, IL‐12p40, IL‐17A, IL‐22) were suppressed by 3–4 weeks. In vitro, TNF‐α and IL‐17A coordinately stimulated the expression of the IL‐20 subfamily in normal keratinocytes. Conclusions  Based on the rapid suppression of regenerative hyperplasia, chemokines and other keratinocyte‐derived products, including the IL‐20 subfamily, we propose that epidermal activation is a very early target of etanercept. As many of these keratinocyte markers are stimulated by TNF‐α, their rapid downregulation is likely to reflect etanercept’s antagonism of TNF‐α. Additionally, decreased epidermal hyperplasia might result specifically from acute suppression of the IL‐20 subfamily, which is also a likely consequence of etanercept’s antagonism of TNF‐α. Thus, the IL‐20 subfamily has potential importance in the pathogenesis of psoriasis and therapeutic response to etanercept.     

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin,but not epidermal Langerhans cells,are depleted by treatment with cyclosporin A

Summary Since cyclosporin A (CsA) is an immuno-suppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1⁺ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1⁺DR⁺ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1⁺DR⁺), were also reduced after CsA, epidermal non-Langerhans CD1^-DR⁺ cells (macrophages, activated T cells, DR^- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1⁺DR⁺ Langerhans cells/non-Langerhans CD1^-DR⁺ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1^-DR⁺ cells while leaving LC relatively intact in the epidermis.This work was supported in part by the Babcock Foundation