Endocrine Active Compounds: From Biology to Dose Response Assessment

Histone deacetylase (HDAC) inhibitors target key steps of tumor development: They inhibit proliferation, induce differentiation and/or apoptosis, and exhibit potent antimetastatic and antiangiogenic properties in transformed cells in vitro and in vivo. Preliminary studies in animal models have revealed a relatively high tumor selectivity of HDAC inhibitors, strenghtening their promising potential in cancer chemotherapy. Until now, preclinical in vitro research has almost exclusively been performed in cancer cell lines and oncogene-transformed cells. However, as cell proliferation and apoptosis are essential for normal tissue and organ homeostasis, it is important to investigate how HDAC inhibitors influence the regulation of and interplay between proliferation, differentiation, and apoptosis in primary cells as well. This review highlights the discrepancies in molecular events triggered by trichostatin A, the reference compound of hydroxamic acid-containing HDAC inhibitors, in hepatoma cells and primary hepatocytes (which are key targets for drug-induced toxicity). The implications of these differential outcomes in both cell types are discussed with respect to both toxicology and drug development. In view of the future use of HDAC inhibitors as cytostatic drugs, it is highly recommended to include both tumor cells and their healthy counterparts in preclinical developmental studies. Screening the toxicological properties of compounds early in their development process, using a battery of different cell types, will enable researchers to discard those compounds bearing undesirable adverse activity before entering into expensive clinical trials. This will not only reduce the risk for harmful exposure of patients but also save time and money.     

Crossing borders: Discussing the evidence relating to the mental health needs of women exposed to female genital mutilation

The terms ‘Female Circumcision’ (FC), ‘FG Cutting’ (FGC) and ‘FG Mutilation’ (FGM) refer to procedures involving the partial or total removal of the external female genitalia for non‐medical reasons. In practicing countries, FGC/FC is more widely used, as it is believed to be inoffensive, providing more impartial ways of discussing the practice. Positive beliefs about FC/FGC include virginity, marriage prospects, family reputation, or passage to adulthood. Regardless of terminology, the practice exists in at least 28 African counties, and a few Asian and Middle Eastern countries. In Western society, FGM is considered a breach of human rights, being outlawed in a number of countries. With immigration trends, FGC is now prominent in Western society among practicing communities. While the past decade has seen an increase in studies and recommendations for health‐care support related to the physical health consequences of FGM, little is known about the psychological impact and its management. For many girls and women, FGC is a traumatic practice, transforming it to FGM and affecting their mental health. This discussion paper focuses on evidence relating to the mental health consequences of FGM, therapeutic interventions, and the mental health nurse's role in addressing the needs of this group of women.     

An open-label,prospective, randomized,controlled, multicenter,phase 1b study of StrataGraft skin tissue versus autografting in patients with deep partial-thickness thermal burns

ObjectiveThis open-label, controlled, randomized study assessed the safety, tolerability, and efficacy of StrataGraft tissue compared to autograft in the treatment of deep partial-thickness (DPT) burns.MethodsThirty subjects with DPT thermal burns (3%–43% total body surface area) were treated with StrataGraft tissue as follows: cohort 1, ≤220 cm² refrigerated tissue; cohort 2, ≤440 cm² refrigerated tissue; and cohort 3, ≤440 cm² cryopreserved tissue. On each subject, two comparable areas of DPT burn were randomized to receive StrataGraft tissue or autograft. Coprimary end points were the percent area of the StrataGraft tissue treatment site undergoing salvage autografting by Day 28 and wound closure of treatment sites by 3 months.ResultsBy Day 28, no StrataGraft tissue treatment sites underwent autografting. By 3 months, 93% and 100% of the StrataGraft tissue and autograft treatment sites achieved complete wound closure, respectively. No significant differences in observer total and overall opinion POSAS scores between StrataGraft tissue and autograft treatment sites were observed at any timepoint. The most common adverse event was pruritus (17%).ConclusionsStrataGraft tissue treatment of DPT thermal burns reduced the need for autograft, resulted in wound closure and treatment-site cosmesis comparable to that of autograft, and was well tolerated.