Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling

YesWound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism

Unterschiedliche Abheilungsdauer und Häufigkeit der Hospitalisation bei Ulcus cruris verschiedener Ursachen

BACKGROUND: Leg ulcers are a symptom of a heterogeneous group of diseases. Their treatment causes substantial costs due to the long healing times and extensive wound care measures. There is a paucity of information about healing times and the necessity of hospital treatment for leg ulcers of different etiologies. MATERIALS AND METHODS: In this retrospective study, healing times and the frequency of in-hospital treatment of 355 patients with leg ulcers attending a wound care clinic of a university hospital were examined. RESULTS: The proportion of healed ulcers was 32.0 % after 3 months and 54.3 % after 6 months with an average treatment duration of 6.1 months for all ulcers. This proportion of healed ulcers was higher for venous ulcers with 45.5 % after 3 months and 63.0 % after 6 months, whereas only 30.0 % of mixed arterial-venous ulcers and 35.0 % of hypertensive ischemic leg ulcers (HYTILU) were healed after 6 months. Of the latter group, 71 % of patients were hospitalized at least once during the observation period as compared to 47 % of patients with a venous ulcer. The duration of the hospital stay was longer for mixed ulcers and HYTILU with an average of 30 days vs. 23 days for venous ulcers. CONCLUSIONS: These data indicate that the healing times of ulcers of different etiologies differ substantially and that especially ulcers with arteriosclerosis as a causative factor have longer healing times. The fact that they require in-hospital treatment more frequently and for longer periods has significant socio-economic consequences

EpiDex® Swiss field trial 2004-2008

BACKGROUND: Approximately 20% of leg ulcers remain unresponsive to the best conservative standard of care. So far, these patients could either receive conventional skin grafts or had to accept their intractable wound. Skin substitutes from cell culture may represent a promising alternative to heal a major part of these patients on a non-surgical, potentially more cost-effective basis. OBJECTIVE: To systematically evaluate the first 68 patients treated in Switzerland (Swiss EpiDex® field trial 2004-2008). METHODS: Retrospective study on EpiDex treatment of a complete consecutive series of 68 patients with chronic wounds (66 chronic leg ulcers, 2 sores) unresponsive to best conservative standard of care. The primary end point was complete wound closure within 9 months after transplantation, the secondary end points change of wound surface area, pain reduction and overall judgement by the patient. Adverse effects were infection, dermatitis and others. Calculation of treatment costs was made. RESULTS: By the end of the study, 50/68 (74%) of patients had their wound completely healed [venous 29/37 (78%); mixed 7/9 (78%); others 14/22 (64%)]; 10/68 (15%) had the wound surface area reduced by >50%, and 8/68 (12%) did not respond to the EpiDex treatment. Wound pain disappeared completely in 78% and partially in 13%. Fifteen patients (22%) received antibiotics for wound infection, and 2 (3%) developed dermatitis (not related to the local therapy). Average treatment costs for venous ulcers amounted to EUR 5,357, compared to EUR 5,722-8,622 reimbursed according to the German DRG system (2010) for an in-patient skin graft. CONCLUSION: EpiDex may effectively heal up to three quarters of recalcitrant chronic leg ulcers. Thus, it represents an intermediate step to avoid costly in-patient split-skin mesh graft treatments. Patients remain mobilized, and a donor site is avoided. Large wound size or a necrotic wound bed limit the use of EpiDex. Otherwise, it offers the opportunity to avoid conventional skin grafts in a significant number of chronic leg ulcer patients. Copyright © 2010 S. Karger AG, Basel