RESUMEN
The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing.
Asunto(s)
Envejecimiento , Antiinfecciosos/administración & dosificación , Terapia por Estimulación Eléctrica/métodos , Terapia de Presión Negativa para Heridas/métodos , Úlcera Cutánea/terapia , Ingeniería de Tejidos/métodos , Administración Tópica , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Canadá/epidemiología , Enfermedad Crónica , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Ratones , Calidad de Vida , Úlcera Cutánea/inmunología , Úlcera Cutánea/patología , Estados Unidos/epidemiología , Cicatrización de HeridasRESUMEN
BACKGROUND: Sorafenib is currently approved for advanced hepatocellular carcinoma (HCC) and is presently being studied as an adjuvant treatment for HCC following resection. The effects of sorafenib on liver regeneration have not been clearly defined. Our objective was to identify the effects of sorafenib on liver regeneration in a murine partial hepatectomy (PH) model. MATERIALS AND METHODS: We performed PH in C57Bl/6 mice treated with a range of sorafenib doses with assessments at several time points. Liver sinusoidal endothelial cells (LSEC) and hepatocyte DNA synthesis and proliferation were assessed with 5-bromo-2'-deoxyuridine (BrdU) and Ki67 by flow cytometry and immunohistochemistry. RESULTS: Treatment with sorafenib did not result in any deaths following PH. When we measured BrdU uptake to assess DNA synthesis, there was a statistically significant increase at 48 h post-PH for nonfibrotic LSEC following treatment with 60 mg/kg of sorafenib. However, BrdU and Ki67 staining among LSEC and hepatocytes was not significantly affected by sorafenib at any of the other doses or time points. BrdU and Ki67 flow cytometry data correlated with immunohistochemistry findings and postoperative liver weights. CONCLUSION: In a murine PH model, sorafenib did not alter the repair response of normal or fibrotic livers following PH as measured by changes in liver weight, DNA synthesis, and cellular proliferation. These findings suggest sorafenib administered following hepatic resection does not impair liver regeneration.