RESUMEN
In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α4 and ß2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α4 and ß2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α4ß1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in ß2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α4ß1 and ß2 was significantly reduced 70 and 67%, respectively), but α4ß1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.
Asunto(s)
Oxigenoterapia Hiperbárica , Integrina alfa4beta1/antagonistas & inhibidores , Neutrófilos/inmunología , Peptidomiméticos/uso terapéutico , Úlcera Cutánea/terapia , Anciano , Anciano de 80 o más Años , Antígenos CD18/análisis , Antígenos CD18/metabolismo , Adhesión Celular/inmunología , Enfermedad Crónica/terapia , Terapia Combinada/métodos , Femenino , Estudios de Seguimiento , Humanos , Integrina alfa4beta1/análisis , Integrina alfa4beta1/metabolismo , Masculino , Persona de Mediana Edad , Infiltración Neutrófila , Neutrófilos/metabolismo , Peptidomiméticos/farmacología , Cultivo Primario de Células , Úlcera Cutánea/sangre , Úlcera Cutánea/inmunología , Úlcera Cutánea/patología , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/inmunologíaRESUMEN
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
OBJECTIVE: To observe the effect of mild moxibustion on the number of macrophages and contents of collagen I and III in the raw surface tissue in chronic skin ulcer rats so as to study its mechanism underlying promoting scar formation. METHODS: Eighty male SD rats were randomly divided into normal (n = 8), model (n = 24), TDP (n = 24) and moxibustion (n = 24) groups. Chronic refractory skin ulcer was established by making an open wound at the back and local intramuscular injection of hydrocortisone sodium succinate. For rats of the TDP and moxibustion groups, TDP irradiation or mild moxibustion was applied to the raw surface, bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 7, 10 and 14 days, respectively. The number of macrophages in the raw surface tissue was counted under light microscope after H. E. staining and col- lagen I and III expressions of the raw surface tissue were detected by immunohistochemistry. RESULTS: In comparison with the normal group, the numbers of macrophages in the raw surface tissue were increased significantly in the model group on day 7, 10 and 14 (P < 0.05); while compared with the model group, the numbers of macrophages were increased further obviously in the moxibustion group on day 7 and 10 and in the TDP group on day 10 after the treatment (P < 0.05). Compared with the model group, the numbers of macrophages in both TDP and moxibustion groups were down-regulated obviously (P < 0. 05). In regard to collagen I and III expression of the raw surface tissue, compared with the normal group, the collagen I protein expression level was down-regulated markedly in the model group on the 7th day (P < 0.01); whereas in comparison with the model group, the expression levels of collagen I and III were increased considerably in the TDP and moxibustion groups on day 7 and 14 after the treatment (P < 0.05, P < 0.01). The ratios of collagen I/III expression were remarkably higher in the model group than in the normal group on day 7 and 14 (P < 0.05), and significantly lower in the TDP group on day 7 and 14 and in the moxibustion group on day 14 than in the model group (P < 0.05, P < 0.01). The effects of moxibustion were obviously superior to those of TDP in up-regulating macrophage number on day 10, up-regulating collagen I and III expressions on day 14, and down-regulating macrophage number on day 14 after the treatment (P < 0.05, P < 0.01). No significant differences were found between the TDP and moxibustion groups in up-regulating macrophage number, and collagen I and III protein expressions, and in down-regulating the ratios of collagen I/III expression on day 7 after the treatment (P > 0.05). CONCLUSION: Mild moxibustion can regulate the number of macrophages and strengthen the expression of collagen proteins in the raw surface tissue in the chronic skin ulcer rats, which may contribute to its effect in promoting wound healing and reducing scar formation.
Asunto(s)
Colágeno/genética , Macrófagos/inmunología , Moxibustión , Úlcera Cutánea/terapia , Animales , Recuento de Células , Enfermedad Crónica/terapia , Colágeno/inmunología , Humanos , Macrófagos/citología , Masculino , Ratas Sprague-Dawley , Úlcera Cutánea/genética , Úlcera Cutánea/inmunología , Úlcera Cutánea/fisiopatología , Cicatrización de HeridasRESUMEN
A 58-year-old man with chronic "idiopathic' pyoderma gangrenosum, recurrent secondary staphylococcal infection, nail candidiasis, markedly impaired lymphocyte function and a serum blocking factor is described. Despite an initially favourable response to immunosuppressive therapy, the patient later relapsed whilst on high dose systemic corticosteroids and azathioprine. Immune function remains abnormal 3 years cessation of azathioprine. Attempted immunostimulation with Corynebacterium parvum proved unsuccessful. A striking but transient increase in lymphocyte function followed parenteral iron therapy for an unexplained iron-deficiency anaemia. Gradual reduction in prednisone dosage to 5 mg daily has coincided with a period of clinical resolution and modest improvement in lymphocyte reactivity. Prolonged immunosuppressive therapy may be inadvisable in chronic idiopathic pyoderma gangrenosum associated with defective cellular immunity.