RESUMEN
PURPOSE: To define the efficacy and safety of narrowband ultraviolet A1 (UVA1) for the treatment of dermal fibrosis in bleomycin-induced mouse model of scleroderma. MATERIALS AND METHODS: 42 DBA/2 strain mice were included in the study: healthy mice and mice with established scleroderma, treated with high or medium dose of UVA1. Non-treated groups served as control. The equipment emitting 365±5nm UVA1 radiation was used in the study. The average cumulative doses were 1200J/cm2 for high and 600J/cm2 for medium dose course. Histological analysis was performed for the evaluation of the dermal thickness and mast cells density. The expressions of p53 and Ki-67 proteins were assessed by immunohistochemical analyses. RESULTS: Skin thickness of mice with scleroderma, treated with high and medium dose of UVA1, were lower (272.9±113.2µm and 394±125.9µm, respectively) in comparison to the dermal thickness of non-treated animals (599±55.7µm). The dermal mast cells count in mice with scleroderma was reduced after high and medium dose treatment to 11±1.7 and 13±2.2, respectively, as compared to that in non-treated mice (23±3.0). No significant upregulation of p53 nor Ki-67 proteins was observed in the skin of healthy mice and mice with scleroderma after high- and medium-dose of UVA1. CONCLUSIONS: The results of this study indicate that 365nm UVA1 with the cumulative doses of 1200J/cm2 and 600J/cm2 is safe and effective for the dermal fibrosis treatment.
Asunto(s)
Esclerodermia Localizada/inducido químicamente , Esclerodermia Localizada/radioterapia , Terapia Ultravioleta/efectos adversos , Animales , Bleomicina , Dermis/patología , Dermis/efectos de la radiación , Femenino , Antígeno Ki-67/metabolismo , Mastocitos/patología , Ratones Endogámicos DBA , Esclerodermia Localizada/patología , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: The main purpose of the present study was to define the impact of high-dose of 365±5nm ultraviolet A1 (UVA1) on dermal fibrosis in the pre-established, bleomycin-induced mouse model of scleroderma. METHODS: DBA/2 strain mice with the pre-established, bleomycin-induced scleroderma were irradiated with cumulative UVA1 dose of 1200J/cm2 and in parallel were challenged with prolonged administration of bleomycin. Non-treated groups served as the control. Light source emitting a narrow band UVA1 light of 365±5nm and 21mW/cm2 power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The expressions of matrix-metalloproteinase-1 (MMP-1), matrix-metalloproteinase-3 (MMP-3), collagen types I and III were evaluated by immunohistochemical analyses. The Mann - Whitney U test was used for statistical analysis. RESULTS: Dermal thickness in mice injected with bleomycin during all the experiment (8weeks) and irradiated with UVA1 for the last 5weeks was significantly lower than that in mice challenged only with bleomycin for 8weeks (253.96±31.83µm and 497.43±57.83µm, respectively; P=0.002). The dermal thickness after phototherapy was lower as compared with the pre-existing fibrotic changes observed after 3weeks of bleomycin injections (253.96±31.83µm and 443.87±41.76µm, respectively; P=0.002). High-dose of UVA1 induced the 5.8- and 5.2-fold increase in MMP-1 and MMP-3 expressions, respectively, and the 1.2- and 1.4-fold decrease in collagen type I and collagen type III expressions in the pre-established, bleomycin-induced scleroderma model as compared to that in the control non-irradiated mice (P=0.002). CONCLUSIONS: Our study has demonstrated that a cumulative 365±5nm UVA1 radiation dosage of 1200J/cm2 not only prevents the progression of dermal fibrosis, but also induces a regression of pre-existing fibrotic changes.
Asunto(s)
Colágeno/metabolismo , Dermis/efectos de la radiación , Metaloproteinasas de la Matriz/metabolismo , Esclerodermia Localizada/radioterapia , Rayos Ultravioleta , Animales , Bleomicina/toxicidad , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Dermis/fisiología , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Ratones , Ratones Endogámicos DBA , Esclerodermia Localizada/inducido químicamente , Grosor de los Pliegues Cutáneos , Terapia UltravioletaRESUMEN
SUMMARY: Coma is the disorder of consciousness because of the damage to diffused bilateral cerebral hemisphere cortex or reticular activating system. Coma can be caused by neurogenic (head brain injury), metabolic (endogenic), and toxic (exogenic) factors. To determine the cause of metabolic and toxic coma, laboratory tests are performed; in case of neurogenic coma, the neurologic examination is essential, when five systems are evaluated: the level of consciousness (according to Glasgow Coma Scale or Full Outline of Unresponsiveness Scale), photoreaction of pupils and ophthalmoscopic examination, oculomotoric, motoric, and cardiopulmonary systems. For the treatment of coma, adequate oxygenation and correction of blood circulation disorders are important. The treatment of metabolic coma is guided by special schemes; antidotes often are needed in the treatment of toxic coma, and surgery helps if traumatic brain injury is present. The prognosis and outcomes of the comatose patient depend on the age and comorbid diseases of the patient, the underlying cause of coma, timely medical help and its quality, and intensive treatment and care of the patient in coma.