Uso de esteroides sistémicos en quemaduras de segundo grado en modelo animal / Systemic steroid use in second degree burns in an animal model

El uso de esteroide está reconocido en el tratamiento crítico del paciente quemado y es útil en el choque séptico que no responde a vasopresores. Este grupo de medicamentos ayuda a regular la respuesta hemodinámica mejorando el aporte de sangre a la piel, aunque sabemos que tienen un efecto nocivo en el proceso de cicatrización. Evaluamos el efecto histopatológico del empleo de esteroides en quemaduras usando un modelo animal. Empleamos 2 grupos de 10 ratas (Wistar) en las que colocamos un cilindro de metal en el dorso durante 15 segundos a 95oC, produciendo una quemadura. En ese momento, uno de los grupos recibió esteroide a dosis de estrés (hidrocortisona 5 mg/kg) y el otro no recibió ningún medicamento. Al quinto día resecamos la escara y cubrimos el defecto con cultivo de queratinocitos. Los animales fueron sacrificadas a los 14 días. Realizamos análisis histopatológico. Macroscópicamente evaluamos la (..) (AU)

The use of steroids is well recognized in critical care specially in septic shock. There are some reports of their utility in severe burns. It helps to regulate the hemodynamic response in order to improve the blood supply to the skin, although it is well known their negative effect in wound healing. Our objective is to know the hystopathologic effect of steroids in burn healing. We used 2 groups of 10 rats (Wistar). Both groups were exposed in their backs to a metallic cylinder at 95 oC for 15 seconds. At the moment of the burn, one group was given steroid (hydrocortisone at stress dose 5 mg/kg) and the other group didn't received any medication. The scar was removed at the 5th day and the burn injury was covered with queratinocyte culture. The rats were sacrificed at 14th day. We evaluated the presence of clinical signs of infection and the percentage of new epithelium. In the microscope we evaluated the following parameters: fibrosis, inflammatory process, presence of fibroblast and vascular proliferation. We compared both groups using Chi2 test (SPSS program version 10). A p =/<. 05 was considered as statistical significant. We found no difference between each group in fibrosis (p .47), inflammatory process (p .27), or fibroblast presence (p.16). But there was a difference in vascular proliferation (p .05) against the first group (steroid group). There were no signs of infection and all of them were epithelised at the 14th day. In conclusion, the use of steroids in burns in an animal model could have a final effect in wound healing. In humans it is important to say that they can be helpful in those cases with clear evidence of benefit, as for example failure to vassopresor response in septic shock. We are not sure about the final effect in wound healing in the steroid group as for example wound contracture in long term (AU)

Combinatorial gene therapy induces regression of hepatic encephalopathy.

Capillarization of the sinusoid impedes the clearance of neurotoxic substances in liver fibrosis. These events may result in hepatic encephalopathy. Neurological and hepatic features of rats after bile duct ligation (BDL) supplemented with Manganese (BDL+Mn(2+)) were examined. The 4-week-old BDL rats had elevated levels of ammonia and were concomitantly fed with 1 mg ml(-1) of MnCl(2) in drinking water (BDL/Mn(+2)). Five out of fifteen rats were killed and the serum, liver and brain tissue (striatum and substantia nigra) were recovered. Of the remaining BDL/Mn(+2)-cirrhotic animals (n=10), five were injected with a combination of Adenovirus-human plasminogen activator (Ad-huPA) and Adenovirus-matrix metalloproteinase-8 (Ad-MMP-8) (3 × 10(11)+1.5 × 10(11) vector particles per kg), and five with 4.5 × 10(11) vector particles per kg of Adenovirus-ß-galactosidase (Ad-ß-Gal). This treatment was carried on for 10 days. The BDL/Mn(+2) rats displayed tremor, rigidity and gait abnormalities, which improved notably with combinatorial gene therapy, as well as motor coordination. Liver fibrosis was evidently less after treatment with Ad-huPA+Ad-MMP-8 (25%). In the brain (striatum), Ad-huPA+Ad-MMP-8 treatment rendered higher concentrations of dopamine compared with Ad-ß-Gal-treated encephalopathic rats (210 and 162 ng g(-1) of tissue, respectively). The BDL/Mn(+2) animals and controls treated with Ad-ß-Gal showed abnormal morphology in astrocytes (gliosis) in striatum and substantia nigra, in which expressions of green fibrillar acidic protein and tyrosine hydroxylase were altered. These abnormalities decreased with Ad-huPA+Ad-MMP-8 treatment. Importantly, the latter animals showed an increment in sprouting of nervous fibers in substantia nigra. Combinatorial gene therapy improves neuroanatomical and neurochemical characteristics similar to human hepatic encephalopathy.