RESUMO
Elevation in [Ca(2+)]i and activation of calpain-1 occur in central nervous system of SOD1(G93A) transgenic mice model of amyotrophic lateral sclerosis (ALS), but few data are available about the early stage of ALS. We here investigated the level of activation of the Ca(2+)-dependent protease calpain-1 in spinal cord of SOD1(G93A) mice to ascertain a possible role of the protease in the aetiology of ALS. Comparing the events occurring in the 120 day old mice, we found that [Ca(2+)]i and activation of calpain-1 were also increased in the spinal cord of 30 day old mice, as indicated by the digestion of some substrates of the protease such as nNOS, αII-spectrin, and the NR2B subunit of NMDA-R. However, the digestion pattern of these proteins suggests that calpain-1 may play different roles depending on the phase of ALS. In fact, in spinal cord of 30 day old mice, activation of calpain-1 produces high amounts of nNOS active species, while in 120 day old mice enhanced-prolonged activation of calpain-1 inactivates nNOS and down-regulates NR2B. Our data reveal a critical role of calpain-1 in the early phase and during progression of ALS, suggesting new therapeutic approaches to counteract its onset and fatal course.
Assuntos
Esclerose Lateral Amiotrófica/genética , Cálcio/metabolismo , Calpaína/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Proteólise , Receptores de N-Metil-D-Aspartato/genética , Superóxido Dismutase/genética , Superóxido Dismutase-1RESUMO
The inappropriate and careless use of permanent fillers causes severe and undesirable side effects, as shown by a number of reported clinical cases. The dramatic case described in this report strongly demonstrates that inadequate knowledge of implanted materials has a heavy impact on the patient's health and his or her desired results. Both are aspects that sometimes prove very difficult to ameliorate. Moreover, the solution for the reported case clearly demonstrates that only the careful application of fine surgery can solve these problems. This is true also for cases initially believed to be hopeless.
Assuntos
Resinas Acrílicas/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Fístula Cutânea/cirurgia , Granuloma de Corpo Estranho/cirurgia , Lábio/cirurgia , Resinas Acrílicas/administração & dosagem , Antibacterianos/uso terapêutico , Materiais Biocompatíveis , Fístula Cutânea/etiologia , Granuloma de Corpo Estranho/etiologia , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica , Reoperação , Supuração/etiologiaRESUMO
The widespread and inappropriate use of permanent fillers has given rise to several problems. The reported case clearly demonstrates that inadequate knowledge of the surgical technique and the material implanted has a heavy impact on the postoperative outcome. The application of fine surgical techniques and adequate knowledge of the materials can solve and prevent these problems.
