RESUMO
The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.
Assuntos
Inibidores da Colinesterase/farmacologia , Distrofia Muscular de Duchenne/complicações , Brometo de Piridostigmina/farmacologia , Transtornos Respiratórios , Músculos Respiratórios/efeitos dos fármacos , Fatores Etários , Animais , Inibidores da Colinesterase/uso terapêutico , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Técnicas In Vitro , Lipossomos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Contração Muscular/efeitos dos fármacos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Pletismografia , Brometo de Piridostigmina/uso terapêutico , Transtornos Respiratórios/tratamento farmacológico , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/patologia , Taxa Respiratória/efeitos dos fármacos , Espectrofotometria Ultravioleta , Volume de Ventilação Pulmonar/efeitos dos fármacosRESUMO
An algorithm is described to extract cardiac from a pletysmographic signal based on the maximum value of the second derivative. An initial set of points is detected and filtered with two consecutive temporal analyses...