Asunto(s)
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Humanos , Animales , Porcinos , Esófago/cirugía , Endoscopía , Inyecciones , Resultado del TratamientoRESUMEN
INTRODUCTION: Treatment for long-gap esophageal atresia (LGEA) aims at achieving primary anastomosis with minimal tension. Previous studies have shown that intramural injections with botulinum toxin type-A (BTX-A) from the adventitial side can increase the elongation of the piglet and rat esophagus before bursting, and that this effect is dose and time dependent. Our aim was to determine if endoscopic injections would be feasible, safe, and with an effect on the mechanical properties of the esophagus. METHODS: Twenty-two male piglets (5.15 kg) were randomized into two groups, one receiving 2 units/kg BTX-A, the other equal volume 0.9% NaCl. On day 3, the esophagus was harvested and tested in a stretch-tension machine to evaluate elongation and maximum load, followed by histological examination. RESULTS: No adverse effects to the procedure were observed. No statistically significant difference in elongation or maximum load before bursting between the treatment and placebo group was found. In histopathological analysis, inflammation and abscess formation were observed with no statistically significant difference between the two groups. CONCLUSION: Endoscopic placement of BTX-A injections in the piglet esophagus was safe and feasible but did not result in any difference in the mechanical properties or histology of the esophagus.
Asunto(s)
Toxinas Botulínicas Tipo A , Atresia Esofágica , Fármacos Neuromusculares , Animales , Atresia Esofágica/tratamiento farmacológico , Atresia Esofágica/cirugía , Inyecciones/métodos , Masculino , Solución Salina/uso terapéutico , Porcinos , Resultado del TratamientoRESUMEN
The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the ß-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the role of AMPK in neuronal physiology is poorly defined. Here we show that AMPK is important in the nervous system for maintaining neuronal integrity and for stress survival and longevity in Drosophila. To understand the impact of this signaling system on behavior and its potential contribution to the 1q21.1 deletion syndrome, we focused on sleep, an important role of which is proposed to be the reestablishment of neuronal energy levels that are diminished during energy-demanding wakefulness. Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKß loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. Our data also suggest that AMPKß loss may contribute to the increased risk of developing mental disorders and sleep disturbances associated with the human 1q21.1 deletion.
Asunto(s)
Proteínas Quinasas Activadas por AMP/genética , Anomalías Múltiples/enzimología , Anomalías Múltiples/genética , Megalencefalia/enzimología , Megalencefalia/genética , Neuronas/enzimología , Esquizofrenia/enzimología , Esquizofrenia/genética , Sueño/genética , Sueño/fisiología , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/deficiencia , Animales , Deleción Cromosómica , Cromosomas Humanos Par 1/enzimología , Cromosomas Humanos Par 1/genética , Proteínas de Drosophila/deficiencia , Proteínas de Drosophila/genética , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Femenino , Técnicas de Silenciamiento del Gen , Predisposición Genética a la Enfermedad , Humanos , Aprendizaje/fisiología , Longevidad/genética , Longevidad/fisiología , Masculino , Modelos Animales , Neuronas/citología , Factores de Riesgo , Transducción de Señal , Trastornos del Sueño-Vigilia/enzimología , Trastornos del Sueño-Vigilia/genéticaRESUMEN
Introduction One in 4,000 infants is born with oesophageal atresia. Approximately 15% of these have a long gap oesophageal atresia, where primary anastomosis is difficult or impossible. Previous studies have shown an effect of intramural botulinum toxin type A (BTX-A) injections on the elongation and max load of the esophagus 1 hour after injection. We hypothesized that a longer waiting period of 2 hours could increase this effect. Methods Forty-five piglets were randomized into three groups. Two treatment groups received 2 units/kg of BTX-A and one group received saline. After 1 or 2 hours, a segment of the esophagus was harvested and put in a stretch-tension device to assess elongation and max load. Results Elongation from preload to max load and percentage elongation in the BTX-A 2h group (17.09 mm, 46.46%) was significantly higher compared with the BTX-A 1h group (13.59 mm, 40.16%) and the placebo group (13.77 mm, 39.92%). Conclusion Elongation of the piglet esophagus was significantly improved with a 2-hour waiting period after BTX-A injection. Injections with BTX-A could be useful in oesophageal atresia, where primary anastomosis is not possible.
