RESUMEN
The effect of stimulant medication use by children with attention deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)-heart rate (HR) relationship was examined. Children with ADHD (n=20; 11.3±1.8 yrs) and children without ADHD (n=25; 11.2±2.1 yrs) were studied. Children with ADHD were examined while on their usual dose of medication on the day of study. HR and RPE, using the OMNI RPE scale, were assessed during a graded exercise to peak voluntary effort. The RPE-HR relationship was determined individually and the intercept and slope responses were compared between groups. The intercept was 132.4±19.5 bpm for children with ADHD and 120.6±15.7 bpm for children without ADHD. The slope was 7.3±1.9 bpm/RPE for the children with ADHD and 8.1±1.6 bpm/ RPE for the children without ADHD. For the group with ADHD the intercept and slope values fell outside of the 95% CI observed in the control group. The altered relationship between RPE and HR with stimulant medication use in children with ADHD has practical implications with respect to the use of HR and RPE to monitor exercise intensity.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Estimulantes del Sistema Nervioso Central/administración & dosificación , Prueba de Esfuerzo/métodos , Frecuencia Cardíaca/efectos de los fármacos , Esfuerzo Físico/efectos de los fármacos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Estudios de Casos y Controles , Niño , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Modelos Lineales , Masculino , Percepción/fisiología , Esfuerzo Físico/fisiología , Valores de Referencia , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
Patients on a statin regimen have a decreased risk of death due to bacterial sepsis. We have found that protection by simvastatin includes the inhibition of host cell invasion by Staphylococcus aureus, the most common etiologic agent of sepsis. Inhibition was due in part to depletion of isoprenoid intermediates within the cholesterol biosynthesis pathway and led to the cytosolic accumulation of the small GTPases CDC42, Rac, and RhoB. Actin stress fiber disassembly required for host invasion was attenuated by simvastatin and by the inhibition of phosphoinositide 3-kinase (PI3K) activity. PI3K relies on coupling to prenylated proteins, such as this subset of small GTPases, for access to membrane-bound phosphoinositide to mediate stress fiber disassembly. Therefore, we examined whether simvastatin restricts PI3K cellular localization. In response to simvastatin, the PI3K isoform p85, coupled to these small-GTPases, was sequestered within the cytosol. From these findings, we propose a mechanism whereby simvastatin restricts p85 localization, inhibiting the actin dynamics required for bacterial endocytosis. This approach may provide the basis for protection at the level of the host in invasive infections by S. aureus.
