ABSTRACT
Prior work established that exercise alleviates muscle function loss in a clinically relevant rodent model mimicking the clinical sequelae of severely burned patients. On the basis of these data, we posit that pharmacologic treatment with insulin combined with exercise further mitigates loss of muscle function following severe burn with immobilization. Twenty-four Sprague-Dawley rats were assessed and trained to complete a climbing exercise. All rats followed a standardized protocol to mimic severe burn patients (40% total body surface area scald burn); all rats were immediately placed into a hindlimb unloading apparatus to simulate bedrest. The rats were then randomly assigned to four treatment groups: saline vehicle injection without exercise (VEH/NEX), insulin (5 U/kg) injection without exercise (INS/NEX), saline vehicle with daily exercise (VEH/EX), and insulin with daily exercise (INS/EX). The animals were assessed for 14 days following injury. The groups were compared for multiple variables. Isometric tetanic (Po) and twitch (Pt) forces were significantly elevated in the plantaris and soleus muscles of the INS/EX rats (P < 0.05). Genomic analysis revealed mechanistic causes with specific candidate changes. Molecular analysis of INS/EX rats revealed Akt phosphorylated by PDPK1 was increased with this treatment, and it further activated downstream signals mTOR, eEF2, and GSK3-ß (P < 0.05). Furthermore, muscle RING-finger protein-1 (MuRF-1), an E3 ubiquitin ligase, was reduced in the INS/EX group (P < 0.05). Insulin and resistance exercise have a positive combined effect on the muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments altered signaling pathways of increasing protein synthesis and decreasing protein degradation.
Subject(s)
Burns/therapy , Insulin/therapeutic use , Muscle, Skeletal/metabolism , Physical Conditioning, Animal/methods , 3-Phosphoinositide-Dependent Protein Kinases/genetics , 3-Phosphoinositide-Dependent Protein Kinases/metabolism , Animals , Burns/drug therapy , Elongation Factor 2 Kinase/genetics , Elongation Factor 2 Kinase/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Hindlimb Suspension/methods , Insulin/administration & dosage , Male , Muscle Contraction , Muscle Proteins/genetics , Muscle Proteins/metabolism , Muscle, Skeletal/physiopathology , Rats , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
BACKGROUND/PURPOSE: Fecal incontinence is a prevalent pediatric condition with psychosocial impacts on both children and their caregivers. We sought to develop and validate the Cincinnati Fecal Incontinence Scale (CINCY-FIS) as a psychometrically valid measure to assess the quality of life and caregiver impacts of pediatric fecal incontinence. METHODS: Items were generated through review of previous measures, expert consensus, and pilot testing with feedback from 8 families. Initial study measures were completed by 222 caregivers. Following item reduction, 18 items were subjected to confirmatory factor analysis. Convergent and criterion validity were assessed using correlation. Reliability was established using internal consistency statistics and test-retest reliability at baseline and 2-week follow-up. RESULTS: A five factor first-order structure with two higher-order factors demonstrated acceptable fit to the data, was consistent with a priori hypotheses, and was more parsimonious than the alternative model. Convergent validity and criterion-related validity were established for all of the CINCY-FIS scales. Reliability was high and consistent across both measurement occasions. CONCLUSIONS: The CINCY-FIS is a reliable and valid assessment of pediatric fecal incontinence-specific quality of life and parenting stress. The score is highly sensitive to patient changes making it suitable for both clinical and research purposes. TYPE OF STUDY: Prospective observational. LEVEL OF EVIDENCE: Study of Diagnostic Test Level II.
