RESUMO
BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.
Assuntos
Distrofia Muscular de Duchenne , Masculino , Humanos , Citocinas , Músculos/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regeneração , RNA Mensageiro/metabolismo , Músculo Esquelético/metabolismoRESUMO
Abstract Duchenne muscular dystrophy (DMD) is an X-linked inherited disorder. Patients present with decreased bone mineral density (BMD) due to glucocorticoid therapy and progressive muscle weakness. Bone remodeling allows bone volume and structure to be maintained and controlled by local and systemic factors. These include the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, a determining pathway in the balance between bone formation and resorption. Disruptions in this complex, caused by factors such as glucocorticoids, can affect bone metabolism. The extensive action of the RANK/RANKL/OPG pathway suggests an influence on dystrophic muscle pathophysiology. This review aimed to highlight some aspects of the RANK/RANKL/OPG system, the effect of glucocorticoids on this pathway, and the pathophysiology of the patient with DMD.
Resumen La distrofia muscular de Duchenne (DMD) es un trastorno hereditario ligado al cromosoma X. Los pacientes presentan una disminución de la densidad mineral ósea (DMO) debido a los efectos adversos del tratamiento con glucocorticoides y a la debilidad muscular progresiva. El remodelado óseo permite mantener el volumen y la estructura ósea, proceso controlado por factores locales y sistémicos. Entre ellos destaca el sistema del receptor activador del factor nuclear-kB (RANK), su ligando natural RANKL (RANKL) y la osteoprotegerina (OPG), una vía determinante en el equilibrio entre la resorción y formación ósea. Las alteraciones en este complejo, originadas por factores como los glucocorticoides, pueden afectar el metabolismo óseo. La amplia acción de RANKL y OPG ha sugerido una influencia en la fisiopatología de la DMD. El objetivo de esta revisión fue destacar algunos aspectos del sistema RANK/RANKL/OPG, el efecto de los glucocorticoides en esta vía y la fisiopatología del paciente con DMD.
RESUMO
Introducción. Una alimentación adecuada es esencial en el manejo del niño en estado crítico. Este estudio analiza la correlación entre el aporte total de energía (ATE) y el gasto energético total (GET) de pacientes hospitalizados en una Unidad de Cuidados Intensivos Neonatales (UCIN), considerando si nació pretérmino (PT), recibió alimentación parenteral (AP), o tratamiento quirúrgico (TQ). Métodos. Estudio transversal con 29 pacientes evaluados después de alcanzar estabilidad hemodinámica y ventilatoria. El GET se estimó mediante calorimetría indirecta, y el ATE sumando la energía administrada por vía enteral y parenteral. El análisis estadístico incluyó correlación de Spearman, U Mann-Whitney, prueba exacta de Fisher y regresión múltiple. Resultados. Catorce pacientes nacieron PT, y 21 recibieron TQ. Al momento del estudio, 14 recibían AP y 63% estaban desnutridos. El ATE fue mayor para los PT (P =0.022), los de AP (P =0.038) y los de TQ (P =0.046); el GET fue mayor en los PT (P =0.003). La correlación entre GET y ATE fue significativa sólo para alimentación enteral (r =0.518, P =0.046). El ATE fue inadecuado en 85.1% de los pacientes. Conclusiones. El ATE para niños atendidos en la UCIN parece ser inadecuado cuando se calcula por ecuaciones; se sugiere utilizar la determinación del gasto energético por calorimetría indirecta por lo menos en pacientes bajo el régimen de AP total.
Introduction. An adequate feeding is essential in the management of critically ill infants. This study analyzes the association between total energy intake (TEI) and total energy consumption (TEC) of patients hospitalized in a neonatal intensive care unit (NICU) taking into account whether were born preterm (PT), received parenteral nutrition (PN), or underwent surgical treatment (ST). Methods. A cross-sectional design including 29 patients hospitalized in a NICU after hemodynamic and ventilatory stability was conducted. TEC was determined by indirect calorimetry and TEI by the summation of the energy administered by enteral and parenteral pathways. The statistical analysis included, Spearman correlation, U Mann-Whitney test, exact Fisher test, and multiple regression. Results. Fourteen patients were born PT, 21 underwent ST; 14 were under PN regime at the moment of the study and 63% were undernourished. TEI was higher in PT (P =0.022), PN (P =0.038), and ST (P =0.046) patients; TEC was greater only in PT infants (P =0.003). TEC correlated with TEI only in patients receiving enteral nutrition (r=0.518, P =046). TEI was inadequate in 85.1% of the patients. Conclusion. The amount of energy administered to patients hospitalized in the NICU is inadequate when it is estimated by standardized equations. We suggest determining TEC by indirect calorimetry at least in patients under total PN.