ABSTRACT
To date, 22q11.2 deletion syndrome (DS) is regarded as the most commonly diagnosed DS in humans. The location of the deletion on chromosome 22 affects the phenotypic presentation, which ranges from subtle to severe. Common manifestations include congenital heart defects, calcium deficiency, clefts and other midline defects, immunodeficiencies, and neurocognitive delay. This wide range of clinical manifestations can complicate diagnostic reasoning as many align with other disease processes commonly observed in preterm neonates. This article presents the case of a preterm neonate born at 25-weeks' gestation with 22q11.2 DS. The clinical presentation of this neonate included a right aortic arch, ventricular septal defect, hypocalcemia, borderline severe combined immunodeficiency, and abnormal thyroid function. The infant's hospital course is followed to highlight the challenges clinicians face when suspicious of a genetic disorder in a preterm neonate.
Subject(s)
DiGeorge Syndrome , Heart Defects, Congenital , Heart Septal Defects, Ventricular , Humans , Infant, Newborn , Chromosome Deletion , Chromosomes, Human, Pair 22 , DiGeorge Syndrome/diagnosis , DiGeorge Syndrome/genetics , DiGeorge Syndrome/therapy , Heart Defects, Congenital/diagnosis , Heart Septal Defects, Ventricular/complications , Heart Septal Defects, Ventricular/geneticsABSTRACT
BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin-induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation. METHODS: To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers. RESULTS: The level of expression of UPR transcription factor XBP-1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin-induced ER stress, attenuating ER stress via the protein kinase RNA-like ER kinase (PERK)-Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC. CONCLUSION: Our data suggest that MSC operate on ER stress via several pathways, but the PERK-Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.
Subject(s)
Endoplasmic Reticulum Stress , Mesenchymal Stem Cell Transplantation , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/therapy , Unfolded Protein Response , Animals , Bleomycin , Disease Models, Animal , Endoplasmic Reticulum Chaperone BiP , Female , Heat-Shock Proteins/metabolism , Humans , Mice , NF-E2-Related Factor 2/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/physiopathology , X-Box Binding Protein 1/metabolism , eIF-2 Kinase/metabolismABSTRACT
Justificación: existe un grupo de pacientes con angina de pecho crónica refractaria, que no son candidatos a revascularización quirúrgica o percutánea y que a pesar de recibir un manejo médico óptimo, aún experimentan severos episodios de angina. El estimulador eléctrico espinal es un neuromodulador que se emplea como alternativa de manejo en estos pacientes. Objetivos: se realizó una revisión sobre estimulación eléctrica espinal en el manejo de la angina, su mecanismo de acción, sus beneficios y su costo-efectividad. Materiales y métodos: se llevó a cabo una búsqueda en MedLine, según la metodología Cochrane, de artículos publicados desde enero de 1980 a enero de 2007, mediante los términos ®spinal cord stimulation¼; de ésta se seleccionaron los manuscritos que los autores consideraron relevantes. Conclusiones: el efecto anti-isquémico del estimulador espinal eléctrico reduce los episodios de angina de pecho, mejora la calidad de vida y la tolerancia al ejercicio, disminuye la estancia hospitalaria y retarda la aparición de signos de isquemia.