ABSTRACT
Back pain is a relatively common complaint in children and adolescents. The pediatric patient presenting with back pain can often be challenging, and there are many well-known organic diagnoses that should not be missed. In younger children, an organic cause of back pain can often be found. However, back pain in older children and adolescents is often "non-specific." The differential diagnosis of back pain in children includes neoplasms, developmental, and inflammatory conditions. Basic steps should include an in-depth anamnesis, a systematic physical examination, and standard spine radiographs (anteroposterior and lateral). Nevertheless, advanced diagnostic imaging and laboratory studies should be included when indicated to avoid missing or delaying a serious diagnosis. If other types of imaging tests are necessary (magnetic resonance imaging, computed tomography, bone scan, or single photon emission computed tomography), they should be guided by diagnostic suspicion.
ABSTRACT
Hyperhomocysteinemia reduces neurogenesis in the adult mouse brain. Homocysteine (Hcy) inhibits postnatal neural progenitor cell (NPC) proliferation by specifically impairing the fibroblast growth factor receptor (FGFR)-Erk1/2-cyclin E signaling pathway. We demonstrate herein that the inhibition of FGFR-dependent NPC proliferation induced by Hcy is mediated by its capacity to alter the cellular methylation potential. Our results show that this alteration modified the expression pattern and activity of Sprouty2 (Spry2), a negative regulator of the above mentioned pathway. Both elevated concentrations of Hcy and methyltransferase activity inhibition induced Spry2 promoter demethylation in NPC cultures leading to a sustained upregulation of the expression of Spry2 mRNA and protein. In addition, protein levels of two kinases responsible for Spry2 activation/deactivation were altered by Hcy: Spry2 kinase Dyrk1A levels diminished while Spry2 phosphatase PP2A increased, leading to changes in the phosphorylation pattern, activity and stability of Spry2. In conclusion, Hcy inhibits NPC proliferation by indirect mechanisms involving alterations in DNA methylation, gene expression, and Spry2 function, causing FGFR signaling impairment.
Subject(s)
Gene Expression Regulation, Developmental/drug effects , Homocysteine/pharmacology , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Neural Stem Cells/drug effects , Protein Phosphatase 2/genetics , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics , Animals , Cell Proliferation/drug effects , Cyclin E/genetics , Cyclin E/metabolism , DNA Methylation/drug effects , Homocysteine/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Mice , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neurogenesis/drug effects , Neurogenesis/genetics , Phosphorylation , Promoter Regions, Genetic , Protein Phosphatase 2/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Stability , Protein-Tyrosine Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Fibroblast Growth Factor/genetics , Receptors, Fibroblast Growth Factor/metabolism , Signal Transduction , Spheroids, Cellular/cytology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism , Dyrk KinasesABSTRACT
Introducción: el síndrome nefrótico (SN) es una de las enfermedades glomerulares más frecuentes en la infancia y son pocos los estudios realizados en Colombia sobre esta enfermedad. Objetivo: describir las características clínicas y epidemiológicas de los niños con SN atendidos en el Hospital Universitario San Vicente de Paúl, de Medellín, Colombia, entre los años 1960-2009. Metodología: estudio descriptivo retrospectivo. Resultados: el 87,9% de los pacientes fueron corticosensibles, entre 1,7%-5,4% se tornaron corticorresistentes. La histopatología predominante fue la del síndrome nefrótico con cambios mínimos (43,6%) seguida por la glomeruloesclerosis focal y segmentaria (37,3%). El 40% requirieron inmunosupresión adicional; en 88,8% de estos se utilizó ciclofosfamida con remisión en 85,7%. Se presentaron complicaciones en 56% y 52% de ellas fueron infecciosas. El 9% de los pacientes llegaron a la insuficiencia renal crónica. La tasa de mortalidad fue del 5,7%. Discusión: esta es una de las series más grandes de pacientes con SN reportadas hasta el momento y con un período de seguimiento de hasta 35 años, lo que aporta información valiosa sobre el comportamiento local de la enfermedad y la respuesta al tratamiento inmunosupresor, El seguimiento a largo plazo de estos pacientes es fundamental para ofrecer el mejor tratamiento disponible y nos plantea nuevos interrogantes sobre la evolución del SN en nuestra población.
Introduction: Nephrotic syndrome (NS) is a glomerular disease that frequently affects children. There have been few studies on it in Colombia. Objective: To describe the clinical and epidemiological features of children with SN treated at HUSVP between 1960 and 2009. Methodology: Retrospective and descriptive study. Results: Steroid-sensitive nephrotic syndrome was diagnosed in 87.9% of the patients, and between 1.7%-5.4% turned steroid-resistant. Biopsies revealed disease with minimal changes in 43.6% and focal segmental glomerulosclerosis in 37.3%. Additional immunosuppressive therapy was required by 40% of the patients; in 88.8% of these, cyclophosphamide was used, and remission was achieved in 85.7%. In 56% of the cases there were complications that were infectious in 52%. Nine percent of the patients progressed to end-stage renal disease. Mortality rate was 5.7%. Discussion: The large number of patients with nephrotic syndrome studied in this series and the long period of follow-up (up to 35 years) provide valuable information about the clinical behavior of this syndrome in Colombia and on its response to immunosuppressive therapy.
