Adverse remodeling following myocardial infarction (MI) leading to heart failure is driven by an imbalanced resolution of inflammation. The macrophage cell is an important control of post-MI inflammation, as macrophage subtypes secrete mediators to either promote inflammation and extend injury (M1 phenotype) or suppress inflammation and promote scar formation (M2 phenotype). We have previously shown that the absence of caveolin-1 (Cav1), a membrane scaffolding protein, is associated with adverse cardiac remodeling in mice, but the mechanisms responsible remain to be elucidated. We explore here the role of Cav1 in the activation of macrophages using wild type C57BL6/J (WT) and Cav1tm1Mls/J (Cav1−/−) mice. By echocardiography, cardiac function was comparable between WT and Cav1−/− mice at 3 days post-MI. In the absence of Cav1, there were a surprisingly higher percentage of M2 macrophages (arginase-1 positive) detected in the infarcted zone. Conversely, restoring Cav1 function after MI in WT mice by adding back the Cav1 scaffolding domain reduced the M2 activation profile. Further, adoptive transfer of Cav1 null macrophages into WT mice on d3 post-MI exacerbated adverse cardiac remodeling at d14 post-MI. In vitro studies revealed that Cav1 null macrophages had a more pronounced M2 profile activation in response to IL-4 stimulation. In conclusion, Cav1 deletion promotes an array of maladaptive repair processes after MI, including increased TGF-β signaling, increased M2 macrophage infiltration and dysregulation of the M1/M2 balance. Our data also suggest that cardiac remodeling can be improved by therapeutic intervention regulating Cav1 function during the inflammatory response phase.
IMPORTANCEIntense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels. OBJECTIVE To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia. DESIGN, SETTING, AND PARTICIPANTS This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials.
Background: Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subtype of pediatric leukemia with high risk factors and poor outcome. There are few reports of its prevalence in Latin America.Aim: This study evaluated the frequency and clinical and biological characteristics of Ph-like ALL in a pediatric cancer center in Colombia.
Methods:The Ph-like genetic profile was analyzed by a low-density array (LDA).Samples from patients with Ph-like ALL were analyzed by fluorescent in situ hybridization for cytokine receptor like factor 2 (CRLF2) and ABL proto-oncogene 1, nonreceptor tyrosine kinase (ABL1) rearrangements. Copy number variations were assessed by multiplex ligation probe amplification.Results: Data from 121 patients were analyzed. Fifteen patients (12.4%) had Ph-like ALL, and these patients had significantly higher leukocyte counts at diagnosis and higher levels of minimal residual disease on days 15 and 33 of induction than patients without the Ph-like subtype. There were no significant differences in sex, age, or response to prednisone at day 8 between the two groups. CRLF2 rearrangements were identified in eight patients, and ABL1 rearrangements were identified in two patients. Other genetic alterations alone or in combination were identified in 77% of patients, including deletions in cyclin dependent kinase inhibitor 2 A/B (46.2%), IKAROS family zinc finger 1 (38.3%), and paired box 5 (30.8%).Conclusions: Ph-like ALL had a 12.4% prevalence in our cohort of patients with pediatric ALL. The identification of this group of patients has importance for risk stratification and future targeted therapy.Adriana Linares and Luz Karime Yunis contributed equally as first authors.
Los tumores del sistema nervioso central (SNC) son las neoplasias sólidas más prevalentes en pediatría. El meduloblastoma (MB) es el tumor embrionario del SNC más frecuente y corresponde aproximadamente al 20 % de los casos. Objetivo: describir la experiencia en el diagnóstico, tratamiento y resultados de los pacientes con MB en un centro de referencia en Colombia. Método: se incluyeron 38 pacientes desde enero de 2011 hasta diciembre de 2018. Resultados: los menores de 3 años recibieron tratamiento basado en el protocolo CCG9921 y los mayores de 3 años tratamiento basado en el protocolo ACNS0332. La supervivencia global a 5 años fue de 50.6 %. La supervivencia global de todo el grupo es baja comparada con países de mayores ingresos, por múltiples factores como las barreras de acceso. Conclusiones: Es importante establecer guías de manejo nacional que permitan un diagnóstico más temprano y un tratamiento oportuno y ajustado al riesgo, generar rutas de atención y la recolección de información de múltiples centros para evaluar los resultados y plantear mejoras en las políticas de salud.
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