Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas

IMPORTANCE: Infantile hemangiomas (IHs) vary substantially in localization and extent of tissue involvement, but IH biological progression is remarkably unique and predictable. Propranolol is an effective treatment for symptomatic IH, but its mechanism of action remains unknown and understudied. OBJECTIVE: To compare excreted proteins in infants with IH being treated with propranolol vs prednisolone. DESIGN, SETTING, AND PARTICIPANTS: Exploratory urine proteomics profiling of patients with IH from July 2010 to September 2012 at a tertiary pediatric hospital. Participants were infants with IH treated at our institution who were participating in a blinded, randomized trial comparing prednisolone vs propranolol. They ranged in age from 14 days to 15 months at enrollment. Exclusion criteria included a history of diabetes mellitus, asthma, and/or cardiovascular disease including hypertension or hypotension. Urine samples were longitudinally collected from all participants. Specimens were desalted, concentrated, and gel fractionated, and the protein content was identified using liquid chromatography tandem mass spectrometry.Western blot analyses and enzyme-linked immunosorbent assays (ELISAs) were performed to validate mass spectrometry findings. INTERVENTION: Treatment with propranolol or prednisolone administered starting before the age of 6 months. MAIN OUTCOMES AND MEASURES: Proteins present in urine samples and change in urinary levels of proteins over time. RESULTS: Samples were obtained from 3 patients treated with prednisolone, 3 patients treated with propranolol, and 5 untreated controls with IH. More than 1000 urinary proteins were identified by proteomics. Patients treated with propranolol demonstrated attenuation of excreted matrix metalloproteinase 9 (MMP-9) in urine over the proliferative phase of the condition compared with prednisolone-treated patients. These findings were validated with Western blot analysis and quantified with ELISA, which confirmed mean urinary MMP-9 levels in the first year of life to be significantly lower in propranolol-treated patients with IH compared with prednisolone-treated patients with IH (0.118 vs 0.501 ng/mL; P = .03) or with nontreated patients with IH (0.118 vs 3.69 ng/mL; P = .02). CONCLUSIONS AND RELEVANCE: Propranolol treatment decreases urinary excretion of MMP-9 in patients with IH. Matrix metalloproteinase 9may be a biomarker for IH propranolol responsiveness, and its signaling pathways may represent the molecular target of this drug

Propranolol-mediated attenuation of MMP-9 excretion in infants with hemangiomas

IMPORTANCE: Infantile hemangiomas (IHs) vary substantially in localization and extent of tissue involvement, but IH biological progression is remarkably unique and predictable. Propranolol is an effective treatment for symptomatic IH, but its mechanism of action remains unknown and understudied. OBJECTIVE: To compare excreted proteins in infants with IH being treated with propranolol vs prednisolone. DESIGN, SETTING, AND PARTICIPANTS: Exploratory urine proteomics profiling of patients with IH from July 2010 to September 2012 at a tertiary pediatric hospital. Participants were infants with IH treated at our institution who were participating in a blinded, randomized trial comparing prednisolone vs propranolol. They ranged in age from 14 days to 15 months at enrollment. Exclusion criteria included a history of diabetes mellitus, asthma, and/or cardiovascular disease including hypertension or hypotension. Urine samples were longitudinally collected from all participants. Specimens were desalted, concentrated, and gel fractionated, and the protein content was identified using liquid chromatography tandem mass spectrometry.Western blot analyses and enzyme-linked immunosorbent assays (ELISAs) were performed to validate mass spectrometry findings. INTERVENTION: Treatment with propranolol or prednisolone administered starting before the age of 6 months. MAIN OUTCOMES AND MEASURES: Proteins present in urine samples and change in urinary levels of proteins over time. RESULTS: Samples were obtained from 3 patients treated with prednisolone, 3 patients treated with propranolol, and 5 untreated controls with IH. More than 1000 urinary proteins were identified by proteomics. Patients treated with propranolol demonstrated attenuation of excreted matrix metalloproteinase 9 (MMP-9) in urine over the proliferative phase of the condition compared with prednisolone-treated patients. These findings were validated with Western blot analysis and quantified with ELISA, which confirmed mean urinary MMP-9 levels in the first year of life to be significantly lower in propranolol-treated patients with IH compared with prednisolone-treated patients with IH (0.118 vs 0.501 ng/mL; P = .03) or with nontreated patients with IH (0.118 vs 3.69 ng/mL; P = .02). CONCLUSIONS AND RELEVANCE: Propranolol treatment decreases urinary excretion of MMP-9 in patients with IH. Matrix metalloproteinase 9may be a biomarker for IH propranolol responsiveness, and its signaling pathways may represent the molecular target of this drug

Le Paléolithique supérieur de l’abri Pataud (Dordogne)

La fouille de l’abri Pataud (Les Eyzies, Dordogne) fut dans la seconde moitié du xxe s. l’un des grands programmes de recherche internationaux et interdisciplinaires sur la Préhistoire française. Conduit par H. L. Movius. Jr., il donna lieu à des innovations dans le domaine des techniques de fouille et de l’analyse des objets et contribua ainsi à une synthèse méthodologique qui servit de base à la recherche actuelle. L’abri Pataud est une des séquences clefs des débuts du Paléolithique supérieur dans le Sud-Ouest. La publication, qui débuta en 1975, resta inachevée à la mort du Pt Movius en 1987. Ses plus proches collaborateurs ont résumé ici les résultats de ce programme, incluant des études inédites d’occupations du Protomagdalénien, du Périgordien moyen et de l’Aurignacien, de nouvelles datations par le radiocarbone et une réévaluation de la géochronologie. S’y ajoute un inventaire critique des sites aurignaciens et périgordiens de Dordogne replaçant l’abri Pataud dans son contexte régional.One of the large international and interdisciplinary research projects on the Palaeolithic of France during the middle of the 20th century was the excavation of the abri Pataud (Les Eyzies, Dordogne). From this project, directed by Hallam L. Movius, Jr., came innovations in excavation technique and artifact analysis that have contributed to the methodological synthesis underlying current research. The abri Pataud is one of the key sequences of the earlier Upper Palaeolithic in the Southwest. The publication began in 1975 but was left unfinished because of the death of Pr Movius in 1987. His closest collaborators have summarized here the results of the project, including unpublished studies of the Protomagdalenian, Middle Perigordian, and Aurignacian occupations, new radiocarbon dates, a reappraisal of the geochronology, and an extensively annotated catalogue of Aurignacian and Perigordian sites in Dordogne which allows the abri Pataud to be seen in its regional context