A polymeric nanomedicine diminishes inflammatory events in renal tubular cells

The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-kB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-kB transcriptional activity and chemokine expression, despite failing to inhibit NF-kB-p65 nuclear translocation and NF-kB DNA binding. QM56 prevented JAK2 activation and NF-kB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-12/2 cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by downmodulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance.This work was supported by grants from the Instituto de Salud Carlos III (www.isciii.es), FIS: PI07/0020, CP08/1083, PS09/00447 and ISCIII-RETICS REDINREN RD 06/0016; Sociedad Española de Nefrología (www.senefro.org). Álvaro Ucero, Sergio Berzal and Carlos Ocaña supported by Fundacion Conchita Rabago (www.fundacionconchitarabago.net), Alberto Ortiz by the Programa de Intensificación de la Actividad Investigadora in the Sistema Nacional de Salud of the Instituto de Salud Carlos III and the Agencia ‘‘Pedro Lain Entralgo’’ of the Comunidad de Madrid and CIFRA S-BIO 0283/2006 www.madrid.org/lainentralgo) and Adrián Ramos, by FIS (Programa Miguel Servet)

Hypoxic regulation of neutrophil function and consequences for Staphylococcus aureus infection.

Staphylococcal infection and neutrophilic inflammation can act in concert to establish a profoundly hypoxic environment. In this review we summarise how neutrophils and Staphylococcus aureus are adapted to function under hypoxic conditions, with a particular focus on the impaired ability of hypoxic neutrophils to effect Staphylococcus aureus killing.This work was supported by a Wellcome Trust Research Training Fellowship awarded to K.M.L, Papworth Hospital Research and Development Department and the NIHR Cambridge Biomedical Research Centre

Social and behavioural aspects and their consequences in obese teenagers - importance of family's history ASPECTOS SOCIALES Y CONDUCTUALES Y SUS CONSECUENCIAS EN ADOLESCENTES OBESOS -IMPORTANCIA DE LOS ANTECEDENTES FAMILIARES Resumen

Objetivos: El sobrepeso, el síndrome metabólico y sus enfermedades asociadas son problemas que están aumentando de forma notable. Investigamos las variables sociales y conductuales que influyen en el sobrepeso en adolescentes y probamos su influencia sobre los marcadores plasmáticos relacionados con la diabetes y la disfunción endotelial. Métodos: Se reclutaron 79 adolescentes varones (edad 13-17 años). Se contaron las células progenitoras endoteliales con citometría de flujo. Se determinaron la adiponectina y la selectina-e soluble (selectina-s) mediante ELISA. Resultados:El peso corporal difiera significativamente si los antecedentes familiares son positivos para hipertensión arterial (p < 0,001), diabetes (p < 0,001), hipercolesterolemia (p < 0,001) y arteriopatía coronaria (APC, p < 0,01). Las horas de actividad física representan un predictor del IMC en el análisis de regresión linear (p < 0,001; r 2 = 0,195). Los marcadores de lesión endotelial están alterados en los adolescentes con unos antecedentes familiares positivos para hiperlipidemia y APC. Conclusión: Los antecedentes familiares son una variable importante que influye en el peso corporal de los adolescentes. A través de la obesidad y de forma independiente, influye en el desarrollo precoz de lesión endotelial. Podría servir para detectar a los adolescentes con riesgo para realizar una intervención apropiada. (Nutr Abstract Objectives: Overweight, the metabolic syndrome and accompanying diseases are dramatically increasing problems. We investigated social and behavioral variables that influence overweight in adolescents and tested their influence on plasma markers related to diabetes and endothelial dysfunction. Methods: 79 male adolescents were enrolled (age 13-17 years). Endothelial progenitor cells were counted by flow cytometry. Adiponectin and soluble E-selectin (sEselectin) were determined by ELISA. Conclusion: The family's history is an important variable influencing the body weight of teenagers. Via obesity and independently, it influences the early development of endothelial damage. It might serve to detect teenagers at risk for appropriate intervention