Diez años de experiencia de dialisis peritoneal aguda en el periodo 2007-2016 en el Instituto Nacional De Salud Del Niño de Lima-Perú

La Diálisis Peritoneal Aguda (DPA) es una alternativa de terapia de reemplazo renal (TRR) en niños con injuria renal aguda (IRA), enfermedad renal crónica (ERC) reagudizada y en condiciones críticas de enfermedad con afectación renal. Objetivo: Evaluar la experiencia en Diálisis Peritoneal Aguda (DPA) en niños con falla renal atendidos en el Instituto Nacional de Salud del Niño (INSN) a fin de determinar caracteres epidemiológicos, clínicos, de laboratorio, las indicaciones que las motivaron, evolución y complicaciones relacionadas a esta modalidad de Terapia de Reemplazo Renal. Material y métodos: Es un estudio es de tipo descriptivo, retrospectivo de revisión de historias clínicas de pacientes sometidos a DPA en el período 2007-2016 registrados en el Libro de Procedimientos del Servicio de Nefrología Pediátrica del INSN. Resultados: De un total de 191 pacientes el 54.9% fueron varones y el 45.1% mujeres. 59% menores de 5 años. La procedencia fue de Lima 52% y provincias 48%. La DPA se realizó en los Servicios de Nefrología en 52%, en UCI 27%, en Emergencia 13%, en la Unidad postoperatoria cardiovascular 7% y otros 1%. Se utilizó catéter rígido en el 69% de casos y la clínica evidenció edema en 96%, HTA en 72.5%, sobrecarga hídrica en 47%. 151 pacientes cursaron con IRA oligúrica y fue indicación de DPA en el 79 % de casos. Recuperaron diuresis 77%. Se reportó un 30.3% de complicaciones. La mortalidad fue 15% Conclusiones: La diálisis peritoneal aguda (DPA) es una modalidad de terapia de reemplazo renal frecuente en niños con IRA y de soporte en pacientes críticos. Se describe la experiencia de la DPA en el período de 10 años del 2007- 2016 en el INSN con la colocación del catéter rígido de urgencia y del catéter flexible de tipo thenckoff . El SUH, la ERC Reagudizada y la sepsis fueron las causas más frecuentes de IRA tributarias de DPA

Neuronal survival induced by neurotrophins requires calmodulin

It has been reported that phosphoinositide 3-kinase (PI 3-kinase) and its downstream target, protein kinase B (PKB), play a central role in the signaling of cell survival triggered by neurotrophins (NTs). In this report, we have analyzed the involvement of Ca2+ and calmodulin (CaM) in the activation of the PKB induced by NTs. We have found that reduction of intracellular Ca2+ concentration or functional blockade of CaM abolished NGF-induced activation of PKB in PC12 cells. Similar results were obtained in cultures of chicken spinal cord motoneurons treated with brain-derived neurotrophic factor (BDNF). Moreover, CaM inhibition prevented the cell survival triggered by NGF or BDNF. This effect was counteracted by the transient expression of constitutive active forms of the PKB, indicating that CaM regulates NT-induced cell survival through the activation of the PKB. We have investigated the mechanisms whereby CaM regulates the activation of the PKB, and we have found that CaM was necessary for the proper generation and/or accumulation of the products of the PI 3-kinase in intact cells

Multilayer OMIC data in medullary thyroid carcinoma identifies the STAT3 pathway as a potential therapeutic target in RETM918T tumors

Purpose: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on the role of aberrant DNA methylation in MTC development.Experimental Design: We performed genome-wide DNA methylation profiling assessing more than 27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. mRNA and miRNA expression data were available for 33 and 31 tumors, respectively. Two human MTC cell lines and 101 paraffin-embedded MTCs were used for validation.Results: The most distinctive methylome was observed for RETM918T-related tumors. Integration of methylation data with mRNA and miRNA expression data identified genes negatively regulated by promoter methylation. These in silico findings were confirmed in vitro for PLCB2, DKK4, MMP20, and miR-10a, -30a, and -200c. The mutation-specific aberrant methylation of PLCB2, DKK4, and MMP20 was validated in 25 independent MTCs by bisulfite pyrosequencing. The methylome and transcriptome data underscored JAK/Stat pathway involvement in RETM918T MTCs. Immunostaining [immunohistochemistry (IHC)] for the active form of signaling effector STAT3 was performed in a series of 101 MTCs. As expected, positive IHC was associated with RETM918T-bearing tumors (P < 0.02). Pharmacologic inhibition of STAT3 activity increased the sensitivity to vandetanib of the RETM918T-positive MTC cell line, MZ-CRC-1.Conclusions: Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined MTCs and revealed JAK/Stat signaling effector STAT3 as a potential therapeutic target for the treatment of RETM918T MTCs.This work was supported by the Fondo de Investigaciones Sanitarias (FIS) project PI14/00240 and the Comunidad de Madrid (Grant S2011/BMD-2328 TIRONET) to MR. LI-P is supported by the Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER). VM was supported by a predoctoral fellowship from the "la Caixa"/CNIO international PhD programme. CM-C is supported by a postdoctoral fellowship from the Fundación AECC

Phisically based modelling of induction lamps: aplication to the improvement of energy efficiency in the lighting system of a University building. Poster

To manage efforts in energy efficiency, the Polytechnic University of Cartagena (UPCT) decided in 2003 to develop an ambitious project to reduce energy use intensity and costs during the period 2003-2008. To accomplish this objective in lighting end-use demand -one of the two main electrical uses together with space cooling/heating-, the UPCT joins, in July 2002, the U.E. GreenLight program as a partner. This paper describes the University experience in the second year (2003/04) of partnership in this UE initiative. The objectives were: to manage the demand, to improve the quality of lighting, working and environmental conditions, and reduce significantly energy and O&M expenses. Basically, the work developed in this year is focused in the change of conventional High Intensity Discharge (HID) lighting systems in classrooms (2000 m2) through the evaluation of advantages and drawbacks of different alternatives. The most promising one, the change to a new technology -165W induction lamps-, will be analyzed in detail in the paper

Sprouty1 controls genitourinary development via its N-terminal tyrosine

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is a group of diseases that include a broad spectrum of developmental defects of the genitourinary system. Mouse models indicate that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of CAKUT. Sprouty1 is an intracellular Ret inhibitor whose mutation results in supernumerary kidneys, megaureters, and hydronephrosis in mice. Both the molecular mechanisms and the structural domains critical for Sprouty function are a matter of controversy, partly because studies pursuing this objective rely on ectopic overexpression in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for their function in vitro. Methods: We have generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We have characterized development of the genitourinary systems of these mice via different methods, including the use of reporter mice expressing EGFP form the Ret locus, and whole mount cytokeratin staining. Results: Mice lacking this tyrosine grow ectopic ureteric buds that ultimately will form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position. Conclusions: Tyrosine 53 is absolutely necessary to convey Sprouty1 function during genitourinary development.This work was supported by grants BFU2010-47175-P and BFU2017-83646-P (AEI/FEDER, UE) from MINECO to ME. MV was supported by a predoctoral fellowship from AGAUR. CA was supported by a predoctoral fellowship from Universitat de Lleida. SC was supported by a Cofund action from the Marie Curie program of the EU. We are grateful to Dr. Sanjay Jain (Washington University, St Louis) for sharing RetEGFP mice, and to Dr. Tung-Tien Sun (New York University) for Uroplakin antibody. We thank Anna Macià (IRB Lleida) for her contribution to the initial development of this manuscript, as well as Marta Hereu, Maria Santacana, Mónica Domingo and Maria Carrele for their excellent technical assistance

Sprouty1 is a broad mediator of cellular senescence

Genes of the Sprouty family (Spry1-4) restrain signaling by certain receptor tyrosine kinases. Consequently, these genes participate in several developmental processes and function as tumor suppressors in adult life. Despite these important roles, the biology of this family of genes still remains obscure. Here we show that Sprouty proteins are general mediators of cellular senescence. Induction of cellular senescence by several triggers in vitro correlates with upregulation of Sprouty protein levels. More importantly, overexpression of Sprouty genes is sufficient to cause premature cellular senescence, via a conserved N-terminal tyrosine (Tyrosine 53 of Sprouty1). Accordingly, fibroblasts from knockin animals lacking that tyrosine escape replicative senescence. In vivo, heterozygous knockin mice display delayed induction of cellular senescence during cutaneous wound healing and upon chemotherapy-induced cellular senescence. Unlike other functions of this family of genes, induction of cellular senescence appears to be independent of activation of the ERK1/2 pathway. Instead, we show that Sprouty proteins induce cellular senescence upstream of the p38 pathway in these in vitro and in vivo paradigms

A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers

To evaluate senescence mechanisms, including senescence-associated secretory phenotype (SASP), in the motor neuron disease model hSOD1-G93A, we quantified the expression of p16 and p21 and senescence-associated Ji-galactosidase (SA-Ji-gal) in nervous tissue. As SASP markers, we measured the mRNA levels of Il1a , Il6 , Ifna and Ifnb. Furthermore, we explored whether an alteration of alternative splicing is associated with senescence by measuring the Adipor2 cryptic exon inclusion levels, a specific splicing variant repressed by TAR DNA-binding protein (TDP-43; encoded by Tardbp). Transgenic mice showed an atypical senescence profile with high p16 and p21 mRNA and protein in glia, without the canonical increase in SA-Ji-gal activity. Consistent with SASP, there was an increase in Il1a and Il6 expression, associated with increased TNF-R and M-CSF protein levels, with females being partially protected. TDP-43 splicing activity was compromised in this model, and the senolytic drug Navitoclax did not alter the disease progression. This lack of effect was reproduced in vitro , in contrast to dasatinib and quercetin, which diminished p16 and p21. Our findings show a non-canonical profile of senescence biomarkers in the model hSOD1-G93A