miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-alpha, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer

An autopsy study of maternal mortality in Mozambique: the contribution of infectious diseases

Background Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. Methods and Findings We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. Conclusions In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement

Guía de práctica clínica SENPE/SEGHNP/SEFH sobre nutrición parenteral pediátrica

Introduction: Parenteral nutrition (PN) in childhood is a treatment whose characteristics are highly variable depending on the age and pathology of the patient. Material and methods: The Standardization and Protocols Group of the Spanish Society for Parenteral and Enteral Nutrition (SENPE) is an interdisciplinary group formed by members of the SENPE, the Spanish Society of Gastroenterology, Hepatology and Pediatric Nutrition (SEGHNP) and the Spanish Society of Hospital Pharmacy (SEFH) that intends to update this issue. For this, a detailed review of the literature has been carried out, looking for the evidences that allow us to elaborate a Clinical Practice Guide following the criteria of the Oxford Center for Evidence-Based Medicine. Results: This manuscript summarizes the recommendations regarding indications, access routes, requirements, modifications in special situations, components of the mixtures, prescription and standardization, preparation, administration, monitoring, complications and home NP. The complete document is published as a monographic number. Conclusions: This guide is intended to support the prescription of pediatric PN. It provides the basis for rational decisions in the context of the existing evidence. No guidelines can take into account all of the often compelling individual clinical circumstances.Introducción: la nutrición parenteral (NP) en la infancia es un tratamiento cuyas características son muy variables en función de la edad y la patología que presente el paciente. Material y métodos: el grupo de Estandarización y Protocolos de la Sociedad Española de Nutrición Parenteral y Enteral (SENPE) es un grupo interdisciplinar formado por miembros de la SENPE, Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y Sociedad Española de Farmacia Hospitalaria (SEFH) que pretende poner al día este tema. Para ello, se ha realizado una revisión pormenorizada de la literatura buscando las evidencias que nos permiten elaborar una Guía de Práctica Clínica siguiendo los criterios del Oxford Centre for Evidence-Based Medicine. Resultados: este manuscrito expone de forma resumida las recomendaciones en cuanto a indicaciones, vías de acceso, requerimientos, modificaciones en situaciones especiales, componentes de las mezclas, prescripción y estandarización, preparación, administración, monitorización, complicaciones y NP domiciliaria. El documento completo se publica como número monográfico. Conclusiones: esta guía pretende servir de apoyo para la prescripción de la NP pediátrica. Constituye la base para tomar decisiones en el contexto de la evidencia existente. Ninguna guía puede tener en cuenta todas las circunstancias clínicas individuale

Administration of pediatric parenteral nutrition

128 páginas : gráficasObjetivo: Diseñar y elaborar la formulación de Dantroleno sódico en solución inyectable para el tratamiento de la hipertermia maligna, incluyendo validación de la técnica analítica y el estudio de estabilidad acelerada. Materiales y Métodos: Se empleó una metodología enfocada en herramientas QbD para llevar a cabo el desarrollo, en la cual se plantearon siete etapas; inicialmente se realizó una revisión bibliográfica tanto del producto como del principio activo, excipientes y del material de envase a utilizar; con ello se plantearon los atributos críticos de calidad a tener en cuenta, se propusieron tres posibles formulaciones a evaluar, para posteriormente realizar los ensayos de pre-estabilidad a cuatro condiciones diferentes (30°C, 40°C, 25°C y 2°C-8°C) en envases de bolsa de polipropileno con sobre bolsa de aluminio y Frasco de Vidrio tipo I ámbar por 60 mL con tapón de bromobutilo, con los resultados obtenidos se eligió una formulación final, posteriormente se realizó el protocolo de fabricación para la elaboración de los pilotos, se llevó a cabo la manufactura de los mismos (ADS01DN19, ADS02DN19 y AS03DN19 ) y se sometieron a estudios de estabilidad acelerada, durante seis meses, a condiciones de temperatura de 30°C y humedad relativa de 75% para que por medio de un estudio estadístico se pudiera realizar la predicción de tiempo de vida útil del medicamento. Resultados: Se seleccionó la formulación más estable y el material de envase primario apropiado como lo es la bolsa de polipropileno en sobre bolsa de aluminio a unas condiciones de almacenamiento de 2°C a 8°C conveniente para el medicamento, así mismo se estandarizo el proceso de manufactura de Dantroleno sódico en solución inyectable, para la fabricación de tres lotes pilotos, se validó la metodología analítica para materia prima y producto terminado, se realizó un estudio de estabilidad acelerada a tres lotes pilotos, estableciendo una predicción de tiempo de vida útil de 24 meses. Conclusión: Se diseñó y elaboró la formulación de Dantroleno sódico en solución inyectable para el tratamiento de la hipertermia maligna, incluyendo validación de la técnica analítica y el estudio de estabilidad acelerada, con una predicción de tiempo de vida útil de 24 meses.Dantrolene Sodium is a pharmacological antidote used in the treatment for malignant hyperthermia, according to SCARE has been alerted about the risk posed by the lack of availability in Colombia for sometimes surgical people, which is why it was recognized by INVIMA as a vital medicine not available. It is cataloged of difficult access and that is marketed specifically in vials each with 20mg of lyophilized Dantrolene and currently the national pharmaceutical industry does not have the technological advance necessary to carry out the production of lyophilized drugs, therefore the objective of this study It is specific and develop a formulation of Dantrolene sodium in solution for injection for the treatment of malignant hyperthermia, including the validation of the analytical technique together with the study of accelerated stability. A methodology focused on QbD tools was used throughout the development process; in which seven stages were raised; specifically, a bibliographic review of both the product and the active substance, excipients and the packaging material to be used was performed; with this, the critical quality attributes to be taken into account were raised, three possible formulations were proposed for evaluation, to subsequently carry out the pre-stability tests, with the results obtained a final formulation was chosen, which was once to studies of Accelerated stability, confirming that the proposed formulation is stable since the analysis of the statistical studies carried out the prediction of the useful life of the drug developed is 24 months.Incluye bibliografíaPregradoQuímico(a) Farmacéutic