Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime?

Glioblastoma (GBM) is the most aggressive and common primary tumor of the central nervous system. It is characterized by having an infiltrating growth and by the presence of an excessive and aberrant vasculature. Some of the mechanisms that promote this neovascularization are angiogenesis and the transdifferentiation of tumor cells into endothelial cells or pericytes. In all these processes, the release of extracellular microvesicles by tumor cells plays an important role. Tumor cell-derived extracellular microvesicles contain pro-angiogenic molecules such as VEGF, which promote the formation of blood vessels and the recruitment of pericytes that reinforce these structures. The present study summarizes and discusses recent data from different investigations suggesting that Netrin-1, a highly versatile protein recently postulated as a non-canonical angiogenic ligand, could participate in the promotion of neovascularization processes in GBM. The relevance of determining the angiogenic signaling pathways associated with the interaction of Netrin-1 with its receptors is posed. Furthermore, we speculate that this molecule could form part of the microvesicles that favor abnormal tumor vasculature. Based on the studies presented, this review proposes Netrin-1 as a novel biomarker for GBM progression and vascularization.

Factores determinantes psicosociales asociados a patologías de stress laboral en funcionarios administrativos en una EPS de Bogotá / Psychosocial determinants associated to work stress pathologies in administrative staff in an EPS of Bogotá

RESUMEN Objetivo Identificar y determinar los factores que inciden en la aparición de enfermedades no trasmisibles de salud mental, en el área de la salud pública y/o laboral en las personas que prestan sus servicios en una EPS de la ciudad de Bogotá D.C Colombia. Metodología La investigación se realiza a través del estudio descriptivo, con una muestra aleatoria de 50 empleados donde se aplica una encuesta como herramienta investigativa de Guillermo Bocanument "factor de riesgo Psicosocial". Resultados Dentro de las principales variables identificadas encontramos los efectos significativos de los factores de riesgo psicosocial, como lo es el aumento a padecer una enfermedad no transmisible a causa de la carga laboral y/o el trabajo bajo presión, así mismo la incidencia en la aparición de enfermedades laborales y estrés. Discusión En la actualidad se han generado acciones para mitigar aquellos riesgos identificados en la propagación de enfermedades no trasmisibles y/o laborales, realmente su implementación ha aportado en la disminución en las cargas excesivas laborales o en la mejora de la calidad de vida del empleado.(AU)

ABSTRACT Objective To identify and determine the factors that affect the onset of noncommunicable mental disorders in the area of public and/or occupational health in people who work in a healthcare service provider (EPS in Spanish) in the city of Bogotá D.C Colombia. Methods This is a descriptive study with a random sample of 50 employees. The survey Factor de Riesgo Psicosocial (Psychosocial Risk Factor) developed by Guillermo Bocanument was applied as a research tool. Result The main variables identified include the significant effects of psychosocial risk factors, such as the increased likelihood of suffering from a noncommunicable disease due to workload and/or working under pressure, as well as the incidence in the onset of occupational diseases and stress. Discussion Several actions have been proposed to mitigate the identified risks associated with the spread of no communicable and/or work-related illnesses. In fact, their implementation has contributed to reduce excessive workloads or improve the quality of life of the workers.(AU)

Reaccion acneiforme noduloquistica secundaria a vemurafenib con buena respuesta a isotretinoina oralSevere acneiform eruption associated with vemurafenib with response to isotretinoin.

Vemurafenib, a kinase inhibitor that targets tumors with the BRAF V600E mutation, is a promising option for unresectable or metastatic melanoma. Cutaneous side-effects have been reported including alopecia, photosensitivity, squamous cell carcinoma, keratoacanthomas, keratosis pilaris-like eruption, and palmoplantar hyperkeratosis. Acneiform eruptions have been reported in 3%-6% of the patients treated with BRAF inhibitors,and 5 cases are described in the literature. Although they responded well to topical therapies, oral antibiotics, or observation, one case required oral etretinate and the withdrawal of vemurafenib because the adverse event reached grade 3. We report one case of a severe acneiform eruption associated with vemurafenib with a good response to isotretinoin allowing continuation of the BRAF inhibitor.

A case of de novo palmoplantar psoriasis with psoriatic arthritis and autoimmune hypothyroidism after receiving nivolumab therapy.

Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD-1), has shown promising results in patients with advanced malignancies, including melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs) have been reported, including both organ-specific toxicities and skin toxicities. Herein, we report a case of predominantly palmoplantar psoriasis with severe nail involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving nivolumab treatment for lung cancer. We also summarize the case reports that have been published previously. The knowledge of these irAEs in patients undergoing anti-PD1 therapy is important since it will enable earlier recognition and appropriate management, with the aim of maintaining effective dose without disruption.

Cutaneous infection due to Mycobacterium immunogenum: an European case report and review of the literature.

(no more than 200 words): In the last few years, the incidence of cutaneous infections caused by nontuberculous mycobacteria is increasing. Since Mycobacterium immunogenum was first described in 2001, few case reports have been described, all of them in the American continent. We report a case with cutaneous infection caused by this newly discovered NTB in Europe.A 65-year-old woman presented with a 3-months history of pruritic lesions on abdomen. Examination revealed erythematous inflammatory papules, pustules, and crusts. Three weeks later, mycobacteria were cultured from the biopsy specimen. Mycobacterium immunogenum was identified based on susceptibility test results and polymerase chain reaction (PCR) restriction enzyme analysis. Treatment with clarithromycin was started. M. immunogenum is a nontuberculous mycobacterium that was first described by Wilson et al. in 2001 as a rapidly growing variety and new species in the Mycobacterium chelonae-Mycobacterium abscessus group. PCR-restriction analysis of a 439-bp segment of the hsp65 gene and/or sequencing the species-specific region of the 16S rDNA can confirm this new species. Since the description of M. immunogenum, 8 clinical case reports have been published, most involving cutaneous infections and all of them in the American continent. We present a case of cutaneous infection caused by M. immunogenum in a Spanish woman.

Efecto de antioxidantes fenólicos en cultivos de epimastigotos de Tripanosoma cruzi / Effects of phenolic antioxidants on Trypanosoma cruzi epimastigotes culture growth

Como trabajos previos de nuestro laboratorio han revelado que los antioxidantes fenólicos BHA (2(3)-terbutil-p-hidroxianisol) y BHT (3,5-diterbutil-p-hidroxitolueno) producen inhibición de la respiración de epimastigotos intactos de Trypanosoma cruzi, se estudió el efecto de estos compuestos sobre el crecimiento de cultivos de dichas células. Se pudo establecer que: ambos antioxidantes fenólicos inhiben el crecimiento de los cultivos al usarse concentraciones mayores de 0,1 mM. El BHT es más efectivo en su acción, ya que a una concentración 1 mM presenta efecto tripanocida; en cambio, a esa concentración BHA solamente inhibe el crecimiento. La acción de dichos compuestos afecta los procesos bioenergéticos del parásito. En aerobiosis, al adicionar glucosa 1% al medio Diamond, tanto BHA como BHT a una concentración de 50 uM inhiben el crecimiento de los cultivos. Tal efecto inhibitorio no ocurre si los cultivos son crecidos solamente en medio Diamond, ni tampoco si se mantienen en anaerobiosis. Otro compuesto antioxidante estudiado fue el ácido ascórbico. Al utilizarlo a una concentración de 1 mM, se produjo aumento del crecimiento de cultivos, por lo cual se puede concluir que los efectos de BHA y del BHT sobre T cruzi obedecen más bien a la estructura química de esos compuestos y no a su capacidad antioxidante. También fueron esayados algunos ésteres del ácido gálico y pudo comprobarse que el efecto sobre el crecimiento de los cultivos depende de su hidrofobicidad: el laurilgalato presenta acción tripanocida, en cambio los ésteres cuya cadena alcohólica es más corta - como propilalato y metilgalato - no alteran el crecimiento de los cultivos. Los resultados obtenidos con BHA y BHT ofrecen posibilidades para la terapia racional de la Enfermedad de Chagas, que deben seguir siendo estudiadas

Efecto de la glucosa y del oxígeno en cultivos de epimastigotos de trypanosoma cruzi / The effect of glucose and oxygen in epimastigotes cultures of trypanosama cruzi

Se analiza el crecimiento en cultivo de epimastigotos de las cepas Tulahuén, Ypsilón y LQ de trypanosoma cruzi en medio Diamond. Como este medio es pobre en hidratos de carbono y en consideración que una de las primcipales diferencias entre T cruzi y los mamíferos es el proceso de "fermentación aeróbica de la glucosa", se estudió el efecto de agregar glucosa al medio Diamond, en presencia y ausencia de oxígeno. Se pudo establecer que las 4 concentraciones del azúcar utilizadas aumentan el crecimiento de los cultivos en presencia de oxígeno y que tal efecto no se manifestaba en anaerobiosis. En las 3 cepas estudiadas la concentración óptima de glucosa para aumentar el crecimiento fué 0,25% (13,8 mM). Estos resultados indican que el crecimiento de los cultivos de epimastigotos de trypanosoma cruzi es menor en medios pobres en hidratos de carbono, pues este protozoo necesita en forma imprescindible de azúcares como base de su metabolismo energético