Molecular mechanism involved in the mutagenicity induced by Aflatoxin B1

The aflatoxin B1 (AFB1) is a mycotoxin that has been identified as the most potent hepatocarcinogen. The metabolite resulting from detoxification process of AFB1 in liver, has the ability to react with the genomic DNA, generating AFB1-DNA adducts; during DNA replication process, this adduct induced the G:C→T:A transversion. Polymorphism in genes encoding for enzymes involved in the activation and detoxification of AFB1 and DNA repair enzymes has been associated with the risk of hepatocellular carcinoma (HCC) development. Additionally, in populations of high exposure to aflatoxin and high prevalence of hepatitis B virus (HBV) infection, has been demonstrated a synergism between these two risk factors for the development of HCC.

The use of insect cells to identify potent and selective inhibitors of the replication of the Dengue and Chikungunya viruses and unravel their molecular mechanism of action

Dengue and Chikungunya viruses cause the most important arthropod-borne viral infections for humans. These viruses are predominant in tropical and subtropical regions. In addition, these viruses are predominant in tropical and subtropical regions. Dengue mortality rate is around 1.2 to 3.5% and deaths due to chikungunya fever are around 1 in 1000; however, half of chikungunya-infected patients evolve into a chronic state that can persist for months up to years. There are no antiviral drugs available for DENV and CHIKV treatment and prevention. Moreover, vector control strategies have failed so far. Thus, the development of potent inhibitors for a broad spectrum of RNA viruses is urgently needed. We established and characterized a new embryonic insect cell line from Culex quinquefasciatus mosquito. Also we established the flaviviruses and alphavirus replication, both in C6/36 and Lulo insect cell lines, as well as in Vero cell line. In addition we carried out a reference compound library and reference panel of assays and data for DENV, which provides a benchmark for further studies. During this study, a panel of 9 antiviral molecules, with proven in vitro anti-dengue virus activity and that act at different stages of the DENV life cycle, was selected. Finally, Favipiravir or T-705, was identified as inhibitor in vitro and in vivo of alphaviruses and the mutation K291R in nsP4, which is responsible of the polymerase activity, was found as the mode of action in CHIKV. Interestingly, lysine in motif F1 is also highly conserved in positive-stranded RNA viruses and this might explain the broad spectrum of T-705 antiviral activity.

Resultado postnatal de fetos con malformación adenomatoide quística pulmonar en la unidad maternofetal Clínica Colombia

Introducción La Malformación Adenomatoide Quística Pulmonar es una patología que se desarrolla durante estadíos tempranos de desarrollo embriológico y su pronóstico depende del tamaño de la lesión pulmonar. Existen muy pocos estudios que caractericen esta patología, ninguno en nuestro país. Metodología Se realizó una serie de casos para describir el resultado postnatal de los casos registrados en la Clínica Colombia entre 2005 hasta 2013. Resultados: Se incluyeron un total de 20 casos. La malformación más frecuente fue MAQ III con 45% de los casos, de localización izquierda (75%), el 65% nacieron después de la semana 35 y con un peso mayor de 2500 g. Tan solo 30 % desarrollaron hidrops asociado. Hubo una mortalidad de 35% (7 casos). Discusion La MAQ es un patología infrecuente que genera una alta morbimortalidad en la vida perinatal. Se requieren estudios con muestras más amplias para determinar los factores pronósticos para la ocurrencia de los desenlaces adversos como la necesidad de cirugía de urgencia, deterioro respiratorio o mortalidad.