Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in BAG3 gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy (DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant correlation with systolic and diastolic blood pressure, A wave, left atrium length, and left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination, suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show diagnostic value. Further studies will require long-term follow-up, and validation in larger populations.post-print729 K

Dengue en el embarazo: efectos en el feto y el recién nacido.

The risk of dengue virus infection during pregnancy has increased due to the current rash of frequent and severe dengue epidemics. The effects of dengue virus in the fetus and newborn children have been studied only superficially and with contradictory results. Therefore, a retrospective cohort study was conducted in Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus infection acquired during pregnancy. Twenty-two babies born from mothers who suffered dengue during the epidemics of 1998 were compared with babies from non-infected mothers. In the exposed cohort, three premature births occurred, three children suffered from fetal anomalies and four children were born with low weight. In the non-exposed children, none of these problems were found. Psychomotor development was normal in both groups. Only the low weight subgroup was statistically significant (Fisher test, p = 0.045). These results suggested that the children from women with dengue during pregnancy present low weight, greater frequency of premature birth and increased fetal distress. A larger sample is necessary to confirm these results.El riesgo de infección por el virus del dengue durante el embarazo se está incrementando ante mayores y más severas epidemias, y las consecuencias sobre el feto y el recién nacido han sido poco estudiadas y, en otros casos, los resultados han sido contradictorios. Por esta razón, se realizó en Medellín un estudio de cohorte retrospectiva, cuyo objetivo fue determinar los efectos que produce el dengue durante el embarazo sobre el feto y el recién nacido. En dicho estudio se evaluaron 22 recién nacidos hijos de mujeres que presentaron dengue durante la epidemia de 1998 y se compararon con 24 recién nacidos, hijos de mujeres embarazadas sin dengue. En la cohorte con dengue se encontraron 3 niños prematuros, 3 niños con sufrimiento fetal y 4 niños con bajo peso al nacer. En la cohorte no expuesta no se encontraron niños con estos problemas. El desarrollo psicomotor fue normal en ambos grupos. De las observaciones anteriores, sólo fue estadísticamente significativa la frecuencia de niños con bajo peso al nacer (prueba exacta de Fisher, p=0,045). Estos resultados preliminares muestran que los recién nacidos de madres que sufrieron dengue durante la gestación tuvieron riesgo de bajo peso al nacer y presentaron con mayor frecuencia prematurez y sufrimiento fetal, aunque se requiere aumentar el tamaño de la muestra para confirmar estos resultados. Sin embargo, es necesario estrechar la vigilancia a las madres embarazadas con dengue dados los efectos nocivos sobre la evolución del recién nacido

Internalization of the anti-carcinogenic IBB1, a major Bowman-Birk isoinhibitor from soybean (Glycine max), in HT29 colon cancer cells

Proceedings of the I Congress PIIISA celebrado en la Estación Experimental del Zaidín (Granada), en mayo de 2013.Protease inhibitors of the Bowman-Birk type, a major protease inhibitor family in legume seeds, which inhibit potently trypsin- and chymotrypsin-like proteases, are currently being investigated as colorectal chemopreventive agents. Although the therapeutic target/s and the action mechanism/s of Bowman-Birk inhibitors (BBI) have not yet been elucidated, the emerging evidence suggests that BBI exert their chemopreventive properties via protease inhibition; in this sense, serine proteases should be considered as primary targets in early stages of carcinogenesis. In this work, we have demonstrated that IBB1, a major protease inhibitor of the Bowman-Birk family in soybean (Glycine max), exerts anti-proliferative effect in human colorectal HT29 cancer cells at concentrations higher than 15 μM, in a dose dependent manner. By using confocal microscopy, we have demonstrated that IBB1 is taken up by HT29 colon cancer cells in a time-dependent manner, being the bulk of the internalized protease inhibitor localized in the cytoplasm where might interact with their potential therapeutic target/s.This work was supported by ERDF-co-financed grants AGL2011-26353 (Spanish Ministry of Economy and Competitiveness) and PE2010-CVI-5767 (Junta de Andalucía).Peer reviewe

Revisión bibliográfica de implantología bucofacial del año 2009. 1ª parte

Debido al amplio número de publicaciones que existen sobre Implantología Bucofacial, resultadifícil para el odontólogo seleccionar y leer de forma crítica una cantidad suficiente de artículos que puedan aportarle una información útil para su praxis diaria. En este artículo se pretende sintetizar la información más relevante que se encuentra en las revistas indexadas de la especialidad publicadas durante el año 2009

Revisión bibliográfica de implantología bucofacial del año 2009. 2ª parte

Debido al amplio número de publicaciones que existen sobre Implantología Bucofacial, resulta difícil para el odontólogo seleccionar y leer de forma crítica una cantidad suficiente de artículos que puedan aportarle una información útil para su praxis diaria. En este artículo pretendemos sintetizar la información más relevante que se encuentra en las revistas indexadas de la especialidad publicadas el año 2009

Revisión bibliográfica de implantología bucofacial del año 2009. 2ª parte

Debido al amplio número de publicaciones que existen sobre Implantología Bucofacial, resulta difícil para el odontólogo seleccionar y leer de forma crítica una cantidad suficiente de artículos que puedan aportarle una información útil para su praxis diaria. En este artículo pretendemos sintetizar la información más relevante que se encuentra en las revistas indexadas de la especialidad publicadas el año 2009

Synthetic inhibitors of bacterial cell division targeting the GTP-binding site of FtsZ

Cell division protein FtsZ is the organizer of the cytokinetic Z-ring in most bacteria and a target for new antibiotics. FtsZ assembles with GTP into filaments that hydrolyze the nucleotide at the association interface between monomers and then disassemble. We have replaced FtsZ's GTP with non-nucleotide synthetic inhibitors of bacterial division. We searched for these small molecules among compounds from the literature, from virtual screening (VS), and from our in-house synthetic library (UCM), employing a fluorescence anisotropy primary assay. From these screens we have identified the polyhydroxy aromatic compound UCM05 and its simplified analogue UCM44 that specifically bind to Bacillus subtilis FtsZ monomers with micromolar affinities and perturb normal assembly, as examined with light scattering, polymer sedimentation, and negative stain electron microscopy. On the other hand, these ligands induce the cooperative assembly of nucleotide-devoid archaeal FtsZ into distinct well-ordered polymers, different from GTP-induced filaments. These FtsZ inhibitors impair localization of FtsZ into the Z-ring and inhibit bacterial cell division. The chlorinated analogue UCM53 inhibits the growth of clinical isolates of antibiotic-resistant Staphylococcus aureus and Enterococcus faecalis. We suggest that these interfacial inhibitors recapitulate binding and some assembly-inducing effects of GTP but impair the correct structural dynamics of FtsZ filaments and thus inhibit bacterial division, possibly by binding to a small fraction of the FtsZ molecules in a bacterial cell, which opens a new approach to FtsZ-based antibacterial drug discovery.This work was supported by grants from Plan Nacional de Investigación BFU 2011-23416 (J.M.A.), BFU2099-09552 (P.C.), and SAF2010-22198 (M.L.L.-R.), grant CM S2010/BMD-2353 (M.L.L.-R, P.C., J.M.A.), and fellowships FPI (L.B.R.-A.), FPU (M.A.) and CSIC-JAE (E.R.-A.)