Integrating the diagnosis of childhood malignancies

Significant progress has been made in understanding the molecular basis of pediatric malignancies. Mechanisms of pediatric acute leukemia induction include hyperdiploidy, aberrant expression of proto-oncogenes, and activation of transcription factors or kinases by aberrant fusion genes. Molecular analysis of these alterations has facilitated the recognition of distinct groups with different sensitivity to therapy, and identified potential targets for antileukemic agents. Similar analysis of pediatric soft tissue and bone tumors also resulted in the identification of specific fusion genes, and their characterization has contributed greatly to understand their biology. Molecular assays for these rearrangements have become important tools in classifying these tumors, providing important prognostic data. However, the understanding of mechanisms involved in the pathogenesis of many other pediatric malignancies, including some embryonal tumors -believed to arise due to perturbation of the normal developmental program- is still vastly incomplete. The Department of Pathology at Texas Children’s Hospital is one of the Children’s Oncology Group (COG) reference centers for pediatric liver tumors. We have been particularly interested in the biology of hepatoblastoma, the most common type of pediatric liver tumor. Although a number of cytogenetic and molecular abnormalities have been described for this type of embryonal tumor, its pathogenesis is still poorly understood. In an attempt to explore the role of different signaling pathways in this disease, we analyzed the expression patterns of different histologic subtypes of hepatoblastoma using cDNA microarray analysis, QRT-PCR and immunohistochemistry. Wnt signaling pathway, critical both in development and in neoplasia, appears to be particularly relevant in these tumors. Mutations of the β-catenin gene are present in over 90% of hepatoblastomas, leading to activating transcription of a number of target genes. The pattern of β-catenin expression and type of mutation in groups of tumors are crucial to understand the corresponding differences in their gene expression profiles. Our findings are consistent with a relationship between poor histologic phenotype and β-catenin activation, indicating the potential utility of targeted gene expression assays to identify molecular events related to the pathogenesis and prognosis of hepatoblastomas

International competitiveness of organic beef production in Germany

The main objective of the project presented in this article was to analyse the strengths and weaknesses of German organic beef production as compared with France, Austria, the Czech Republic and Argentina. Additionally, a number of marketing initiatives in France, Austria, Great Britain and Switzerland were analysed to examine their applicability to German conditions. Within the framework of the International Farm Comparison Network, eleven case studies of organic beef farms in the countries considered were analysed. The strength of the German farms lies on the return side, which is dominated by direct payments. Germany and Austria produce at the highest cost, and profitability in Germany is relatively low. Competitive pressure from France and Austria can not be expected as long as product price levels are higher than in Germany. On the other hand, export opportunities for Germany are limited due to the preference for beef of national / regional origin. There appears to be an incentive for conversion to organic farming on marginal grassland locations in the Czech Republic. On the other hand, future cost increases can be expected. Price differences between domestic and potential export markets will determine the extent of expansion of organic beef production. Argentina, the lowest cost producer, shows major similarities between organic and conventional beef production. However, its potential for further expansion appears to be limited by the local competition with crop production, the use of GMO-seed, and limited potential for expanding production to locations outside the Humid Pampa. The analysis of marketing initiatives shows, however, that the most pressing need for action lies on the marketing side and among the actors themselves. Improved product quality, price premiums, differentiation of marketing channels, and improved communication (towards consumers and in the supply chain) are key words. As the elbow room for price increases appears to be rather limited in the foreseeable future, cost reductions remain a strategy for the producers, for example through specialisation, growth, productivity improvements and reduction of labour costs

Efecto de dietas suplementadas con taninos sobre la calidad bromatológica de carne bovina

Las nuevas tendencias que hay en el mercado de carnes, es producir más con menos, que pueda dejar mayores rendimientos sin perder las propiedades químicas de la carne, ya que éstas son las que definen el precio. El objetivo del trabajo fue determinar el efecto de las dietas suplementadas con taninos sobre la calidad bromatológica de carne bovina. Se trabajó con 16 becerros machos en prueba de respuesta productiva en corral de engorda, con duración de 40 días, con adaptación previa al experimento de 30 días a la etapa de finalización. Los tratamientos consistieron en: dieta típica para bovinos en finalización (testigo) y dieta similar adicionando 0.3 % de extracto de taninos condensados y solubles; correspondiente a 1 g de extracto de taninos por cada 10 kg de peso vivo. Después del sacrificio se tomaron muestras de carne, haciendo cortes de manera transversal entre la 12ª y 13ª costilla, los cortes consistieron en cuatro chuletas con grosor de 2.5 cm de cada canal. A las muestras se les determinó contenido de proteína, cenizas, humedad, grasas y materia seca bajo métodos de la AOAC. Los resultados obtenidos, en este estudio, mostraron que el contenido promedio de proteínas fue de 20.18 %, grasas de 5.47 %, humedad de 74.35 %, cenizas de 2.01 % y materia seca 25.65 %, para ambos grupos. Se observó que no hubo diferencias significativas con respecto al grupo testigo (P ≤ 0.01); solo el contenido de grasa fue mayor a lo reportado, por lo tanto, la concentración de taninos empleada en las dietas de bovinos no influye sobre la composición bromatológica de la carne

Engineering synergistically active and bioavailable cost-effective medicines for neglected tropical diseases; the role of excipients

Leishmaniasis is a neglected tropical disease responsible for the ninth largest disease burden in the world threatening 350 million people mostly in developing countries. The lack of efficacy, severe adverse effects, long duration, high cost and parenteral administration of the current therapies result in poor patient compliance and emergence of resistance. Leishmaniasis' unmet need for safer, affordable and more effective treatments is only partly addressed by today's global health product pipeline that focuses on products amenable to rapid clinical development, mainly by reformulating or repurposing existing drugs for new uses. Excipients are necessary for ensuring the stability and bioavailability of currently available antileishmaniasis drugs which in their majority are poorly soluble or have severe side-effects. Thus, selection of excipients that can ensure bioavailability and safety as well as elicit a synergistic effect against the Leishmania parasites without compromising safety will result in a more efficacious, safe and fast to market medicine. We have evaluated the in vitro activity of 30 commercially available generally regarded as safe (GRAS) excipients against different Leishmania spp., their cytotoxicity and potential use for inclusion in novel formulations. Amongst the tested excipients, the compounds with higher selectivity index were Eudragit E100 (cationic triblock copolymer of dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate), CTAB (cetyltrimethylammonium bromide, cationic), lauric acid, Labrasol (non-ionic, caprylocaproyl polyoxyl-8 glycerides) and sodium deoxycholate. An ideal excipient needs to possess amphiphilic nature with ionic/polar groups and possess a short or medium fatty acid chain such as lauric (C12), capric (C10) or caprylicacid (C8). Inclusion of these excipients and identification of the optimal combination of drug and excipients would lead to a more effective and safer antileishmanial therapies