Lack of mutations of exon 2 of the MEN1 gene in endocrine and nonendocrine sporadic tumors

In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.86186

Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis

So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis. In this article, Nascimento and colleagues demonstrate that neonatal apex resection stimulates cardiomyocyte proliferation and permanent scarring in the apex. Newly formed cardiomyocytes compensate muscle loss by resection, and resected hearts recover functional competence in adulthood. These findings endorse this model for studies aiming to block cardiac fibrosis and/or favoring CM proliferation

DESARROLLO, IMPLEMENTACIÓN Y BENEFICIOS DEL SISTEMA DE ASESORAMIENTO AL REGANTE - SAI EN BRASIL

[ES] Un Servicio de Asesoramiento al regante (SAR) tiene como objetivo principal la optimización del uso del agua en la agricultura, dando respuesta a las demandas tecnológicas de los regantes. El objetivo del trabajo es evaluar la implantación y los beneficios de un modelo de SAR en Brasil, planteado para ofrecer una programación individualizada de riego en parcela a cada uno de los usuarios, basado en el uso de la herramienta on-line “Web S@I”. La herramienta incluye en su base de datos una parte fija con información relativa a cada parcela (características del suelo, cultivo, caracterización del sistema de riego, etc ) y otra dinámica que incorpora, tanto la información obtenida de las estaciones agrometeorológicas en la zona que permite calcular la Evapotranspiración de referencia (ETo) diaria utilizando el método de Penman-Monteith, como los valores de los coeficientes de cultivo (Kc), obtenidos en base al seguimiento en campo de lso técnicos. Las encuestas indican que el 31% de los agricultores siguen la información que se les facilita y que la productividad del agua (WP) aumenta en los usuarios del sistema S@I mejorando la gestión del agua en el Distrito de riego DIBAU.Silva Do Nascimento, AA.; Tarjuelo Martín-Benito, J.; Ribeiro Vieira Lima, S.; Martinez-Romero, A.; Frizzone, J. (2015). DESARROLLO, IMPLEMENTACIÓN Y BENEFICIOS DEL SISTEMA DE ASESORAMIENTO AL REGANTE - SAI EN BRASIL. En XXXIII CONGRESO NACIONAL DE RIEGOS. Valencia 16-18 junio de 2015. Editorial Universitat Politècnica de València. https://doi.org/10.4995/CNRiegos.2015.1446OC

Novel coumarins active against Trypanosoma cruzi and toxicity assessment using the animal model Caenorhabditis elegans

From 2nd Latin American Congress of Clinical and Laboratorial Toxicology Porto Alegre, Brazil. 3-6 June 2018Background: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, Caenorhabditis elegans has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds. Methods: Trypanocidal activity: Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of Trypanosoma cruzi (Tulahuen 2 strain) by inhibitory concentration 50% (IC50). Toxicity assays: Lethal dose 50% (LD50) and Body Area were determined by Caenorhabditis elegans N2 strain (wild type) after acute exposure. Structure-activity relationship: A classificatory model was built using 3D descriptors. Results: Two of these coumarins demonstrated near equipotency to Nifurtimox (IC50 = 5.0 ± 1 μM), with values of: 11 h (LaSOM 266), (IC50 = 6.4 ± 1 μM) and 11 g (LaSOM 231), (IC50 = 8.2 ± 2.3 μM). In C. elegans it was possible to observe that Nfx showed greater toxicity in both the LD50 assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11 h and 11 g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the C. elegans model is efficient for screening potentially toxic compounds. Conclusion: Two coumarins (11 h and 11 g) showed activity against T. cruzi epimastigote similar to Nifurtimox, however with lower toxicity in both LD50 and development of C. elegans assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs