Biotransformation of digitoxigenin by Cochliobolus lunatus

The biotransformation of digitoxigenin (1) by Cochliobolus lunatus was investigated. The biotransformation reaction was carried out in a 4-day process, resulting in the isolation of four products, whose structures were elucidated as 1beta-hydroxydigitoxigenin (2), 7beta-hydroxydigitoxigenin (3), 8beta-hydroxydigitoxigenin (4) and digitoxigenone (5). The production of these derivatives under the employed conditions has never been described so far. This is also the first report on the production of compound 4 by a biotransformation reaction

New 99mTc-Labeled Digitoxigenin Derivative for Cancer Cell Identification

In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs. Digitoxigenin (DIG) and other CGs have been shown to bind and inhibit Na+/K+-adenosinetriphosphatase (ATPase). Tumor cells show a higher expression rate of the Na+/K+-ATPase protein or a stronger affinity towards the binding of CGs and are therefore more prone to CGs than non-tumor cells. Cancer imaging techniques using radiotracers targeted at specific receptors have yielded successful results. Technetium-99m (99mTc) is one of the radionuclides of choice to radiolabel pharmaceuticals because of its favorable physical and chemical properties along with reasonable costs. Herein, we describe a new Na+/K+-ATPase targeting radiotracer consisting of digitoxigenin and diethylenetriaminepentaacetic acid (DTPA), a bifunctional chelating ligand used to prepare 99mTc-labeled complexes, and its evaluation as an imaging probe. We report the synthesis and characterization of the radiolabeled compound including stability tests, blood clearance, and biodistribution in healthy mice. Additionally, we investigated the binding of the compound to A549 human non-small-cell lung cancer cells and the inhibition of the Na+/K+-ATPase by the labeled compound in vitro. The 99mTc-labeled DTPA–digitoxigenin (99mTc-DTPA–DIG) compound displayed high stability in vitro and in vivo, a fast renal excretion, and a specific binding towards A549 cancer cells in comparison to non-tumor cells. Therefore, 99mTc-DTPA–DIG could potentially be used for non-invasive visualization of tumor lesions by means of scintigraphic imaging

Ferramentas para a caracterização de painéis fotovoltaicos

Neste trabajo apresentamos procedimientos y herramientas para la caracterización completa de paneles fotovoltaicos. Como punto de partida, fueron obtenidas las curvas caracteristicas provenidas por el fabricante. En un segundo momento fueron hechas coletas manuales de dados para la confección de las curvas caracteristicas. A partir de las propriedades fisicas de semiconductores el modelamento del panel fue establecido. El procedimiento establecido és muy fatigoso y reiterativo, podendo llevar a imprecisiones. Para la automatización deste procedimiento, lo siguiente sistema fue proyectado y montado: un conversor dc/dc permite realizar el control electronico de carga resistiva; un computadora realiza el control cíclico de la variación de carga del panel. Un sistema de aquisición de dados permite la obtención de los parámetros en el panel. A partir desta coleta de dados automatizada un software constroe las curvas caracteristicas.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

In Vitro

Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity

New 99mTc-labeled digitoxigenin derivative for cancer cell identification

In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs. Digitoxigenin (DIG) and other CGs have been shown to bind and inhibit Na+ /K+ -adenosinetriphosphatase (ATPase). Tumor cells show a higher expression rate of the Na+ /K+ - ATPase protein or a stronger affinity towards the binding of CGs and are therefore more prone to CGs than non-tumor cells. Cancer imaging techniques using radiotracers targeted at specific receptors have yielded successful results. Technetium99m (99mTc) is one of the radionuclides of choice to radiolabel pharmaceuticals because of its favorable physical and chemical properties along with reasonable costs. Herein, we describe a new Na+ /K+ -ATPase targeting radiotracer consisting of digitoxigenin and diethylenetriaminepentaacetic acid (DTPA), a bifunctional chelating ligand used to prepare 99mTc-labeled complexes, and its evaluation as an imaging probe. We report the synthesis and characterization of the radiolabeled compound including stability tests, blood clearance, and biodistribution in healthy mice. Additionally, we investigated the binding of the compound to A549 human non-small-cell lung cancer cells and the inhibition of the Na+ /K+ - ATPase by the labeled compound in vitro. The 99mTc-labeled DTPA−digitoxigenin (99mTc-DTPA−DIG) compound displayed high stability in vitro and in vivo, a fast renal excretion, and a specific binding towards A549 cancer cells in comparison to nontumor cells. Therefore, 99mTc-DTPA−DIG could potentially be used for non-invasive visualization of tumor lesions by means of scintigraphic imaging

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio