Novel SUZ12 mutations in Weaver‐like syndrome

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Trypanocidal Activity Of Brazilian Plants Against Epimastigote Forms From Y And Bolivia Strains Of Trypanosoma Cruzi

Chagas disease is one of the main public health problems in Latin America. Since the available treatments for this disease are not effective in providing cure, the screening of potential antiprotozoal agents is essential, mainly of those obtained from natural sources. This study aimed to provide an evaluation of the trypanocidal activity of 92 ethanol extracts from species belonging to the families Annonaceae, Apiaceae, Cucurbitaceae, Lamiaceae, Lauraceae, Moraceae, Nyctaginaceae, and Verbenaceae against the Y and Bolivia strains of Trypanosoma cruzi. Additionally, cytotoxic activity on LLCMK2 fibroblasts was evaluated. Both the trypanocidal activity and cytotoxicity were evaluated using the MTT method, in the following concentrations: 500, 350, 250, and 100 μg/mL. Benznidazole was used for positive control. The best results among the 92 samples evaluated were obtained with ethanol extracts of Ocotea paranapiacabensis (Am93) and Aegiphila lhotzkiana (Am160). Am93 showed trypanocidal activity against epimastigote forms of the Bolivia strain and was moderately toxic to LLCMK2 cells, its Selectivity Index (SI) being 14.56, while Am160 showed moderate trypanocidal activity against the Bolivia strain and moderate toxicicity, its SI being equal to 1.15. The screening of Brazilian plants has indicated the potential effect of ethanol extracts obtained from Ocotea paranapiacabensis and Aegiphila lhotzkiana against Chagas disease.223528533Bastos, J.K., Albuquerque, S., Silva, M.L.A., Evaluation of the trypanocidal activity of lignans isolated from the leaves of Zanthoxylum naranjillo (1999) Planta Med, 65, pp. 1-4Batista Jr., J.M., Lopes, A.A., Ambrósio, D.L., Regasini, L.O., Kato, M.J., Bolzani, V.S., Cicarelli, R.M., Furlan, M., Natural chromenes and chromene derivatives as potencial antitrypanosomal agents (2008) Biol Pharm Bull, 31, pp. 538-540Botsaris, A., Plants used traditionally to treat malaria in Brazil: The archives of Flora Medicinal (2007) J Ethnobiol Ethnomed, 1, p. 18Buainain, A., Giazzi, J.F., Belda Neto, F.M., Martini, A.S., Rosa, J.A., Pozetti, G.L., Estudo da atividade de extratos vegetais sobre o desenvolvimento de Trypanosoma cruzi em meio líquido de Warren (1992) Rev Cien Farm, 14, pp. 93-102Cabral, M.M., Barbosa-Filho, J.M., Maia, G.L., Chaves, M.C., Braga, M.V., de Souza, W., Neolignans from plants in northeastern Brazil (Lauraceae) with activity against (2010) Trypanosoma Cruzi. Exp Parasitol, 124, pp. 319-324Costa-Lotufo, L.V., Silveira, E.R., Barros, M.C., Lima, M.A., de Moraes, M.E., de Moraes, M.O., Pessoa, C., Antiproliferative effects of abietane diterpenes from aegiphilla lhotzkyana (2004) Planta Med, 70, pp. 180-182Cotinguiba, F., Regasini, L.O., Bolzani, V.S., Debonsi, H.M., Passerini, D.O., Cicarelli, R.M.B., Kato, M.J., Furlan, M., Piperamides and their derivatives as potential antitrypanosomal agents (2009) Med Chem Res, 18, pp. 703-711Coura, J.R., Castro, S.L., A critical review on Chagas disease chemotherapy (2002) Mem I Oswaldo Cruz, 97, pp. 3-24Coura, J.R., Present situation and new strategies for Chagas disease chemotherapy: A proposal (2009) Mem I Oswaldo Cruz, 104, pp. 549-554Fernandes, O., Souto, R.P., Castro, J.A., Pereira, J.B., Fernandes, N.C., Junqueira, A.C., Naiff, R.D., Coura, J.R., Brazilian isolates of Trypanosoma cruzi from humans and triatomines classified into two lineages using mini-exon and ribosomal RNA sequences (1998) Am J Trop Med Hyg, 58, pp. 807-811Fournet, A., Ferreira, M.E., Rojas de Arias, A., Guy, I., Guinaudeau, H., Heinzen, H., Phytochemical and antiprotozoal activity of (2007) Ocotea Lancifolia. Fitoterapia, 78, pp. 382-384Lopes, A.A., López, S.N., Regasini, L.O., Batista, J.M., Ambrósio, D.L., Kato, M.J., da Silva, B.V., Furlan, M., In vitro activity of compounds isolated from Piper crassinervium against Trypanosoma cruzi (2008) Nat Prod Res, 22, pp. 1040-1046Macedo, A.M., Oliveira, R.P., Pena, S.D.J., Chagas disease: Role of parasite genetic variation in pathogenesis (2002) Exp Mol Med, 4, pp. 1-16Muelas-Serrano, S., Nogal-Ruiz, J.J., Gómez-Barrio, A., Setting of a colorimetric method to determine the viability of Trypanosoma cruzi epimastigotes (2000) Parasitol Res, 86, pp. 999-1002Nwaka, S., Ridley, R.G., Virtual drug discovery and development for neglected diseases through publicprivate partnerships (2003) Nat Rev Drug Discov, 2, pp. 919-928Osorio, E., Arango, G.J., Jiménez, N., Alzate, F., Ruiz, G., Gutiérrez, D., Paco, M.A., Robledo, S., Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae (2007) J Ethnopharmacol, 111, pp. 630-635Regasini, L.O., Cotinguiba, F., Passerini, G.D., Bolzani, V.S., Cicarelli, R.M.B., Kato, M.J., Furlan, M., Trypanocidal activity of Piper arboreum and Piper tuberculatum (Piperaceae) (2009) Rev Bras Farmacog, 19, pp. 199-203Saraiva, J., Vega, C., Rolon, M., da Silva, R., Silva, M.L., Donate, P.M., Bastos, J.K., de Albuquerque, S., In vitro and in vivo activity of lignan lactones derivatives against Trypanosoma cruzi (2007) Parasitol Res, 100, pp. 791-795Tibayrenc, M., Ayala, F.J., The clonal theory of parasitic protozoa: 12 years on (2002) Trends Parasitol, 18, pp. 405-410(2010), http://www.who.int/mediacentre/factsheets/fs340/en/index.html, World Health Organization 2010, accessed in Au

Interconverting flavanone glucosides and other phenolic compounds in Lippia salviaefolia Cham. ethanol extracts

Four interconverting flavanone glycosides [(2R)- and (2S)-3',4',5,6-tetrahydroxyflavanone 7-O-beta-D-glucopyranoside, and (2R)- and (2S)-3',4',5,8-tetrahydroxyflavanone 7-O-beta-D-glucopyranoside], in addition to eight known flavonoids [naringenin, asebogenin, sakuranetin, 6-hydroxyluteolin 7-O-beta-D-glucoside, (2R)- and (25)-eriodictyol 7-O-beta-D-glucopyranoside, aromadendrin and phloretin], three phenylpropanoid glycosides [forsythoside B. alyssonoside and verbascoside] and the epoxylignan lariciresinol 4'-O-beta-D-glucopyranoside were isolated and identified in the EtOH extract of the aerial parts of Lippia salviaefolia Cham. The phytochemical study herein was guided by preliminary antioxidant tests, namely, beta-carotene protection and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity. The crude extracts, their active fractions and the isolated compounds were assayed against intracellular reactive oxygen species (ROS) and human embryonic kidney HEK-293 and human melanoma M14 cancer cell growth. Aromadendrin and phloretin were able to counteract elevation of ROS induced by the oxidant t-butylhydroperoxide (t-BOOH) in HEK-293 cells, whereas phloretin strongly protected HEK-293 cells from ROS damage at 1 mu M. Additionally, phloretin exhibited a significant growth inhibitory effect at 20-40 mu M in both HEK-293 and M14 cells and induced a concentration dependent apoptosis at 20 mu M in M14 cells, suggesting a selective action towards malignant cells. Due to their equilibria, the four interconverting flavanone glycosides were studied using 10 and 2D NMR, HPLC-CD-PDA and HRMS analyses. (C) 2011 Elsevier Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Synchronous In Situ ATPase Activity, Mechanics, and Ca2+Ca2^+ Sensitivity of Human and Porcine Myocardium

Flash-frozen myocardium samples provide a valuable means of correlating clinical cardiomyopathies with abnormalities in sarcomeric contractile and biochemical parameters. We examined flash-frozen left-ventricle human cardiomyocyte bundles from healthy donors to determine control parameters for isometric tension (P(o)) development and Ca(2+) sensitivity, while simultaneously measuring actomyosin ATPase activity in situ by a fluorimetric technique. P(o) was 17 kN m(-2) and pCa(50%) was 5.99 (28 degrees C, I = 130 mM). ATPase activity increased linearly with tension to 132 muM s(-1). To determine the influence of flash-freezing, we compared the same parameters in both glycerinated and flash-frozen porcine left-ventricle trabeculae. P(o) in glycerinated porcine myocardium was 25 kN m(-2), and maximum ATPase activity was 183 microM s(-1). In flash-frozen porcine myocardium, P(o) was 16 kN m(-2) and maximum ATPase activity was 207 microM s(-1). pCa(50%) was 5.77 in the glycerinated and 5.83 in the flash-frozen sample. Both passive and active stiffness of flash-frozen porcine myocardium were lower than for glycerinated tissue and similar to the human samples. Although lower stiffness and isometric tension development may indicate flash-freezing impairment of axial force transmission, we cannot exclude variability between samples as the cause. ATPase activity and pCa(50%) were unaffected by flash-freezing. The lower ATPase activity measured in human tissue suggests a slower actomyosin turnover by the contractile proteins