Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi
ilustraciones, fotografías, graficas
- Autores:
-
Perez Lozada, Jhindy Tatiana
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/81783
- Palabra clave:
- 610 - Medicina y salud::615 - Farmacología y terapéutica
Enfermedad de Chagas
Técnicas In Vitro
Chagas Disease
In Vitro Techniques
Trypanosoma cruzi
Trypanosoma cruzi
Epimastigote
In vitro
- Rights
- openAccess
- License
- Atribución-NoComercial-CompartirIgual 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| dc.title.translated.eng.fl_str_mv |
Optimization of an in vitro pharmacological test for the evaluation of substances with possible activity against Trypanosoma cruzi epimastigotes |
| title |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| spellingShingle |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi 610 - Medicina y salud::615 - Farmacología y terapéutica Enfermedad de Chagas Técnicas In Vitro Chagas Disease In Vitro Techniques Trypanosoma cruzi Trypanosoma cruzi Epimastigote In vitro |
| title_short |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| title_full |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| title_fullStr |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| title_full_unstemmed |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| title_sort |
Optimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruzi |
| dc.creator.fl_str_mv |
Perez Lozada, Jhindy Tatiana |
| dc.contributor.advisor.none.fl_str_mv |
Garavito Cardenas, Giovanny Arias Marciales, María Helena |
| dc.contributor.author.none.fl_str_mv |
Perez Lozada, Jhindy Tatiana |
| dc.contributor.researchgroup.spa.fl_str_mv |
Fametra |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud::615 - Farmacología y terapéutica |
| topic |
610 - Medicina y salud::615 - Farmacología y terapéutica Enfermedad de Chagas Técnicas In Vitro Chagas Disease In Vitro Techniques Trypanosoma cruzi Trypanosoma cruzi Epimastigote In vitro |
| dc.subject.other.spa.fl_str_mv |
Enfermedad de Chagas Técnicas In Vitro |
| dc.subject.other.eng.fl_str_mv |
Chagas Disease In Vitro Techniques |
| dc.subject.other.none.fl_str_mv |
Trypanosoma cruzi |
| dc.subject.proposal.none.fl_str_mv |
Trypanosoma cruzi Epimastigote In vitro |
| description |
ilustraciones, fotografías, graficas |
| publishDate |
2021 |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2022-08-04T17:14:29Z |
| dc.date.available.none.fl_str_mv |
2022-08-04T17:14:29Z |
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Trabajo de grado - Maestría |
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info:eu-repo/semantics/masterThesis |
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info:eu-repo/semantics/acceptedVersion |
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Text |
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http://purl.org/redcol/resource_type/TM |
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acceptedVersion |
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https://repositorio.unal.edu.co/handle/unal/81783 |
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Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
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https://repositorio.unal.edu.co/handle/unal/81783 https://repositorio.unal.edu.co/ |
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Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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eng |
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eng |
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RedCol LaReferencia |
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AA, G., & MG, L. (2017). Triatomine physiology in the context of trypanosome infection. Journal of Insect Physiology, 97, 66–76. https://doi.org/10.1016/J.JINSPHYS.2016.07.005 AL, V., P, R., M, W., P, M., E, M., & MG, de L. (2010). Fetal bovine serum concentration affects delta9 desaturase activity of Trypanosoma cruzi. Lipids, 45(3), 275–283. https://doi.org/10.1007/S11745-010-3387-2 Álvarez-Hernández, D.-A., Franyuti-Kelly, G.-A., Díaz-López-Silva, R., González-Chávez, A.-M., González-Hermosillo-Cornejo, D., & Vázquez-López, R. (2018). Chagas disease: Current perspectives on a forgotten disease. Revista Médica Del Hospital General de México, 81(3), 154–164. https://doi.org/10.1016/j.hgmx.2016.09.010 AM, C., JM, B., AM, P., CM, P. B., LJ, S., D, X., CL, B., & RL, T. (2010). In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds. PLoS Neglected Tropical Diseases, 4(7). https://doi.org/10.1371/JOURNAL.PNTD.0000740 Amato Neto, V. (n.d.). Origin of the “Y strain” of Trypanosoma cruzi. Revista Do Instituto de Medicina Tropical de Sao Paulo, 52(3), 171. https://doi.org/10.1590/s0036- 46652010000300012 Bhattacharya, A., Corbeil, A., Monte-Neto, R. L. do, & Fernandez-Prada, C. (2020). Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery. Genes, 11(7), 1–24. https://doi.org/10.3390/GENES11070722 Carneiro, P. F., Do Nascimento, S. B., Pinto, A. V., Pinto, M. D. C. F. R., Lechuga, G. C., Santos, D. O., Dos Santos Júnior, H. M., Resende, J. A. L. C., Bourguignon, S. C., & Ferreira, V. F. (2012). New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms. Bioorganic & Medicinal Chemistry, 20(16), 4995–5000. https://doi.org/10.1016/J.BMC.2012.06.027 CDC. (2019). American Trypanosomiasis. https://www.cdc.gov/dpdx/trypanosomiasisamerican/index.html Ceole, L. F., Gandhi, H., Villamizar, L. H., Soares, M. J., & O’Sullivan, T. P. (2018). Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi. Future Medicinal Chemistry, 10(4), 391–408. https://doi.org/10.4155/FMC-2017- 0184 CMBD, S., A, L., RL, K., RCP, R., AH, I., MA, K., DP, P., & CM, P. (2018). Trypanosoma cruzi transcriptome during axenic epimastigote growth curve. Memorias Do Instituto Oswaldo Cruz, 113(5). https://doi.org/10.1590/0074-02760170404 Cortez, C., Martins, R. M., Alves, R. M., Silva, R. C., Bilches, L. C., Macedo, S., Atayde, V. D., Kawashita, S. Y., Briones, M. R. S., & Yoshida, N. (2012). Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain. PLoS Neglected Tropical Diseases, 6(10). https://doi.org/10.1371/JOURNAL.PNTD.0001804 Cos, P., Vlietinck, A. J., Berghe, D. Vanden, & Maes, L. (2006). Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept.’ Journal of Ethnopharmacology, 106(3), 290–302. https://doi.org/10.1016/J.JEP.2006.04.003 De Lima, A. R., Noris-Suárez, K., Bretaña, A., Contreras, V. T., Navarro, M. C., PérezYbarra, L., & Bubis, J. (2017). Growth arrest and morphological changes triggered by emodin on Trypanosoma cruzi epimastigotes cultivated in axenic medium. Biochimie, 142, 31–40. https://doi.org/10.1016/J.BIOCHI.2017.08.005 Dias, J. C. P., Ramos, A. N., Gontijo, E. D., Luquetti, A., Shikanai-Yasuda, M. A., Coura, J. R., Torres, R. M., Melo, J. R. da C., Almeida, E. A. de, Oliveira, W. de, Silveira, A. C., Rezende, J. M. de, Pinto, F. S., Ferreira, A. W., Rassi, A., Fragata, A. A., Sousa, A. S. de, Correia, D., Jansen, A. M., … Alves, R. V. (2016). II Consenso Brasileiro em Doença de Chagas, 2015. Epidemiologia e Servicos de Saude : Revista Do Sistema Unico de Saude Do Brasil, 25(spe), 7–86. https://doi.org/10.5123/S1679- 49742016000500002 ENFERMEDAD DE CHAGAS Ministerio de Salud y Protección Social-Federación Médica Colombiana. (2012). ENGEL, J. C., & DVORAK, J. A. (1988). Trypanosoma cruzi: Cell Biological Behavior of Epimastigote and Amastigote Forms in Axenic Culture. The Journal of Protozoology, 35(4), 513–518. https://doi.org/10.1111/J.1550-7408.1988.TB04140.X Fallas, J. J., & Chavarría, J. (2011). Implementación del Análisis en Componentes Principales con el software estadístico R. Revista Digital Matemática, Educación e Internet, 11(2), 1659–0643. https://repositoriotec.tec.ac.cr/handle/2238/12882 Gómez Marin, J. E. (2016). Need for a national pharmacy: An issue of national security. Infectio, 20(1), 1–2. https://doi.org/10.1016/j.infect.2015.08.001 Heger, J. I., Froehlich, K., Pastuschek, J., Schmidt, A., Baer, C., Mrowka, R., Backsch, C., Schleußner, E., Markert, U. R., & Schmidt, A. (2018). Human serum alters cell culture behavior and improves spheroid formation in comparison to fetal bovine serum. Experimental Cell Research, 365(1), 57–65. https://doi.org/10.1016/J.YEXCR.2018.02.017 Hernández, R., Cevallos, A. M., Nepomuceno-Mejía, T., & López-Villaseñor, I. (2012). Stationary phase in Trypanosoma cruzi epimastigotes as a preadaptive stage for metacyclogenesis. In Parasitology Research (Vol. 111, Issue 2, pp. 509–514). https://doi.org/10.1007/s00436-012-2974-y Isabel, L., Jaramillo, J., Mejía, R., María, L., Sánchez, M., & Henao, S. V. (2017). Enfermedad de Chagas: una mirada alternativa al tratamiento Chagas disease: an alternative look to treatment. In Revista Cubana de Medicina Tropical (Vol. 69, Issue 2). http://scielo.sld.cu Jaimes-Dueñez, J., Triana-Chávez, O., Cantillo-Barraza, O., Hernández, C., Ramírez, J. D., & Góngora-Orjuela, A. (2017). Molecular and serological detection of Trypanosoma cruzi in dogs (Canis lupus familiaris) suggests potential transmission risk in areas of recent acute Chagas disease outbreaks in Colombia. Preventive Veterinary Medicine, 141, 1–6. https://doi.org/10.1016/j.prevetmed.2017.03.009 JC, E., & JA, D. (1988). Trypanosoma cruzi: cell biological behavior of epimastigote and amastigote forms in axenic culture. The Journal of Protozoology, 35(4), 513–518. https://doi.org/10.1111/J.1550-7408.1988.TB04140.X Kessler, R. L., Contreras, V. T., Marliére, N. P., Aparecida Guarneri, A., Villamizar Silva, L. H., Mazzarotto, G. A. C. A., Batista, M., Soccol, V. T., Krieger, M. A., & Probst, C. M. (2017). Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host. Molecular Microbiology, 104(5), 712–736. https://doi.org/10.1111/mmi.13653 Kitamura, Y., Suzuki, M., Tsukioka, T., Isobe, K., Tsujino, T., Watanabe, T., Watanabe, T., Okudera, H., Nakata, K., Tanaka, T., & Kawase, T. (2018). Spectrophotometric determination of platelet counts in platelet-rich plasma. International Journal of Implant Dentistry, 4(1). https://doi.org/10.1186/S40729-018-0140-8 Kratz, J. M. (2019). Drug discovery for chagas disease: A viewpoint. Acta Tropica, 198, 105107. https://doi.org/10.1016/j.actatropica.2019.105107 Lidani, K. C. F., Andrade, F. A., Bavia, L., Damasceno, F. S., Beltrame, M. H., MessiasReason, I. J., & Sandri, T. L. (2019). Chagas Disease: From Discovery to a Worldwide Health Problem. Frontiers in Public Health, 7. https://doi.org/10.3389/fpubh.2019.00166 Lima, D. B., Mello, C. P., Bandeira, I. C. J., De Menezes, R. R. P. P. B., Sampaio, T. L., Falcão, C. B., Morlighem, J. É. R. L., Rádis-Baptista, G., & Martins, A. M. C. (2018). The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity. Biological Chemistry, 399(2), 187–196. https://doi.org/10.1515/HSZ-2017-0198 Lourenço, A. M., Faccini, C. C., Costa, C. A. de J., Mendes, G. B., & Fragata Filho, A. A. (2018). Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination. Revista Da Sociedade Brasileira de Medicina Tropical, 51(1), 52–56. https://doi.org/10.1590/0037-8682-0285-2017 Martínez-Díaz, R. A., Escario, J. A., Nogal-Ruiz, J. J., & Gómez-Barrio, A. (2001). Biological Characterization of Trypanosoma cruzi Strains. Memorias Do Instituto Oswaldo Cruz, 96(1), 53–59. https://doi.org/10.1590/S0074-02762001000100006 Martinez, F., Perna, E., Perrone, S. V, & Liprandi, A. S. (2019). Chagas DiseZingales, B., Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M. G., … Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect. European Cardiology Review, 14(2), 82–88. https://doi.org/10.15420/ecr.2018.30.2 MC, E., JP, da C., FP, de F., RA, M., E, F., & S, S. (2007). Morphological events during the Trypanosoma cruzi cell cycle. Protist, 158(2), 147–157. https://doi.org/10.1016/J.PROTIS.2006.10.002 Olivera, M. J., Fory, J. A., Porras, J. F., & Buitrago, G. (2019). Prevalence of Chagas disease in Colombia: A systematic review and meta-analysis. In PLoS ONE (Vol. 14Issue 1). Public Library of Science. https://doi.org/10.1371/journal.pone.0210156 OMS | Notas descriptivas: enfermedades tropicales desatendidas. (2017). WHO; World Health Organization. https://www.who.int/es/news-room/fact-sheets/detail/chagasdisease-(american-trypanosomiasis) Özbilgin, A., Çavuş, İ., Nuraydın, A., & Ö Özbilgin, A., Çavuş, İ., Nuraydın, A., & Özel, Y. (2020). The Production of Trypanosoma Brucei Rhodesiense, Cause of African Sleeping Sickness, and Trypanosoma Cruzi, Cause of American Chagas Disease, on Different Medias and Testing a New Media. Turkiye Parazitolojii Dergisi, 44(1), 7–11. https://doi.org/10.4274/TPD.GALENOS.2019.6656 Özbilgin, A., Kaya, T., Çavuş, İ., Yıldırım, A., & Özpınar, N. (2018). Comparison of Reproduction Densities in Different Liquid Media of Trypanosoma cruzi and Cryopreservation. Turkiye Parazitolojii Dergisi, 42(4), 249–253. https://doi.org/10.5152/TPD.2018.5750 Padilla, J. C., Lizarazo, F. E., Murillo, O. L., Mendigaña, F. A., Pachón, E., & Vera, M. J. (2017). Epidemiología de las principales enfermedades transmitidas por vectores en Colombia, 1990-2016. Biomedica : Revista Del Instituto Nacional de Salud, 37, 27– 40. https://doi.org/10.7705/biomedica.v37i0.3769 Querales, M., Torres, J., Graterol, D., Arteaga, R., Navarro, M., Contreras, V., Pineda, W., & De Lima, A. R. (2013). Cambios metabólicos durante la epimastigogénesis in vitro de Trypanosoma cruzi. Salus, 17(3). http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S1316-71382013000300003 Quinn, G. (2016). What plates to use for measuring bacterial growth in Plate reader?..swer. Https://Www.Researchgate.Net/Post/What_plates_to_use_for_measuring_bacterial_ growth_in_Plate_reader/57d07e54b0366dfb10602cd4/Citation/Download. . https://www.researchgate.net/post/What_plates_to_use_for_measuring_bacterial_gr owth_in_Plate_reader/57d07e54b0366dfb10602cd4/citation/download Ribeiro, A. R., Lima, L., Almeida, L. A. de, Monteiro, J., Moreno, C. J. G., Nascimento, J. D., Araújo, R. F. de, Mello, F., Martins, L. P. A., Graminha, M. A. S., Teixeira, M. M. G., Silva, M. S., Steindel, M., & Rosa, J. A. da. (2018). Biological and Molecular Characterization of Trypanosoma cruzi Strains from Four States of Brazil. The American Journal of Tropical Medicine and Hygiene, 98(2), 453. Rodríguez-Monguí, E., Cantillo-Barraza, O., Prieto-Alvarado, F. E., & Cucunubá, Z. M. (2019). Heterogeneity of Trypanosoma cruzi infection rates in vectors and animal reservoirs in Colombia: A systematic review and meta-analysis. In Parasites and Vectors (Vol. 12, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13071-019- 3541-5 Rodríguez, Y. V., Arias, M. H., García, J. O., Deharo, E., & Garavito, G. (2018). Pharmacological activity of Curarea toxicofera in combination with classical antimalarial treatments. Journal of Ethnopharmacology, 222, 288–294. https://doi.org/10.1016/J.JEP.2018.04.008 Romanha, A. J., de Castro, S. L., Soeiro, M. de N. C., Lannes-Vieira, J., Ribeiro, I., Talvani, A., Bourdin, B., Blum, B., Olivieri, B., Zani, C., Spadafora, C., Chiari, E., Chatelain, E., Chaves, G., Calzada, J. E., Bustamante, J. M., Freitas-Junior, L. H., Romero, L. I., Bahia, M. T., … Andrade, Z. de A. (2010). In vitro and in vivo experimental models for drug screening and development for Chagas disease. Memorias Do Instituto Oswaldo Cruz, 105(2), 233–238. https://doi.org/10.1590/S0074-02762010000200022 RR, K., AH, A. S., E, A.-E. R., AO, S., & HN, O. (2019). Addressing the impact of different fetal bovine serum percentages on mesenchymal stem cells biological performance. Molecular Biology Reports, 46(4), 4437–4441. https://doi.org/10.1007/S11033-019- 04898-1 Rueda, K., Trujillo, J. E., Carranza, J. C., & Vallejo, G. A. (2014). Transmisión oral de Trypanosoma cruzi: Una nueva situación epidemiológica de la enfermedad de Chagas en Colombia y otros países suramericanos. Biomedica, 34(4), 631–641. https://doi.org/10.7705/biomedica.v34i4.2204 Santos, S. S., de Araújo, R. V., Giarolla, J., Seoud, O. El, & Ferreira, E. I. (2020). Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. International Journal of Antimicrobial Agents, 55(4), 105906. https://doi.org/10.1016/J.IJANTIMICAG.2020.105906 Shafaie, S., Hutter, V., Brown, M. B., Cook, M. T., & Chau, D. Y. S. (2017). Influence of surface geometry on the culture of human cell lines: A comparative study using flat, round-bottom and v-shaped 96 well plates. PLOS ONE, 12(10), e0186799. Tapia, R. A., Salas, C. O., Vázquez, K., Espinosa-Bustos, C., Soto-Delgado, J., Varela, J., Birriel, E., Cerecetto, H., González, M., & Paulino, M. (2014). Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents. Bioorganic & Medicinal Chemistry Letters, 24(16), 3919–3922. https://doi.org/10.1016/J.BMCL.2014.06.044 Veiga-Santos, P., Pelizzaro-Rocha, K. J., Santos, A. O., Ueda-Nakamura, T., Filho, B. P. D., Silva, S. O., Sudatti, D. B., Bianco, E. M., Pereira, R. C., & Nakamura, C. V. (2010). In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea. Parasitology, 137(11), 1661–1670. https://doi.org/10.1017/S003118201000034X Vela, A., Coral-Almeida, M., Sereno, D., Costales, J. A., Barnabé, C., & Brenière, S. F. (2021). In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: A systematic review and meta-analysis. PLOS Neglected Tropical Diseases, 15(3), e0009269. https://doi.org/10.1371/JOURNAL.PNTD.0009269 Zingales, B., Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M. G., Schijman, A. G., Llewellyn, M. S., Lages-Silva, E., Machado, C. R., Andrade, S. G., & Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 12(2), 240–253. https://doi.org/10.1016/j.meegid.2011.12.009 |
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Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Garavito Cardenas, Giovannycb742e0bd2788f9a1b4014da4c24700aArias Marciales, María Helenab98dd40a73a6e8a5262f52a03f2fe202Perez Lozada, Jhindy Tatianaf43dadaaa2617b1cbc6058ad0b28a2efFametra2022-08-04T17:14:29Z2022-08-04T17:14:29Z2021https://repositorio.unal.edu.co/handle/unal/81783Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, graficasLa enfermedad de Chagas causada por el parásito Trypanosoma cruzi, representa un problema de salud pública a nivel mundial. Su tratamiento está restringido a dos fármacos, Benznidazol y Nifurtimox, que poseen efectos adversos, eficacia limitada y su oportunidad de acceso es igualmente limitado. Las pruebas farmacológicas in vitro constituyen la herramienta inicial para el tamizaje de alternativas promisorias, sin embargo, en este caso particular, no existe un consenso en los protocolos utilizados, por lo que es fundamental optimizar una prueba farmacológica in vitro para evaluar sustancias con potencial actividad frente a Trypanosoma cruzi, con el fin de obtener resultados reproducibles y comparables que aporten al avance del desarrollo de nuevo fármacos. En el presente trabajo se optimizó las condiciones más relevantes usadas en las pruebas farmacológicas in vitro a partir de epimastigotes de la cepa Y de Trypanosoma cruzi. Se determinó que el parásito tiene un crecimiento sostenido hasta el día 8 con una estabilización o disminución a partir del día 9 de incubación. El recambio de medio de cultivo debe ser cada 3 días para garantizar un porcentaje de epimastigotes mayor al 90%. Para el cultivo óptimo del parásito se puede usar tanto el medio LIT como el BHI suplementado con 10 % de SFB. En cuanto a la prueba farmacológica se determinó que se puede usar indistintamente placas con fondo en U o fondo plano sin afectar el crecimiento del parásito, los mejores resultados los obtuvimos empleando una concentración de 1x10 6 parásitos/mL como inóculo inicial y una incubación de 72 horas. Se determinó una CI50 de 16,6 µM (4,32 µg/mL) de benznidazole frente a epimastigotes de T. cruzi de la Cepa Y, coincidente con reportes previos bajo las mismas condiciones. (Texto tomado de la fuente)Chagas disease caused by the parasite Trypanosoma cruzi represents a worldwide public health problem. Its treatment is restricted to two drugs, Benznidazole and Nifurtimox, which have adverse effects, limited efficacy, and their opportunity for access is equally limited. In vitro pharmacological tests are the initial tool for screening promising alternatives, however, in this particular case, there is no consensus on the protocols used, so it is essential to optimize an in vitro pharmacological test to evaluate substances with potential activity against Trypanosoma cruzi, in order to obtain reproducible and comparable results that contribute to the advancement of the development of new drugs. In the present work, the most relevant conditions used in vitro pharmacological tests were optimized from epimastigotes of the Y strain of Trypanosoma cruzi. It was determined that the parasite has a sustained growth until day 8 with a stabilization or decrease from day 9 of incubation. The change of culture medium should be every 3 days to guarantee a percentage of epimastigotes greater than 90%. For optimal culture of the parasite, both LIT medium and BHI supplemented with 10% FBS can be used. Regarding the pharmacological test, it was determined that plates with a U-bottom or flat bottom can be used interchangeably without affecting the growth of the parasite; The best results were obtained using a concentration of 1x10 6 parasites / mL as initial inoculum and an incubation of 72 hours. An IC50 of 16.6 µM (4.32 µg/mL) of benznidazole was determined against epimastigotes of T. cruzi of Strain Y, which coincides with previous reports under the same conditions.MaestríaMagíster en Ciencias - Microbiología123 páginasapplication/pdfengUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaInstituto de Biotecnología (IBUN)Facultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticaEnfermedad de ChagasTécnicas In VitroChagas DiseaseIn Vitro TechniquesTrypanosoma cruziTrypanosoma cruziEpimastigoteIn vitroOptimización de una prueba farmacológica in vitro para la evaluación de sustancias con posible actividad frente a epimastigotes de Trypanosoma cruziOptimization of an in vitro pharmacological test for the evaluation of substances with possible activity against Trypanosoma cruzi epimastigotesTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMRedColLaReferenciaAA, G., & MG, L. (2017). Triatomine physiology in the context of trypanosome infection. Journal of Insect Physiology, 97, 66–76. https://doi.org/10.1016/J.JINSPHYS.2016.07.005AL, V., P, R., M, W., P, M., E, M., & MG, de L. (2010). Fetal bovine serum concentration affects delta9 desaturase activity of Trypanosoma cruzi. Lipids, 45(3), 275–283. https://doi.org/10.1007/S11745-010-3387-2Álvarez-Hernández, D.-A., Franyuti-Kelly, G.-A., Díaz-López-Silva, R., González-Chávez, A.-M., González-Hermosillo-Cornejo, D., & Vázquez-López, R. (2018). Chagas disease: Current perspectives on a forgotten disease. Revista Médica Del Hospital General de México, 81(3), 154–164. https://doi.org/10.1016/j.hgmx.2016.09.010AM, C., JM, B., AM, P., CM, P. B., LJ, S., D, X., CL, B., & RL, T. (2010). In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds. PLoS Neglected Tropical Diseases, 4(7). https://doi.org/10.1371/JOURNAL.PNTD.0000740Amato Neto, V. (n.d.). Origin of the “Y strain” of Trypanosoma cruzi. Revista Do Instituto de Medicina Tropical de Sao Paulo, 52(3), 171. https://doi.org/10.1590/s0036- 46652010000300012Bhattacharya, A., Corbeil, A., Monte-Neto, R. L. do, & Fernandez-Prada, C. (2020). Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery. Genes, 11(7), 1–24. https://doi.org/10.3390/GENES11070722Carneiro, P. F., Do Nascimento, S. B., Pinto, A. V., Pinto, M. D. C. F. R., Lechuga, G. C., Santos, D. O., Dos Santos Júnior, H. M., Resende, J. A. L. C., Bourguignon, S. C., & Ferreira, V. F. (2012). New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms. Bioorganic & Medicinal Chemistry, 20(16), 4995–5000. https://doi.org/10.1016/J.BMC.2012.06.027CDC. (2019). American Trypanosomiasis. https://www.cdc.gov/dpdx/trypanosomiasisamerican/index.htmlCeole, L. F., Gandhi, H., Villamizar, L. H., Soares, M. J., & O’Sullivan, T. P. (2018). Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi. Future Medicinal Chemistry, 10(4), 391–408. https://doi.org/10.4155/FMC-2017- 0184CMBD, S., A, L., RL, K., RCP, R., AH, I., MA, K., DP, P., & CM, P. (2018). Trypanosoma cruzi transcriptome during axenic epimastigote growth curve. Memorias Do Instituto Oswaldo Cruz, 113(5). https://doi.org/10.1590/0074-02760170404Cortez, C., Martins, R. M., Alves, R. M., Silva, R. C., Bilches, L. C., Macedo, S., Atayde, V. D., Kawashita, S. Y., Briones, M. R. S., & Yoshida, N. (2012). Differential Infectivity by the Oral Route of Trypanosoma cruzi Lineages Derived from Y Strain. PLoS Neglected Tropical Diseases, 6(10). https://doi.org/10.1371/JOURNAL.PNTD.0001804Cos, P., Vlietinck, A. J., Berghe, D. Vanden, & Maes, L. (2006). Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept.’ Journal of Ethnopharmacology, 106(3), 290–302. https://doi.org/10.1016/J.JEP.2006.04.003De Lima, A. R., Noris-Suárez, K., Bretaña, A., Contreras, V. T., Navarro, M. C., PérezYbarra, L., & Bubis, J. (2017). Growth arrest and morphological changes triggered by emodin on Trypanosoma cruzi epimastigotes cultivated in axenic medium. Biochimie, 142, 31–40. https://doi.org/10.1016/J.BIOCHI.2017.08.005Dias, J. C. P., Ramos, A. N., Gontijo, E. D., Luquetti, A., Shikanai-Yasuda, M. A., Coura, J. R., Torres, R. M., Melo, J. R. da C., Almeida, E. A. de, Oliveira, W. de, Silveira, A. C., Rezende, J. M. de, Pinto, F. S., Ferreira, A. W., Rassi, A., Fragata, A. A., Sousa, A. S. de, Correia, D., Jansen, A. M., … Alves, R. V. (2016). II Consenso Brasileiro em Doença de Chagas, 2015. Epidemiologia e Servicos de Saude : Revista Do Sistema Unico de Saude Do Brasil, 25(spe), 7–86. https://doi.org/10.5123/S1679- 49742016000500002ENFERMEDAD DE CHAGAS Ministerio de Salud y Protección Social-Federación Médica Colombiana. (2012).ENGEL, J. C., & DVORAK, J. A. (1988). Trypanosoma cruzi: Cell Biological Behavior of Epimastigote and Amastigote Forms in Axenic Culture. The Journal of Protozoology, 35(4), 513–518. https://doi.org/10.1111/J.1550-7408.1988.TB04140.XFallas, J. J., & Chavarría, J. (2011). Implementación del Análisis en Componentes Principales con el software estadístico R. Revista Digital Matemática, Educación e Internet, 11(2), 1659–0643. https://repositoriotec.tec.ac.cr/handle/2238/12882Gómez Marin, J. E. (2016). Need for a national pharmacy: An issue of national security. Infectio, 20(1), 1–2. https://doi.org/10.1016/j.infect.2015.08.001Heger, J. I., Froehlich, K., Pastuschek, J., Schmidt, A., Baer, C., Mrowka, R., Backsch, C., Schleußner, E., Markert, U. R., & Schmidt, A. (2018). Human serum alters cell culture behavior and improves spheroid formation in comparison to fetal bovine serum. Experimental Cell Research, 365(1), 57–65. https://doi.org/10.1016/J.YEXCR.2018.02.017Hernández, R., Cevallos, A. M., Nepomuceno-Mejía, T., & López-Villaseñor, I. (2012). Stationary phase in Trypanosoma cruzi epimastigotes as a preadaptive stage for metacyclogenesis. In Parasitology Research (Vol. 111, Issue 2, pp. 509–514). https://doi.org/10.1007/s00436-012-2974-yIsabel, L., Jaramillo, J., Mejía, R., María, L., Sánchez, M., & Henao, S. V. (2017). Enfermedad de Chagas: una mirada alternativa al tratamiento Chagas disease: an alternative look to treatment. In Revista Cubana de Medicina Tropical (Vol. 69, Issue 2). http://scielo.sld.cuJaimes-Dueñez, J., Triana-Chávez, O., Cantillo-Barraza, O., Hernández, C., Ramírez, J. D., & Góngora-Orjuela, A. (2017). Molecular and serological detection of Trypanosoma cruzi in dogs (Canis lupus familiaris) suggests potential transmission risk in areas of recent acute Chagas disease outbreaks in Colombia. Preventive Veterinary Medicine, 141, 1–6. https://doi.org/10.1016/j.prevetmed.2017.03.009JC, E., & JA, D. (1988). Trypanosoma cruzi: cell biological behavior of epimastigote and amastigote forms in axenic culture. The Journal of Protozoology, 35(4), 513–518. https://doi.org/10.1111/J.1550-7408.1988.TB04140.XKessler, R. L., Contreras, V. T., Marliére, N. P., Aparecida Guarneri, A., Villamizar Silva, L. H., Mazzarotto, G. A. C. A., Batista, M., Soccol, V. T., Krieger, M. A., & Probst, C. M. (2017). Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host. Molecular Microbiology, 104(5), 712–736. https://doi.org/10.1111/mmi.13653Kitamura, Y., Suzuki, M., Tsukioka, T., Isobe, K., Tsujino, T., Watanabe, T., Watanabe, T., Okudera, H., Nakata, K., Tanaka, T., & Kawase, T. (2018). Spectrophotometric determination of platelet counts in platelet-rich plasma. International Journal of Implant Dentistry, 4(1). https://doi.org/10.1186/S40729-018-0140-8Kratz, J. M. (2019). Drug discovery for chagas disease: A viewpoint. Acta Tropica, 198, 105107. https://doi.org/10.1016/j.actatropica.2019.105107Lidani, K. C. F., Andrade, F. A., Bavia, L., Damasceno, F. S., Beltrame, M. H., MessiasReason, I. J., & Sandri, T. L. (2019). Chagas Disease: From Discovery to a Worldwide Health Problem. Frontiers in Public Health, 7. https://doi.org/10.3389/fpubh.2019.00166Lima, D. B., Mello, C. P., Bandeira, I. C. J., De Menezes, R. R. P. P. B., Sampaio, T. L., Falcão, C. B., Morlighem, J. É. R. L., Rádis-Baptista, G., & Martins, A. M. C. (2018). The dinoponeratoxin peptides from the giant ant Dinoponera quadriceps display in vitro antitrypanosomal activity. Biological Chemistry, 399(2), 187–196. https://doi.org/10.1515/HSZ-2017-0198Lourenço, A. M., Faccini, C. C., Costa, C. A. de J., Mendes, G. B., & Fragata Filho, A. A. (2018). Evaluation of in vitro anti-Trypanosoma cruzi activity of medications benznidazole, amiodarone hydrochloride, and their combination. Revista Da Sociedade Brasileira de Medicina Tropical, 51(1), 52–56. https://doi.org/10.1590/0037-8682-0285-2017Martínez-Díaz, R. A., Escario, J. A., Nogal-Ruiz, J. J., & Gómez-Barrio, A. (2001). Biological Characterization of Trypanosoma cruzi Strains. Memorias Do Instituto Oswaldo Cruz, 96(1), 53–59. https://doi.org/10.1590/S0074-02762001000100006Martinez, F., Perna, E., Perrone, S. V, & Liprandi, A. S. (2019). Chagas DiseZingales, B., Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M. G., … Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect. European Cardiology Review, 14(2), 82–88. https://doi.org/10.15420/ecr.2018.30.2MC, E., JP, da C., FP, de F., RA, M., E, F., & S, S. (2007). Morphological events during the Trypanosoma cruzi cell cycle. Protist, 158(2), 147–157. https://doi.org/10.1016/J.PROTIS.2006.10.002Olivera, M. J., Fory, J. A., Porras, J. F., & Buitrago, G. (2019). Prevalence of Chagas disease in Colombia: A systematic review and meta-analysis. In PLoS ONE (Vol. 14Issue 1). Public Library of Science. https://doi.org/10.1371/journal.pone.0210156OMS | Notas descriptivas: enfermedades tropicales desatendidas. (2017). WHO; World Health Organization. https://www.who.int/es/news-room/fact-sheets/detail/chagasdisease-(american-trypanosomiasis) Özbilgin, A., Çavuş, İ., Nuraydın, A., & ÖÖzbilgin, A., Çavuş, İ., Nuraydın, A., & Özel, Y. (2020). The Production of Trypanosoma Brucei Rhodesiense, Cause of African Sleeping Sickness, and Trypanosoma Cruzi, Cause of American Chagas Disease, on Different Medias and Testing a New Media. Turkiye Parazitolojii Dergisi, 44(1), 7–11. https://doi.org/10.4274/TPD.GALENOS.2019.6656Özbilgin, A., Kaya, T., Çavuş, İ., Yıldırım, A., & Özpınar, N. (2018). Comparison of Reproduction Densities in Different Liquid Media of Trypanosoma cruzi and Cryopreservation. Turkiye Parazitolojii Dergisi, 42(4), 249–253. https://doi.org/10.5152/TPD.2018.5750Padilla, J. C., Lizarazo, F. E., Murillo, O. L., Mendigaña, F. A., Pachón, E., & Vera, M. J. (2017). Epidemiología de las principales enfermedades transmitidas por vectores en Colombia, 1990-2016. Biomedica : Revista Del Instituto Nacional de Salud, 37, 27– 40. https://doi.org/10.7705/biomedica.v37i0.3769Querales, M., Torres, J., Graterol, D., Arteaga, R., Navarro, M., Contreras, V., Pineda, W., & De Lima, A. R. (2013). Cambios metabólicos durante la epimastigogénesis in vitro de Trypanosoma cruzi. Salus, 17(3). http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S1316-71382013000300003Quinn, G. (2016). What plates to use for measuring bacterial growth in Plate reader?..swer. Https://Www.Researchgate.Net/Post/What_plates_to_use_for_measuring_bacterial_ growth_in_Plate_reader/57d07e54b0366dfb10602cd4/Citation/Download. . https://www.researchgate.net/post/What_plates_to_use_for_measuring_bacterial_gr owth_in_Plate_reader/57d07e54b0366dfb10602cd4/citation/downloadRibeiro, A. R., Lima, L., Almeida, L. A. de, Monteiro, J., Moreno, C. J. G., Nascimento, J. D., Araújo, R. F. de, Mello, F., Martins, L. P. A., Graminha, M. A. S., Teixeira, M. M. G., Silva, M. S., Steindel, M., & Rosa, J. A. da. (2018). Biological and Molecular Characterization of Trypanosoma cruzi Strains from Four States of Brazil. The American Journal of Tropical Medicine and Hygiene, 98(2), 453.Rodríguez-Monguí, E., Cantillo-Barraza, O., Prieto-Alvarado, F. E., & Cucunubá, Z. M. (2019). Heterogeneity of Trypanosoma cruzi infection rates in vectors and animal reservoirs in Colombia: A systematic review and meta-analysis. In Parasites and Vectors (Vol. 12, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13071-019- 3541-5Rodríguez, Y. V., Arias, M. H., García, J. O., Deharo, E., & Garavito, G. (2018). Pharmacological activity of Curarea toxicofera in combination with classical antimalarial treatments. Journal of Ethnopharmacology, 222, 288–294. https://doi.org/10.1016/J.JEP.2018.04.008Romanha, A. J., de Castro, S. L., Soeiro, M. de N. C., Lannes-Vieira, J., Ribeiro, I., Talvani, A., Bourdin, B., Blum, B., Olivieri, B., Zani, C., Spadafora, C., Chiari, E., Chatelain, E., Chaves, G., Calzada, J. E., Bustamante, J. M., Freitas-Junior, L. H., Romero, L. I., Bahia, M. T., … Andrade, Z. de A. (2010). In vitro and in vivo experimental models for drug screening and development for Chagas disease. Memorias Do Instituto Oswaldo Cruz, 105(2), 233–238. https://doi.org/10.1590/S0074-02762010000200022RR, K., AH, A. S., E, A.-E. R., AO, S., & HN, O. (2019). Addressing the impact of different fetal bovine serum percentages on mesenchymal stem cells biological performance. Molecular Biology Reports, 46(4), 4437–4441. https://doi.org/10.1007/S11033-019- 04898-1Rueda, K., Trujillo, J. E., Carranza, J. C., & Vallejo, G. A. (2014). Transmisión oral de Trypanosoma cruzi: Una nueva situación epidemiológica de la enfermedad de Chagas en Colombia y otros países suramericanos. Biomedica, 34(4), 631–641. https://doi.org/10.7705/biomedica.v34i4.2204Santos, S. S., de Araújo, R. V., Giarolla, J., Seoud, O. El, & Ferreira, E. I. (2020). Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. International Journal of Antimicrobial Agents, 55(4), 105906. https://doi.org/10.1016/J.IJANTIMICAG.2020.105906Shafaie, S., Hutter, V., Brown, M. B., Cook, M. T., & Chau, D. Y. S. (2017). Influence of surface geometry on the culture of human cell lines: A comparative study using flat, round-bottom and v-shaped 96 well plates. PLOS ONE, 12(10), e0186799.Tapia, R. A., Salas, C. O., Vázquez, K., Espinosa-Bustos, C., Soto-Delgado, J., Varela, J., Birriel, E., Cerecetto, H., González, M., & Paulino, M. (2014). Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents. Bioorganic & Medicinal Chemistry Letters, 24(16), 3919–3922. https://doi.org/10.1016/J.BMCL.2014.06.044Veiga-Santos, P., Pelizzaro-Rocha, K. J., Santos, A. O., Ueda-Nakamura, T., Filho, B. P. D., Silva, S. O., Sudatti, D. B., Bianco, E. M., Pereira, R. C., & Nakamura, C. V. (2010). In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea. Parasitology, 137(11), 1661–1670. https://doi.org/10.1017/S003118201000034XVela, A., Coral-Almeida, M., Sereno, D., Costales, J. A., Barnabé, C., & Brenière, S. F. (2021). In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: A systematic review and meta-analysis. PLOS Neglected Tropical Diseases, 15(3), e0009269. https://doi.org/10.1371/JOURNAL.PNTD.0009269Zingales, B., Miles, M. A., Campbell, D. A., Tibayrenc, M., Macedo, A. M., Teixeira, M. M. G., Schijman, A. G., Llewellyn, M. S., Lages-Silva, E., Machado, C. R., Andrade, S. G., & Sturm, N. R. (2012). The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 12(2), 240–253. https://doi.org/10.1016/j.meegid.2011.12.009Público generalORIGINAL1010215217.2022.pdf1010215217.2022.pdfTesis de Maestría en Ciencias - Microbiologíaapplication/pdf3339784https://repositorio.unal.edu.co/bitstream/unal/81783/3/1010215217.2022.pdf492af2005ec9181de2707960716d43e1MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/81783/4/license.txt8153f7789df02f0a4c9e079953658ab2MD54THUMBNAIL1010215217.2022.pdf.jpg1010215217.2022.pdf.jpgGenerated Thumbnailimage/jpeg5914https://repositorio.unal.edu.co/bitstream/unal/81783/5/1010215217.2022.pdf.jpg209a55aec911a83ff36c34e2d5857c2bMD55unal/81783oai:repositorio.unal.edu.co:unal/817832024-08-07 23:10:52.778Repositorio Institucional Universidad Nacional de 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