Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana
Digital
- Autores:
-
González-Ocampo, Juan Pablo
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2024
- Institución:
- Universidad de Santander
- Repositorio:
- Repositorio Universidad de Santander
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.udes.edu.co:001/10834
- Palabra clave:
- Células Endoteliales
Confluencia
Ensayo de Cicatrización de Herida
IFN-Gamma
TNF-Alfa
Endothelial Cells
Confluence
Wound Healing Assay
IFN-Gamma
TNF-Alpha
- Rights
- embargoedAccess
- License
- http://purl.org/coar/access_right/c_f1cf
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| dc.title.spa.fl_str_mv |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| dc.title.translated.none.fl_str_mv |
In Vitro Study of the Effect of Proinflammatory Cytokines on the Migration of Endothelial Cells of the Human Glomerular Microvasculature |
| title |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| spellingShingle |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana Células Endoteliales Confluencia Ensayo de Cicatrización de Herida IFN-Gamma TNF-Alfa Endothelial Cells Confluence Wound Healing Assay IFN-Gamma TNF-Alpha |
| title_short |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| title_full |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| title_fullStr |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| title_full_unstemmed |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| title_sort |
Estudio in Vitro del Efecto de Citoquinas Proinflamatorias en la Migración de Células Endoteliales de la Microvasculatura Glomerular Humana |
| dc.creator.fl_str_mv |
González-Ocampo, Juan Pablo |
| dc.contributor.advisor.none.fl_str_mv |
Montes-Rincón, Claudia Ximena |
| dc.contributor.author.none.fl_str_mv |
González-Ocampo, Juan Pablo |
| dc.contributor.jury.none.fl_str_mv |
Giraldo, Yessica Silva-Sayago, Jorge |
| dc.contributor.researchgroup.none.fl_str_mv |
Grupo de Investigación Biomédica Traslacional de la Fundación Cardiovascular de Colombia (FCV) |
| dc.subject.proposal.spa.fl_str_mv |
Células Endoteliales Confluencia Ensayo de Cicatrización de Herida IFN-Gamma TNF-Alfa |
| topic |
Células Endoteliales Confluencia Ensayo de Cicatrización de Herida IFN-Gamma TNF-Alfa Endothelial Cells Confluence Wound Healing Assay IFN-Gamma TNF-Alpha |
| dc.subject.proposal.eng.fl_str_mv |
Endothelial Cells Confluence Wound Healing Assay IFN-Gamma TNF-Alpha |
| description |
Digital |
| publishDate |
2024 |
| dc.date.accessioned.none.fl_str_mv |
2024-08-21T16:07:30Z |
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2024-08-21T16:07:30Z 2029-12-31 |
| dc.date.issued.none.fl_str_mv |
2024-06-14 |
| dc.type.none.fl_str_mv |
Trabajo de grado - Pregrado |
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http://purl.org/coar/resource_type/c_7a1f |
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http://purl.org/coar/version/c_71e4c1898caa6e32 |
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Text |
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Universidad de Santander |
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T 17.24 G669e |
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Repositorio Digital Universidad de Santander |
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https://repositorio.udes.edu.co |
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https://repositorio.udes.edu.co/handle/001/10834 |
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Universidad de Santander T 17.24 G669e Repositorio Digital Universidad de Santander |
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https://repositorio.udes.edu.co https://repositorio.udes.edu.co/handle/001/10834 |
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spa |
| language |
spa |
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Medical Subject Headings. National Library of Medicine. 2004 [cited 2024 May 26]. Endothelial Cells. Available from: https://meshb.nlm.nih.gov/record/ui?ui=D042783 Rodriguez LG, Wu X, Guan JL. Wound-Healing Assay. In: Cell Migration [Internet]. New Jersey: Humana Press; 2005 [cited 2023 Sep 25]. p. 023–30. Available from: https://doi.org/10.1385/1-59259-860-9:023 Medical Subject Headings. National Library of Medicine. 1988 [cited 2024 May 26]. Tumor Necrosis Factor-alpha. Available from: https://meshb.nlm.nih.gov/record/ui?ui=D014409 Medical Subject Headings. National Library of Medicine. 1983 [cited 2024 May 26]. Interferon-gamma. Available from: https://meshb.nlm.nih.gov/record/ui?ui=D007371 Organización Mundial de la Salud, Organización Nacional de Trasplantes. WHO-ONT Global Observatory on Donation and Transplantation. 2021 [cited 2023 Aug 13]. Data from the Data from the WHO-ONT Global Observatory on Donation and Transplantation. Available from: https://www.transplant-observatory.org Instituto Nacional de Salud. Instituto Nacional de Salud. 2023 [cited 2024 Mar 8]. Trasplantes en Colombia siguen senda de recuperación. Available from: https://www.ins.gov.co/Noticias/Paginas/Balance-de-trasplantes.aspx#:~:text=En%20los%20útimos%20dos%20años,3.328%20personas%20esperan%20un%20riñón. Wilmar P, Rincón B, Martínez R, Puerto R. Incidencia de rechazo agudo y crónico en receptores de trasplante renal atendidos en la FOSCAL en el periodo 2011 a 2018. SaludUIS. 2018;50 No. 4:19. García PK, Huerfano M, Rodríguez M, Caicedo A, Berrío F, Gonzalez C. Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia. Int J Organ Transplant Med [Internet]. 2016 [cited 2023 May 20];7(3):161. Available from: https://pubmed.ncbi.nlm.nih.gov/27721962/ Thurman JM, Ljubanović D, Royer PA, Kraus DM, Molina H, Barry NP, et al. Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion. Journal of Clinical Investigation [Internet]. 2006 Feb 2 [cited 2023 May 31];116(2):357. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1352158/ Lee HW, Shin JH, Simons M. Flow goes forward and cells step backward: endothelial migration. Exp Mol Med [Internet]. 2022 Jun 1 [cited 2024 Feb 24];54(6):711. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256678/ Li B, Li L, Zhang Q, Zhang H, Xiu R. Effects of tumor necrosis factor-α-induced exosomes on the endothelial cellular behavior, metabolism and bioenergetics. Microcirculation [Internet]. 2019 Jan 1 [cited 2023 May 31];26(1). Available from: https://doi.org/10.1111/micc.12515 Yetkin-Arik B, Vogels IMC, Neyazi N, van Duinen V, Houtkooper RH, van Noorden CJF, et al. Endothelial tip cells in vitro are less glycolytic and have a more flexible response to metabolic stress than non-tip cells. Sci Rep [Internet]. 2019 Dec 1 [cited 2023 May 31];9(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639367/ Dimou P, Wright RD, Budge KL, Midgley A, Satchell SC, Peak M, et al. The human glomerular endothelial cells are potent pro-inflammatory contributors in an in vitro model of lupus nephritis. Sci Rep [Internet]. 2019 Jun 6 [cited 2023 May 25];9(1):8348. Available from: https://doi.org/10.1038/s41598-019-44868-y Gunawardana H, Romero T, Yao N, Heidt S, Mulder A, Elashoff DA, et al. Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses. Scientific Reports 2021 11:1 [Internet]. 2021 Jan 21 [cited 2023 May 31];11(1):1–20. Available from: https://doi.org/10.1038/s41598-020-80102-w Ng CT, Fong LY, Sulaiman MR, Moklas MAM, Yong YK, Hakim MN, et al. Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration. Journal of Interferon and Cytokine Research [Internet]. 2015 Jul 1 [cited 2024 May 25];35(7):513–22. Available from: https://doi.org/10.1089/jir.2014.0188 Lee LYH, Oldham WM, He H, Wang R, Mulhern R, Handy DE, et al. Interferon-gamma Impairs Human Coronary Artery Endothelial Glucose Metabolism via Tryptophan Catabolism and Activates Fatty Acid Oxidation. Circulation [Internet]. 2021 Nov 11 [cited 2023 May 3];144(20). Available from: https://doi.org/10.1161/CIRCULATIONAHA.121.053960 Mannam VKR, Lewis RE, Cruse JM. The fate of renal allografts hinges on responses of the microvascular endothelium. Exp Mol Pathol [Internet]. 2013 Apr 1 [cited 2023 May 31];94(2):398–411. Available from: https://doi.org/10.1016/j.yexmp.2012.06.002 Bodnar RJ. Chemokine Regulation of Angiogenesis During Wound Healing. Adv Wound Care (New Rochelle) [Internet]. 2015 Nov 11 [cited 2023 May 31];4(11):641. Available from: https://doi.org/10.1089/wound.2014.0594 Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods [Internet]. 2007 May [cited 2024 Jun 27];39(2):175–91. Available from: https://doi.org/10.3758/BF03193146 Belouafa S, Habti F, Benhar S, Belafkih B, Tayane S, Hamdouch S, et al. Statistical tools and approaches to validate analytical methods: methodology and practical examples. International Journal of Metrology and Quality Engineering [Internet]. 2017 Mar 8 [cited 2024 Jun 27];8:9. Available from: https://doi.org/10.1051/ijmqe/2016030 Gebäck T, Schulz MMP, Koumoutsakos P, Detmar M. TScratch: A novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques [Internet]. 2009 Apr 25 [cited 2023 May 31];46(4):265–74. Available from: https://doi.org/10.2144/000113083 Escobedo Nicot MM, Herold García S, Ferreira Gomes L, Delgado Font WE, Machado C, Monteiro Pereira E. Clasificación morfológica de células endoteliales de venas del cordón umbilical humano en imágenes digitales de cultivos in vitro. MEDISAN [Internet]. 2018 [cited 2023 Apr 21];22(2):123–31. Available from: https://www.medigraphic.com/pdfs/medisan/mds-2018/mds182b.pdf Agilent Technologies. Agilent Technologies. 2019 [cited 2023 Apr 21]. Agilent Seahorse XF Cell Mito Stress Test Kit. Available from: https://www.agilent.com/cs/library/usermanuals/public/XFp_Cell_Mito_Stress_Test_Kit_User_Guide.pdf Adair TH, Montani JP. Overview of Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences [Internet]. 2010 [cited 2024 May 12]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK53238/ Rajnoch J, Viklický O. Angiogenesis and organ transplantation. Folia Microbiol (Praha) [Internet]. 2004 [cited 2023 Apr 12];49(5):499–505. Available from: https://doi.org/10.1007/BF02931524 Zhang X, Rozengurt E, Reed EF. HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration. Sci Signal [Internet]. 2010 Nov 23 [cited 2023 May 31];3(149). Available from: https://doi.org/10.1126/scisignal.2001158 Salehi S, Sosa RA, Jin YP, Kageyama S, Fishbein MC, Rozengurt E, et al. Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial-monocyte interactions via mTOR in transplant antibody-mediated rejection. Am J Transplant [Internet]. 2018 May 1 [cited 2023 May 31];18(5):1096. Available from: https://doi.org/10.1111/ajt.14544 Jin YP, Valenzuela NM, Zhang X, Rozengurt E, Reed EF. HLA Class II Triggered Signaling Cascades Cause Endothelial Cell Proliferation and Migration: Relevance to Antibody-Mediated Transplant Rejection. J Immunol [Internet]. 2018 Apr 4 [cited 2023 May 31];200(7):2372. Available from: https://doi.org/10.4049/jimmunol.1701259 Jin YP, Valenzuela NM, Ziegler ME, Rozengurt E, Reed EF. Everolimus Inhibits Anti-HLA I Antibody-Mediated Endothelial Cell Signaling, Migration and Proliferation More Potently than Sirolimus. Am J Transplant [Internet]. 2014 [cited 2023 May 31];14(4):806. Available from: https://doi.org/10.1111/ajt.12669 Lamalice L, Le Boeuf F, Huot J. Endothelial Cell Migration During Angiogenesis. Circ Res [Internet]. 2007 Mar 30 [cited 2023 Jun 4];100(6):782–94. Available from: https://doi.org/10.1161/01.RES.0000259593.07661.1e Fortunato IC, Sunyer R. The Forces behind Directed Cell Migration. Biophysica 2022, Vol 2, Pages 548-563 [Internet]. 2022 Dec 1 [cited 2024 May 18];2(4):548–63. Available from: https://doi.org/10.3390/biophysica2040046 Stroka KM, Vaitkus JA, Aranda-Espinoza H. Endothelial cells undergo morphological, biomechanical, and dynamic changes in response to tumor necrosis factor-α. European Biophysics Journal [Internet]. 2012 Nov 2 [cited 2023 Sep 15];41(11):939–47. Available from: https://doi.org/10.1007/s00249-012-0851-3 Xu C, Wu X, Hack BK, Bao L, Cunningham PN. TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase-dependent mechanism. Physiol Rep [Internet]. 2015 [cited 2024 May 25];3(12). Available from: https://doi.org/10.14814/phy2.12636 Palm MM, Dallinga MG, van Dijk E, Klaassen I, Schlingemann RO, Merks RMH. Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression. PLoS One [Internet]. 2016 Nov 9 [cited 2024 May 25];11(11):e0159478. Available from: https://doi.org/10.1371/journal.pone.0159478 Leckie-Harre A, Silverman I, Wu H, Humphreys BD, Malone AF. Sequencing of Physically Interacting Cells in Human Kidney Allograft Rejection to Infer Contact-dependent Immune Cell Transcription. Transplantation [Internet]. 2024 Feb 19 [cited 2024 May 25];108(2):421–9. Available from: https://doi.org/10.1097/TP.0000000000004762 Hernández AM. El factor HIF-1 y la glucólisis en las células tumorales. Revista de educación bioquímica [Internet]. 2009 [cited 2024 Mar 16];28(2):42–51. Available from: https://www.medigraphic.com/pdfs/revedubio/reb-2009/reb092c.pdf Sainson RCA, Johnston DA, Chu HC, Holderfield MT, Nakatsu MN, Crampton SP, et al. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood [Internet]. 2008 May 15 [cited 2023 Sep 15];111(10):4997–5007. Available from: https://doi.org/10.1182/blood-2007-08-108597 INS. INS. 2023 [cited 2024 May 23]. Crece cifra de donación y trasplantes en Colombia. Available from: https://www.ins.gov.co/Noticias/Paginas/Crece-cifra-de-donación-y-trasplantes-en-Colombia.aspx Milone G, Bellofiore C, Leotta S, Milone GA, Cupri A, Duminuco A, et al. Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology. J Clin Med [Internet]. 2022 Jan 26 [cited 2024 May 25];11(3):623. Available from: https://doi.org/10.3390/jcm11030623 Fiorello ML, Treweeke AT, Macfarlane DP, Megson IL. The impact of glucose exposure on bioenergetics and function in a cultured endothelial cell model and the implications for cardiovascular health in diabetes. Scientific Reports 2020 10:1 [Internet]. 2020 Nov 11 [cited 2024 May 23];10(1):1–12. Available from: https://doi.org/10.1038/s41598-020-76505-4 |
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Universidad de Santander |
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Bucaramanga |
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Facultad de Ciencias Médicas y de la Salud |
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Bucaramanga, Colombia |
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Bacteriología y Laboratorio Clínico |
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Montes-Rincón, Claudia Ximenac2a78994-b537-40d0-be7f-fd41473e28aa-1González-Ocampo, Juan Pablo698ea9f3-58f7-40f5-a4bc-65f31430fa3b-1Giraldo, Yessica081b22f0-8bdd-4d7c-9653-eea53da709d6-1Silva-Sayago, Jorge0d5da3a0-6cfa-4dc5-a9d9-593d720d6639-1Grupo de Investigación Biomédica Traslacional de la Fundación Cardiovascular de Colombia (FCV)2024-08-21T16:07:30Z2029-12-312024-08-21T16:07:30Z2024-06-14DigitalIntroducción. El trasplante renal es un procedimiento quirúrgico utilizado para el tratamiento de enfermedades renales avanzadas. Durante el trasplante, las células endoteliales del injerto desempeñan un papel activo en la angiogénesis, la cual es crucial para la conservar la funcionalidad y supervivencia a largo plazo del riñón trasplantado. La presencia de citoquinas proinflamatorias, afecta significativamente las células endoteliales, la cuales responden con cambios fenotípicos y metabólicos. Objetivo. Describir el efecto de citoquinas proinflamatorias en la migración de células endoteliales de la microvasculatura glomerular humana, in vitro. Metodología. Para la determinación de los cambios en la migración inducida por citoquinas proinflamatorias en las células endoteliales, se implementó la prueba de cierre de herida. Para la cuantificación de la actividad migratoria se realizó con el software T-Scratch. Los cambios observados en la migración se correlacionaron con cambios morfológicos y reprogramación metabólica utilizando los resultados obtenidos previamente por el grupo de investigación al que está vinculada esta propuesta (no publicados). Resultados. Se observo que la exposición a IFN-γ y TNF-α genera una disminución en la migración de las células endoteliales con respecto a las células control. El tratamiento con las citoquinas hace que las células adquieren una morfología elongada. Este compromiso de la capacidad migratoria se relaciona con una disminución en la función mitocondrial en las células endoteliales expuestas a las citoquinas. Conclusión. La afectación de la migración que sufren las células endoteliales expuestas a las IFN-γ y TNF-α probablemente retarda la cicatrización del tejido en el trasplante renal con consecuencias negativas en la recuperación de la funcionalidad en el injerto.Introduction. Kidney transplantation is a surgical procedure used for the treatment of advanced kidney diseases. During transplantation, graft endothelial cells play an active role in angiogenesis, which is crucial for preserving the functionality and long-term survival of the transplanted kidney. The presence of proinflammatory cytokines significantly affects endothelial cells, which respond with phenotypic and metabolic changes. Objective. To describe the effect of proinflammatory cytokines on the migration of endothelial cells from the human glomerular microvasculature, in vitro. Methodology. To determine the changes in migration induced by proinflammatory cytokines in endothelial cells, the wound closure test was implemented. To quantify migratory activity, it was carried out with the T-Scratch software. The observed changes in migration were correlated with morphological changes and metabolic reprogramming using the results previously obtained by the research group to which this proposal is linked (unpublished). Results. It was observed that exposure to IFN-γ and TNF-α generates a decrease in the migration of endothelial cells with respect to control cells. Treatment with cytokines causes the cells to acquire an elongated morphology. This compromise of migratory capacity is related to a decrease in mitochondrial function in endothelial cells exposed to cytokines. Conclusion. The impaired migration of endothelial cells exposed to IFN-γ and TNF-α probably delays tissue healing in kidney transplantation with negative consequences on the recovery of graft functionality.PregradoBacteriólogo(a) y Laboratorista ClínicoInmunometabolismoIntroducción 18 Planteamiento del problema 22 Hipótesis 24 Objetivos 25 Objetivo General 25 Objetivos Específicos 25 Justificación 26 Metodología y Diseño Experimental 28 Desarrollo del Objetivo 1 29 Citoquinas 29 Línea Celular 29 Cultivo Celular 29 Estandarización de la Prueba de Cierre de Herida 30 Número de Células por Pozo en Placa de Cultivo 30 Medio de Cultivo 31 Tiempo del Cierre de la Herida 31 Evaluación del Efecto de IFN-γ y TNF-α Sobre la Migración de las HGMEC. 31 Preparación de las HGMEC 31 Ensayo del Cierre de la Herida 32 Análisis de Datos en el Software T-Scratch 33 Desarrollo del Objetivo 2 34 Cambios Morfológicos 34 Reprogramación Metabólica 35 Operacionalización de Variables 37 Análisis Estadístico 37 Estado del Arte 38 Migración Endotelial 38 Efecto de IFN-γ sobre Características Fenotípicas de las Células Endoteliales 41 Efecto de TNF-α Sobre Características Fenotípicas de las Células Endoteliales 43 Resultados 45 Objetivo 1 45 Estandarización de la Prueba de Cierre de Herida 45 Número de Células por Pozo 45 Medio de Cultivo 45 Tiempo de Cierre de la Herida 45 Evaluación del Efecto de las Citoquinas Sobre la Migración de las HGMEC. 47 Objetivo 2 49 Cambios Morfológicos 49 Cambios Metabólicos 50 Discusión de Resultados 53 Referencias Bibliográficas 5864 papplication/pdfapplication/mswordUniversidad de SantanderT 17.24 G669eRepositorio Digital Universidad de Santanderhttps://repositorio.udes.edu.cohttps://repositorio.udes.edu.co/handle/001/10834spaUniversidad de SantanderBucaramangaFacultad de Ciencias Médicas y de la SaludBucaramanga, ColombiaBacteriología y Laboratorio ClínicoMedical Subject Headings. 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