878 resultados para Age-related diseases
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Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7β-hydroxycholesterol, to trigger cell death, activate inflammation, and modulate lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols, it is important to determine their biological activities and identify their signaling pathways, when they are used either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures has been observed with cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of phospholipidosis. This basic knowledge about oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since oxysterols have a number of biological activities, and as oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation, inflammation, and phospholipidosis).
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There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.
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Diabetic retinopathy, age-related macular degeneration and glaucoma are the leading causes of blindness worldwide. Automatic methods for diagnosis exist, but their performance is limited by the quality of the data. Spectral retinal images provide a significantly better representation of the colour information than common grayscale or red-green-blue retinal imaging, having the potential to improve the performance of automatic diagnosis methods. This work studies the image processing techniques required for composing spectral retinal images with accurate reflection spectra, including wavelength channel image registration, spectral and spatial calibration, illumination correction, and the estimation of depth information from image disparities. The composition of a spectral retinal image database of patients with diabetic retinopathy is described. The database includes gold standards for a number of pathologies and retinal structures, marked by two expert ophthalmologists. The diagnostic applications of the reflectance spectra are studied using supervised classifiers for lesion detection. In addition, inversion of a model of light transport is used to estimate histological parameters from the reflectance spectra. Experimental results suggest that the methods for composing, calibrating and postprocessing spectral images presented in this work can be used to improve the quality of the spectral data. The experiments on the direct and indirect use of the data show the diagnostic potential of spectral retinal data over standard retinal images. The use of spectral data could improve automatic and semi-automated diagnostics for the screening of retinal diseases, for the quantitative detection of retinal changes for follow-up, clinically relevant end-points for clinical studies and development of new therapeutic modalities.
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Memory is a multi-component cognitive ability to retain and retrieve information presented in different modalities. Research on memory development has shown that the memory capacity and the processes improve gradually from early childhood to adolescence. Findings related to the sex-differences in memory abilities in early childhood have been inconsistent. Although previous research has demonstrated the effects of the modality of stimulus presentation (auditory versus verbal) and the type of material to be remembered (visual/spatial versus auditory/verbal) on the memory processes and memory organization, the recent research with children is rather limited. The present study is a secondary analysis of data, originally collected from 530 typically developing Turkish children and adolescents. The purpose of the present study was to examine the age-related developments and sex differences in auditory-verbal and visual-spatial short-term memory (STM) in 177 typically developing male and female children, 5 to 8 years of age. Dot-Locations and Word-Lists from the Children's Memory Scale were used to measure visual-spatial and auditory-verbal STM performances, respectively. The findings of the present study suggest age-related differences in both visual-spatial and auditory-verbal STM. Sex-differences were observed only in one visual-spatial STM subtest performance. Modality comparisons revealed age- and task-related differences between auditory-verbal and visual-spatial STM performances. There were no sex-related effects in terms of modality specific performances. Overall, the results of this study provide evidence of STM development in early childhood, and these effects were mostly independent of sex and the modality of the task.
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Thèse réalisée dans le cadre d'une cotutelle entre l'Université de Montréal et l'Université d'Auvergne en France
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Objectif: Évaluer les défis de la mobilité chez les personnes âgées atteintes de dégénérescence maculaire reliée à l’âge (DMLA), de glaucome ou de dystrophie cornéenne de Fuchs et les comparer avec les personnes âgées n’ayant pas de maladie oculaire. Devis: Étude transversale de population hospitalière Participants: 253 participants (61 avec la DMLA, 45 avec la dystrophie cornéenne de Fuchs, 79 avec le glaucome et 68 contrôles) Méthodes: Nous avons recruté les patients parmi ceux qui se font soigner dans les cliniques d’ophtalmologie de l’Hôpital Maisonneuve-Rosemont (Montréal, Canada) de septembre 2009 à octobre 2010. Les patients atteints de la DMLA ou de la maladie de Fuchs ont une acuité visuelle inférieure à 20/40 dans les deux yeux, tandis que les patients avec du glaucome ont un champ visuel dans le pire oeil inférieur ou égal à -4dB. Les patients contrôles, qui ont été recrutés à partir des mêmes cliniques, ont une acuité visuelle et un champ visuel normaux. Nous avons colligé des données concernant la mobilité à partir des questionnaires (aire de mobilité et chutes) et des tests (test de l’équilibre monopodal, timed Up and Go (TUG) test). Pour mesurer la fonction visuelle nous avons mesuré l’acuité visuelle, la sensibilité au contraste et le champ visuel. Nous avons également révisé le dossier médical. Pour les analyses statistiques nous avons utilisé les régressions linéaire et logistique. Critères de jugement principaux: aire de mobilité, équilibre, test timed Up and Go, chutes Résultats: Les trois maladies oculaires ont été associées à des patrons différents de limitation de la mobilité. Les patients atteints de glaucome ont eu le type le plus sévère de restriction de mobilité; ils ont une aire de mobilité plus réduite, des scores plus bas au test TUG et ils sont plus enclins à avoir un équilibre faible et à faire plus de chutes que les contrôles (p < 0.05). De plus, comparativement aux contrôles, les patients ayant de la DMLA ou la dystrophie cornéenne de Fuchs ont eu une aire de mobilité réduite (p < 0.05). Les chutes n’ont pas été associées aux maladies oculaires dans cette étude. Conclusions: Nos résultats suggèrent que les maladies oculaires, et surtout le glaucome, limitent la mobilité chez les personnes âgées. De futures études sont nécessaires pour évaluer l’impact d’une mobilité restreinte chez cette population pour pouvoir envisager des interventions ciblées qui pourraient les aider à maintenir leur indépendance le plus longtemps possible.
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De récents travaux ont mis en évidence que des dysfonctionnements dans l’expression de gènes impliqués dans la plasticité synaptique contribuent aux déclins cognitifs qu’on observe chez les gens âgés et à la progression de la maladie d’Alzheimer. Notre étude avait comme objectif d’étudier le profil d’expression d’ARNm spécifiques impliqués dans la plasticité synaptique chez des rats jeunes et âgés et chez des souris transgéniques 3xTg et WT. Des expériences en qRT-PCR ont été effectuées dans des extraits de cortex et d’hippocampe de rats jeunes et âgés et de souris 3xTg et WT, respectivement. Les résultats ont démontré une augmentation significative de l’expression d’ARNm MAP1B, Stau2, BDNF, CREB et AGO2 principalement dans l’hippocampe (régions CA1-CA3) des souris 3xTg comparé aux souris WT. Une diminution significative a également été observée pour l’ARNm αCaMKII dans le cortex des souris 3xTg comparé aux souris WT. Contrairement à ces observations, aucun changement n’a été observé pour l’expression de gènes impliqués dans la plasticité synaptique chez les rats âgés comparé aux rats jeunes. Ces résultats démontrent qu’un dysfonctionnement existe réellement au début de la maladie d’Alzheimer dans l’expression de gènes spécifiques impliqués dans la plasticité synaptique et contribue potentiellement à la progression de la maladie en engendrant un déséquilibre entre la LTP et la LTD. De plus, les différences d’expressions sont particulièrement observées dans l’hippocampe (régions CA1-CA3) ce qui est consistant avec les études sur la progression de la maladie d’Alzheimer puisqu’il est connu que la région CA1 de l’hippocampe est la plus vulnérable à l’apparition de la maladie. Ces résultats permettent une meilleure compréhension des événements moléculaires qui deviennent dérégulés à l’apparition de la maladie d’Alzheimer.
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La démence d'Alzheimer est une maladie neurodégénérative caractérisée par une perte progressive et irreversible des fonctions cognitives et des compétences intellectuelles. La maladie d’Alzheimer se présente sous deux formes: la forme familiale ou précoce (EOAD) qui représente 5% des cas et elle est liée à des mutations génétiques affectant le métabolisme des peptides amyloïde; et la forme tardive ou sporadique (LOAD) qui représente 95% des cas mais son étiologie est encore mal définie. Cependant, le vieillissement reste le principal facteur de risque pour développer LOAD. Les changements épigénétiques impliquant des modifications des histones jouent un rôle crucial dans les maladies neurodégénératives et le vieillissement lié à l'âge. Des données récentes ont décrit LOAD comme un désordre de l'épigénome et ont associé ce trouble à l'instabilité génomique. Les protéines Polycomb sont des modificateurs épigénétiques qui induisent le remodelage de la chromatine et la répression des gènes à l'hétérochromatine facultative. Nous rapportons que les souris hétérozygotes pour une protéine Polycomb développent avec l'âge un trouble neurologique ressemblant à LOAD caractérisé par l’altération des fonctions cognitives, la phosphorylation de la protéine tau, l'accumulation des peptides amyloïde, et le dysfonctionnement synaptique. Ce phénotype pathologique est précédé par la décondensation de l’hétérochromatine neuronale et l'activation de la réponse aux dommages à l'ADN. Parallèlement, une réduction d’expression de polycomb, malformations de l'hétérochromatine neuronale, et l'accumulation de dommages à l'ADN étaient également présents dans les cerveaux de patients LOAD. Remarquablement, les dommages de l'ADN ne sont pas distribués de façon aléatoire sur le génome mais sont enrichis au niveau des séquences répétitives. Les conclusions présentées dans cette thèse ont identifié des modifications épigénétiques spécifiques qui conduisent à une instabilité génomique aberrante menant à la formation de LOAD. Ces résultats vont aider au développement de nouveaux traitements qui peuvent potentiellement ralentir la neurodégénérescence.
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I) To study the changes in the content of brain rrrorroamirres in streptozotocirr-irrduced tliabetes as a lirnction of age and to lirrd the role oliadrenal lrornroncs in diabetic state. 2) To assess the adrenergic receptor function in the brain stem ofstreptozotocin-induced diabetic rats ofdillerent ages. 3) To study the changes in the basal levels of second messenger cAMP in the brain stenr ofstreptozotocin-induced diabetic rats as a function of age. 4) To study the changes occurring in the content ofmorroamines and their metabolites in whole pancreas and isolated pancreatic islets of streptozotocin-diabetic rats as a function ofage and the effect of adrenal hormones. 5) To study the adrenergic receptors and basal levels of cAMP in isolated pancreatic islets in young and old streptozotoein-diabetic rats. 6) The in virro study of CAMP content in pancreatic islets of young and old rats and its ellect on glucose induced insulin secretion. 7) 'lhe in vitro study on the involvement of dopamine and corticosteroids in glucose induced insulin secretion in pancreatic islets as a function of age.
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Las infecciones asociadas a catéter son la primera causa de infección nosocomial descrita en las unidades de cuidado crítico y un control de estas conlleva a disminuir la morbilidad y mortalidad en estos pacientes, tiempos de estancia hospitalaria y aliviar el costo de una hospitalización prolongada para su familia y la sociedad. Objetivo : evaluar la evidencia en las estrategias de prevención de las infecciones asociadas a catéter en recién nacidos. Materiales y métodos : se realizó una búsqueda sistemática en: Cochrane, Pubmed, desde 1995 hasta Abril de 2009. Se seleccionaron revisiones sistmáticas, ensayos clínicos y estudios observacionales. Se utilizó le metodología SIGN para la calificación de los estudios y evaluar el grado de recomendación basada en la evidencia. Resultados : se evaluaron 13 estudios que cumplían con los criterios de inclusión y que respondían a 6 preguntas sobre las diferentes estrategias para la prevención de infecciones asociadas a catéter en recién nacidos. La heterogenicidad de las investigaciones no permitió la realización de metananálisis. Conclusiones : la implementación de un sistema de control y vigilancia en el seguimiento de todos los procesos con mayor atención en todas las medidas de colocación, cuidado y manejo de los catéteres centrales son de forma integral la mejor estrategia en la prevención de infecciones asociadas a catéter en recién nacidos.
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Experimental and epidemiological studies demonstrate that fetal growth restriction and low birth weight enhance the risk of chronic diseases in adulthood. Derangements in tissue-specific epigenetic programming of fetal and placental tissues are a suggested mechanism of which DNA methylation is best understood. DNA methylation profiles in human tissue are mostly performed in DNA from white blood cells. The objective of this study was to assess DNA methylation profiles of IGF2 DMR and H19 in DNA derived from four tissues of the newborn. We obtained from 6 newborns DNA from fetal placental tissue (n = 5), umbilical cord CD34+ hematopoietic stem cells (HSC) and CD34- mononuclear cells (MNC) (n = 6), and umbilical cord Wharton jelly (n = 5). HCS were isolated using magnetic-activated cell separation. DNA methylation of the imprinted fetal growth genes IGF2 DMR and H19 was measured in all tissues using quantitative mass spectrometry. ANOVA testing showed tissue-specific differences in DNA methylation of IGF2 DMR (p value 0.002) and H19 (p value 0.001) mainly due to a higher methylation of IGF2 DMR in Wharton jelly (mean 0.65, sd 0.14) and a lower methylation of H19 in placental tissue (mean 0.25, sd 0.02) compared to other tissues. This study demonstrates the feasibility of the assessment of differential tissue specific DNA methylation. Although the results have to be confirmed in larger sample sizes, our approach gives opportunities to investigate epigenetic profiles as underlying mechanism of associations between pregnancy exposures and outcome, and disease risks in later life.
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Los movimientos anormales se pueden definir como síndromes neurológicos en los que puede haber un exceso de movimiento o por enlentecimiento de movimientos automáticos o voluntarios, que no estén relacionados con debilidad o espasticidad. Estos se pueden reunir en 2 grandes grupos. Uno en el que hay movimientos excesivos (hiperquinesias), dentro de los cuales se encuentran el temblor, las coreas, distonías, mioclonus y los tics. Por otro lado, puede haber enlentecimiento de los movimientos (hipoquinesia), en el que los síndromes parkinsonianos son la causa más frecuente de este grupo.
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Introducción: Los desórdenes hipertensivos en el embarazo son la mayor causa de morbimortalidad materna en el mundo, su tratamiento habitualmente se realiza con nifedipino o enalapril durante el postparto indistintamente, pero no hay estudios que los comparen. Metodología: Se realizó un estudio de corte transversal con fines analíticos en el cual se incluyeron las historias clínicas de pacientes con trastorno hipertensivo durante el postparto que recibieron alguno de estos dos medicamentos y se evaluó el control de tensión arterial, necesidad de otros antihipertensivos, efectos adversos, presencia de complicaciones en ambos grupos. Resultados: Se estudió una muestra representativa, homogénea de 139 pacientes (p 0,43). Todas controlaron las cifras tensionales con el medicamento recibido. El 45% (n=62) recibió enalapril 20 mg cada 12 horas, el 40% (n=56) recibió nifedipino 30 mg cada 8 horas, el 15% (n=21) recibió nifedipino 30 mg cada 12 horas. No se presentaron efectos adversos, complicaciones o mortalidad en ninguno de los grupos. Las pacientes con enalapril requirieron más antihipertensivos comparado con las pacientes que recibieron nifedipino con diferencia estadísticamente significativa (p 0,001). Discusión La escogencia de un antihipertensivo durante el postparto debe estar encaminada al tipo de trastorno antihipertensivo: aquellos que se presentan por primera vez durante el embarazo se les administra nifedipino con excelentes resultados; aquellos con antecedente de hipertensión previa se les administra enalapril con buenos resultados. Ambos medicamentos controlaron la presión arterial adecuadamente sin complicaciones ni mortalidad.
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Introducción A pesar de que los nevos melanocíticos son un motivo de consulta frecuente en nuestra población no existen estudios a nivel de Colombia acerca de su tratamiento, a nivel mundial existe muy poca literatura al respecto por lo que hay un vacío conceptual en este campo. Objetivos Evaluar los cambios en cuanto a la presencia de pigmento y cicatrización, en los nevos melanocíticos adquiridos tratados con láser, basados en la experiencia de un solo centro en Bogotá. Materiales y métodos Es un estudio observacional de antes y después, en una cohorte histórica, de 90 casos de nevos melanocíticos adquiridos, tratados con láser en Uniláser Medica, en los que se evaluó la presencia de pigmento, cicatrización, y otras variables, con un control realizado a no menos de 3 meses de la intervención. Resultados Se encontró un rango de edad entre los 18 -51 años, promedio 27,59 años; fototipo de III-V; en el 32% de los casos, solo fue requerida una sesión de láser de Co2 y Erbio, para el aclaramiento completo de la misma. La duración del eritema en el 54,4% los casos fue de 1 a 3 meses. En un 64,4% quedó pigmento residual al control, pero de éstos casos el 48,2% fue entre un 5 a un 10% del inicial. El 58,9% hizo cicatriz, de éstos el 63% fue estética. La satisfacción por parte de los pacientes es alta a pesar de la persistencia pigmentaria y/o la presencia de cicatriz. Discusión El tratamiento de nevos melanocíticos adquiridos con láser es una opción terapéutica que genera cambios estadísticamente significativos en cuanto a pigmento, cicatriz estética y alta satisfacción por parte de los pacientes. Se requieren estudios, analíticos, para determinar eficacia del tratamiento.
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Introducción: La enfermedad celiaca (EC) es una enfermedad autoinmune (EA) intestinal desencadenada por la ingesta de gluten. Por la falta de información de la presencia de EC en Latinoamérica (LA), nosotros investigamos la prevalencia de la enfermedad en esta región utilizando una revisión sistemática de la literatura y un meta-análisis. Métodos y resultados: Este trabajo fue realizado en dos fases: La primera, fue un estudio de corte transversal de 300 individuos Colombianos. La segunda, fue una revisión sistemática y una meta-regresión siguiendo las guías PRSIMA. Nuestros resultados ponen de manifiesto una falta de anti-transglutaminasa tisular (tTG) e IgA anti-endomisio (EMA) en la población Colombiana. En la revisión sistemática, 72 artículos cumplían con los criterios de selección, la prevalencia estimada de EC en LA fue de 0,46% a 0,64%, mientras que la prevalencia en familiares de primer grado fue de 5,5 a 5,6%, y en los pacientes con diabetes mellitus tipo 1 fue de 4,6% a 8,7% Conclusión: Nuestro estudio muestra que la prevalencia de EC en pacientes sanos de LA es similar a la notificada en la población europea.