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1.
JCI Insight ; 8(24)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37943618

RESUMO

Germline adenomatous polyposis coli (APC) mutation in patients with familial adenomatous polyposis (FAP) promotes gastrointestinal polyposis, including the formation of frequent gastric fundic gland polyps (FGPs). In this study, we investigated how dysregulated Wnt signaling promotes FGPs and why they localize to the corpus region of the stomach. We developed a biobank of FGP and surrounding nonpolyp corpus biopsies and organoids from patients with FAP for comparative studies. Polyp biopsies and polyp-derived organoids exhibited enhanced Wnt target gene expression. Polyp-derived organoids with intrinsically upregulated Wnt signaling showed poor tolerance to further induction, suggesting that high Wnt restricts growth. Targeted genomic sequencing revealed that most gastric polyps did not arise via APC loss of heterozygosity. Studies in genetic mouse models demonstrated that heterozygous Apc loss increased epithelial cell proliferation in the corpus but not the antrum, while homozygous Apc loss was not maintained in the corpus yet induced hyperproliferation in the antrum. Our findings suggest that heterozygous APC mutation in patients with FAP may be sufficient to drive polyp formation in the corpus region while subsequent loss of heterozygosity to further enhance Wnt signaling is not tolerated. This finding contextualizes the abundant yet benign nature of gastric polyps in FAP patient corpus compared with the rare, yet adenomatous polyps in the antrum.


Assuntos
Polipose Adenomatosa do Colo , Pólipos Adenomatosos , Humanos , Animais , Camundongos , Via de Sinalização Wnt , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia
2.
Rev. cuba. reumatol ; 25(1)mar. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1559954

RESUMO

Introducción: El efecto del tratamiento no quirúrgico periodontal en los pacientes con artritis reumatoide es escaso y controversial. Objetivo: Evaluar el efecto de la terapia periodontal no quirúrgica en la actividad de la artritis reumatoide. Métodos: Se realizó un estudio cuasi experimental de intervención terapéutica en 30 pacientes de ambos sexos entre 35 y 70 años de edad con diagnóstico clínico de artritis reumatoide y periodontitis. Fueron incluidos en este estudio los pacientes con más de ocho dientes presentes y aprobación escrita para participar en la investigación y excluidos las embarazadas, fumadores y los que recibieron terapia periodontal o antibiótica. Los parámetros clínicos-serológicos y periodontales fueron evaluados antes y 30 días después de la terapia periodontal. Las variables estudiadas fueron: formas de periodontitis y actividad de la enfermedad reumática (DAS-28/VSG). Se utilizaron frecuencias absolutas, relativas, chi-cuadrado y correlación de Spearman al 95 % de confianza. Resultados: El grupo de edad de 45-54 años y el sexo femenino fueron predominantes. La periodontitis incipiente y moderada fue la más prevalente antes del tratamiento periodontal y estuvo asociada a los niveles de actividad moderada de la AR. Tras el tratamiento periodontal se confirmó disminuciones en el estado periodontal y en la actividad de la afección reumática en el 73.3 % de los pacientes. Conclusiones: La terapia periodontal no quirúrgica mejoró el estado periodontal y redujo la actividad de la artritis reumatoide.


Introduction: The effect of nonsurgical periodontal treatment in patients with rheumatoid arthritis is limited and controversial. Objective: To evaluate the effect of non-surgical periodontal therapy on the activity of rheumatoid arthritis. Methods: a quasi-experimental study of therapeutic intervention was carried out in 30 patients of both sexes between 35 and 70 years of age with a clinical diagnosis of rheumatoid arthritis and periodontitis. Patients with more than eight teeth present and written approval to participate in the research and excluded were included in this study: pregnant women, smokers and those who received periodontal or antibiotic therapy. The clinical - serological rheumatoid and periodontal parameters were evaluated: before and 30 days after periodontal therapy. The variables studied were: forms of periodontitis and activity of the arthritic disease. Absolute and relative frequencies, chi-square and Spearman's correlation at 95 % confidence were used. Results: The age group of 45-54 years and the female sex were predominant. Early and moderate periodontitis was the most prevalent before periodontal treatment and was associated with moderate levels of rheumatoid activity. After periodontal treatment, decreases in periodontal status and rheumatic disease activity were confirmed in 73.3 % of patients. Conclusions: Non-surgical periodontal therapy improved the periodontal status and activity levels of rheumatoid arthritis.

3.
Front Cell Infect Microbiol ; 12: 878496, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711667

RESUMO

What genes determine in vitro growth and nutrient utilization in asexual blood-stage malaria parasites? Competition experiments between NF54, clone 3D7, a lab-adapted African parasite, and a recently isolated Asian parasite (NHP4026) reveal contrasting outcomes in different media: 3D7 outcompetes NHP4026 in media containing human serum, while NHP4026 outcompetes 3D7 in media containing AlbuMAX, a commercial lipid-rich bovine serum formulation. To determine the basis for this polymorphism, we conducted parasite genetic crosses using humanized mice and compared genome-wide allele frequency changes in three independent progeny populations cultured in media containing human serum or AlbuMAX. This bulk segregant analysis detected three quantitative trait loci (QTL) regions [on chromosome (chr) 2 containing aspartate transaminase AST; chr 13 containing EBA-140; and chr 14 containing cysteine protease ATG4] linked with differential growth in serum or AlbuMAX in each of the three independent progeny pools. Selection driving differential growth was strong (s = 0.10 - 0.23 per 48-hour lifecycle). We conducted validation experiments for the strongest QTL on chr 13: competition experiments between ΔEBA-140 and 3D7 wildtype parasites showed fitness reversals in the two medium types as seen in the parental parasites, validating this locus as the causative gene. These results (i) demonstrate the effectiveness of bulk segregant analysis for dissecting fitness traits in P. falciparum genetic crosses, and (ii) reveal intimate links between red blood cell invasion and nutrient composition of growth media. Use of parasite crosses combined with bulk segregant analysis will allow systematic dissection of key nutrient acquisition/metabolism and red blood cell invasion pathways in P. falciparum.


Assuntos
Malária Falciparum , Plasmodium falciparum , Animais , Cruzamentos Genéticos , Meios de Cultura , Frequência do Gene , Malária Falciparum/parasitologia , Camundongos , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Locos de Características Quantitativas
5.
Rev. colomb. anestesiol ; 43(4): 269-277, Oct.-Dec. 2015. ilus, tab
Artigo em Inglês | LILACS, COLNAL | ID: lil-767534

RESUMO

Introduction: The modified Wilson infraclavicular approach (MWIA) was described in our institution for brachial plexus blocks in paediatric patients. However, concordance studies between this approach and ultrasound for the identification of ideal puncture site have no been reported. Objective: To determine the concordance between MWIA and ultrasound for localization of the ideal puncture site. Materials and methods: Descriptive observational study; we included 100 healthy patients between 1 and 16 years of age, with parental consent, over a 5-month period. Continuous variables were described and kappa statistics were used for concordance evaluation. We also conducted a multivariate analysis to confirm the relationship between the measured distances and weight and height. Results: The distance fromthe skin to the brachial plexus, aswell as the distance between the coracoid process and the brachial plexus, and the distance from the coracoid process to the pleura were all smaller in abduction, with no statistically significant difference. Height and weight are independent factors that determine the distance between the coracoid process and the posterior cord, both in adduction and abduction. The concordance of MWIA vs. ultrasound for determining the ideal puncture site was 47% in both positions. Conclusions: Concordance between MWIA and ultrasound for the determination of the ideal puncture site is low when it comes to anatomic localization; however, this technique must be evaluated in randomized clinical studies in order to determine its efficacy and usefulness. Height and weight are independent factors that determine the distance between the coracoid process and the posterior cord in adduction and abduction.


Introducción: En pacientes pediátricos, el sitio óptimo de inyección para el abordaje infraclavicular sigue siendo sujeto de debate; no hay estudios de concordancia entre el abordaje infraclavicular de Wilson modificado para bloqueo del plexo braquial (AIWM) y el ultrasonido para la localización del sitio ideal de punción. Objetivo: Determinar la concordancia entre AIWM y ultrasonido para localizar el sitio ideal de punción. Materiales y métodos: estudio observacional descriptivo; se incluyeron 100 niños sanos entre 1-16 años, en un periodo de 5 meses. Se describieron variables continuas y se evaluó la concordancia mediante la estadística kappa. Se realizó análisis multivariado para confirmar la correlación entre las distancias, el peso y la talla. Resultados: Se encontró una menor profundidad del plexo braquial y menor distancia entre el plexo braquial y la apófisis coracoides y entre la coracoides y la pleura en abducción, sin significancia estadística. El peso y la talla son factores independientes que determinan la distancia entre la apófisis coracoides y el cordón posterior en abducción y en aducción. La concordancia del sitio ideal de punción entre AIWM y ultrasonido fue 0,47 en ambas posiciones. Conclusiones: La concordancia entre el AIWM y el ultrasonido para determinar el sitio ideal de punción es sorprendentemente baja. Sin embargo, desde el punto de vista de utilidad y eficacia clínica, estas técnicas deben ser comparadas y evaluadas con estudios clínicos aleatorizados. El peso y la talla determinan de forma independiente la distancia entre el cordón posterior y la apófisis coracoides en aducción y abducción del brazo.


Assuntos
Humanos
6.
Rev. medica electron ; 35(5): 461-469, sep.-oct. 2013.
Artigo em Espanhol | LILACS | ID: lil-691261

RESUMO

Se realizó un estudio observacional analítico de tipo transversal de base poblacional para estimar la prevalencia de la hipertensión arterial en la población matancera y determinar la presencia de los factores de riesgo atribuibles a esta enfermedad durante el año 2009-2010. El universo estuvo constituido por la población del municipio Matanzas entre 15 y 74 años de edad que corresponde a 112 348 habitantes. La muestra quedó conformada por 2 640 personas. En la recolección de la información se aplicó un cuestionario validado por la Organización Panamericana de la Salud para la vigilancia de factores de riesgos de las enfermedades no transmisibles. Los datos fueron procesados en el programa EpiInfo 3.4.3 2007. Para el análisis de los datos se emplearon medidas de frecuencias absolutas y relativas, medidas de tendencia central como la media, mediana, y moda; se utilizó el enfoque de riesgo en análisis bivariado, con cálculo de Odds Ratio con sus intervalos de confianza. Se utilizó la prueba de Chi Cuadrado. También Fracción Atribuible de riesgo con sus Intervalos de Confianza del 95 por ciento. Se consideraron diferencias significativas cuando los valores p fueron menores que 0.,05 y los intervalos de confianza del Odds Ratio no incluyera el valor de 1. Se obtuvo una prevalencia de hipertensión arterial de 31,3 por ciento, siendo los controlados de un 67,4 por ciento. De las nueve variables que resultaron significativas en el análisis bivariado, ocho de ellas se mostraron como verdaderos factores asociados al hipertenso al ser analizadas mediante la regresión logística: el colesterol alto, la edad mayor de 50 años, la diabetes mellitus, el hábito de fumar (tabaquismo), la obesidad, los antecedentes familiares de hipertensión arterial, el sobre peso y el bajo nivel escolar.


We carried out a cross-sectional analytic observational research on the population basis to estimate the arterial hypertension prevalence in the Matanzasan population and determine the presence of risk factors that could be attributed to this disease during the year 2009-2010. The universe was formed by the population of the municipality of Matanzas whose age ranged from 15 to 70 years, corresponding to 112 348 inhabitants. The sample was formed by 2 640 persons. In collecting information we applied a questionnaire validated by the Pan-American Health Organization for the surveillance of the non- transmissible disease risk factors. Data were processed in the program EpiInfo 3.4.3 2007. For the data analysis there were used measures of absolute and relative frequencies, central tendency measures like average, medium, and fashion; we used the risk approach in bi-variable analysis, calculating the odds ratio with their confidence intervals. In this case we used the Chi square test. We also used the attributed risk fraction with its confidence intervals 95 per cent. We considered significant differences when the value p were less than 0.05 and the confidence interval did not included the value 1. From the nine variables that were significant in the bi-variable study, 8 were shown true factors associated to the hypertensive persons when they were analyzed through the logistic regression: high levels of cholesterol, people aged more than 50 years, Diabetes Mellitus, the habit of smoking, obesity, arterial hypertension familiar antecedents, overweight, and low level of scholarship.


Assuntos
Adolescente , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Diabetes Mellitus , Fatores de Risco , Hipertensão/epidemiologia , Fumar , Obesidade , Estudos Transversais , Estudos Observacionais como Assunto
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