RESUMEN
Accurate celiac disease (CD) diagnosis must be performed in individuals following a gluten containing diet. Diagnostic procedures for individuals already on a gluten-free diet (GFD) avoiding long gluten reintroductions are still challenging. To deal with this issue, we developed an accurate but simple method that requires only a 3-day gluten challenge and circumvents the main limitations of previously suggested proposals such as requirement of specific peptides and unusual specialized lab facilities or high cost. In an attempt to standardize this methodology to be used in daily clinical practice, we describe here an optimized protocol for assessing activated gut-homing CD8+ T cells in blood combined with a short gluten challenge. Details about the amount and type of gluten antigen and the starting material are included, as well as the strategy to easily characterize and identify the cells of interest using flow cytometry. This methodology constitutes a diagnostic tool for CD diagnosis of high specificity and sensitivity for seropositive disease (>95%) as an alternative to long-term gluten challenge and open new possibilities to test the response to gluten in research and clinical trials.
Asunto(s)
Linfocitos T CD8-positivos , Glútenes , Humanos , Citometría de FlujoRESUMEN
BACKGROUND AND AIMS: Daylength determines flowering dates. However, questions remain regarding flowering dates in the natural environment, such as the synchronous flowering of plants sown simultaneously at highly contrasting latitudes. The daily change in sunrise and sunset times is the cue for the flowering of trees and for the synchronization of moulting in birds at the equator. Sunrise and sunset also synchronize the cell circadian clock, which is involved in the regulation of flowering. The goal of this study was to update the photoperiodism model with knowledge acquired since its conception. METHODS: A large dataset was gathered, including four 2-year series of monthly sowings of 28 sorghum varieties in Mali and two 1-year series of monthly sowings of eight rice varieties in the Philippines to compare with previously published monthly sowings in Japan and Malaysia, and data from sorghum breeders in France, Nicaragua and Colombia. An additive linear model of the duration in days to panicle initiation (PI) and flowering time using daylength and daily changes in sunrise and sunset times was implemented. KEY RESULTS: Simultaneous with the phyllochron, the duration to PI of field crops acclimated to the mean temperature at seedling emergence within the usual range of mean cropping temperatures. A unique additive linear model combining daylength and daily changes in sunrise and sunset hours was accurately fitted for any type of response in the duration to PI to the sowing date without any temperature input. Once calibrated on a complete and an incomplete monthly sowing series at two tropical latitudes, the model accurately predicted the duration to PI of the concerned varieties from the equatorial to the temperate zone. CONCLUSIONS: Including the daily changes in sunrise and sunset times in the updated photoperiodism model largely improved its accuracy at the latitude of each experiment. More research is needed to ascertain its multi-latitudinal accuracy, especially at latitudes close to the equator.
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Oryza , Sorghum , Aclimatación , Flores , Humanos , Fotoperiodo , TemperaturaRESUMEN
La embolización de la arteria uterina ha sido descrita como un método efectivo y seguro en el tratamiento de los miomas sintomáticos. Se presentan 3 casos de pacientes con útero miomatoso sintomático, y su tratamiento mediante esta técnica. En estos 3 casos, las complicaciones postembolización de los miomas hizo necesaria la práctica de una histerectomía. Así mismo se describen otras complicaciones derivadas de la técnica señaladas en la revisión bibliográfica realizada
Uterine artery embolization has been described as an effective and safe treatment for women with symptomatic uterine leiomyomata. We report three cases of women with symptomatic myomatous uterus and their treatment by this approach. In these three cases, hysterectomy was required due to complications following the embolizations. We also describe other complications of this therapeutic approach that came to light in the literature review
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Humanos , Femenino , Adulto , Leiomioma/terapia , Embolización de la Arteria Uterina/métodos , Histerectomía/métodos , Enfermedad Granulomatosa Crónica/diagnóstico por imagen , Embolización de la Arteria Uterina/efectos adversos , Resultado del Tratamiento , Enfermedad Granulomatosa Crónica/patologíaRESUMEN
Klüver-Bucy syndrome (KBS) is a rare behavioral phenotype described in monkeys and humans that appears most often after bilateral temporal damage. The main features of KBS are compulsion to examine objects orally, increased sexual activity, placidity, hypermetamorphosis, visual agnosia, and amnesia. Cases in children are scarce, and the most frequently reported etiology is herpes encephalitis. Hyperorality (90%), hypersexuality (82%), and epilepsy (70%) were the most common features of the 51 cases reported in the literature to date. Carbamazepine, selective serotonin reuptake inhibitors (SSRIs), and neuroleptics have been used for symptomatic treatment with variable control. Corticosteroids or immunosupressive agents, such as rituximab, can be an option to use in some cases, according to etiology suspicion. Cognitive and behavioral disturbances after KBS are often severe, but improvement can occur over a long time and residual disabilities vary from major to fairly mild.We report two new encephalitis-associated pediatric patients and review all of the pediatric KBS cases in the literature to better describe the clinical features of this rare neurobehavioral condition.
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Encéfalo/patología , Epilepsia/etiología , Síndrome de Kluver-Bucy/patología , Adolescente , Animales , Encéfalo/diagnóstico por imagen , Preescolar , Femenino , Fluorodesoxiglucosa F18 , Humanos , Síndrome de Kluver-Bucy/complicaciones , Síndrome de Kluver-Bucy/terapia , Imagen por Resonancia Magnética , Masculino , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Air pollution is thought to raise the risk of neurological disease by promoting neuroinflammation, oxidative stress, glial activation and cerebrovascular damage. Multiple Sclerosis is a common auto-immune disorder, primarily affecting young women. We conducted, to a large prospective study of particulate matter (PM) exposure and multiple sclerosis (MS) risk in two prospective cohorts of women: the Nurses Health Study (NHS) and the Nurses Health Study II (NHS II). METHODS: Cumulative average exposure to different size fractions of PM up to the onset of MS was estimated using spatio-temporal models. We used multivariable Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of MS associated with each size fraction of PM independently. Participants were followed from 1998 through 2004 in NHS and from 1988 through 2007 for NHS II. We conducted additional sensitivity analyses stratified by smoking, region of the US, and age, as well as analyses restricted to women who did not move during the study. Analyses were adjusted for age, ancestry, smoking, body mass index at age 18, region, tract level population density, latitude at age 15, and UV index. RESULTS: We did not observe significant associations between air pollution and MS risk in our cohorts. Among women in the NHS II, the HRs comparing the top vs. bottom quintiles of PM was 1.11 (95% Confidence Intervals (CI): 0.74, 1.66), 1.04 (95% CI: 0.73, 1.50) and 1.09 (95% CI: 0.73, 1.62) for PM10 (≤10µm in diameter), PM2.5 (≤2.5µm in diameter), and PM2.5-10 (2.5 to 10µm in diameter) respectively, and tests for linear trends were not statistically significant. No association between exposure to PM and risk of MS was observed in the NHS. CONCLUSIONS: In this study, exposure to PM air pollution was not related to MS risk.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Esclerosis Múltiple/epidemiología , Material Particulado/análisis , Adulto , Estudios de Cohortes , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Esclerosis Múltiple/etiología , Enfermeras y Enfermeros , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Celiac disease (CD) is developed after gluten ingestion in genetically susceptible individuals. It can appear at any time in life, but some differences are commonly observed between individuals with onset early in life or in adulthood. We aimed to investigate the molecular basis underlying those differences. We collected 19 duodenal biopsies of children and adults with CD and compared the expression of 38 selected genes between each other and with the observed in 13 non-CD controls matched by age. A Bayesian methodology was used to analyze the differences of gene expression between groups. We found seven genes with a similarly altered expression in children and adults with CD when compared to controls (C2orf74, CCR6, FASLG, JAK2, IL23A, TAGAP and UBE2L3). Differences were observed in 13 genes: six genes being altered only in adults (IL1RL1, CD28, STAT3, TMEM187, VAMP3 and ZFP36L1) and two only in children (TNFSF18 and ICOSLG); and four genes showing a significantly higher alteration in adults (CCR4, IL6, IL18RAP and PLEK) and one in children (C1orf106). This is the first extensive study comparing gene expression in children and adults with CD. Differences in the expression level of several genes were found between groups, being notorious the higher alteration observed in adults. Further research is needed to evaluate the possible genetic influence underlying these changes and the specific functional consequences of the reported differences.
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Enfermedad Celíaca/genética , Perfilación de la Expresión Génica , Adulto , Estudios de Casos y Controles , Enfermedad Celíaca/inmunología , Niño , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Células Th17/inmunologíaRESUMEN
Objetivos: Evaluar el impacto del síndrome metabólico y de sus componentes individuales en los hallazgos en la biopsia de próstata, la pieza de prostatectomía radical y en la recidiva bioquímica. Material y métodos: Estudio observacional de 1.319 varones sometidos a biopsia de próstata entre enero de 2007 y diciembre de 2011. El impacto en los hallazgos en la biopsia, en la pieza de prostatectomía radical y en la recidiva bioquímica se ha evaluado mediante regresión logística y regresión de Cox. Resultados: De los 1.319 pacientes 275 (21%) presentaban Síndrome metabólico y se diagnosticaron 517 cánceres de próstata. Se encontró un mayor porcentaje de síndrome metabólico entre pacientes con cáncer de próstata que entre pacientes sin cáncer de próstata (25% frente a 18%; p = 0,002). Se encontraron peores hallazgos en la pieza de prostatectomía radical (grado de Gleason ≥ 7, p < 0,001; estadio ≥ T2c, p < 0,001; márgenes quirúrgicos positivos, p < 0,001) y un mayor porcentaje de recidivas bioquímicas en pacientes con síndrome metabólico que sin síndrome metabólico (24% frente a 13%; p = 0,003). El síndrome metabólico se comportó como factor predictivo independiente de encontrar un grado de Gleason de la pieza ≥ 7, así como de encontrar un estadio de la pieza ≥ T2c, y fue capaz de predecir de forma independiente una mayor tasa de recidivas bioquímicas (p < 0,001, OR: 3,6; p < 0,001 OR: 3,2; p = 0,03 HR: 1,7, respectivamente). Conclusiones: El síndrome metabólico se asocia a peores hallazgos en la pieza de prostatectomía radical y es un factor pronóstico independiente de recidiva bioquímica
Objectives: To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. Material and methods: An observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression.Results: Of the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P = .002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥ 7, P < .001; stage ≥ T2c, P < .001; positive surgical margins, P < .001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P = .003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥ 7 for the specimen, as well as for finding a specimen stage ≥ T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P < .001; OR: 3.2, P = .03; HR: 1.7; respectively). Conclusions: Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence
Asunto(s)
Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Síndrome Metabólico/epidemiología , Adenocarcinoma/epidemiología , Neoplasias de la Próstata/epidemiología , Prostatectomía/métodos , Modelos Logísticos , Pronóstico , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Antígeno Prostático Específico/sangreRESUMEN
OBJECTIVES: To evaluate the impact of metabolic syndrome and its individual components on prostate biopsy findings, the radical prostatectomy specimen and on biochemical recurrence. MATERIAL AND METHODS: An observational study was conducted of 1319 men who underwent prostate biopsy between January 2007 and December 2011. The impact on the biopsy findings, the radical prostatectomy specimen and biochemical recurrence was evaluated using logistic regression and Cox regression. RESULTS: Of the 1319 patients, 275 (21%) had metabolic syndrome, and 517 prostate cancers were diagnosed. A greater percentage of metabolic syndrome was found among patients with prostate cancer than among patients without prostate cancer (25% vs. 18%; P=.002). Poorer results were found in the radical prostatectomy specimens (Gleason score ≥ 7, P<.001; stage ≥ T2c, P<.001; positive surgical margins, P<.001), and there was a greater percentage of biochemical recurrence in patients with metabolic syndrome than in those without metabolic syndrome (24% vs. 13%; P=.003). Metabolic syndrome behaved as an independent predictive factor of finding a Gleason score ≥ 7 for the specimen, as well as for finding a specimen stage ≥ T2c. Metabolic syndrome was also able to independently predict a greater rate of biochemical recurrence (OR: 3.6, P<.001; OR: 3.2, P=.03; HR: 1.7; respectively). CONCLUSIONS: Metabolic syndrome is associated with poorer findings in the radical prostatectomy specimens and is an independent prognostic factor of biochemical recurrence.
Asunto(s)
Adenocarcinoma/epidemiología , Síndrome Metabólico/epidemiología , Neoplasias de la Próstata/epidemiología , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Presión Sanguínea , Índice de Masa Corporal , Comorbilidad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Estimación de Kaplan-Meier , Lípidos/sangre , Masculino , Síndrome Metabólico/patología , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Modelos de Riesgos Proporcionales , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugíaRESUMEN
This research was aimed at developing a high content protein beverage from the mixture of liquid extracts of a pseudocereal, quinoa (Chenopodium quinoa Willd) and two legumes: mesquite (Prosopis chilensis (Mol.) Stunz) and lupine (Lupinus albus L.), native from the Andean highlands of the Chilean northern macro-zone, flavored with raspberry pulp, to help in the feeding of children between 2 and 5 years of lower socioeconomic status with nutritional deficiencies. The formulation was defined by linear programming, its composition was determined by proximate analysis and physical, microbiological and sensory acceptance tests were performed. After 90 days of storage time, the beverage got a protein content of 1.36%, being tryptophan the limiting amino acid; for its part, the chromaticity coordinates of CIEL*a*b* color space showed no statistical significant differences (p < 0.05) maintaining the "dark pink" tonality, the viscosity and the sensory evaluation were acceptable for drinking.
Asunto(s)
Chenopodium quinoa/química , Proteínas en la Dieta/análisis , Alimentos Formulados/análisis , Lupinus/química , Prosopis/química , Preescolar , Chile , Dieta , Grasas de la Dieta/análisis , Fibras de la Dieta/análisis , Femenino , Microbiología de Alimentos , Almacenamiento de Alimentos , Humanos , Masculino , Extractos Vegetales/química , Deficiencia de Proteína/dietoterapia , Clase Social , Gusto/fisiología , Triptófano/análisis , ViscosidadRESUMEN
En la presente investigación se desarrolló una bebida de alto contenido proteico a partir de la mezcla de los extractos líquidos de un pseudocereal, quinua (Chenopodium quinoa Willd) y de dos plantas leguminosas: algarrobo (Prosopis chilensis (Mol.) Stunz) y lupino (Lupinusalbus L.), provenientes del altiplano andino de la macro zona norte de Chile, saborizándose con pulpa de frambuesa, para contribuir en la alimentación de niños entre 2y 5 años de estrato socio-económico bajo con deficiencias nutricionales. La formulación se definió por Programación Lineal, se determinó su composición por análisis proximal y se realizaron pruebas físicas, microbiológicas y de aceptación sensorial. Al concluir los 90 días de almacenamiento la bebida obtuvo un contenido de proteínas de1,36%, siendo el triptófano el aminoácido limitante; por su parte, las coordenadas de cromaticidad del espacio de color CIEL*a*b* no presentaron diferencias significativas (p < 0,05) manteniéndose la tonalidad de "rosado oscuro", la viscosidad y la evaluación sensorial resultaron aceptables (AU)
This research was aimed at developing a high content protein beverage from the mixture of liquid extracts of apseudocereal, quinoa (Chenopodium quinoa Willd) andtwo legumes: mesquite (Prosopis chilensis (Mol.) Stunz) and lupine (Lupinus albus L.), native from the Andeanhighlands of the Chilean northern macro-zone, flavored with raspberry pulp, to help in the feeding of children between 2 and 5 years of lower socioeconomic status with nutritional deficiencies. The formulation was defined by linear programming, its composition was determined by proximate analysis and physical, microbiological and sensory acceptance tests were performed. After 90 days of storage time, the beverage got a protein content of 1.36%,being tryptophan the limiting amino acid; for its part, the chromaticity coordinates of CIEL*a*b* color space showed no statistical significant differences (p < 0.05)maintaining the "dark pink" tonality, the viscosity and the sensory evaluation were acceptable for drinking (AU)
Asunto(s)
Extractos Vegetales/uso terapéutico , Zumos , Proteínas en la Dieta/administración & dosificación , Lupinus , Prosopis , Chenopodium quinoa , Análisis de los Alimentos/métodosRESUMEN
The revaluation of the Andean cultivations, quinua (Chenopodium quinua Willd) and lupin (Lupinus albus L.), to be used in nutritional mixtures, with traditional cereals like corn (Zea mays L.) and rice (Oryza sativa L.), originate mixtures without gluten which constitute a good alternative for the nutrition of children under 24 months that suffer from celiac disease, since they improve the quality of the protein, by essential amino acids compensation, and also impacts in the product's diversification strategy. In the present work, the percentage composition of each flour in the mixture was determined by means of Linear Programming by means of the Solver form from the Excel spreadsheet. Prolamines were determined in the quinua and lupin flours by the ELISA test and the HPLC technique was used in both products obtained called "sweet mix" and "dessert mix", to define the quantity of amino acids with the purpose of providing around the 15% of the proteins required in the day. The flour mixtures selected as optimum, sweet mix, suitable for the preparation of sweet pancakes, as well as for the dessert mix, that by addition of water or milk produce a semi solid dessert, were evaluated after three months of storage, being acceptable their microbiological, bromatological and sensorial requirements, corroborating the results with the good acceptance of the products, prepared from the formulated mixtures, by the children of two Day Care centers of the City of Antofagasta-Chile.
Asunto(s)
Enfermedad Celíaca/dietoterapia , Grano Comestible , Fabaceae , Harina/análisis , Aminoácidos/análisis , Chenopodium quinoa/química , Chile , Cromatografía Líquida de Alta Presión , Grano Comestible/química , Ensayo de Inmunoadsorción Enzimática , Fabaceae/química , Microbiología de Alimentos , Alimentos Formulados/análisis , Humanos , Lactante , Lupinus/química , GustoRESUMEN
La revalorización de los cultivos andinos, quinua (Chenopodiumquinua Willd) y lupino (Lupinus albus L), para ser utilizados en mezclas alimenticias, con cereales tradicionales como maíz (Zea mays L.) y arroz (Oryza sativa L.), originan mezclas sin gluten que constituyen una buena alternativa para la alimentación de niños menores de 24 meses que sufren la enfermedad celíaca, ya que mejoran la calidad de la proteína, por compensación de los aminoácidos es enciales,e incide en la diversificación de productos. En el presente trabajo se determinó la composición de los porcentajes de cada harina en la mezcla mediante Programación Lineal empleando la planilla Solver de la hoja de cálculo Excel. Se determinaron las prolaminas en las harinas de quinua y lupino por el método ELISA y se empleó la técnica delHPLC en los dos productos obtenidos, denominados mezcladulce y mezcla postre, para definir la cantidad de aminoácidos con la finalidad de suplementar alrededor del 15% de las proteínas requeridas en el día. Las mezclas deharina seleccionadas como óptimas, mezcla dulce, apropiada para la preparación de queques, así como para la mezcla postre, que por adición de agua o leche, da origen a un postre, se evaluaron después de tres meses de almacenamiento,siendo aceptables sus requisitos microbiológicos,bromatológicos y sensoriales, corroborándose los resultados,con la buena aceptación de los productos preparados a partir de las mezclas formuladas, por parte de los menores de 2 Jardines Infantiles de la Ciudad de Antofagasta-Chile (AU)
The revaluation of the Andean cultivations, quinua(Chenopodium quinua Willd) and lupin (Lupinus albusL.), to be used in nutritional mixtures, with traditional cereals like corn (Zea mays L.) and rice (Oryza sativa L.),originate mixtures without gluten which constitute a good alternative for the nutrition of children under 24 monthsthat suffer from celiac disease, since they improve the quality of the protein, by essential amino acids compensation,and also impacts in the products diversification strategy. In the present work, the percentage composition of each flour in the mixture was determined by means of Linear Programming by means of the Solver form from the Excel spreadsheet. Prolamines were determined in the quinua and lupin flours by the ELISA test and theHPLC technique was used in both products obtainedcalled sweet mix and dessert mix, to define the quantity of amino acids with the purpose of providing aroundthe 15% of the proteins required in the day. The flourmixtures selected as optimum, sweet mix, suitable for thepreparation of sweet pancakes, as well as for the dessertmix, that by addition of water or milk produce a semisolid dessert, were evaluated after three months of storage,being acceptable their microbiological, bromatological and sensorial requirements, corroborating the results with the good acceptance of the products, prepared from the formulated mixtures, by the children of two Day Carecenters of the City of Antofagasta-Chile (AU)
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Humanos , Grano Comestible , Enfermedad Celíaca/dietoterapia , Fórmulas Infantiles/métodos , Alimentos Formulados/análisis , Suplementos Dietéticos , Proteínas en la Dieta , Programación LinealRESUMEN
Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles=1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p=0.07) and ESR2 polymorphism rs1255998 (p=0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated.
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Cafeína/metabolismo , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Polimorfismo de Nucleótido Simple , Receptores de Estrógenos/genética , Estudios de Casos y Controles , Citocromo P-450 CYP1A2/genética , Terapia de Reemplazo de Estrógeno/efectos adversos , Femenino , Humanos , Masculino , Factores de Riesgo , Distribución por SexoRESUMEN
Introducción: el adalimumab ha demostrado, en ensayos clínicoscontrolados con placebo y en estudios no controlados, serefectivo en la EC luminal y fistulosa perianal.Objetivo: evaluar la eficacia y seguridad del adalimumabcomo tratamiento de inducción y mantenimiento en la EC.Metodología: se incluyeron 22 pacientes con EC tratadoscon adalimumab (16 por enfermedad luminal y 6 por enfermedadfistulosa perianal activa). Veintiún pacientes habían recibido previamenteIFX. Se realizó tratamiento de inducción con 160 mgs.c. en la semana 0 y 80 mg s.c. a las 2 semanas. Los respondedoresrecibieron 40 mg s.c. cada 14 días como tratamiento demantenimiento. Se valoró la respuesta a las 4 semanas de la dosisinicial, y se clasificó la respuesta como remisión, respuesta parcialo ausencia de respuesta.Resultados: tras la inducción, el 25% de los pacientes conenfermedad luminal tuvieron remisión completa y el 56,3% respuestaparcial. La respuesta clínica se mantuvo al año en el71,6% de los pacientes, a los 18 meses en el 53,7% y a los 48meses en el 35,8%. No se objetivaron diferencias en la respuestaentre pacientes que presentaron reacciones de hipersensibilidad opérdida de respuesta a IFX.Todos los pacientes con enfermedad fistulosa perianal (n = 6) habíanrecibido previamente tratamiento con IFX. Tras la inducción un16,7% entran en remisión y un 66,7% presentan respuesta parcial.Todos los pacientes mantienen remisión o respuesta en el tiempocon una mediana de seguimiento de 15 meses.Conclusiones: el adalimumab es un tratamiento eficaz y seguroen la inducción y mantenimiento de la respuesta en la EC luminaly fistulosa perianal. Estos resultados confirman que los hallazgosobtenidos en los ensayos clínicos controlados sonreproducibles en la práctica clínica diaria
Background: adalimumab has been shown in placebo-controlledclinical trials and uncontrolled studies to be effective in luminaland perianal fistulizing CD.Objective: to evaluate the efficacy and safety of adalimumabfor induction and maintenance therapy in CD.Methods: twenty-two patients with CD treated with adalimumab(16 for luminal disease and 6 for active perianal fistulizingdisease) were included. Twenty-one patients had previously receivedIFX. All patients received induction therapy with 160 mgs.c. at week 0, and 80 mg s.c. at week 2. Responders receivedmaintenance therapy with 40 mg s.c. every 14 days. Responsewas assessed at 4 weeks after the initial dose, and classified as remission,partial response, or non-response.Results: after induction, 25% of patients with luminal diseasehad a complete remission, and 56.3% had a partial response.Clinical response was maintained in 71.6% of patients at 1 year,in 53.7% at 18 months, and in 35.8% at 48 months. No differencesin response were observed between patients with hypersensitivityreactions or loss of response to IFX.All patients with perianal fistulizing disease (n = 6) had beenpreviously treated with IFX. After induction 16.7% entered remission,and 66.7% had a partial response. All patients maintainedremission or response over time, with a median follow-up of 15months.Conclusions: adalimumab is an effective and safe treatmentfor the induction and maintenance of response in luminal and perianalfistulizing CD. These results confirm that the findings obtainedin controlled clinical trials are reproducible in clinical practice
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Humanos , Masculino , Femenino , Adolescente , Adulto , Enfermedad de Crohn/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Interferón-alfa/antagonistas & inhibidores , Estudios de SeguimientoRESUMEN
BACKGROUND: adalimumab has been shown in placebo-controlled clinical trials and uncontrolled studies to be effective in luminal and perianal fistulizing CD. OBJECTIVE: to evaluate the efficacy and safety of adalimumab for induction and maintenance therapy in CD. METHODS: twenty-two patients with CD treated with adalimumab (16 for luminal disease and 6 for active perianal fistulizing disease) were included. Twenty-one patients had previously received IFX. All patients received induction therapy with 160 mg s.c. at week 0, and 80 mg s.c. at week 2. Responders received maintenance therapy with 40 mg s.c. every 14 days. Response was assessed at 4 weeks after the initial dose, and classified as remission, partial response, or non-response. RESULTS: after induction, 25% of patients with luminal disease had a complete remission, and 56.3% had a partial response. Clinical response was maintained in 71.6% of patients at 1 year, in 53.7% at 18 months, and in 35.8% at 48 months. No differences in response were observed between patients with hypersensitivity reactions or loss of response to IFX.All patients with perianal fistulizing disease (n = 6) had been previously treated with IFX. After induction 16.7% entered remission, and 66.7% had a partial response. All patients maintained remission or response over time, with a median follow-up of 15 months. CONCLUSIONS: adalimumab is an effective and safe treatment for the induction and maintenance of response in luminal and perianal fistulizing CD. These results confirm that the findings obtained in controlled clinical trials are reproducible in clinical practice.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Adalimumab , Adolescente , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Enfermedad de Crohn/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Fístula Rectal/tratamiento farmacológico , Fístula Rectal/etiología , Inducción de Remisión , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
En estudios previos hemos demostrado que la hormona de crecimiento(GH) induce la proliferación y diferenciación de células cerebrocorticalesembrionarias. El papel de la GH en el desarrollo de los oligodendrocitos(OD) y mielinización es poco conocido. Es este estudio se pretendió investigarsi la GH promueve el desarrollo de oligodendrocitos y los mecanismosde señalización implicados en este proceso. También se estudió, la acción deGH en remielinización cerebral durante el envejecimiento. Células cerebrocorticalesembrionarias se cultivaron en DMEM, 15% de FCS, durante6 horas, se mantuvieron 4 días en medio definido con FGFb (25ng/ml) y seexpusieron a GH (50ng/ml) durante 8 días. Los inhibidores de quinasas seañadieron 45 minutos antes que la GH. Ratas adultas (3 meses) y viejas (27meses) se trataron con GH subcutánea (150 µg/12hr) durante 7 días. Paraverificar el efecto de GH en desarrollo de oligodendrocitos y mielinogenesis,pre-OD y oligodendrocitos maduros se detectaron por inmunocitoquímicacon anticuerpos frente a O4 y proteína básica de mielina (MBP) respectivamente.MBP se analizó en cerebro por inmunohistoquímica. GHincrementó el número de células positivas a O4 (Control: 100%; GH:166±5%) y MBP. Para establecer si las vías de señalización MAPK y PI3Kparticipaban en la acción de GH sobre oligodendrogénesis, los inhibidoresde quinasas PD 098059 (10, 30 and 50 µM) y LY294002 (2,5, 5,10 y 20µM)respectivamente. Tanto la expresión basal como la inducida por GH de O4y MBP se abolió totalmente por PD 30µM y LY 2,5µM, y parcialmente porPD 10µM. El tratamiento con GH también incrementó la expresión deMBP en cerebro de ratas viejas. Estos resultados indican que la GH promuevela oligodendrogénesis incrementando el número de pre-OD y la mielinogénesis.También indican que la activación de las vías MAPK y PI3-Kes necesaria para la inducción de OD por GH y así como para el desarrollobasal de los OD. Además, este estudio demuestra que la GH induce el procesode remielinización en el cerebro de la rata vieja
We have previously reported that Growth Hormone (GH) inducesproliferation and differentation of prenatal cerebrocortical cells. The roleof GH in oligodendrocyte (OD) development and myelination is poorlyunderstood. The aim of the study was to investigate whether GH promotesOD maturation and to establish the signaling pathways involved in itsaction. Also, the action of GH on brain remyelination during aging wasstudied. Prenatal rat cerebrocortical cells incubated in DMEM 15% FCSfor 6 h were cultured for 4 days in defined medium with 25ng/ml bFGFand treated for 8 days with 50 ng/ml human recombinat GH. Kinase inhibitors,when used, were added 30 minutes before GH treatment. Adult(3 months) and 27 month-old Wistar rats were treated subcutaneouslywith rhGH (150 µg/12hr). To verify the effect of GH on OD developmentand myelination, pre-OD and mature OD were detected by immunocytochemistryusing O4 and myelin basic protein (MBP) antibodies respectively.MBP was detected in brain by immunohistochemistry. GH increasedthe number of O4 (Control: 100%; GH: 166±5%) and MBPpositive cells. To elucidate whether the MAPK and PI3K signaling pathwayswere involved in GH-induced OD development, the kinase inhibitorsPD 098059 (10, 30 and 50µM) and LY294002 (2.5, 5.10 and 20µM)were used. GH-induced and basal appearance of O4 and MBP positivecells was completely prevented by 30µM PD and 2.5µM LY and partly by10µM PD. GH treatment increased the expression of MBP in the old rats.These results indicate that GH promotes oligodendrogenesis by increasingthe number of pre-OD and myelination. They also show that the activationof MAPK and PI3K pathways is crucial for GH induction of ODas well as basal OD development. In addition, GH promotes remyelinationin the CNS during aging
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Ratas , Animales , Hormona del Crecimiento/fisiología , Oligodendroglía/fisiología , Envejecimiento/fisiología , Factores de Transcripción , Sistema Nervioso Central/crecimiento & desarrollo , Vaina de Mielina/fisiologíaRESUMEN
In previous studies we demonstrated that vasoactive intestinal peptide (VIP) mediation, and interactions between mitogen-activated protein kinase (MAPK) and cAMP/protein kinase A (PKA) signaling pathways are implicated in insulin-like growth factor I (IGF-I)- and VIP-induced lactotroph proliferation. These facts led us to investigate the intracellular mechanisms involved in IGF-I- and VIP-induced lactotroph proliferation. Exposure of cultured male rat pituitary cells to IGF-I (10(-7) M) or VIP (10(-7) M) stimulated the MAPK cascade. Studies in GH4C1 cells, with an expression vector for Rap1 GTPase-activating protein (Rap1 GAP1), demonstrated reduced VIP-induced MAPK activation, indicating that VIP-dependent activation of the extracellular signal-regulated kinase (ERK) pathway requires PKA-Rap1 signaling. IGF-I induced cAMP-response element (CRE)-binding protein (CREB) phosphorylation through the Ras-MAPK pathway, whereas VIP phosphorylated CREB directly via PKA. The mechanisms that regulate IGF-I-and VIP-CREB-dependent gene transcription were examined using GH4C1 cells transiently transfected with a CRE reporter gene. IGF-I and VIP stimulation of CRE-mediated transcription required activation of both Ras-MAPK and cAMP/PKA signaling. This activation was blocked in the presence of Rap1 GAP1. In summary, we showed that IGF-I and VIP stimulated MAPK activity and the phosphorylation of CREB in pituitary cells. Furthermore, VIP-dependent activation of PKA-Rap1-ERK pathways mediated VIP and IGF-I effects on CREB-dependent transcription in GH4C1 cells. Thus, it is possible that VIP- and IGF-I-induced lactotroph proliferation may involve Rap1.
Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Regulación de la Expresión Génica/fisiología , Factor I del Crecimiento Similar a la Insulina/fisiología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Adenohipófisis/metabolismo , Transcripción Genética/fisiología , Péptido Intestinal Vasoactivo/metabolismo , Proteínas de Unión al GTP rap1/fisiología , Animales , Western Blotting , Células Cultivadas , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Inmunohistoquímica , Masculino , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Fosforilación , Adenohipófisis/enzimología , Ratas , Ratas Sprague-DawleyRESUMEN
In previous studies we demonstrated that IGF-I induces proliferation of pituitary lactotrophs. In addition to its mitotrophic actions, IGF-I is known to prevent apoptosis induced by diverse stimuli in several cell types. In this study, we investigated the action of IGF-I on pituitary cell survival and the intracellular signaling transduction pathway implicated in this effect. Treatment of cultured male rat pituitary cells with IGF-I (10(-7) M) for 24 h prevented pituitary cell death induced by serum deprivation. The protective effect of IGF-I was blocked by phosphoinositide 3-kinase (PI3-kinase) inhibitor, LY294002, but was unaffected by PD98059, which inhibits MAP/ERK kinase (MEK1). IGF-I activation of PI3-kinase induced the phosphorylation and activation of the serine/threonine kinase Akt. Moreover, IGF-I increased the phosphorylation of the pro-apoptotic factor Bad and the levels of the anti-apoptotic protein Bcl-2 through the PI3-kinase pathway in primary pituitary cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Adenohipófisis/citología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Animales , Células Cultivadas , Activación Enzimática , Adenohipófisis/enzimología , Proteínas Proto-Oncogénicas c-akt , Ratas , Proteínas Recombinantes/farmacologíaRESUMEN
OBJECTIVE: To undertake a comprehensive investigation into the very high incidence of congenital deafness on the Macano peninsula of Margarita Island, Venezuela. METHODS: Numerous visits were made to the isolated island community over a 4-year-period. During these visits, it became apparent that a significant number of individuals complained of problems with hearing and vision. Socioeconomic assessments, family pedigrees and clinical histories were recorded on standard questionnaires. All individuals underwent thorough otolaryngologic and ophthalmologic examinations. Twenty milliliters of peripheral venous blood was obtained from each participant. A genome-wide linkage analysis study was performed. Polymorphic microsatellite markers were amplified by polymerase chain reaction and separated on polyacrylamide gels. An ABI 377XL sequencer was used to separate fragments and LOD scores were calculated by using published software. RESULTS: Twenty-four families were identified, comprising 329 individuals, age range 1-80 years, including 184 children. All families were categorized in the lower two (least affluent) socioeconomic categories. A high incidence of consanguinity was detected. Fifteen individuals (11 adults, 4 children) had profound congenital sensorineural hearing loss, vestibular areflexia and retinitis pigmentosa. A maximum LOD score of 6.76 (Linkage >3.0), between markers D11s4186 and D11s911, confirmed linkage to chromosome 11q13.5. The gene myosin VIIA (MYO7A) was confirmed in the interval. Clinical and genetic findings are consistent with a diagnosis of Usher syndrome 1B for those with hearing and vision problems. CONCLUSIONS: We report 15 Usher syndrome 1B individuals from a newly detected Latin American socio-demographic origin, with a very high prevalence of 76 per 100,000 population.