RESUMEN
The differential diagnosis and treatment of seronegative enteropathy, also termed seronegative villous atrophy (SNVA), is a clinical challenge. Although seronegative coeliac disease (CD) is a frequent cause of SNVA, the aetiology can include immune-mediated, inflammatory, infectious, and drug-related forms. As a misdiagnosis of SNVA can result in patients being unnecessarily placed on a lifelong strict gluten-free diet or even given incorrect immunosuppressive therapy, the aim of this paper is to provide an evidence-based and practical approach for the workup and management of SNVA.
Asunto(s)
Atrofia/dietoterapia , Dieta Sin Gluten , Enfermedades Intestinales/dietoterapia , Enfermedad Celíaca/dietoterapia , Diagnóstico Diferencial , Humanos , Mucosa IntestinalRESUMEN
Glucagon-like peptide-2 (GLP-2) plays a major role in repairing impaired intestinal mucosa, but its mechanism in the improvement of intestinal barrier function during the aging process remains unclear. In this study, 26-month-old male Sprague-Dawley rats were randomized to control group and GLP-2 group treated with a dose of 250 µgâ¢kg-1â¢d-1 by intraperitoneal injection. After 14 days of treatment, intestinal mucosal morphometric changes were observed by light microscopy and transmission electron microscopy (TEM). Small intestinal permeability was evaluated by fluorescein isothiocyanate (FITC)-labeled dextran. The mRNA and protein expression of Zonula Occludens-1 (ZO-1), occludin, claudin-1 and the GLP-2 receptor (GLP-2R) were detected by Real-time PCR and Western blot. Our results showed that GLP-2 administration significantly improved the age-related atrophy of intestinal mucosa and villi and increased small intestinal permeability. The mRNA and protein expression of ZO-1and occludin in ileum were up regulated in the GLP-2-treated old rats. In addition, the serum GLP-2 levels were negatively correlated with small intestinal permeability measured by FITC-dextran levels (r=-0.610, P<0.01). Taking all these data together, it is concluded that GLP-2 improved small intestinal epithelial barrier function in aged rats mainly by facilitating intestinal mucosa growth, alleviating the increased small intestinal permeability and increasing ZO-1 and occludin expression. Our observations provide evidence for the clinical significance of GLP-2 in preventing the intestinal epithelial barrier dysfunction during aging.
Asunto(s)
Atrofia/prevención & control , Péptido 2 Similar al Glucagón/farmacología , Receptor del Péptido 2 Similar al Glucagón/biosíntesis , Mucosa Intestinal/fisiología , Ocludina/biosíntesis , Proteína de la Zonula Occludens-1/biosíntesis , Animales , Atrofia/dietoterapia , Claudina-1/biosíntesis , Masculino , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Uniones EstrechasRESUMEN
BACKGROUND: Adequate gluten-free diet (GFD) is the only treatment for coeliac disease (CD). However, no agreement has been reached on either how and when to assess patient adherence to GFD or its effectiveness on villous atrophy. AIM: To assess, in a prospective study, patient adherence to and efficacy of GFD on histological recovery after 1-year of GFD. METHODS: Between 2009 and 2012, we enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18-70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of GFD with duodenal histology, serological assays, symptoms and a dietary interview based on a validated questionnaire. Complete histological recovery was defined as the absence of villous atrophy and ≤30/100 intraepithelial lymphocytes. RESULTS: Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved complete histological recovery (P < 0.00001). Among ADA patients, antibody seroconversion and symptoms were not significantly different between patients who achieved complete histological recovery and those who achieved partial histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate analysis showed that Marsh 3C was a risk factor for incomplete histological recovery in ADA patients (OR 8.74, 95% CI: 1.87-40.83). CONCLUSIONS: This study shows that complete histological recovery after 1-year of GFD in adult patients, who are assessed as adherent to the GFD, can be obtained in 66% of patients. Patients with severe histological damage at diagnosis are at risk for incomplete histological recovery 1 year later.
Asunto(s)
Enfermedad Celíaca/dietoterapia , Dieta Sin Gluten , Duodeno/patología , Adulto , Atrofia/dietoterapia , Atrofia/patología , Biopsia , Enfermedad Celíaca/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits.
Asunto(s)
Trastornos del Conocimiento/dietoterapia , Trastornos del Conocimiento/tratamiento farmacológico , Memantina/uso terapéutico , Enfermedades Neurodegenerativas/dietoterapia , Enfermedades Neurodegenerativas/tratamiento farmacológico , Nootrópicos/uso terapéutico , Animales , Atrofia/dietoterapia , Atrofia/tratamiento farmacológico , Atrofia/patología , Atrofia/fisiopatología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Trastorno Depresivo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología , Masculino , Trastornos de la Memoria/dietoterapia , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Neuroinmunomodulación/efectos de los fármacos , Neuroinmunomodulación/fisiología , Fármacos Neuroprotectores/uso terapéutico , Trastornos del Olfato/patología , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/fisiopatología , Agitación Psicomotora/dietoterapia , Agitación Psicomotora/tratamiento farmacológico , Agitación Psicomotora/patología , Agitación Psicomotora/fisiopatología , Ratas , Ratas Sprague-Dawley , Percepción Espacial/efectos de los fármacos , Percepción Espacial/fisiología , Sulfato de ZincRESUMEN
Protein energy malnutrition is associated with cerebral atrophy which may be detrimental to intellectual development. The aim of this study was to document the anatomical abnormalities which lead to the appearance of cerebral atrophy using magnetic resonance imaging (MRI) in the acute stage of kwashiorkor and to monitor changes during nutritional rehabilitation. Twelve children aged 6 to 37 months requiring admission to hospital for the treatment of kwashiorkor were studied. The children were evaluated clinically, biochemically, and by MRI of their brains on admission and 30 and 90 days later. Brain shrinkage was present in every child on admission. White and grey matter appeared equally affected and the myelination was normal for age. At 90 days, the cerebral changes had resolved in nine and improved substantially in the remainder, by which time serum proteins and weight for age were within the normal range. The findings of this study suggest that brain shrinkage associated with kwashiorkor reverses rapidly with nutritional rehabilitation.
Asunto(s)
Encéfalo/patología , Kwashiorkor/diagnóstico , Imagen por Resonancia Magnética , Atrofia/clasificación , Atrofia/diagnóstico , Atrofia/dietoterapia , Preescolar , Femenino , Humanos , Lactante , Kwashiorkor/clasificación , Kwashiorkor/dietoterapia , Masculino , Inducción de Remisión , Factores de TiempoRESUMEN
In gyrate atrophy the blood ornithine is grossly elevated, due to deficiency of ornithine ketoacid transaminase, which converts ornithine towards glutamic acid. Two patients with gyrate atrophy have been treated with a low arginine diet and their blood ornithine levels have been reduced to near normal. At this level hyperammonemia may result from overtreatment, but this can be quickly cleared by a small dose of arginine. There has also been some improvement in vision, but no clearing of the gyrate areas. Future care with this regimen seems possible and improvements in handling of these patients are likely.