NLRP3 inflammasome inhibitor MCC950 can reduce the damage of pancreatic and intestinal barrier function in mice with acute pancreatitis

Purpose: Abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome can lead to the occurrence and progression of acute pancreatitis. This study investigated the protective effect of MCC950 on pancreatitis mice. Methods: Eighteen mice were randomly divided into control group, severe acute pancreatitis (SAP) group and SAP+MCC950 group. Serum interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA. Hematoxylin and eosin (HE) staining was used to evaluate the pathological damage. Western blotting was used to detect the expression of NLRP3 inflammasome and tight junction proteins in the small intestine and pancreas. Results: MCC950 could reduce the levels of IL-6 and IL-1ß in SAP mice. After treatment with MCC950, the expression levels of NLRP3 inflammasome in the pancreas of SAP mice were significantly reduced and the pathological damage to the pancreas and intestine was alleviated. Compared with the control group, the expression of tight junction protein (ZO-1,occludin and claudin-4) in the intestinal mucosa of SAP mice was decreased, and the expression of claudin-4 and occludin were upregulated after MCC950 treatment. Conclusions: MCC950 can inhibit NLRP3 inflammasome activation and significantly reduce the inflammatory response and delay the process of pancreatitis. It has therapeutic potential in the treatment of acute pancreatitis.

Dietas altas en grasas y sus efectos sobre el intestino / Diets high in fats and their effects on the intestine

El objetivo de esta revisión fue exponer el conocimiento actual sobre la relación existente entre dietas altas en grasa (DAG), alteraciones morfológicas de la mucosa intestinal, efectos inflamatorios y cáncer intestinal. Las DAG inicialmente producen aumento de la microbiota patógena, lo que reduce la cantidad y calidad de la secreción de los exocrinocitos caliciformes, disminuyendo la efectividad de la barrera intestinal. Las bacterias y sus lipopolisacaridos (LPS) promueven la secreción de citoquinas proinflamatorias activando vías de inflamación, que a su vez afectan la integridad de las uniones intercelulares alterando la barrera intestinal. Lo anterior, permite que los LPS ingresen a la lámina propia y circulación sanguínea produciendo inflamación local y sistémica. Así mismo, las DAG generan efectos nocivos en la morfología y función de la mucosa gastrointestinal lo que podría favorecer el desarrollo de cáncer. Lo anterior, podría deberse a que el consumo de DAG es capaz de aumentar la proliferación de células de la mucosa y el número y proliferación de células madres tumorales en el intestino.

The aim of this review was to present current knowledge about the relationship between high fat diets (HFD), morphological alterations of intestinal mucosa, inflammatory effects and intestinal cancer. The HFD initially produces an increase in the pathogenic microbiota, which reduces quantity and quality of secretion of goblet cells, decreasing the effectiveness of intestinal barrier. Bacteria and their lipopolysaccharides (LPS) stimulate the secretion of proinflammatory cytokines by activating inflammation pathways, which in turn affect the integrity of intercellular junctions by changing intestinal barrier. The above allows the LPS enter to lamina propria and blood circulation producing local and systemic inflammation. Likewise, HFD generate deleterious effects on morphology and function of gastrointestinal mucosa, which could favor the development of cancer. This could be due to the fact that consumption of HFD is capable of increasing proliferation of mucosal cells and number and proliferation of tumor stem cells in the intestine.

Skin barrier in atopic dermatitis: beyond filaggrin

Abstract: Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis, where changes in skin barrier and imbalance of the immune system are relevant factors. The skin forms a mechanic and immune barrier, regulating water loss from the internal to the external environment, and protecting the individual from external aggressions, such as microorganisms, ultraviolet radiation and physical trauma. Main components of the skin barrier are located in the outer layers of the epidermis (such as filaggrin), the proteins that form the tight junction (TJ) and components of the innate immune system. Recent data involving skin barrier reveal new information regarding its structure and its role in the mechanic-immunological defense; atopic dermatitis (AD) is an example of a disease related to dysfunctions associated with this complex.

Caracterización de las causas de alopecia infantil / Aetiology of childhood alopecia

Introducción: La alopecia infantil es una afección poco frecuente en la consulta dermatológica pediátrica. Su etiología es variable según el grupo etario estudiado. El objetivo fue estudiar la causa de alopecia en niños en 2 hospitales pediátricos de referencia nacional en Chile. Pacientes y método: Análisis descriptivo de registros clínicos del total de pacientes atendidos entre enero de 2007 y junio de 2010 en los Servicios de Dermatología de los Hospitales Roberto del Río y Luis Calvo Mackenna. Se incluyeron pacientes con diagnóstico clínico de alopecia. Resultados: Se encontraron 345 registros clínicos, 179 varones (51,9%). La mediana de edad fue 72 meses. Los diagnósticos más prevalentes fueron alopecia areata (AA) (36,8%), tiña capitis (TC) (21%), nevo sebáceo (13,2%) y efluvio telógeno (8,7%). Según el grupo etario predominaron en recién nacidos: aplasia cutis y nevo sebáceo; en lactantes, preescolares y escolares: nevo sebáceo, AA y TC. En escolares se agregó tricotilomanía. En adolescentes nevo sebáceo, AA y efluvio telógeno. Se observó una correlación significativa entre AA con enfermedad autoinmune, enfermedad tiroidea, alteraciones ungueales, enfermedad psiquiátrica y síndrome de Down. En TC el agente etiológico más prevalente fue Microsporum Canis (86,6%). La tricotilomanía se correlacionó con enfermedad psiquiátrica significativamente. Conclusiones: Las principales causas de alopecia infantil fueron adquiridas y no cicatriciales. La etiología varía de acuerdo al grupo etario estudiado. Algunos tipos de alopecia infantil presentaron alta prevalencia de enfermedad psiquiátrica.

Introduction: Childhood alopecia is a relative rare event in general paediatric dermatology practice. Hair loss in children may have multiple causes, and there are different types of alopecia according to age groups. The aim of the study was to describe the clinical and epidemiological profile of alopecia in children from two Chilean paediatric hospitals. Patients and method: Descriptive analysis of clinical records of patients from the Dermatology Department of Roberto del Rio and Luis Calvo Mackenna Hospitals between January 2007 and June 2010. Patients with clinical diagnosis of alopecia were included. Results: A total of 345 clinical records were analysed, with 179 males (51.9%). The median age was 72 months. Overall, the most common diagnoses were: alopecia areata (AA), (36.8%), tinea capitis (TC), (21%), nevus sebaceous (13.2%), and tellogen effluvium (8.7%). According to age groups, in newborns, the most common causes were aplasia cutis and nevus sebaceous. In toddlers, pre-school and school children, the principal causes were nevus sebaceous, AA and TC. Trichotillomania was also significant in school children. In adolescents, nevus sebaceous, AA and tellogen effluvium were the most frequent diagnoses. AA was statistically associated with autoimmune disease, thyroid disease, nail disorder, psychiatric disease, and Down's syndrome. The most common aetiological agent in TC was M. canis (86.6%). Trichotillomania was also statistically associated to psychiatric disorders. Conclusions: In this study, the main causes of alopecia in children were acquired and non-scarring alopecia. In our results, the type of alopecia varies according to age group. Some types of childhood alopecia showed a close correlation to psychiatric disorders.

Estudo da interação de Desulfovibrio indonesiensis com células epiteliais intestinais: influência sobre as junções celulares e função imunológica / Interaction between desulfovibrio indonesiensis and intestinal epithelial cells - influence on celular junctions and immunological function

A imunopatologia das doenças inflamatórias intestinais (DIIs) está associada a níveis aumentados de citocinas pró-inflamatórias, alterações na microbiota local e perda da integridade da barreira epitelial. De fato, a relação parasita-hospedeiro, definida aqui pela interação da microbiota com o microambiente da mucosa, tem sido relatada como fator central na imunopatogênese das DIIs. Neste contexto, o presente trabalho teve como objetivo avaliar o efeito da interação de Desulfovibrio indonesiensis, bactéria redutora de sulfato (BRS), com a linhagem de célula epitelial intestinal Caco-2, sobre a integridade das junções oclusivas e seu papel na modulação da produção de IL-8. Células Caco-2 foram incubadas (3h a 37ºC) com D. indonesiensis (proporção 10:1 bactéria–célula hospedeira), e a interação foi interrompida após 24h e 48h. Microscopia correlativa foi empregada para avaliar a integridade das junções celulares, sendo as culturas controle e as que interagiram com D. indonesiensis processadas para imunofluorescência indireta e microscopia eletrônica de varredura (MEV). Análises da expressão de ocludina, proteína de junção oclusiva, e permeabilidade paracelular foram realizadas por Western blot e resistência elétrica transepitelial (RET), respectivamente. Microscopia de contraste interferencial diferencial (DIC) e microscopia de fluorescência das culturas de células Caco-2 revelaram intensa coesão entre células da monocamada celular, com junções oclusivas visualizadas pela detecção de ocludina e ZO-1. A presença da BRS não acarretou mudanças nas junções celulares e na distribuição espacial de ocludina e ZO-1...

The immunopathology of inflammatory bowel diseases (IBD) is associated withincreased levels of pro-inflammatory cytokines, changes in local microbiota and loss of epithelial barrier integrity. In fact, the host-parasite relationship, here defined by the interaction of microbes with the mucosal microenvironment, has been reported as a central factor in IBD immunopathogenesis. Herein, we aimed to evaluate the interaction of Desulfovibrio indonesiensis, a sulfate reducing bacteria (SRB), with anintestinal epithelial cell strain, Caco-2, and its effect on the integrity of tight junctions and on IL- 8 production. Caco-2 cells were incubated (3h at 37°C) with D. indonesiensis (10:1 bacteria-host cell ratio), and the interaction stopped after 24h and 48h. Correlative microscopy was used to assess the integrity of cell junctions, and both control and D. indonesiensis interaction cultures were processed for indirectimmunofluorescence and scanning electron microscopy (SEM). Expression analysis of occludin, a tight junction protein, and paracellular permeability were performed by Western blot and transepithelial electrical resistance (TEER), respectively. Differential interference contrast (DIC) and fluorescence microscopy analyses ofCaco-2 monolayer cultures revealed intense cell cohesion, with tight junctions visualized by occludin and ZO-1 labeling. Cell junctions and spatial distribution of occludin and ZO-1 were not altered in the presence of BRS. Ultrastructural analysisshowed isolated bacteria and biofilm structures bound to Caco-2 cells without anyalteration in intercellular association. This inaltered junctional integrity was also seenby TEER assays, and Western blot results revealed no changes in occludinexpression...

Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-á) on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-á (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-á treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-á decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-á did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-á increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

Efeitos da infusão de Luffa operculata sobre o epitélio e a atividade mucociliar do palato isolado de rã / Effects of Luffa operculata infusion on the epithelium and the mucociliary activity of the isolated frog palate

Luffa operculata é uma planta medicinal popularmente usada para tratamento de rinites e rinossinusites. A infusão de seu fruto seco é usada no nariz, liberando secreção mucosa profusa, mas pode causar irritação, epistaxe ou anosmia. Avaliamos os efeitos de diferentes concentrações da infusão do fruto seco da Luffa operculata na velocidade de transporte mucociliar (VTM), freqüência de batimento ciliar (FBC), diferença de potencial transepitelial (DPT) e morfologia do epitélio (microscopia de luz e eletrônica de transmissão), no modelo do palato isolado de rã. /Luffa operculata is a medicinal plant popularly used for treatment of rhinitis and rhinosinusitis. Its dry fruit infusion is used into the nose, delivering profuse mucous secretion, but may cause nasal mucosa irritation, epistaxis or anosmia. We evaluated the effects of different concentrations of Luffa operculata dry fruit infusion on mucociliary transport velocity (MTV), ciliary beat frequency (CBF), transepithelial potential difference (TPD) and epithelial morphology (light and electron transmission microscopy) of the isolated frog palate preparation. Results pointed to dose-dependent epithelial damage on mucociliary epithelium, suggesting that it is potentially noxious to the human nasal mucosa...

Enfermedad de Crohn: un criterio para resección

Los pacientes con enfermedad de Crohn usualmente tienen estrecheces intestinales de varios grados de severidad, pero no se sabe con certeza el diámetro mínimo al cual dichas estrecheces causan cambios en la presion intraluminal y en el flujo. El propósito de este trabajo fue el de examinar la relación existente entre el diámetro de la estrechez y la presión intraluminal, para así determinar cuales estrecheces requieren intervención quirúrgica. En un modelo experimental, segmentos de intestino humano fueron perfundidos con soluciones problema de diferente viscosidad (sol. salina, aceite de autos), y la presión intraluminal fue medida utilizando un transductor con un sistema de amplificador-impresora. Estrecheces de diámetro conocido fueron construidas a lo largo del segmento intestinal y los cambios en la presión intraluminal y el flujo se obtuvieron y analizaron. Cuando el diametro de la estrechez fue menor de 0.6 cms, hubo un aumento significativo de la presión desde una basal de 7.3 cms de H2O hasta una presion media de 13 cms de H2O (x²=p0.01)y esto se acompaño de una caida en el flujo intraluminal de 1.4 ml/min. a 0.9 ml/min (x²=p.0.05). Al utilizar la solución de mayor viscosidad, el diámetro crítico en el cual se produjeron cambios significativos de flujo/presión, fue por debajo de 0.95 cms. Estrecheces con diámetros menores a este, requieren dilatación y tratamiento quirúrgico para prevenir obstrucción. Los cambios en la viscosidad y el contenido intraluminal, alteran este equilibrio