RESUMO
Particulate matter exposure and related chemical changes in drinking water have been associated with health problems and inflammatory disorders. This study aimed to examine the effect of orally administered ash-water dilution on the gut of mice under normal and inflammatory conditions. Balb/c mice received ash-released soluble and dust-suspended components in the drinking water for 14 days. On day 7, animals were intrarectally instilled with TNBS in ethanol or flagellin from Salmonella typhimurium in PBS. At sacrifice, colon segments were collected and histologic damage, mRNA expression and cytokine levels in tissue were evaluated. In addition, these parameters were also evaluated in IL-10 null mice. We found that mice that received 5% w. fine-ash dilution in the drinking water worsened colitis signs. Weight loss, shortening of the colon, tissue edema with mucosa and submucosa cell infiltration and production of pro-inflammatory cytokines and chemokines were enhanced compared to control mice. A more pronounced inflammation was observed in IL-10 null mice. In addition, markers of NLRP3-dependent inflammasome activation were found in animals exposed to ash. In conclusion, ingestion of contaminated water with dust-suspended particulate matter enhanced the inflammatory response in the gut, probably due to alteration of the gut barrier and promoting an intense contact with the luminal content. This study critically appraises the response for fine particulate matter in uncommon illnesses reported for volcanic ash pollution. We suggest actions to enable better prediction and assessment the health impacts of volcanic eruptions.
Assuntos
Colite , Erupções Vulcânicas , Animais , Colite/induzido quimicamente , Inflamação/induzido quimicamente , Camundongos , Material Particulado/toxicidadeRESUMO
BACKGROUND/AIM: primary sclerosing cholangitis (PSC) is associated with ulcerative colitis (UC) and seems to be a risk factor for colon cancer. However, taking into account that no data are available in South American population, we analyzed the prevalence of PSC in 1,333 patients with UC and the risk for developing colon cancer. MATERIAL: patients with persistent increases of alkaline phosphatase were studied by cholangiography and liver biopsy. To assess the risk of colon cancer, each patient with PSC and UC was matched with two control patients with UC without PSC of the same age, gender, extent and duration of UC. RESULTS: the whole prevalence of PSC was 2.9% (39 patients) reaching 6.2% in extensive colitis. Seven (18%) out of 39 patients with PSC developed colorectal carcinoma compared with 2 out of 78 (2.6%) in the control group (p=0.006). The cumulative risk of colorectal carcinoma was 11% and 18% after 10 and 20 years in the PSC group compared with 2% and 7% in the control group, respectively (p=0.002). CONCLUSION: this is the first prospective study performed in Latin America showing that the prevalence of PSC in patients with UC is similar to that reported in the Anglo-Saxon population. Patients with UC and PSC have a high risk of colorectal cancer.
Assuntos
Fosfatase Alcalina/sangue , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Lesões Pré-Cancerosas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Biomarcadores Tumorais/sangue , Biópsia , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/patologia , Colite Ulcerativa/patologia , Neoplasias Colorretais/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Colite Ulcerativa/genética , Genes MDR , Biópsia , Colite Ulcerativa/metabolismo , Colo/química , Bolsas Cólicas , Células Epiteliais/química , Expressão Gênica , Humanos , Imuno-Histoquímica , Mucosa Intestinal/químicaRESUMO
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.
Assuntos
Doença de Crohn/diagnóstico , Índice de Gravidade de Doença , Biomarcadores/análise , HumanosRESUMO
Background/aim: primary sclerosing cholangitis (PSC) is associated with ulcerative colitis (UC) and seems to be a risk factor for colon cancer. However, taking into account that no data are available in South American population, we analyzed the prevalence of PSC in 1.333 patients with UC and the risk for developing colon cancer. Material: patients with persistent increases of alkaline phosphatase were studied by cholangiography and liver biopsy. To assess the risk of colon cancer, each patient with PSC and UC was matched with two control patients with UC without PSC of the same age, gender, extent and duration of UC. Results: the whole prevalence of PSC was 2.9% (39 patients) reaching 6.2% in extensive colitis. Seven (18 %) out of 39 patients with PSC developed colorectal carcinoma compared with 2 out of 78 (2.6%) in the control group (p=0.006). The cumulative risk of colorectal carcinoma was 11% and 18% after 10 and 20 years in the PSC group compared with 2% and 7% in the control group, respectively (p=0.002). Conclusion: this is the first prospective study performed in Latin America showing that the prevalence of PSC in patients with UC is similar to that reported in the Anglo-Saxon population. Patients with UC and PSC have a high risk of colorectal cancer.
Introducción/objetivos: la colangitis esclerosante primaria (CEP) se asocia a colitis ulcerosa (CU) y parece ser un factor de riesgo para cáncer de colon. Sin embargo, teniendo en cuenta que no existen datos disponibles en población de Sudamérica, nosotros analizamos la prevalencia de CEP en 1.333 pacientes con CU y el riesgo de desarrollar cáncer de colon. Material: los pacientes con fosfatasa alcalina persistentemente elevada fueron estudiados con colangiografía y biopsia hepática. Para determinar el riesgo de cáncer de colon cada paciente con CEP y CU fueron apareados con dos pacientes controles con CU sin CEP de la misma edad, sexo, extensión y duración de la CU. Resultados: la prevalencia total de CEP fue de 2.9% (39 pacientes), alcanzando una prevalencia del 6.2% en colitis extensa. Siete (18%) de 39 pacientes con CEP desarrollaron cáncer colorectal comparado con 2 de 78 en el grupo control (p=0.006). El riesgo acumulado de cáncer colorectal fue 11 y 18% después de 10 y 20 años en el grupo con CEP comparado con 2 y 7% en el grupo control, respectivamente (p=0.002). Conclusión: este es el primer estudio prospectivo realizado en Latinoamérica mostrando que la prevalencia de CEP en pacientes con CU es similar a la reportada en población anglosajona. Los pacientes con CU y CEP tienen un alto riesgo de cáncer colorectal.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Neoplasias Colorretais/etiologia , Lesões Pré-Cancerosas/patologia , Argentina/epidemiologia , Biópsia , Estudos de Casos e Controles , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/patologia , Colite Ulcerativa/patologia , Neoplasias Colorretais/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Biomarcadores Tumorais/sangueRESUMO
BACKGROUND: P-Glycoprotein (P-gp), a product of the MDR-1 gene, is a transmembrane efflux pump involved in drug transport, first described in cancer refractoriness. In the normal bowel P-gp is detectable on superficial epithelial cells, but has not been described in crypt epithelium. The role of P-gp and its intestinal expression in steroid-refractory ulcerative colitis (UC) are controversial. AIM: to compare P-gp immunostaining pattern in colonic epithelial cells of steroid-refractory versus steroid-responder UC patients. METHODS: P-gp was assessed by immunohistochemistry in rectal biopsies obtained from 19 patients with active UC, including pre-surgical samples from 11 refractory patients who underwent colectomy, and 8 responders. We devised a 5-point (0-4) score, according to the percentage of epithelial surface with positive immunostaining in the superficial and crypt epithelium (apical, lateral and cytoplasmic areas). RESULTS: Compared with responders, steroid-refractory patients had significantly higher immunostaining scores in the superficial epithelium, both in apical (2.8+/-0.5 versus 1.1+/-0.5, p=0.023) and cytoplasmic cellular areas (2.7+/-0.5 versus 1.2+/-0.5, p=0.032). Positive immunostaining of the superficial epithelium was frequently detected in refractory patients (apical: 9/11 cases, cytoplasmic: 10/11 cases) but was only observed in 4/8 responders. P-gp was also detected in similar areas of the crypt epithelium in 6/11 refractory patients, while it was infrequent in the group of 8 responders (1 apical 1 case, cytoplasmic 2 cases). Samples from the mucosa of normal ileal pouch-anal anastomoses obtained several years after the surgical procedure had a P-gp immunostaining pattern which was similar to that of rectal samples from patients with refractory UC. CONCLUSIONS: These results suggest a critical role of P-gp overexpression in steroid-refractory UC.
Antecedentes. La glicoproteína P (P-gp), un producto del gen MDR-1, es una bomba de eflujo transmembranainvolucrada en el transporte de drogas, descripta por primera vez en el cáncer refractario. En el intestino normal, P-gp se detecta sobre las célulasepiteliales superficiales, pero no se la ha descripto en el epitelio de las criptas. El papel de P-gp y su expresiónintestinal en la colitis ulcerosa (CU) refractaria a esteroides es controvertido. Objetivo. Comparar elpatrón de inmunotinción de P-gp en células epiteliales colónicas de pacientes con CU refractaria vs.respondedora a esteroides. Métodos. Se estudió P-gp por inmunohistoquímica en biopsias rectales obtenidasde 19 pacientes con CU activa, incluyendo muestras prequirúrgicas de 11 pacientes refractarios que fueronsometidos a una colectomía y muestras de 8 respondedores. Ideamos un score de 5 puntos (0-4), según elporcentaje de superficie epitelial con inmunotinción positiva en el epitelio superficial y críptico (áreas apical,lateral y citoplásmica). Resultados. Comparados con los respondedores, los pacientes refractarios a esteroides tenían scores de inmunotinción significativamente mayores en el epitelio superficial, tanto en lasáreas celulares apical (2.8+0.5 vs. 1.1+0.5, p=0.023) como citoplásmica (2.7+0.5 vs. 1.2+0.5, p=0.032). Se detectó frecuentemente inmunotinción positiva en el epitelio superficial en los pacientes refractarios (apical: 9/11 casos, citoplásmica: 10/11 casos), pero la misma se observó sólo en 4/8 respondedores. P-gp también sedetectó en áreas similares del epitelio de las criptas en 6/11 pacientes refractarios, en tanto que fue infrecuenteen el grupo de los 8 respondedores (1 caso en el área apical y 2 en la citoplásmica). Fuerón estudiadasbiopsias de la mucosa de la anastomosis pouch ileal - anal, obtenidas varios años después del procedimeinto quirúrgico, observándose un patrón de...
Assuntos
Humanos , Colite Ulcerativa/genética , Genes MDR , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Imuno-Histoquímica , Biópsia , Bolsas Cólicas , Colite Ulcerativa/metabolismo , Colo/química , Células Epiteliais/química , Expressão Gênica , Mucosa Intestinal/químicaRESUMO
No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia.
The gold standard to quantify Crohn's disease activity is still not defined and a world consensus to unify criteria is necessary. Criticism has been directed towards every existing indexes. We summarize some of the currently used criteria for the assessment of disease activity, point out the controversies and issues that will need further investigations, and discuss their usefulness based on our experience.