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The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC). This study aimed to evaluate the ABCC expression in UC patients and its role in a dextran sulfate sodium (DSS)-induced colitis mice model under 5-aminosalicylates or methylprednisolone treatment and compared with control without inflammation. DSS-induced colitis mice were treated with 5-aminosalicylates (50 mg/kg 24 h) or methylprednisolone (2 mg/kg 24 h). Human rectal biopsies were obtained from UC patients. The abcc-relative mRNA levels and protein expression were determined by RT-PCR and immunohistochemistry. abcc4, abcc5, and abcc6 mRNA levels were significantly increased in DSS-induced colitis compared to the other groups. The 5-aminosalicylate treatment dramatically increased the abcc2 and abcc3 mRNA levels vs. control. Methylprednisolone treatment increased abcc1 vs. DSS-induced colitis and colitis treated with 5-aminosalicylate. Immunohistochemical analysis revealed down-regulation of ABCC1/ABCC2/ABCC5/ABCC7 in mice colitis vs. control. Treatment with 5-aminosalicylate restored ABCC5 levels, while methylprednisolone restored ABCC2/ABCC5/ABCC7 in colitis mice at similar control levels. Relative mRNA levels of mrp1-5 were increased in active UC patients vs. control. ABCC2/ABCC4/ABCC7 were conspicuously expressed in the mucosa of 5-aminosalicylate and/or methylprednisolone-treated UC patients, while ABCC2/ABCC4/ABCC5/ABCC7 in submucosa, ABCC1/ABCC5/ABCC7 in muscular, and ABCC1/ABCC4/ABCC5/ABCC7 in serosa were expressed vs. controls. This is the first report about the differential up-regulation of the ABCC subfamily gene and protein expression in DSS-induced colitis under aminosalicylates or methylprednisolone treatment.
Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Metilprednisolona , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Animais , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Camundongos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Metilprednisolona/uso terapêutico , Metilprednisolona/farmacologia , Masculino , Modelos Animais de Doenças , Proteína 2 Associada à Farmacorresistência Múltipla , Feminino , Mesalamina/uso terapêutico , Mesalamina/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/tratamento farmacológico , Colite/genética , Adulto , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos dos fármacosRESUMO
INTRODUCTION: Acute severe ulcerative colitis (ASUC) is a critical manifestation of ulcerative colitis (UC), often necessitating colectomy when medical management fails. Despite advancements in therapeutic interventions such as corticosteroids, biologics, and JAK inhibitors, a significant proportion of patients require surgery, with colectomy rates ranging from 10% to 15%. AREAS COVERED: This paper reviews the factors influencing the timing and necessity of colectomy in ASUC management, emphasizing the importance of multidisciplinary decision-making involving gastroenterologists and surgeons. EXPERT OPINION: Key surgical indications include failure of medical therapy, toxic megacolon, perforation, uncontrolled bleeding, and systemic deterioration. Delays in surgery can result in higher morbidity and mortality rates, making timely intervention essential. This review highlights surgical techniques, including total colectomy and end ileostomy, and discusses potential complications, urging a balanced approach to optimize patient outcomes.
Assuntos
Colectomia , Colite Ulcerativa , Índice de Gravidade de Doença , Humanos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/tratamento farmacológico , Colectomia/efeitos adversos , Doença Aguda , Resultado do Tratamento , Fatores de Risco , Ileostomia/efeitos adversos , Tempo para o Tratamento , Tomada de Decisão Clínica , Fatores de Tempo , Seleção de Pacientes , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: To investigate the alleviation of Nippostrongylus brasiliensis infection on dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice, and to explore the underlying mechanism. METHODS: Thirty male C57BL/6J mice of the SPF grade, each weighing approximately 25 g, were randomly divided into three groups, including the blank control group (NC group), DSS modeling group (DSS group), and N. brasiliensis treatment group (Nb + DSS group), of 10 mice in each group. Mice in the DSS group were orally administered with 3.5% DSS daily since day 1 (D0) for 6 successive days, and given normal drinking water since D6, and animals in the Nb + DSS group were subcutaneously injected with the third-stage larvae of N. brasiliensis at a dose of 500 larvae per mice 5 days prior to D0, followed by oral administration with 3.5% DSS daily since D0 for 6 successive days and normal drinking water since D6, while mice in the NC group were given normal drinking water. Mouse body weight and stool were observed and the disease activity index (DAI) was scored in each group during the study period. All mice were sacrificed on D9. The mouse colon length was measured, and mouse colon specimens were subjected to hematoxylin-eosin (HE) staining and histopathological scoring. In addition, the mRNA and protein expression of interleukin (IL)-1ß and IL-10 was quantified in mouse colon specimens using quantitative fluorescent real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expression of mucosal repair-associated molecules zonula occludens-1 (ZO-1), mucin 2 (MUC2) and claudin-1 was detected in mouse colon specimens using qPCR assay and immunofluorescence assay. RESULTS: The mice body weights, DAI scores and colon lengths were (26.26 ± 1.93), (22.39 ± 1.65), (25.00 ± 1.58) g (F = 8.06, P < 0.01); (1.89 ± 0.34), (0.47 ± 0.39), 0 points (F = 57.61, P < 0.000 1); and (42.50 ± 5.75), (56.20 ± 5.96) mm and (61.17 ± 7.88) mm (F = 13.72, P < 0.001) in the NC, DSS and Nb + DSS groups on D9, respectively, and elevated mouse body weight (P < 0.05), reduced DAI score (P < 0.000 1) and increased colon length (P < 0.01) were observed in the Nb + DSS group relative to the DSS group on D9. Pathological examinations showed that the colonic crypts were relatively intact and the inflammatory cell infiltration was lower in the mouse colon specimens in the Nb + DSS group than in DSS the group. There was a significant difference in the histopathological scores of mouse colon specimens among the NC group (0 point), the DSS group [(2.00 ± 1.22) points] and the Nb + DSS group [(0.20 ± 0.45) points] (F = 10.71, P < 0.01), respectively, and the histopathological score of mouse colon specimens was significantly higher in the DSS group than in the NC and Nb + DSS groups (both P values < 0.01). qPCR assay quantified that the relative IL-10 and IL-1ß mRNA expression was 1.25 ± 0.08, 0.44 ± 0.14 and 1.30 ± 0.45 (F = 10.66, P < 0.01), and 0.22 ± 0.13, 1.14 ± 0.31 and 0.41 ± 0.19 (F = 16.89, P < 0.001) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and higher IL-10 mRNA expression and lower IL-1ß mRNA expression were found in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.01). The relative MUC2, claudin-1 and ZO-1 mRNA expression was 0.87 ± 0.25, 0.34 ± 0.26 and 4.21 ± 0.55 (F = 121.60, P < 0.000 1), 1.05 ± 0.41, 0.16 ± 0.09 and 0.22 ± 0.11 (F = 14.00, P < 0.01), and 1.03 ± 0.10, 0.60 ± 0.11 and 1.64 ± 0.28 (F = 32.16, P < 0.000 1) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and significantly higher MUC2 and ZO-1 mRNA expression was quantified in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). The mean fluorescence intensities of ZO-1 and claudin-1 were 17.18 ± 2.08, 12.38 ± 1.21 and 18.06 ± 2.59 (F = 8.95, P < 0.01) and 13.50 ± 1.63, 9.66 ± 2.03 and 13.61 ± 0.97 (F = 6.96, P < 0.05) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and the mean fluorescence intensities of ZO-1 and claudin-1 were significantly greater in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). CONCLUSIONS: N. brasiliensis infection may remarkably alleviate DSS-induced ulcerative colitis in mice through promoting expression of anti-inflammatory cytokines, inhibiting expression of pro-inflammatory cytokines and facilitating mucosal repair in colon tissues.
Assuntos
Colite Ulcerativa , Sulfato de Dextrana , Nippostrongylus , Infecções por Strongylida , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/terapia , Camundongos Endogâmicos C57BL , Masculino , Animais , Camundongos , Colo/patologia , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Modelos Animais de DoençasRESUMO
BACKGROUND: Inflammatory bowel diseases such as Crohn's disease and ulcerative colitis are influenced by environmental and immunological factors and may differ according to the patient's sex. OBJECTIVE: The objective was to study the differences in the clinical profile of a Brazilian sample of inflammatory bowel disease patients according to sex. METHODS: Retrospective study with chart review of 158 inflammatory bowel disease patients (43 with Crohn's disease and 115 with ulcerative colitis) from a single university hospital in southern Brazil. RESULTS: The Crohn's disease sample showed a female/male ratio of 2.1, and the sample of ulcerative colitis showed a ratio of 1.5. The only significant difference found in the clinical profile was an increased constipation rate in female patients with ulcerative colitis. No other differences in epidemiological, symptom profile, or treatment could be detected. CONCLUSIONS: More females with inflammatory bowel diseases sought healthcare facilities compared to males. The only notable difference was a higher incidence of constipation symptoms among females; all other aspects were similar between the sexes.
Assuntos
Colite Ulcerativa , Constipação Intestinal , Doença de Crohn , Humanos , Feminino , Masculino , Brasil/epidemiologia , Adulto , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Pessoa de Meia-Idade , Distribuição por Sexo , Adulto Jovem , Adolescente , Idoso , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologiaRESUMO
Introducción. Los cuestionarios WPAI-UC/CD-Caregiver evalúan la repercusión laboral y en actividades cotidianas de los padres/cuidadores de pacientes con colitis ulcerosa (CU) o enfermedad de Crohn (EC). El objetivo fue adaptar y validar estos cuestionarios en la población española. Métodos. Se realizó la traducción y la retrotraducción. El documento fue evaluado por un comité de expertos y por un grupo piloto de familias de pacientes con enfermedad inflamatoria intestinal pediátrica (EII-p). Para la validación, se reclutaron padres/cuidadores de pacientes con EII-p (10-18 años). El comité de expertos y el grupo piloto evaluaron subjetivamente el formato y el tiempo necesario para completar los cuestionarios. Se calculó el coeficiente alfa de Cronbach y se realizó el análisis factorial con rotación Varimax. Se calcularon los coeficientes de Kaiser-Meyer-Olkin (KMO) y la prueba de esfericidad de Bartlett para comprobar la adecuación del análisis factorial. Resultados. Se incluyeron 370 pacientes (mediana 14,1 años), y 263 padres/cuidadores de pacientes con colitis ulcerosa o EII no clasificada y 261 padres/cuidadores de pacientes con enfermedad de Crohn. Los coeficientes KMO (0,6947 y 0,7179) y la prueba de esfericidad de Barttlet (p <0,001) confirmaron la adecuación del análisis factorial. Los 6 ítems se dirigieron a la misma dimensión. El modelo factorial explicó el 99,99 % y el 94,68 % de la varianza, y los alfa de Cronbach (0,6581 y 0,6968) indicaron buena consistencia. El formato y la mediana de 2 minutos para completarlos se consideraron óptimos. Conclusiones. Las versiones validadas en la población española de los cuestionarios WPAI-Caregiver pueden considerarse para su uso en familias con hijos con EII.
Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (1018 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. KaiserMeyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.
Assuntos
Humanos , Adolescente , Colite Ulcerativa , Cuidadores/psicologia , Pais/psicologia , Espanha , Traduções , Atividades Cotidianas , Doenças Inflamatórias Intestinais , Doença de Crohn , Inquéritos e Questionários , Características Culturais , EficiênciaRESUMO
Semaphorins are an immunoregulatory protein family. Plexins bind semaphorins (SEMAs) and can form receptor complexes that give them chemotactic capacity. The role and expression profile of semaphorins and plexins in inflammatory bowel disease (IBD) is currently unknown. AIM: Characterize the semaphorins and plexins gene and protein expression in intestinal tissue from IBD patients and correlate them with the clinical phenotype. MATERIAL AND METHODS: This comparative and cross-sectional study enrolled 54 diagnosed IBD patients and 20 controls. Gene and protein expression of semaphorins and plexins were determined by RT-PCR and IHQ for the co-localization with neutrophils (myeloperoxidase, MPO) or CD123 plasmacytoid dendritic cells in intestinal tissue from IBD patients. RESULTS: Colonic mucosa from active and remission ulcerative colitis (UC) had a significantly lower SEMA4D and PLXNA1, but higher PLXNB1 gene expression than the control group. The only significant difference between active UC and remission was observed in the higher gene expression of SEMA6D in remission. It was associated with histological remission (p = 0.01, OR = 15, 95% CI: 1.39-16.1). The low expression of PLXNA1 was associated with mild intermittent activity with two relapses per year (p = 0.003, OR = 0.05, CI = 0.006-0.51). Higher SEMA4D+ positive cells were detected in the submucosa, while PLXNC1+/MPO+ in the mucosal and submucosa of active UC patients compared with controls. CONCLUSIONS: The increased expression of the semaphorin and plexin family in IBD patients suggests their immunoregulatory function and is associated with remission and clinical phenotype in patients with UC.
Assuntos
Doenças Inflamatórias Intestinais , Proteínas do Tecido Nervoso , Receptores de Superfície Celular , Semaforinas , Humanos , Semaforinas/metabolismo , Semaforinas/genética , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Estudos Transversais , Estudos de Casos e Controles , Antígenos CD/metabolismo , Antígenos CD/genética , Moléculas de Adesão CelularRESUMO
Fertility preservation is a major concern for women with ulcerative colitis who require surgical treatment. Previous studies have shown that the risk of infertility after restorative proctocolectomy is approximately four times higher. However, this risk appears to be lower in patients who undergo minimally invasive approaches, such as laparoscopic surgery. The benefits of laparoscopy have led to a debate on whether robotic-assisted surgery could offer better results in terms of fertility. Surgical robotic platforms can provide improved visualization of the pelvis and more precise dissection of anatomical structures. In theory, this could reduce tissue damage and the inflammatory response, leading to lower adhesion formation and fallopian tube blockage, thereby preserving fertility.
Assuntos
Colite Ulcerativa , Preservação da Fertilidade , Infertilidade Feminina , Laparoscopia , Proctocolectomia Restauradora , Procedimentos Cirúrgicos Robóticos , Feminino , Humanos , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Preservação da Fertilidade/métodos , Infertilidade Feminina/etiologia , Infertilidade Feminina/cirurgia , Laparoscopia/métodos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
Background/Objective: Ingestion of dietary fiber can influence in the remission of patients with ulcerative colitis (UC). There are no current recommendations for fiber intake in UC; therefore, we evaluate the association between dietary fiber and the activity of the disease. Methods: Ours is a cross-sectional study in patients with a confirmed diagnosis of UC to whom a 24 h recall was applied; this allowed for the estimation and classification of type of dietary fiber. The patients were divided into two groups: (1) remission and (2) active UC. We analyzed the quantity and type of fiber with the grades of disease activity through Spearman correlation and logistic regression. Results: A total of 152 patients were included; it was found that those with clinically active UC consumed less total fiber (p = 0.016) and insoluble fiber (p = 0.018). Meanwhile, in endoscopic grade, the difference was for insoluble fiber (p = 0.038). Insoluble fiber had an inversely significant correlation with fecal calprotectin levels (r = -0.204; p = 0.018). Logistic regression showed that less than 11 g of insoluble fiber was a risk factor for clinical activity (OR = 2.37; 95% CI 1.107-5.019; p = 0.026). Conclusions: Consumption below the current recommendation of total and insoluble dietary fiber is associated with clinical activity of UC.
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Colite Ulcerativa , Fibras na Dieta , Humanos , Colite Ulcerativa/dietoterapia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/análise , Masculino , Feminino , Estudos Transversais , Adulto , México , Pessoa de Meia-Idade , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Adulto Jovem , Modelos LogísticosRESUMO
BACKGROUND AND AIMS: Vedolizumab is a humanized gut selective drug that targets α4ß7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. METHODS: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. CONCLUSIONS: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.
Assuntos
Anticorpos Monoclonais Humanizados , Artralgia , Artrite , Fármacos Gastrointestinais , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Artralgia/induzido quimicamente , Artralgia/epidemiologia , Artralgia/diagnóstico , Artrite/induzido quimicamente , Artrite/diagnóstico , Artrite/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Incidência , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Ascertainment of disease activation is an important component of therapeutic decisions in ulcerative colitis patients and may present certain clinical challenges. The objective of this study was to determine serum levels of the M30 fragment of cytokeratin 18 and its utility as an activation marker in patients with ulcerative colitis, who are known to have increased apoptosis. METHODS: A total of 60 ulcerative colitis (30 active and 30 remission) patients aged over 18 years and 29 healthy individuals as controls were included in the study. M30, C-reactive protein, and mean platelet volume were evaluated in all participants and compared between ulcerative colitis patients and controls, as well as between those with active disease or remission. RESULTS: Although ulcerative colitis patients with active disease had higher M30 levels than those in remission, the difference was not statistically significant (p=0.085). The mean M30 levels tended to increase with increasing extent of involvement, although the differences were not significant (p=0.065). The comparison of C-reactive protein and mean platelet volume according to the site of involvement, however, showed significant differences (p=0.02 and 0.004, respectively). M30 did not show significant correlations with C-reactive protein, mean platelet volume, and Mayo Score (p=0.0834, 0.768, and 0.401, respectively). CONCLUSIONS: Our results suggest that, in contrast to C-reactive protein and mean platelet volume, M30 levels do not have a significant role as an activation marker in ulcerative colitis patients. Thus, we believe that M30 may not represent an appropriate marker to be used for this purpose.
Assuntos
Biomarcadores , Proteína C-Reativa , Colite Ulcerativa , Queratina-18 , Humanos , Colite Ulcerativa/sangue , Masculino , Feminino , Proteína C-Reativa/análise , Biomarcadores/sangue , Adulto , Estudos de Casos e Controles , Pessoa de Meia-Idade , Queratina-18/sangue , Volume Plaquetário Médio , Adulto Jovem , Apoptose , Índice de Gravidade de Doença , Fragmentos de PeptídeosRESUMO
PURPOSE: To investigate the impact of the Chinese medicine compound Ento-PB on oxazolone (OXZ)-induced ulcerative colitis (UC) in rats. METHODS: UC rats induced by OXZ were treated with Ento-PB. The damage to the colon was assessed using several measures, including the disease activity index (DAI), colon length, colon weight/length ratio, colonic mucosal damage index, and histological score. The levels of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), epidermal growth factor (EGF), inducible nitric oxide synthase, and total nitric oxide synthase (tNOS) in rat serum, as well as the levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in rat colon tissue, were determined using enzyme-linked immunosorbent assay and conventional kits. RESULTS: After being treated with Ento-PB, the DAI score and macroscopic lesion score of OXZ-induced UC rats were significantly reduced. Ento-PB prevented the shortening of rat colons, reduced the ratio of colon weight to length, and improved colon tissue lesions. Meanwhile, Ento-PB could significantly inhibit the activities of proinflammatory cytokines TNF-α, IL-13, and MPO, as well as tNOS and iNOS, while upregulating the expression of anti-inflammatory cytokines IL-4 and IL-10. Moreover, a significant increase in the expression level of EGF was observed in UC rats treated with Ento-PB, indicating that Ento-PB could enhance the repair of damaged intestinal epithelial tissue. CONCLUSIONS: Ento-PB demonstrates significant anti-UC activities in OXZ-induced UC rats by regulating the expression levels of inflammatory factors and promoting the repair of colon tissue. This study provides scientific evidence to support the further development of Ento-PB.
Assuntos
Colite Ulcerativa , Colo , Oxazolona , Peroxidase , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Masculino , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peroxidase/análise , Peroxidase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Ratos , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento Epidérmico/análise , Citocinas/metabolismo , Interleucina-13/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/análise , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.
Assuntos
Colite Ulcerativa , Predisposição Genética para Doença , Interleucina-17 , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-17 , Humanos , Interleucina-17/genética , Interleucina-17/sangue , Colite Ulcerativa/genética , Colite Ulcerativa/sangue , Masculino , Feminino , Receptores de Interleucina-17/genética , Adulto , Polimorfismo de Nucleotídeo Único/genética , Pessoa de Meia-Idade , Haplótipos/genética , Genótipo , Alelos , Estudos de Casos e Controles , Índice de Gravidade de DoençaRESUMO
RATIONALE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by continuous inflammation of the colonic mucosa. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by hypergammaglobulinemia, circulating autoantibodies, interface hepatitis, and favorable response to immunosuppression. An association between IBD and AIH is uncommon, and experts have suggested that in patients with overlapping IBD and AIH, the anti-tumor necrosis factor agents can be used. Therefore, this study reports a rare case of a patient with liver cirrhosis due to AIH and UC refractory to conventional treatment and discusses the risks and benefits of using anti-tumor necrosis factor in both conditions. PATIENT CONCERNS: A 28-year-old female presented with symptoms of diarrhea, abdominal pain, asthenia, and inappetence, accompanied by abdominal collateral circulation, anemia, alteration of liver enzymes, and elevation of C-reactive protein levels. DIAGNOSES: The patient underwent a liver biopsy, which was consistent with liver cirrhosis due to AIH. Colonoscopy showed an inflammatory process throughout the colon, compatible with moderately active UC. INTERVENTIONS: The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC. The patient presented with a clinical response and infliximab therapy was maintained. OUTCOMES: Eight months after starting infliximab therapy, the patient developed pneumonia with complications from disseminated intravascular coagulation and died. LESSONS SUBSECTIONS: AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.
Assuntos
Colite Ulcerativa , Hepatite Autoimune , Cirrose Hepática , Humanos , Feminino , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/complicações , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Medição de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Infliximab/uso terapêutico , Infliximab/efeitos adversosRESUMO
Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.
Introducción. Los cuestionarios WPAI-UC/CD-Caregiver evalúan la repercusión laboral y en actividades cotidianas de los padres/cuidadores de pacientes con colitis ulcerosa (CU) o enfermedad de Crohn (EC). El objetivo fue adaptar y validar estos cuestionarios en la población española. Métodos. Se realizó la traducción y la retrotraducción. El documento fue evaluado por un comité de expertos y por un grupo piloto de familias de pacientes con enfermedad inflamatoria intestinal pediátrica (EII-p). Para la validación, se reclutaron padres/cuidadores de pacientes con EII-p (10-18 años). El comité de expertos y el grupo piloto evaluaron subjetivamente el formato y el tiempo necesario para completar los cuestionarios. Se calculó el coeficiente alfa de Cronbach y se realizó el análisis factorial con rotación Varimax. Se calcularon los coeficientes de Kaiser-Meyer-Olkin (KMO) y la prueba de esfericidad de Bartlett para comprobar la adecuación del análisis factorial. Resultados. Se incluyeron 370 pacientes (mediana 14,1 años), y 263 padres/cuidadores de pacientes con colitis ulcerosa o EII no clasificada y 261 padres/cuidadores de pacientes con enfermedad de Crohn. Los coeficientes KMO (0,6947 y 0,7179) y la prueba de esfericidad de Barttlet (p <0,001) confirmaron la adecuación del análisis factorial. Los 6 ítems se dirigieron a la misma dimensión. El modelo factorial explicó el 99,99 % y el 94,68 % de la varianza, y los alfa de Cronbach (0,6581 y 0,6968) indicaron buena consistencia. El formato y la mediana de 2 minutos para completarlos se consideraron óptimos. Conclusiones. Las versiones validadas en la población española de los cuestionarios WPAI-Caregiver pueden considerarse para su uso en familias con hijos con EII.
Assuntos
Cuidadores , Colite Ulcerativa , Humanos , Espanha , Criança , Cuidadores/psicologia , Adolescente , Feminino , Masculino , Doença de Crohn , Eficiência , Traduções , Inquéritos e Questionários , Doenças Inflamatórias Intestinais , Características Culturais , Pais/psicologia , Atividades CotidianasRESUMO
BACKGROUND: Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition that affects all age groups, predominantly in young individuals. Currently, an increase in the prevalence of IBD has been documented, in parallel with the increase in the elderly population. The scarce number of studies that better characterize the impact of IBD on Quality of Life (QoL) in the elderly motivated the present study. OBJECTIVE: To evaluate the impact of IBD on the QoL of elderly people treated at a Tertiary IBD Center. METHODS: Prospective cross-sectional study that included elderly patients (age ≥60 years) with quiescent or mildly active IBD treated at the HU-UFJF IBD Center between March 2019 and December 2022. Elderly companions without severe comorbidities who attended the consultation with the patients were included as a control group. Sociodemographic and IBD-related characteristics were recorded. QoL was assessed using previously validated questionnaires (WHOQOL-BREF and IBDQ). Patients with IBD with moderate to severe activity, history of recent or imminent hospitalization, serious or opportunistic infections in the last 6 months, previous neoplasia, dementia, and difficulty understanding/fulfilling the questionnaires were excluded. RESULTS: A total of 123 patients were included (74 with IBD and 49 in the control group), with a mean age of 67±6.2 years, 52.7% with CD, and 47.3% with UC. Mild disease activity was observed in 31.1%. Both groups (IBD patients and control) were comparable based on age, sex, BMI, and the Charlson Comorbidity Index. Patients with IBD and controls had similar QoL scores in the different domains assessed by the WHOQOL-BREF. On the other hand, when evaluating the general facet of QoL, IBD patients had significantly lower scores in General QoL (3.71±0.87 versus 4.02±0.62, respectively; P=0.021) and General Health (3.32±1.05 versus 3.69±0.94, respectively; P=0.035). The presence of mildly active IBD negatively impacted the general health score (2.91±0.99 versus 3.47±1.04, respectively; P=0.035) and the physical domain of the WHOQOL-BREF (12.27±2.63 versus 13.86±2.61, respectively; P=0.019) when compared to patients in remission. Conversely, no impact on QoL was observed with the Application of the IBDQ questionnaire regarding the type of the disease (161±38.5 versus 163.1±42.6 for CD and UC, respectively; P=0.84) or the presence of activity (152.5±38.8 versus 166.4±40.5, respectively; P=0.17). CONCLUSION: No statistically significant differences were found between elderly patients with mildly active or quiescent IBD and elderly patients without IBD when observing global QoL scores. However, IBD negatively impacted the general facet of QoL, just as mild activity was associated with lower scores in general health and the physical domain assessed by the WHOQOL-BREF. Patients with IBD treated with biological therapy had better Qol than those on conventional therapy. Future studies are needed to choose the most appropriate tool for assessing QoL in this population.
Assuntos
Qualidade de Vida , Índice de Gravidade de Doença , Humanos , Feminino , Masculino , Estudos Transversais , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Inquéritos e Questionários , Colite Ulcerativa/psicologia , Colite Ulcerativa/complicações , Doença de Crohn/psicologia , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/complicações , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Indução de RemissãoRESUMO
Imbalanced dietary intake is associated with the development of inflammatory bowel diseases (IBDs) and is often observed during the active phases of Crohn's disease (CD) and ulcerative colitis (UC). Cumulative data also suggest the potential for dietary manipulation in avoiding IBD relapse. However, there is a paucity of dietary data from patients in clinical remission to guide such an approach. Our study aimed to characterize the dietary pattern and adequacy of patients with IBD in clinical remission. Data on dietary intake (three alternate 24 h food records) were collected from 40 patients with IBD (20 CD and 20 UC) and 45 gender-matched healthy controls (HC). Statistical comparisons between patients and controls employed Student's t-test, Mann-Whitney U, chi-squared, and Fisher's exact tests. The adequacy of dietary intake of IBD patients was further studied by assessing the nutrient inadequacy prevalence, estimated using the Dietary Reference Intakes (DRI) framework and the Estimated Average Requirement (EAR) parameter. We observed significant dietary imbalances among patients with IBD compared to the HC group, marked by disparities in both macronutrient and micronutrient intakes. Inadequacies with frequencies >80% were observed for the ingestion of total fiber and 13 micronutrients in IBD patients. Our preliminary findings suggest that imbalanced dietary intake is also characteristic among individuals with IBD during clinical remission, corroborating the need for dietary interventions in this population.
Assuntos
Colite Ulcerativa , Doença de Crohn , Dieta , Doenças Inflamatórias Intestinais , Indução de Remissão , Humanos , Feminino , Masculino , Adulto , Colite Ulcerativa/dietoterapia , Doença de Crohn/dietoterapia , Pessoa de Meia-Idade , Doenças Inflamatórias Intestinais/dietoterapia , Micronutrientes/administração & dosagem , Estudos de Casos e Controles , Adulto Jovem , Fibras na Dieta/administração & dosagem , Estado Nutricional , Registros de DietaRESUMO
Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1ß, TGFß, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1ß levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.
Assuntos
Anti-Inflamatórios , Modelos Animais de Doenças , Microbioma Gastrointestinal , Lactobacillus delbrueckii , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Microbioma Gastrointestinal/efeitos dos fármacos , Citocinas/metabolismo , Proteínas de Bactérias/farmacologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Probióticos/farmacologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/patologia , Colo/microbiologia , Colo/metabolismo , MasculinoRESUMO
OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.
Assuntos
Colite Ulcerativa , Malondialdeído , Estresse Oxidativo , Extratos Vegetais , Própole , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Própole/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Malondialdeído/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peroxidase/metabolismo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Dexametasona/farmacologia , Traqueófitas/química , Catalase/metabolismo , Relação Dose-Resposta a Droga , Antioxidantes/farmacologia , Glutationa Transferase/metabolismoRESUMO
INTRODUCTION: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. OBJECTIVE: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. MATERIALS AND METHODS: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multi-gene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. RESULTS: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). CONCLUSION: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.
Assuntos
Predisposição Genética para Doença , Genótipo , Fenótipo , Humanos , Colômbia/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Doenças Inflamatórias Intestinais/genética , Adolescente , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Colite Ulcerativa/genéticaRESUMO
Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.