Progress on Regulation of NLRP3 Inflammasome by Chinese Medicine in Treatment of Ulcerative Colitis / 中国结合医学杂志

Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

Serum expression of microRNA-16 in a cohort of Egyptian patients with ulcerative colitis and its correlation with disease extent and severity / Expressão sérica do microRNA-16 em uma coorte de pacientes egípcios com colite ulcerosa e sua correlação com a extensão e gravidade da doença

Abstract Ulcerative colitis is one of the IBDs. Its etiology and pathogenesis remain undefined with an interaction between environmental, genetic and immunological factors is the most accepted explanation. Several recent studies have examined microRNA expression in the peripheral blood and tissues from IBD patients. The study aims at assessing the expression of serum miR-16 in ulcerative colitis patients and its correlation with disease extent, activity and severity. It included 30 treatment naïve ulcerative colitis patients of different presentations. Serum miR-16 expression was assessed using reverse transcriptase quantitative real time PCR (RT-qPCR), and then correlated with that of a group of 20 healthy subjects to assess its role in diagnosis of ulcerative colitis. Also, it was correlated with disease extent (proctitis, left sided colitis, extensive colitis) and disease activity and severity indices (Truelove and Witts criteria, fecal calprotectin and UCEIS). Thirty ulcerative colitis patients were enrolled, 53% had mild, 37% had moderate, while 10% had severe disease. Concerning endoscopic extent, 8 had proctitis, 14 had left sided colitis and 8 had extensive colitis. Serum expression of miR-16 in the 30 patients were compared to that of the healthy control subjects. The patients' group showed median serum miR-16 expression of 1.91, 1.13 for the control group with a significant difference between both groups. Correlation between serum miR-16 expression with disease extent, activity and severity showed no significant relation. From the current study we can conclude that increased serum expression of miR-16 is associated with ulcerative colitis despite no significant relation to disease activity extent or severity.

Resumo A colite ulcerativa é uma das DII. Sua etiologia e patogênese permanecem indefinidas; a interação entre fatores ambientais, genéticos e imunológicos é a explicação mais aceita. Vários estudos recentes avaliaram a expressão de microRNA no sangue e tecidos periféricos em pacientes com DII. O presente estudo teve como objetivo avaliar a expressão do miR-16 sérico em pacientes com colite ulcerativa e sua correlação com a extensão, atividade e gravidade da doença. Foram incluídos 30 pacientes de colite ulcerativa, com diferentes apresentações, que ainda não haviam sido submetidos a nenhum tipo de tratamento. A expressão sérica de miR-16 foi avaliada usando transcrição reversa seguida de reação em cadeia da polimerase quantitativa (RT-qPCR) e, em seguida, correlacionada com a de um grupo de 20 indivíduos saudáveis para avaliar seu papel no diagnóstico de colite ulcerativa. Além disso, foi feita uma correlação com a extensão da doença (proctite, colite do lado esquerdo, colite extensa) e com os índices de atividade e gravidade da doença (critérios de Truelove e Witts, calprotectina fecal e UCEIS). Trinta pacientes com colite ulcerativa foram incluídos no estudo, classificada como leve em 53%, moderada em 37% e grave em 10%. Quanto à extensão endoscópica, oito apresentavam proctite, 14 apresentavam colite do lado esquerdo e oito apresentavam colite extensa. A expressão sérica de miR-16 nos 30 pacientes foi comparada à dos indivíduos controle saudáveis. No, grupo de pacientes, a expressão sérica de miR-16 foi de 1,91 (grupo controle: 1,13), uma diferença estatisticamente significativa entre os dois grupos. Não foi observada relação significativa entre a expressão sérica de miR-16 e a extensão, atividade e gravidade da doença. A partir do presente estudo, pode-se concluir que o aumento da expressão sérica do miR-16 está associado à colite ulcerativa, apesar de não haver relação significativa com a extensão ou gravidade da atividade da doença.

Fecal calprotectin role in diagnosis of ulcerative colitis and treatment follow-up / Papel da calprotectina fecal no diagnóstico de colite ulcerativa e no acompanhamento do tratamento

ABSTRACT Objective: Ulcerative colitis usually affects the rectum and potentially can involve the whole colon. Noninvasive methods such as fecal calprotectin measurement may be considered as a reliable and inexpensive approach in assessing disease severity or treatment change strategy. Methods: In this retrospective cross-sectional study, records of 56 ulcerative colitis patients who hospitalized with exacerbation between May 2016 and April 2017 were assessed based on IBD Data Bank Software in Gastrointestinal and Liver Diseases and Research Center (GLDRC), Guilan province, Iran between. A questionnaire of demographic characteristics, clinical findings and fecal calprotectin level was completed. Montreal classification severity of ulcerative colitis and Mayo disease activity index were scored. Data were analyzed for descriptive and analytical analysis. Results: Fecal calprotectin was significantly different in terms of disease severity based on both Mayo score (p = 0.007) and Montreal classification (p = 0.001). In patients with mild symptoms, no increase in fecal calprotectin was observed, but in patients with moderate and severe elevations in fecal calprotectin levels was significant. Also, C-Reactive Protein surge was related to disease severity (p = 0.02). Furthermore, regression comparison among high-chance patients based on fecal calprotectin was significantly related to higher Erythrocyte Sedimentation Rate levels and smoking, p = 0.01 and p = 0.05, respectively. Conclusion: It seems fecal calprotectin levels are related to the disease severity. Non-invasive methods, such as fecal calprotectin assay, may seem to be an alternative to aggressive, costly and time-consuming methods, such as colonoscopy and biopsy, to reduce the suffering of patients and ultimately help improve the patients' life quality.

RESUMO Objetivo: A colite ulcerativa geralmente afeta o reto, podendo acometer todo o cólon. Métodos não invasivos, como a dosagem de calprotectina fecal, podem ser uma abordagem confiável e barata para a avaliação da gravidade da doença ou da estratégia de mudança de tratamento. Métodos: Neste estudo transversal retrospectivo, os registros de 56 pacientes com colite ulcerativa que foram hospitalizados devido a exacerbação entre maio de 2016 e abril de 2017 foram avaliados usando o software IBD Data Bank no Centro de Pesquisa e Doenças Gastrointestinais e Hepáticas (GLDRC), na província de Guilan, Irã. Foi aplicado um questionário de características demográficas, achados clínicos e nível de calprotectina fecal. Foram usados o escore de Mayo de atividade da doença e a classificação de Montreal da gravidade da colite ulcerativa. Os dados foram analisados de forma descritiva e analítica. Resultados: A calprotectina fecal apresentou diferença significativa em termos de gravidade da doença com base no escore de Mayo (p = 0,007) e na classificação de Montreal (p = 0,001). Em pacientes com sintomas leves, nenhum aumento na calprotectina fecal foi observado. Entretanto, em pacientes com sintomas moderados e severos, o aumento nos níveis de calprotectina fecal foi significativo. Além disso, o aumento nos níveis de proteína C reativa foi associado à gravidade da doença (p = 0,02). A análise da regressão entre pacientes considerados de alto risco com base na calprotectina fecal indicou uma associação significativa com níveis elevados da taxa de sedimentação de eritrócitos e tabagismo (p = 0,01 e p = 0,05, respectivamente). Conclusão: Os níveis de calprotectina fecal parecem estar relacionados com a gravidade da doença. Métodos não invasivos, como o estudo de calprotectina fecal, podem ser uma alternativa a métodos agressivos, caros e demorados, tais como colonoscopia e biópsia, reduzindo o sofrimento e ajudando a melhorar a qualidade de vida dos pacientes.

Therapeutic effect of adenosine on experimentally induced acute ulcerative colitis model in rats

Abstract Purpose To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. Methods Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels. Results AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). Conclusion Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Hiperplasia neuroendocrina en colitis linfocitica y colitis ulcerativa / Neuroendocrine hiperplasia in linfocitic and ulcerative colitis

Introducción: Algunos autores han demostrado incremento de células neuroendócrinas en colitis microscópica y colitis ulcerativa. Objetivo: El objetivo del presente estudio fue evaluar la presencia de células neuroendócrinas en colitis linfocítica, colitis colagenosa y colitis ulcerativa en comparación a controles. Materiales y métodos: Se usó inmunohistoquímica para identificar a las células neuroendócrinas a través del marcador cromogranina A. El estudio incluyó 10 casos de cada diagnóstico de colitis linfocítica, colitis colagenosa y colitis ulcerativa. Resultados: Se encontró diferencia estadísticamente significativa en el conteo de células neuroendocrinas en colitis linfocítica (p=0,019104) y colitis ulcerativa en comparación con los controles (p=0,0077). En colitis colagenosa, se encontró un incremento de células neuroendocrinas pero no pudimos demostrar diferencias estadísticamente significativa. Conclusión: Se demostró hiperplasia de células neuroendocrinas en colitis linfocítica y colitis ulcerativa, lo que confirma lo reportado por los pocos estudios anteriores realizados sobre el tema.

Introduction: Some authors have found increase of neuroendocrine cells in microscopic colitis and ulcerative colitis. Objective: The aim of this study is to evaluate the presence of neuroendocrine cells in ulcerative colitis and lymphocytic colitis and collagenous colitis. Materials and methods: Immunohistochemistry was performed to identify neuroendocrine cells through marker chromogranin A (CgA). The study included 10 cases of each diagnosis of Lymphocytic colitis, collagenous colitis and ulcerative colitis. Results: There was statistically significant difference in the count of neuroendocrine cells, between lymphocytic colitis and control (p=0.019104), and between ulcerative colitis and controls (p=0.0077). In collagenous colitis there was an increase in neuroendocrine cells but we failed to find statistical differences. Conclusion: We could observe neuroendocrine cell hyperplasia in lymphocytic colitis and ulcerative colitis compared with controls, which confirm previous studies.

Manifestações clínicas iniciais em pacientes com doença inflamatória intestinal / The onset of clinical manifestations in inflammatory bowel disease patients

ABSTRACT BACKGROUND: The diagnosis of inflammatory bowel disease is often delayed because of the lack of an ability to recognize its major clinical manifestations. OBJECTIVE: Our study aimed to describe the onset of clinical manifestations in inflammatory bowel disease patients. METHODS: A cross-sectional study. Investigators obtained data from interviews and the medical records of inflammatory bowel disease patients from a reference centre located in Brazil. RESULTS: A total of 306 patients were included. The mean time between onset of symptoms and diagnosis was 28 months for Crohn's disease and 19 months for ulcerative colitis. The main clinical manifestations in Crohn's disease patients were weight loss, abdominal pain, diarrhoea and asthenia. The most relevant symptoms in ulcerative colitis patients were blood in the stool, faecal urgency, diarrhoea, mucus in the stool, weight loss, abdominal pain and asthenia. It was observed that weight loss, abdominal pain and distension, asthenia, appetite loss, anaemia, insomnia, fever, nausea, perianal disease, extraintestinal manifestation, oral thrush, vomiting and abdominal mass were more frequent in Crohn's patients than in ulcerative colitis patients. The frequencies of urgency, faecal incontinence, faeces with mucus and blood, tenesmus and constipation were higher in ulcerative colitis patients than in Crohn's disease patients. The mean time from the onset of clinical symptoms to the diagnosis of Crohn's disease was 37 months for patients with ileocolonic location, 26 months for patients with ileum location and 18 months for patients with colon location. In ulcerative colitis patients, the mean time from the onset of symptoms to diagnosis was 52 months for proctitis, 12 months for left-sided colitis and 12 months for extensive colitis. CONCLUSION: Ulcerative colitis presented a high frequency of intestinal symptoms, and Crohn's disease showed a high frequency of systemic manifestations at the onset of manifestation. There was a long delay in diagnosis, but individuals with more extensive disease and more obvious symptoms showed a shorter delay.

RESUMO CONTEXTO: O diagnóstico da doença inflamatória intestinal é frequentemente retardado pela falta de capacidade para reconhecer as suas principais manifestações clínicas. OBJETIVO: Nosso estudo teve como objetivo descrever as manifestações clínicas iniciais em pacientes com doença inflamatória intestinal. MÉTODOS: Estudo transversal. Os pesquisadores obtiveram dados por entrevistas e registros médicos de pacientes com doença inflamatória intestinal em um centro de referência localizado na Bahia. RESULTADOS: Foram incluídos 306 pacientes. O tempo entre o início dos sintomas e o diagnóstico foi de 28 (±48) meses para doença de Crohn e 19 (±46) meses para colite ulcerativa. O tempo médio desde o início dos sintomas clínicos até o diagnóstico de doença de Crohn foi de 37 meses para pacientes com localização do ileocolon, 26 meses para a localização do íleo e 18 meses para a localização do cólon. Nos doentes com colite ulcerativa, o tempo médio desde o início dos sintomas até ao diagnóstico foi de 52 meses para proctite, 12 meses para colite no lado esquerdo e 12 meses para colite extensa. As principais manifestações clínicas em pacientes com doença de Crohn foram perda de peso, dor abdominal, diarreia e astenia. Os sintomas mais relevantes da colite ulcerativa foram sangue nas fezes, urgência fecal, diarreia, muco nas fezes, perda de peso, dor abdominal e astenia. Observou-se que a perda de peso, dor abdominal e distensão, astenia, perda de apetite, anemia, insônia, febre, náusea, doença perianal, manifestação extraintestinal, afta oral, vômitos e massa abdominal foram mais frequentes na doença de Crohn. A frequência de urgência e incontinência fecal, fezes com muco e sangue, tenesmo e constipação foram maiores na colite ulcerativa. CONCLUSÃO: A colite ulcerativa apresentou alta frequência de sintomas intestinais e a doença de Crohn mostrou alta frequência de manifestações sistêmicas. Houve um grande atraso no diagnóstico, mas indivíduos com doença mais extensa e sintomas mais exuberantes mostraram um atraso menor.

Factores pronósticos en colitis ulcerosa de reciente diagnóstico / Prognostic factors of ulcerative colitis at the moment of diagnosis

The clinical presentation of ulcerative colitis at the moment of diagnosis is variable, and its clinical course is difficult to predict. It can range from a quiescent to a refractory chronic course that may require hospitalization and surgical procedures. It can also have complications such as colorectal cancer. In this review we discuss the role of demographic, clinical, endoscopic, histological and associated factors, which can help to predict the clinical course of the disease at the moment of diagnosis, and to individualize therapy according to this clinical risk. Accurate identification of patients with a newly diagnosed ulcerative colitis who are at high risk of an unfavorable outcome is still a challenge. However, an effective evaluation allows an early diagnosis, a timely and effective treatment.

Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides: caso clínico / Acute severe ulcerative colitis treated with accelerated infliximab induction: case report

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

Colitis linfocítica en paciente con colitis ulcerosa: caso clínico / Lymphocytic colitis in a patient with ulcerative colitis: report of one case

The relationship between Microscopic Colitis and Inflammatory Bowel Disease is unclear. However, when both are diagnosed they seem to be part of a broader spectrum of the same disease, more than just a coincidence. We report a 55 years old woman with Ulcerative Colitis limited to the rectum with complete clinical and endoscopic response to standard treatment and adequate surveillance for 13 years, who abandoned treatment and control. After eight years, she consulted for mild-to-moderate non-bloody diarrhea lasting several months. Colonoscopy and basic laboratory did not show any alterations. Nevertheless, random biopsies had a characteristically pattern compatible with Lymphocytic Colitis. After the first week of treatment with budesonide the patient was asymptomatic and still in clinical remission, with negative fecal calprotectin at 6 months’ follow-up.

Medical ozone treatment ameliorates the acute distal colitis in rat

PURPOSE: To investigate the effect of medical ozone treatment on the experimental acute distal colitis in rats. METHODS: Eighteen rats were randomly distributed into three equal groups; control, acute distal colitis (ADC) without and with medical ozone treatment. Rats in the control group were taken saline. ADC was performed by rectal way with 4% acetic acid in groups 2 and 3, and the group 3 was treated with medical ozone for three weeks both rectally and intraperitoneally. At the twenty second day the distal colons samples were obtained for malondialdehyde and myeloperoxidase, blood samples were obtained to measure the levels of TNF-α and IL-1β levels. Histolopatological examination was evaluated with Ki-67, IL-1β and VEGF immunostaining densities. RESULTS: There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β after ozone administration. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSIONS: Medical ozone treatment ameliorated the experimental acute distal colitis induced by acetic acid in rats. Its possible effect is by means of decreasing inflammation, edema, and affecting the proliferation and the vascularization.

Measurement and clinical implications of choroidal thickness in patients with inflammatory bowel disease / Determinação da espessura da coróide suas implicações clínicas em pacientes com doença inflamatória intestinal

ABSTRACTPurpose:Ocular inflammation is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and may parallel disease activity. In this study, we evaluated the utility of a choroidal thickness measurement in assessing IBD activity.Methods:A total of 62 eyes of 31 patients with IBD [Crohn's disease (CD), n=10 and ulcerative colitis (UC), n=21] and 104 eyes of 52 healthy blood donors were included in this study. Choroidal thickness was measured using enhanced depth imaging optical coherence tomography. The Crohn's disease activity index (CDAI) and the modified Truelove Witts score were used to assess disease activity in CD and UC, respectively.Results:No significant differences in mean subfoveal, nasal 3000 μm, or temporal 3000 μm choroidal thickness measurements (P>0.05 for all) were observed between IBD patients and healthy controls. Age, smoking, CD site of involvement (ileal and ileocolonic involvement), CDAI, CD activity, and UC endoscopic activity index were all found to be significantly correlated with choroidal thickness by univariate analysis (P<0.05). Smoking (P<0.05) and the CD site of involvement (P<0.01) were the only independent parameters associated with increased choroidal thickness at all measurement locations.Conclusions:Choroidal thickness is not a useful marker of disease activity in patients with IBD but may be an indicator of ileal involvement in patients with CD.

RESUMOObjetivos:Inflamação ocular é uma manifestação extra-intestinal comum de doença inflamatória do intestino (IBD) e pode ser paralela a atividade da doença. Neste estudo, investigamos se a espessura da coroideia pode ser útil para avaliar a atividade da IBD.Método:Um total de 62 olhos de 31 pacientes com IBD [10 com doença de Crohn (CD) e 21 colite ulcerosa (UC)] além de 104 olhos de 52 doadores de sangue saudáveis foram incluídos neste estudo. A espessura da coróide foi medida utilizando-se imagens de tomografia de coerência óptica com profundidade aprimorada. O índice de atividade da doença Crohn (CDAI) e o índice de Truelove Witts modificado foram usados para avaliar atividade da doença em CD e UC, respectivamente.Resultados:Não houve diferença significativa entre os pacientes com IBD e controles saudáveis em termos de medições da espessura da coróide subfoveal média em região 3000 μm nasal e 3000 μm temporal (p>0,05). Com base na análise univariada; idade, tabagismo, local do envolvimento em CD (ileal ou íleo-cecal), CDAI, atividade CD e índice de atividade endoscópica da UC foram significativamente correlacionados com a espessura da coróide (p<0,05). No entanto, fumar (p<0,05) e o local de envolvimento em CD (p<0,01) foram os únicos parâmetros independentes associados com um aumento na espessura da coroideia em todos os pontos de medida.Conclusões:A espessura da coroide não é um marcador útil para refletir a atividade da doença em pacientes com IBD, mas pode ser um indicador de envolvimento ileal em pacientes com CD.

FOCAL ENHANCED GASTRITIS AND MACROPHAGE MICROAGGREGATES IN THE GASTRIC MUCOSA: potential role in the differential diagnosis between Crohn’s disease and ulcerative colitis / Gastrite focal e microagregados de macrófagos na mucosa gástrica: uso potencial no diagnóstico diferencial entre doença de Crohn e colite ulcerativa

Context and Objectives Focally enhanced gastritis and macrophage microaggregates are found in the upper gastrointestinal involvement of Crohn’s disease, and may reflect an underlying defective innate immunity. These features, however, are also described in patients with Helicobacter pylori infection. The role of these gastric abnormalities in the diagnosis of Crohn’s disease was assessed in a population with high prevalence of H. pylori infection. Methods Thirty-seven Crohn’s disease, 26 ulcerative colitis, and 30 control patients were included. The H. pylori status was evaluated by the rapid urease test and histology. The presence of focally enhanced gastritis and macrophage microaggregates was recorded. Results Focally enhanced gastritis was present in 24% of Crohn’s disease patients, 4% of ulcerative colitis patients and 11.5% of controls, presenting an overall sensitivity and specificity for Crohn’s disease of 24% and 88%, respectively. Macrophage microaggregates were found in all groups, but were only detected in ulcerative colitis and controls in association with H. pylori infection, with an overall sensitivity and specificity for Crohn’s disease of 61% and 69%, respectively. In the absence of H. pylori infection, focally enhanced gastritis and macrophage microaggregates were significantly associated with Crohn’s disease (P<0.02 and P = 0.001 respectively). Conclusions Focally gastritis and macrophage microaggregates are suggestive of Crohn’s disease only in H. pylori-negative specimens. HEADINGS - Crohn’s disease. Ulcerative colitis. Gastritis. Macrophages. Helicobacter pylori. .

Contexto e objetivos Gastrite focal e microagregados de macrófagos são encontradas no acometimento gástrico da doença de Crohn, e podem refletir um defeito subjacente na imunidade inata. Estas características, no entanto, são também descritas em pacientes com infecção por Helicobacter pylori. O papel destas anormalidades gástricas no diagnóstico da doença de Crohn foi avaliada em uma população com alta prevalência de infecção por H. pylori. Métodos Trinta e sete pacientes com doença de Crohn, 26 pacientes com colite ulcerativa e 30 pacientes-controle foram incluídos. O status de infecção por H. pylori foi avaliado pelo teste da urease e histologia. A presença de gastrite focal e microagregados de macrófagos foi avaliada. Resultados Gastrite focal estava presente em 24% dos pacientes com doença de Crohn, 4% dos indivíduos com colite ulcerativa e 11,5% dos controles, apresentando uma sensibilidade e especificidade para doença de Crohn de 24% e 88%, respectivamente. Microagregados de macrófagos foram encontrados em todos os grupos, mas foram apenas detectados em colite ulcerativa e controles em associação com infecção por H. pylori, com sensibilidade e especificidade para doença de Crohn de 61% e 69%, respectivamente. Na ausência da infecção por H. pylori comprovada, gastrite focal e microagregados de macrófagos foram significativamente associados com doença de Crohn (P<0,02 e P = 0,001, respectivamente). Conclusões Gastrite focal e microagregados de macrófagos são sugestivos de doença de Crohn apenas em pacientes com avaliação dignóstica negativa para H. pylori. .

Positive correlttion between disease activity idex and matrix metalloproteinasses activity in a rat model of colitis / Correlação positiva entre índice de atividade de doença e metaloproteinase de matriz em modelo de colite em ratos

Context Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. Objectives Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. Methods Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. Results Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (P<0.001) and MMP-9 activities (45 fold) compared to the control group. Conclusions In this study, we observed a disease activity index correlation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase. .

Contexto Doenças inflamatórias intestinais, entre elas colite ulcerativa e doença de Crohn, compreendem um amplo espectro de doenças que apresentam em comum inflamação crônica do trato gastrointestinal, alterações histológicas e um aumento de atividade de determinadas enzimas, tais como, metaloproteinases. Objetivos Avaliar possível correlação do índice de atividade de doença em modelo de colite ulcerativa induzida por dextran sulfato de sódio com o grau de severidade de danos na mucosa colônica e aumento de atividade de metaloproteinases. Métodos Colite foi induzida por administração oral de dextran sulfato de sódio 5% durante sete dias no grupo (n = 10), enquanto que o grupo controle (n = 16) recebeu água. Efeitos foram analisados diariamente pelo índice de atividade de doença. No sétimo dia, os animais foram sacrificados e as medições hematológicas, alterações histológicas (hematoxilina e eosina e coloração de azul Alcian), mieloperoxidase e atividades de metaloproteinases (MMP-2 e MMP-9) foram determinados. Resultados Grupo dextran sulfato de sódio mostrou elevação no índice de atividade de doença e redução dos parâmetros hematológicos. A indução da colite causa lesão no tecido, com perda de mucina e aumento da mieloperoxidase (P<0,001) e as atividades MMP-9 (45 vezes) em comparação com o grupo de controle. Conclusões Neste estudo, observamos uma correlação do índice de atividade de doença com o grau de alterações histopatológicas após indução da colite por dextran sulfato de sódio, podendo associar este resultado ao aumento principalmente da atividade de MMP-9 e de mieloperoxidase. .

Manejo de la colitis ulcerosa grave: experiencia a partir de un hospital ministerial / Management of severe ulcerative colitis: experience from a national health service hospital

Introduction: Ulcerative colitis (UC) may present, or evolve as severe crisis. Although guidelines have defined its management and timing in decision-making, this has not been implemented at national level. Objective: To describe the clinical characteristics and management of patients with severe UC in our hospital. Patients and Methods: Retrospective review of medical records of 116 patients with inflammatory bowel disease during the period 1975-2012. Of 97 patients with UC, 21 patients with at least one severe crisis were identified. Results: The median age among patients with UC crisis was 34 years (17-43). Ten patients debuted with severe crisis. Eleven were in maintenance treatment, all with 5-aminosalicylates (5- ASA), eight with systemic steroids and five with immunomodulators. During the crisis, colonoscopy was performed to 13 patients, 11 with extensive involvement and two left colitis. All patients received steroids and 5-ASA, 14 antibiotics, and seven immunomodulators. No patient received medical rescue therapy (cyclosporine/biological therapy). Nine patients required surgery, two due to toxic megacolon and seven due to intravenous-steroid refractory episode. Five patients received parenteral nutrition and six were hospitalized in the critical patients unit. The range of stay in the hospital was 9-51 days. Conclusions: In this study, a significant percentage of patients with CU presented a severe crisis without having a standardized management. It is necessary to establish a consensus for the multidisciplinary management of severe UC. No patient had access to cyclosporine/biological therapy, more than 40 percent of the cases required surgery. These therapeutic strategies should be incorporated into the therapeutic arsenal in hospitals.

La colitis ulcerosa (CU) puede debutar, o evolucionar, como crisis grave. Aunque guías han definido su manejo y temporalidad en la toma de decisiones,esto no ha sido masificado a nivel nacional. Objetivo: Describir las características clínicas y manejo de pacientes con CU grave en nuestro centro. Pacientes y Métodos: Revisión retrospectiva de fichas clínicas de 116 pacientes con enfermedad inflamatoria intestinal, durante el período 1975-2012. De 97 pacientes con CU se identifican 21 pacientes con al menos una crisis grave. Resultados: La mediana de edad en la crisis fue 34 años (17-43). Diez pacientes debutaron con crisis grave. Once estaban en tratamiento de mantención, todos con 5-aminosalicilatos (5-ASA), ocho con esteroides sistémicos y cinco con inmunomoduladores. Durante la crisis, se realizó colonoscopia a 13 pacientes, 11 con compromiso extenso y dos con colitis izquierda. Todos recibieron esteroides y 5-ASA, 14 antibióticos y siete inmunomoduladores. Ningún paciente recibió terapia médica de rescate (ciclosporina/terapia biológica). Nueve pacientes requirieron cirugía, dos por megacolon tóxico y siete por cortico-refractariedad. Cinco pacientes recibieron nutrición parenteral y seis fueron hospitalizados en una Unidad de Pacientes Críticos. El rango de estadía hospitalaria fue de 9-51 días. Conclusiones: En este estudio un porcentaje importante de los pacientes con CU presentó una crisis grave, sin tener un manejo estandarizado. Es necesario establecer un consenso para el manejo multidisciplinario de la CU grave. Ningún paciente tuvo acceso a ciclosporina/ terapia biológica, requiriendo cirugía más de 40 por ciento de los casos. Estas estrategias terapéuticas deben ser incorporadas al arsenal terapéutico hospitalario.

Linear IgA dermatosis associated with ulcerative colitis: complete and sustained remission after total colectomy / Dermatose bolhosa por IgA linear associada a retocolite ulcerativa: remissao completa e sustentada apos colectomia total

Linear IgA dermatosis has been increasingly associated with inflammatory bowel diseases, particularly ulcerative colitis. A 13-year-old male patient with an 11-month history of ulcerative colitis developed vesicles, pustules and erosions on the skin of the face, trunk and buttocks and in the oral mucosa. The work-up revealed a neutrophil-rich sub-epidermal bullous disease and linear deposition of IgA along the dermoepidermal junction, establishing the diagnosis of linear IgA dermatosis. The patient experienced unsatisfactory partial control of skin and intestinal symptoms despite the use of adalimumab, mesalazine, prednisone and dapsone for some months. After total colectomy, he presented complete remission of skin lesions, with no need of medications during two years of follow-up. A review of previously reported cases of the association is provided here and the role of ulcerative colitis in triggering linear IgA dermatosis is discussed.

A dermatose bolhosa por IgA linear tem sido crescentemente associada com doenças inflamatórias intestinais, especialmente a retocolite ulcerativa. Relatamos o caso de um adolescente masculino, 13 anos de idade, com retocolite ulcerativa diagnosticada 11 meses antes, que desenvolveu vesículas, pústulas e erosões na pele da face, do tronco e das nádegas e na mucosa oral. A investigação revelou doença bolhosa subepidérmica rica em neutrófilos e deposição linear de IgA ao longo da junção dermoepidérmica, estabelecendo o diagnóstico de dermatose bolhosa por IgA linear. O paciente experimentou controle insatisfatório dos sintomas cutâneos e gastrointestinais apesar do uso de adalimumab, mesalazina, prednisona e dapsona por alguns meses. Após colectomia total, ele apresentou remissão completa das lesões cutâneas, sem necessidade de medicações durante os dois anos de seguimento. Neste artigo, revisamos os casos previamente relatados desta associação e debatemos o papel da retocolite ulcerativa no desencadeamento da dermatose bolhosa por IgA linear.

Papel da cápsula endoscópica na reclassificação da doença inflamatória intestinal em crianças / Role of wireless capsule endoscopy in reclassifying inflammatory bowel disease in children

OBJECTIVE: To evaluate the role of wireless capsule endoscopy in identifying small bowel lesions in pediatric patients with newly diagnosed colonic inflammatory bowel disease (IBD) type unclassified (IBDU), and to assess whether capsule endoscopy findings result in altered patient management. METHODS: Ten pediatric patients recently diagnosed with IBDU through standard investigations were recruited from the pediatric gastroenterology clinic at McMaster Children's Hospital to undergo capsule endoscopy using the Pillcam SB TM (Given Imaging) capsule. Findings consistent with a diagnosis of Crohn's disease required the identification of at least three ulcerations. RESULTS: Three out of ten patients had newly identified findings on capsule endoscopy that met criteria for Crohn's disease. Three more patients had findings suspicious for Crohn's disease, but failed to meet the diagnostic criteria. Three additional patients had findings most consistent with ulcerative colitis, and one had possible gastritis with a normal intestine. Findings from capsule endoscopy allowed for changes in the medical management of three patients. In all ten cases, capsule endoscopy allowed for a better characterization of the type and extent of disease. No adverse outcomes occurred in the present cohort. CONCLUSIONS: This prospective study reveals that wireless capsule endoscopy is feasible, valuable, and non-invasive, offering the ability to potentially better characterize newly diagnosed pediatric IBDU cases by identifying lesions in the small bowel and reclassifying these as Crohn's disease. Further investigation is warranted.

OBJETIVO: Avaliar o papel da cápsula endoscópica na identificação de lesões no intestino delgado em pacientes pediátricos com DII inespecífica (DIII) diagnosticada recentemente e avaliar se os achados da cápsula endoscópica resultam em alterações no tratamento dos pacientes. MÉTODOS: Dez pacientes pediátricos recém-diagnosticados com DIII por meio de investigações padrão foram recrutados da clínica de gastroenterologia pediátrica no McMaster Children's Hospital, para serem submetidos a exame com a cápsula endoscópica Pillcam SB TM (Given Imaging). Achados compatíveis com o diagnóstico da doença de Crohn exigiram a identificação de pelo menos três ulcerações. RESULTADOS: De 10 pacientes, três apresentaram achados novos com a cápsula endoscópica que satisfizeram o critério para a doença de Crohn. Outros três apresentaram achados com suspeita de doença de Crohn, porém não atenderam nossos critérios de diagnóstico. Apresentaram achados mais compatíveis com colite ulcerativa outros três pacientes, e um apresentava possível gastrite com intestino normal. Os achados da cápsula endoscópica possibilitaram mudanças no tratamento médico de três pacientes. Em todos os dez casos, a cápsula endoscópica permitiu uma melhor caracterização do tipo e da extensão da doença. Não houve resultado adverso em nossa coorte. CONCLUSÃO: Este estudo prospectivo revela que a cápsula endoscópica é viável, útil e não invasiva, que oferece a possibilidade de melhor caracterização de casos de DIII pediátricos recém-diagnosticados ao identificar lesões no intestino delgado e reclassificá-las como doença de Crohn.

Epidemiological, demographic, and colonic extension of ulcerative colitis in Iran: a systematic review

Ulcerative colitis [UC], as the prototype of inflammatory bowel disease of the large bowel, is increasing in Iran and other developing countries. There are few studies that discuss the properties of this disease in the Islamic Republic of Iran. The result of this review may provide a general consensus about the epidemiological features of UC in Iran. This was a qualitative, systematic review that investigated the incidence, prevalence, and demographic properties of UC in Iran. We evaluated all published studies in the PubMed database, Iran Medex, Magiran, and Scientific Information Database [SID] that pertained to the epidemiology and demographic features of UC in Iran from January 1987 to January 2012. After searching with defined keywords and implementing the inclusion and exclusion criteria, 11 case series and 2 case-control studies fulfilled the criteria for inclusion. The estimated prevalence of UC is 15 per 10[5] persons, and the reported incidences were 3.04 and 3.25 per 10[5] persons in two Iranian provinces. The disease was more commonly observed in women and people in their fourth decade of life. Cigarette smoking conferred protection and familial association seemed to be similar to developed countries. UC did not appear to be more common among the higher socioeconomic class. In addition it less commonly involved the proximal colon and rectum. Although the data is limited, the prevalence and incidence of UC in Iran shows an increasing pattern similar to other countries in the region. There is no clear association with socioeconomic status. Milder forms of the disease are common in Iran. A comprehensive nationwide data bank is needed for a better definition of the disease characteristics

¿Beneficio o riesgo del uso de ácido ursodeoxicólico en prevención de cáncer colorrectal en pacientes con colangitis esclerosante primaria/colitis ulcerosa? / Benefit or risk from the use of ursodeoxycholic acid in prevention of colorectal

cancer in patients with primary sclerosing cholangitis/ulcerative colitis? Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of intra-and extrahepatic bile ducts. About 70 percent of patients with CEP have idiopathic ulcerative colitis (IUC). PSC is considered a premalignant condition with an increased risk of colorectal cancer (CC). Individuals with PSC and IUC have higher risk of developing CC than IUC patients. There are different positions between American and European experts in the fields of hepatology and inflammatory bowel disease regarding the use of ursodeoxycholic acid (UDCA) in PSC and IUC as a chemo preventive. Studies have shown mixed results about the use of UDCA in preventing CC. The following is an update on the role of UDCA as a chemo preventive in this group of patients.

La colangitis esclerosante primaria (CEP) es una enfermedad crónica hepática colestásica caracterizada por inflamación y fibrosis de ductos biliares intra y extrahepáticos. Alrededor de 70 por ciento de los pacientes con CEP presenta colitis ulcerosa idiopática (CUI). La CEP es considerada una condición premaligna con un incremento del riesgo de cáncer colorrectal (CCR). Individuos con CEP más CUI tienen mayor riesgo de desarrollar CCR que pacientes con sólo CUI. Existen distintas posturas a nivel mundial entre expertos americanos y europeos tanto en el área de la hepatología como en el área de las EII (enfermedades inflamatorias intestinales) frente al uso de ácido ursodeoxicólico (AUDOC) en CEP y CUI como quimioprotector. Estudios han mostrado resultados contradictorios para el uso de AUDOC en la prevención de CCR. Se expone una revisión actualizada sobre el rol de AUDOC como quimioprotector en este grupo de pacientes.