A Network Pharmacological Approach to Explore the Mechanisms of TongXieYaoFang in Inflammatory Bowel Disease

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine, demonstrating an increasing incidence every year. TongXieYaoFang (TXYF) has been used widely in China as a complementary therapy to relieve the symptoms of IBD for hundreds of years. In the present research, a network pharmacology-based approach was used to systematically explore the intrinsic mechanisms of TXYF in IBD at the molecular level. Network pharmacology-based methods, which mainly included database mining, screening of bioactive compounds, target prediction, collection of IBD-related targets, gene enrichment analysis, network construction, and molecular docking, were employed in the present study. Network analysis revealed a total of 108 potential targets derived from 22 component compounds of TXYF, among which 34 targets were common with the IBD-related targets. In the protein-protein interaction (PPI) network, 10 key targets were identified. The gene enrichment analysis suggested that anti-inflammatory processes, such as NF-kappa B signaling pathway and Toll-like receptor signaling pathway, could be the core processes involved in the action of TXYF in IBD. Molecular docking results revealed that three compounds present in TXYF exhibited strong binding affinity for PTGS2. The present study provides novel insights into the molecular mechanisms and network approaches of TXYF action in IBD from a systemic perspective. The potential targets and pathways identified in the present study would assist in further research on the clinical application of TXYF in IBD therapy.

Ocular Affection as an Extraintestinal Manifestation in Cases of Inflammatory Bowel Disease at the Kafrelsheikh Governorate / Afecção ocular como manifestação extraintestinal em casos de doença inflamatória intestinal

Abstract Introduction The manifestations of inflammatory bowel disease (IBD) are not restricted to the gastrointestinal tract. Musculoskeletal conditions are considered the most common extraintestinal manifestations, followed by mucocutaneous and ocular diseases. Many general practitioners are unaware of the variety and severity of the ocular affection in IBD patients. Objective To assess the prevalence of extraintestinal manifestations in IBD patients at Kafrelsheikh governorate, and to evaluate the different ocularmanifestations and their relationship to the severity of the disease. Methods A cross-sectional study evaluating 120 patients treated at the Kafrelsheikh University Hospital. The diagnosis of IBD was made between December 2018 and December 2019 through clinical, endoscopic and histopathological examinations. All patients were assessed for any extraintestinal manifestation or evidence of ocular affection through slit-lamp examinations, tonometry, visual acuity, and indirect ophthalmoscopy. Results The mean age of the sample was 35.5 ± 13.3 years. In total, 52 (43.3%) patients were male and 68 (56.7%) were female. Ocular manifestations represent ~ 22.5% of extraintestinal manifestations. The most common ocular findings were conjunctivitis (25.8%) and anterior uveitis (10.8%), followed by scleritis (9.2%) and cataract (8.3%). Other extraintestinal manifestations were observed in 41 (34.1%) 29 (29.9%) of ulcerative colitis cases, and 12 (52%) of Crohn disease cases. There was no statistically significant difference in the presence of ocular involvement in relation to the two types of IBD included in the Montreal classification. Conclusion Ocular manifestations in cases of IBD are common and usually nonspecific in presentation. The severity of the IBD does not reflect the severity of the ocular affection.

Resumo Introdução As manifestações da doença inflamatória intestinal (DII) não se restringem ao trato gastrointestinal. Distúrbios musculoesqueléticos são considerados as manifestações extraintestinais mais comuns, seguidos de doenças oculares e mucocutâneas. Muitos clínicos gerais desconhecem a variedade e a severidade das afecções oculares em casos de DII. Objetivo Determinar a prevalência das manifestações extraintestinais em pacientes com DII na província de Kafrelsheikh, no Egito, e avaliar as diferentes manifestações oculares e sua relação com a gravidade da doença. Métodos Um estudo transversal que avaliou 120 pacientes tratados no Kafrelsheikh University Hospital. O diagnóstico de DII foi feito entre dezembro de 2018 e dezembro de 2019 por meio de exames clínicos, endoscópicos e histopatológicos. Por meio de exames de lâmpada de fenda, tonometria, acuidade visual, e oftalmoscopia indireta, todos os pacientes foram avaliados para se determinar a ocorrência de quaisquer manifestações extraintestinais ou afecções oculares. Resultados Amédia de idade da amostra foi de 35,5 ± 13,3 anos. No total, 52 (43,3%) pacientes com DII eram do sexo masculino, e 68 (56,7%), do sexo feminino. As manifestações oculares representaram ~ 22,5% das manifestações extraintestinais. Os achados oculares mais comuns foram conjuntivite (25,8%) e uveíte anterior (10,8%), seguidas de esclerite (9,2%) e catarata (8,3%). Outras manifestações extraintestinais foram observadas em 41 (34,1%) pacientes, entre elas, 29,9% de casos de colite ulcerativa, e 52% de casos de doença de Crohn. Não houve diferença estatisticamente significativa na presença de envolvimento ocular com relação aos dois tipos de DII descritos na classificação de Montreal. Conclusão Asmanifestações oculares empacientes de DII são comuns e, geralmente, não específicas em termos de apresentação. A gravidade da DII não reflete a gravidade da afecção ocular.

Mecanismos de ação da anexina A1 na doença intestinal inflamatória tratada com infliximabe / Annexin A1 pathways triggered in the inflammatory bowel disease treated with infliximab

As doenças inflamatórias intestinais (DIIs) são enfermidades crônicas desencadeadas por grave inflamação no trato gastrointestinal. Entre os mediadores imunes envolvidos na patogênese das DIIs, o fator de necrose tumoral alfa (TNF-α) e sugerido como citocina primordial. Assim, ferramentas de inativação da via do TNF-α, como o infliximabe (IFX), tem sido amplamente aplicadas no tratamento destas doenças. Embora o IFX seja eficaz na indução/manutenção de remissão das DIIs, ainda há relatos de efeitos adversos ou pacientes refratários a imunoterapia. Por esse motivo, e emergente a necessidade de identificar biomarcadores associados ao sucesso das terapias biológicas. Estudos prévios em pacientes com Doença de Crohn (DC) mostraram que a expressão da proteína anti-inflamatória anexina A1 (AnxA1) sistêmica e na mucosa intestinal e aumentada após IFX e correlacionada com a melhora da qualidade de vida. A AnxA1 e o seu peptídeo N-terminal, Ac2-26, desempenham suas funções na resolução da inflamação via receptores para peptídeo formilado (FPRs). No presente estudo, nós investigamos de que maneira os FPRs e a AnxA1 participam dos mecanismos do IFX. No modelo de colite experimental induzida por dextran sulfato de sódio (DSS) em camundongos selvagens (WT) e deficientes para AnxA1 endógena (AnxA1-/-), o IFX atenuou as manifestações clínicas da doença apenas em animais WT. O bloqueio dos FPRs com o antagonista Boc-2 reverteu a melhora observada nos animais tratados, enquanto a ausência da AnxA1 endógena revogou completamente a eficácia do tratamento. Ainda, a resposta inflamatória da colite foi exacerbada nos animais AnxA1-/- após IFX, que apresentaram redução de células T regulatórias e aumento da MMP9 no colon, encurtamento do intestino grosso, ausência de melhora histológica e mortalidade de 50%. Nos animais WT, por sua vez, o bloqueio dos FPRs impediu a melhora clínica e a regeneração das criptas mucosas, com desorganização da ß-actina e da borda em escova. Nas células epiteliais do intestino da linhagem Caco-2 estimuladas por TNF-α in vitro, confirmamos que os efeitos protetivos do IFX nas junções celulares são perdidos após bloqueio do FPR1 e do FPR2, comprometendo a integridade desta barreira. No colon, o IFX induziu a expressão e secreção da AnxA1 em células da lamina própria após colite, e essa secreção foi dose-dependente em células da lamina própria tratadas ex vivo, demonstrando que a secreção da AnxA1 por células do tecido conjuntivo pode constituir um dos mecanismos resolutivos desta terapia. Em humanos, o tratamento com IFX na DC não modificou as expressões de FPR1 e FPR2 nos leucócitos circulantes ou da AnxA1 plasmática, não permitindo a diferenciação de pacientes responsivos ou não. No entanto, a AnxA1 tecidual estava aumentada em pacientes que respondem ao IFX, e os níveis de AnxA1 e FPR1 foram negativamente correlacionados a remissão histológica. Por fim, análises de bioinformática revelaram expressões diferenciais dos mRNAs de FPR1, FPR2 e AnxA1 no colon entre pacientes remissivos ou refratários mesmo antes do início das infusões, mas esse mesmo padrão não foi observado nos PBMCs do sangue. Em conclusão, sugerimos que a indução da AnxA1 pode ser um dos mecanismos de resolução do IFX, e que é complementado pela ativação de FPRs. Ainda, estes marcadores podem apresentar valor preditivo da eficácia do IFX, contribuindo para o alcance da remissão da DC de maneira mais rápida e permanente

Inflammatory bowel diseases (IBDs) are chronic debilitating illnesses triggered by severe inflammation of the gastrointestinal tract. The tumor necrosis factor alpha (TNF-α) is pointed out as a primordial mediator of IBD pathogenesis; thus, inactivating tools targeting this cytokine have been widely used to treat these diseases. Although IFX is very efficient in inducing/maintaining remission in patients with IBD, side effects and unresponsiveness are still reported, emerging the need for the identification of biomarkers linked to therapeutical efficacy. In the Crohns disease (CD), systemic and tissue expressions of the anti-inflammatory protein, annexin A1 (AnxA1), are increased after IFX treatment and correlate with life quality improvement according to previous reports. AnxA1 and its N-terminal peptide, Ac2-26, act via formyl peptide receptors (FPRs); therefore, the present investigation aimed to understand how FPRs and AnxA1 participate in IFX mechanisms. In the experimental colitis model induced by dextran sulphate sodium (DSS) in wild-type (WT) and AnxA1-deficient mice (AnxA1-/-), IFX attenuated the clinical manifestations only in the WT group. FPRs blockade using the antagonist, Boc-2, impaired IFX effects in WT mice, while AnxA1 absence completely abrogated its efficacy. Furthermore, the inflammatory response was exacerbated after IFX in AnxA1-/- mice, with reduced T regulatory cells, increased tissue MMP9, large intestine shortening, lack of histological remission and 50% mortality. In WT mice, FPR blockade reverted the clinical recovery and mucosal crypts regeneration, with b-actina and brush border disorganization. Using the intestinal epithelial cell line Caco-2 stimulated with TNF-α in vitro, we confirmed that IFX protective effects on tight junctions are lost after FPR1 and FPR2 blockade, compromising the barrier integrity. In the colonic tissue, the expression and secretion of AnxA1 were induced by IFX after colitis. This secretion was shown to be dose-dependent in cells from the intestinal lamina propria treated ex vivo, demonstrating that secreted AnxA1 could constitute one of the resolutive mechanisms of that therapy. In humans with CD, IFX did not modify the expressions of FPR1 and FPR2 in circulating leukocytes or the plasma AnxA1 levels, not differentiating patients responsive or not. However, tissue AnxA1 expression was augmented in responsive patients, and AnxA1/FPR1 levels were negatively correlated with histological remission. Finally, bioinformatic analyses revealed differential expression of FPR1, FPR2 and AnxA1 mRNAs in the colon among remittent or refractory patients even before the beginning of infusions, which was not observed for samples of blood PBCM. In conclusion, we suggest that inducing tissue AnxA1 might be one of the resolution mechanisms of IFX, which is complemented by the activation of FPRs. Moreover, these markers could present predictive value of IFX efficacy, contributing to reaching an early and more permanent remission in IBD

Estudio de la Legalidad Brasileña de las Escuelas Públicas Municipales en Cuanto a la Promoción de la Alimentación Sana para el Control y Prevención de la Salud Oral en el Contexto de las Enfermedades Gastrointestinales Inflamatorias / Study of the Brazilian Legality of the Municipal Public Schools Regarding the Promotion of Healthy Eating for Control and Prevention of Oral Health in the Context of Inflammatory Intestinal Diseases

RESUMEN: Las enfermedades gastrointestinales inflamatorias se caracterizan por la desarmonía de la flora bacteriana del intestino. Estos cambios se caracterizan como un problema de salud pública que demuestra que las principales causas de las enfermedades están asociadas a la alimentación inadecuada y, como consecuencia de cambios en la mucosa oral. Los países desarrollados están actualmente definiendo estrategias para el control de esas enfermedades, teniendo como una de las estrategias públicas para la promoción de la alimentación sana. En este contexto, el objetivo de este trabajo fue evaluar la legislación brasileña vigente en cuanto al cuadro de profesional nutricionista para elaborar y acompañar el menú de la alimentación escolar, conforme prevé la Ley Federal nº 8.234, de 17 de septiembre de 1991, y la Resolución del Consejo Federal de Nutricionistas - CFN n ° 380/2005. Se realizó el levantamiento de las Leyes que establecen un cuadro de profesionales nutricionistas en las escuelas públicas de las principales ciudades brasileñas en los órganos competentes. Los resultados muestran que pocos Estados y Municipios abordan ese tema, entre ellos el Estado de Río de Janeiro, el Estado de São Paulo, la ciudad de Ribeirão Preto, la ciudad de Florianópolis, la ciudad de Belém, el Estado de Santa Catarina, El Estado de Paraná, el Distrito Federal y el Estado de Ceará ya regularon la materia, así como la Ley nº 13.666 / 2018 que modifica la Ley nº 9.394 / 16. Los autores concluyen que además de conocer las pecurialidades de las manifestaciones orales de estos pacientes es imprescindible el conocimiento multidisciplinario del cirujano dentista, creando no sólo oportunidades de diagnóstico precoz, sino también la prevención y promoción de la salud oral.

ABSTRACT: Inflammatory intestinal diseases are characterized by disharmony of the bacterial flora of the intestine. These changes are characterized as a public health problem demonstrating that the main causes of diseases are associated with inadequate nutrition and, as a consequence, changes in the oral mucosa. The developed countries are currently defining strategies for the control of these diseases, having as one of the public strategies to promote healthy eating. In this context, the objective of this study was to evaluate the Brazilian legislation in force regarding the professional dietitian to elaborate and follow the menu of school feeding, according to Federal Law No. 8,234, dated September 17, 1991, and the Resolution of the Federal Council of Nutritionists - CFN n ° 380/2005. It was carried out the survey of the Laws that establish a cadre of nutrition professionals in the public schools of the main Brazilian cities in the competent bodies. The results show that few States and Municipalities address this theme, among them the State of Rio de Janeiro, the State of São Paulo, the city of Ribeirão Preto, the city of Florianópolis, the city of Belém, the State of Santa Catarina, State of Paraná, the Federal District and the State of Ceará have already regulated the matter, as well as Law 13,666 / 2018, which amends Law 9,394 / 16. The authors conclude that besides knowing the characteristics of the oral manifestations of these patients, a multidisciplinary knowledge of the dental surgeon is essential, creating opportunities for early diagnosis, as well as the prevention and promotion of oral health.

The importance of colonoscopy in inflammatory bowel diseases / A importância da colonoscopia nas doenças inflamatórias intestinais

ABSTRACT Introduction: Endoscopic evaluation, particularly the macroscopic mucosal and histological results of ileocolic biopsies, is essential for the management of inflammatory bowel disease. Endoscopic appearance is not always sufficient to differentiate Crohn's disease and ulcerative colitis, but there are some characteristics that favor one or another diagnosis. Both diseases have an increased incidence of colorectal carcinoma; so, surveillance colonoscopy is important for detecting early neoplastic lesions. Objective: To update the importance of endoscopy in the evaluation, diagnosis and prognosis of inflammatory bowel disease. Method: Search was done in the scientific literature of the TRIP database, chosen from clinical questions (PICO) with the following descriptors: "inflammatory bowel disease", "endoscopy/colonoscopy", "Crohn's disease", "ulcerative colitis" and "diagnosis/treatment". Results: Endoscopic investigation in patients with chronic colitis is quite accurate for the differential diagnosis between ulcerative colitis and Crohn's disease. Endoscopy is indicated for ulcerative colitis during severe crisis due to its prognostic value. Another accepted indication for endoscopy in inflammatory bowel disease is its use in the screening for dysplastic lesion. Conclusion: Ileocolonoscopy allows an accurate diagnosis of Crohn's disease or ulcerative colitis in up to 90% of cases. The healing of the mucosa assessed by endoscopy after treatments despite not being consensus is still the gold-standard in the evaluation of remission of the disease. Colonoscopy is essential for long-term cancer surveillance and in the future the implementation of Confocal Laser Endomicroscopy seems to be very promising in assessing the initial dysplasia.

RESUMO Introdução: A avaliação endoscópica, em particular da macroscopia das mucosas e resultados histológicos de biópsias ileocolônicas, é essencial para o manuseio da doença inflamatória intestinal. A aparência endoscópica nem sempre é suficiente para diferenciar doença de Crohn e colite ulcerativa, porém existem algumas características que favorecem um ou outro diagnóstico. Ambas as doenças apresentam um aumento de incidência de carcinoma colorretal, assim, a colonoscopia de vigilância é importante para detectar lesões neoplásicas iniciais. Objetivo: Revisar o papel da endoscopia na avaliação, diagnóstico e prognóstico de doença inflamatória intestinal. Método: Foram pesquisados artigos científicos do banco de dados TRIP, escolhidos a partir de questões clínicas (PICO) com os seguintes descritores: "doença inflamatória intestinal", "endoscopia/colonoscopia", "doença de Crohn/colite ulcerativa" e "diagnóstico/tratamento". Resultados: A investigação endoscópica em pacientes com colite crônica é bastante precisa para o diagnóstico diferencial entre colite ulcerativa e doença de Crohn. Ela é indicada na colite ulcerativa durante as crises graves de doença, por seu valor prognóstico. Outra indicação aceita na doença inflamatória intestinal é a sua utilização no rastreio da lesão displásica . Conclusão: A Ileocolonoscopia permite diagnóstico preciso da doença de Crohn ou colite ulcerativa em até cerca de 90% dos casos. A cicatrização da mucosa avaliado por endoscopia após tratamentos, apesar de não ser consenso, ainda é o padrão-ouro na avaliação da remissão da doença.Colonoscopia é essencial para a vigilância do câncer em longo prazo. Futuramente a realização de Confocal Laser Endomicroscopy parece ser promissora na avaliação da displasia inicial.

Avaliação clínica, endoscópica e histopatológica de cães com doença inflamatória intestinal / Clinical, endoscopic and histopathological evaluation of dogs with inflammatory bowel disease

O presente estudo teve como objetivo avaliar macro e microscopicamente a mucosa gastrintestinal de cães domiciliados, que apresentaram sinais gastrintestinais crônicos, por meio de exame endoscópico e da avaliação histopatológica. Os sinais clínicos, a macro e a microscopia das mucosas gástrica e duodenal foram correlacionados. Foram avaliados 20 cães de diferentes raças, sendo 7 machos e 13 fêmeas, com idade variando entre 1,7 a 15,8 anos, que apresentavam cronicidade dos sinais característicos da Doença Inflamatória Intestinal (DII). O estudo foi prospectivo e transversal, realizado em cães atendidos no Hospital Universitário de Medicina Veterinária da Universidade Federal Fluminense (HUVET - UFF) e em clínicas privadas do município do Rio de Janeiro. Amostras de mucosa gastroduodenal foram obtidas por meio de biópsia endoscópica e foram processadas por técnica histológica de rotina e coradas por Hematoxilina-Eosina e Giemsa. As amostras foram submetidas à análise histopatológica para pesquisa de bactérias espiraladas sugestivas de Helicobacter spp. O teste rápido da urease também foi realizado. Os sinais clínicos, e os achados macro e microscópicos foram confrontados e correlacionados. Neste estudo, foi possível estabelecer correlação positiva entre a perda de peso e a presença de enantema no antro, no corpo e no duodeno além de correlação entre alteração do apetite, a presença de infiltrado inflamatório gástrico e a positividade no teste da urease. Este estudo demonstrou a importância da observação de alguns sinais clínicos como a perda de peso e alterações do apetite no curso da Doença Inflamatória Intestinal. Desta forma, enfatiza-se que cães que apresentem tais sinais clínicos devem ter a Doença Inflamatória Intestinal incluída no grupo de diagnósticos diferenciais evitando, com isso, negligenciar uma enfermidade que, cada vez mais, acomete animais de pequeno porte.(AU)

The aim of this study was to evaluate macro and microscopic gastrointestinal mucosa of domiciled dogs, with chronic gastrointestinal symptoms by endoscopy and histopathological evaluation, correlating clinical signs, macro and microscopy characteristics/aspects/changes of duodenal and gastric mucosa. Twenty dogs of different breeds were evaluated with with chronic characteristic signs of Inflammatory Bowel Disease (IBD), being 7 males and 13 females, with ages ranging from 1.7 to 15.8 years old. The study was prospective and cross-sectional, conducted in dogs treated at the Teaching Veterinary Medicine Hospital of the Universidade Federal Fluminense (HUVET-UFF) and private clinics in the city of Rio de Janeiro. Gastroduodenal mucosal samples were obtained by endoscopic biopsy and were processed by routine histological technique and stained with hematoxylin- eosin and Giemsa. The samples were submitted to histopathological analysis for the detection of spiral bacteria suggestive of Helicobacter spp. The rapid urease test was also performed. The clinical signs, the macro and microscopic findings were compared and correlated. In this study, we established a positive correlation between weight loss and the presence of erythema in the antrum, body and duodenum as well as correlation between change in appetite and the presence of gastric inflammatory infiltrate and positivity in the urease test. This study demonstrated the importance of the observation of some clinical signs such as weight loss and appetite changes in the course of IBD. Thus, it is emphasized that dogs showing these clinical signs should have the IBD included in the differential diagnoses group avoiding thereby neglecting a disease that increasingly affects small animals.(AU)

Neoplasias extra-colónicas en pacientes con enfermedad inflamatoria intestinal / Extra-intestinal malignancies in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have shown to be at increased risk of developing extraintestinal malignancies. Immunomodulators (immunosuppressant and anti-tumor necrosis factor) diminish the mucosal inflammatory response changing the evolution of the disease, especially when these strategies are introduced earlier. However, therapies that alter the immune system may also promote carcinogenesis. Treatment of IBD in patients with prior malignancy is challenging and the final decision regarding therapeutic strategy should be made on a case-by-case basis. The purpose of this review is to show the characteristics of extra-colonic cancer in patients with IBD, including risks, pathogenesis and management of IBD after cancer diagnosis, the effect of neoplasm treatment on IBD, and the effect of IBD and its treatments on cancer outcomes.

Los pacientes con enfermedad inflamatoria intestinal (EII) presentan un mayor riesgo de desarrollar neoplasias extraintestinales. Los inmunomoduladores (inmunosupresores y terapia biológica anti-TNF) disminuyen la respuesta inflamatoria a nivel de la mucosa, modificando la evolución de la enfermedad, especialmente cuando son introducidos precozmente. Sin embargo, estas terapias pueden alterar el sistema inmune y promover la carcinogénesis. El tratamiento de la EII en pacientes con antecedentes de cáncer es un desafío y la decisión final sobre la estrategia terapéutica debe ser determinada caso a caso. Esta revisión tiene como objetivo mostrar las características de las neoplasias extra-intestinales en pacientes con EII, incluyendo los riesgos, patogénesis y manejo de la EII posterior al diagnóstico del cáncer, el efecto de la neoplasia sobre el tratamiento de la EII y el efecto de la EII y su tratamiento sobre el cáncer.

Expressão de citocinas relacionadas à resposta th17 nos tecidos gengival e intestinal de pacientes com periodontite e doença inflamatória intestinal / Expression of Th17 related cytokines response in the gingival and intestinal tissue from patients with periodontitis and inflammatory bowel disease

Aim: The aim of this study was to analyze the levels of IL1-ß, IL-4, IL-6, IL10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, TNF-α and sCD40L in the gingival tissue (G), and compare to the levels of the paired intestinal mucosa (MI)in patients having both chronic periodontitis and InflmmatoryBowel Disease (IBD). Material and methods: Twenty-two IBD patients with chronic periodontitis and IBD, mean age40.0 (±14.5),were enrolled in the study. Patients were assessed using anamnesis and periodontal examination. Gingival and intestinal biopsies were collected and homogenized using a cell disruptor. Cytokine's expression was evaluated through multiplex technology and then compensated by weight. Results: After statistical analysis, significant higher levels of gingival IL-23 (p=0.02) and IFN-γ (p=0.01), and significant lower levels of IL-31(p=0.02) and TNF-α (p=0.01) were found when compared to intestinal mucosa. Significant positive correlation between gingival and intestinal tissue were observedbetweenIL-6 (G) andIL-23 (MIand significant negative correlation between IL-23 (G) and IL-1ß (MI), IL-10 (MI), IL-17A (MI) and IFN-γ (MI). Conclusion: We conclude that IL-23 and IFN-γ are significantly increased in the gingival tissue, when compared to the intestinal tissue, suggesting an important role of these cytokines in the manifestation of periodontitis in patients with IBD.(AU)

Objetivo: O objetivo do estudo foi avaliar a expressão das citocinas: IL1-ß, IL-4, IL-6, IL10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, TNF-α e do ligante solúvel do CD40 (sCD40L) no tecido gengival (G) e compará- la com a expressão na mucosa intestinal (MI) de forma pareada em pacientes com periodontite crônica e Doença Inflamatória Intestinal (DII). Material e métodos: Participaram do estudo 22 pacientes com DII, média de idade de 40 anos (DP ±14,5 anos). Foram registrados os parâmetros clínicos e periodontais, e foram coletadas biópsias gengivais e intestinais pareadas. As mesmas foram homogeneizadas usando um disruptor celular. Os níveis das citocinas foram analisados pelo método multiensaio multiplex e posteriormente compensados pelo peso das amostras. Resultados: Após análise estatística, observamos níveis significativamente maiores de IL-23 (p=0,02) e IFN-γ (p=0,01) e significantemente menores de IL-31 (p=0,02) e TNF-α (p=0,01) no tecido gengival quando comparamos com o intestinal. Correlações significantes ocorreram entre o tecido gengival e o intestinal de forma positiva para a IL-6 (G) com a IL-23(MI) e de forma negativa entre IL-23 (G) com IL-1ß (MI), IL-10(MI), IL-17A (MI) e IFN-γ (MI). Conclusão: Concluímos que a IL-23 e IFN-γ encontram-se significantemente aumentadas no tecido gengival, quando comparados à mucosa intestinal, sugerindo um papel importante destas citocinas na manifestação da periodontite em pacientes com DII.(AU)

Parenteral Nutritional Support in Gastrointestinal and Liver Diseases / 대한소화기학회지

Protein-calorie malnutrition and deficiencies of specific nutrients could commonly occur in various types of gastrointestinal diseases. These nutritional problems could delay recovery from diseases, resulting in increased morbidity and mortality, and impairment of quality of life. Parenteral nutrition (PN) is one of the methods of nutritional support through which macronutrients (glucose, amino acids, and triglycerides), micronutrients (vitamins and trace elements), water, and electrolytes are administered via peripheral or central venous route. PN could play an important role for patients for whom enteral/oral feeding is contraindicated or cannot meet the patients' requirement for adequate nutrition due to anatomical and/or functional problems. Since insufficient and excessive PN supplement could both be harmful for patients, it is very important to adhere to correct indication, optimal timing, and dosage/composition of PN. In this article, the current role of PN for various gastrointestinal diseases will be reviewed and discussed.

Avaliação colonoscópica em pacientes com espondilite anquilosante / Colonoscopic evaluation in patients with ankylosing spondylitis

Introdução: Pacientes com espondilite anquilosante podem apresentar-se com lesões inflamatórias intestinais, e, por isso, deve ser definido o uso da colonoscopia para tais pacientes. Objetivos: Avaliar as alterações colonoscópicas intestinais macroscópicas e achados histopatológicos microscópicos de pacientes com espondilite anquilosante; correlacionar os achados colonoscópicos e histopatológicos; e estudar a relação dos achados histopatológicos com as manifestações extra-articulares da doença, HLA-B27, BASFI and BASDAI. Métodos: Este é um estudo transversal de 22 pacientes com espondilite anquilosante. Os pacientes passaram por uma avaliação clínica, BASDAI e BASFI, coleta de sangue para determinação de HLA-B27, e colonoscopia com biópsia de quarto segmentos intestinais (íleo terminal, cólon direito, cólon sigmoide e reto). Resultados: Resultados colonoscópicos anormais foram obtidos em 13 (59,1%) pacientes, e a principal anormalidade foi a presença de pólipos intestinais. Os grupos de resultados colonoscópicos normais e anormais (n = 9 e n = 13, respectivamente) foram homogêneos no que diz respeito à idade, BASFI, BASDAI, e variáveis categóricas, e o valor P não revelou diferença significativa entre grupos. Dos resultados histopatológicos, 81% tiveram uma biópsia anormal do íleo terminal, 90.9% tiveram uma biópsia anormal do cólon sigmoide, e a biópsia retal estava anormal em 86.4%. Os achados histopatológicos revelaram biópsias anormais em 81%, 90.9%, 90.9% e 86.4% para o íleo terminal, cólon direito, cólon sigmoide e reto, respectivamente. Os resultados histopatológicos não revelaram associação estatisticamente significativa com as manifestações ex...

Introduction: Patients with ankylosing spondylitis can have intestinal inflammatory lesions, thus the use of colonoscopy for such patients should be defined. Objectives: To assess the gross intestinal colonoscopic changes and microscopic histopathologic findings of patients with ankylosing spondylitis; to correlate the colonoscopic and histopathologic findings; and to study the relationship of the histopathologic findings with extra-articular manifestations of the disease, HLA-B27, BASFI and BASDAI. Methods: This is a cross-sectional study of 22 patients with ankylosing spondylitis. The patients underwent clinical assessment, BASDAI and BASFI application, blood collection for HLA-B27 measurement, and colonoscopy with biopsy of four intestinal segments (terminal ileum, right and sigmoid colons, and rectum). Results: Abnormal colonoscopic results were obtained in 13 (59.1%) patients, the major abnormality being intestinal polyps. The groups of normal and abnormal colonoscopic results (n = 9 and n = 13, respectively) were homogeneous regarding age, BASFI, BASDAI, and categorical variables, and the P-value showed no significant difference between groups. The histopathological findings revealed abnormal biopsies in 81%, 90.9%, 90.9% and 86.4% for terminal ileum, right colon, sigmoid colon, and rectum, respectively. The histopathologic results showed no statistically significant association with the extra-articular manifestations, BASFI, BASDAI and HLA-B27 positivity. Conclusions: The histological analysis of the four intestinal segments evidenced inflammatory lesions in patients with normal and abnormal colonoscopic results, independently of bowel symptomatology and therapy used in the treatment of the basal disease. .

Manifestaciones extraintestinales en rectocolitis úlcerativa: a propósito de un caso / Extraintestinal manifestations in ulcerative proctocolitis: a case report

La colitis ulcerativa (CU) forma más común de la enfermedad inflamatoria intestinal (EII),¹ es una enfermedad crónica que cursa con inflamación recurrente no controlada del colon,² caracterizada por ulceración de la mucosa, sangrado rectal, diarrea y dolor abdominal.³ Un tercio de los pacientes pueden desarrollar una manifestación extraintestinal.4,5 En la CU estas manifestaciones suelen estar relacionadas con la actividad de la enfermedad.5,6 Presentamos un caso clínico de una paciente con CU quien presenta manifestaciones extraintestinales cutáneas, oculares y en mucosa bucal, con resolución de las mismas posterior a tratamiento médico

Ulcerative colitis (UC) the most common form of inflammatory bowel disease (IBD),¹ is a chronic disease that causes uncontrolled recurrent inflammation of the colon,² characterized by mucosal ulceration, rectal bleeding, diarrhea and abdominal pain.³ A third of patients may develop extraintestinal manifestation.4,5 In UC these manifestations are often associated with disease activity.5,6 We present a case of a patient with UC who presented extraintestinal cutaneous, ocular and oral mucosa, with resolution of the same post-treatment

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.

Hypertonic saline solution reduces the inflammatory response in endotoxemic rats

OBJECTIVE: Volume replacement in septic patients improves hemodynamic stability. This effect can reduce the inflammatory response. The objective of this study was to evaluate the effect of 7.5% hypertonic saline solution versus 0.9% normal saline solution for volume replacement during an inflammatory response in endotoxemic rats. METHODS: We measured cytokines (serum and gut), nitrite, and lipid peroxidation (TBARS) as indicators of oxidative stress in the gut. Rats were divided into four groups: control group (C) that did not receive lipopolysaccharide; lipopolysaccharide injection without treatment (LPS); lipopolysaccharide injection with saline treatment (LPS +S); and lipopolysaccharide injection with hypertonic saline treatment (LPS +H). Serum and intestine were collected. Measurements were taken at 1.5, 8, and 24 h after lipopolysaccharide administration. RESULTS: Of the four groups, the LPS +H group had the highest survival rate. Hypertonic saline solution treatment led to lower levels of IL-6, IL-10, nitric oxide, and thiobarbituric acid reactive substances compared to 0.9% normal saline. In addition, hypertonic saline treatment resulted in a lower mortality compared to 0.9% normal saline treatment in endotoxemic rats. Volume replacement reduced levels of inflammatory mediators in the plasma and gut. CONCLUSION: Hypertonic saline treatment reduced mortality and lowered levels of inflammatory mediators in endotoxemic rats. Hypertonic saline also has the advantage of requiring less volume replacement.

Percepción de calidad de vida determinada por cuestionario Ibdq-32: en pacientes con enfermedad inflamatoria intestinal / Perception of quality of life questionnaire for certain ibdq-32: in patients with inflammatory bowel disease

La enfermedad inflamatoria intestinal es una patología inmunoinflamatoria crónica que influye en la vida de los pacientes en dimensiones físicas, psicológicas, familiares y sociales. Pacientes y métodos Estudio descriptivo, prospectivo que incluyó a 31 pacientes con enfermedad inflamatoria intestinal de los Servicios de Gastroenterología del "Hospital Vargas de Caracas" y Hospital Militar "Dr. Carlos Arvelo" a quienes se les aplicó el cuestionario Inflammatory Bowel Disease Questionnaire-32.Resultados De 31 pacientes, 10 (32.25%) tenían enfermedad de Crohn y 21 (67.74%) colitis ulcerosa; 15 pacientes (48.38%) de sexo masculino.16 pacientes (51.61%) femeninas, cuyas edades oscilaron entre 16-72 años. 19 pacientes (61.3%) tuvieron una percepción de calidad de vida alta, 57.89% (11) con colitis ulcerosa y 42.11% (8) enfermedad de Crohn. 32.3% (10) con calidad de vida moderada y de ellos 80% (8) con colitis ulcerosa y 20% (2) con enfermedad de Crohn. Sólo 2 pacientes (6.44%) presentaron baja calidad de vida, ambos con colitis ulcerosa. Conclusiones La valoración de la calidad de vida juega un papel importante en la evaluación del tratamiento y consecuencias de ésta entidad a nivel físico, emocional y social, siendo un buen marcador del efecto de las intervenciones terapéuticas y de la respuesta clínica obtenida.

Inflammatory bowel disease is a chronic immunoinflammatory disease that affects the lives of patients in physical dimensions, psychological, familial and social. Patients and methods A prospective descriptive study involving 31 patients with inflammatory bowel disease attending the Gastroenterology service of the "Hospital Vargas de Caracas" and Military Hospital "Dr. Carlos Arvelo". The questionnaire was administered Inflammatory Bowel Disease Questionnaire-32. Results Of 31 patients,10 (32.25%) had Crohn’s disease and 21 (67.74%) ulcerative colitis, 15 patients (48.38%) of sex masculino.16 patients (51.61%) female, aged between 16-72 years. 19 patients (61.3%) had a perception of high quality of life, 11 (57.89%) with ulcerative colitis and 8 (42.11%) Crohn’s disease. 10 (32.3%) with moderate quality of life and of these 8 (80%) with ulcerative colitis and 2 (20%) with Crohn’s disease. Only 2 patients (6.44%) had poor quality of life, both with ulcerative colitis. Conclusions The assessment of quality of life plays an important role in the evaluation of treatment and consequences of this entity on the physical, emotional and social, being a good marker of the effect of therapeutic interventions and clinical response obtained.

Synchronous pyoderma gangrenosum and inflammatory bowel disease, healing after total proctocolectomy / Pioderma gangrenoso associado a doença inflamatória intestinal, com resolução após proctocolectomia total

We present a female patient observed with painful violaceous plaques with central bullae and pustules on the lower limbs, rapidly transformed into ulcers, associated with bloody diarrhea, recurrent oral erosions and hyperthermia in the previous 3 months. Cutaneous biopsy was consistent with pyoderma gangrenosum, and intestinal diagnostic procedures revealed a non-classifiable inflammatory bowel disease with high x-ANCA titers. Soon after admission the patient was submitted to total proctocolectomy following colonic perforation. Complete ulcer healing occurred three months after surgery, without recurrence. Pyoderma gangrenosum is a rare dermatosis frequently associated with inflammatory bowel disease. This case is particularly interesting for the synchronic clinical presentation of cutaneous and intestinal diseases, but also for the prompt regression of the former after total proctocolectomy.

Apresentamos uma paciente do sexo feminino observada com múltiplas placas violáceas dolorosas dos membros inferiores, com bolhas e pústulas evoluindo rapidamente para lesões ulceradas, surgindo no contexto de diarreia sanguinolenta, erosões orais recorrentes e febre com três meses de evolução. A biópsia cutânea foi compatível com pioderma gangrenoso; o estudo complementar revelou doença inflamatória intestinal inclassificável com títulos elevados de x-ANCA. Após perfuração cólica, a doente foi submetida a proctocolectomia total, com rápida cicatrização das lesões cutâneas ulceradas em três meses, sem recorrência. O pioderma gangrenoso é uma dermatose rara frequentemente associada a doença inflamatória intestinal. É interessante verificar neste caso a apresentação clínica sincrónica das doenças cutânea e intestinal, bem como a rápida resolução da primeira após proctocolectomia total.

Signo de la cuerda en enfermedad inflamatoria intestinal / String sign in inflammatory bowel disease

The String Sign corresponds to an image displayed on oral contrast study of the gastrointestinal tract. It is seen as a thin strip of barium resembling a frayed cotton rope which results from a severe narrowing of the bowel loops. This radiographic finding is caused by irritability and ulceration associated with severe spasms, generally secondary to Crohn's disease. It may appear in both stenotic and nonstenotic stages of the disease.

El signo de la cuerda corresponde a una imagen visualiza en estudio de contraste oral en el tubo digestivo observándose como una delgada franja de bario que asemeja una cuerda deshilachada de algodón, debido a un severo estrechamiento de las asas de intestino. Este signo se ha descrito inicialmente para describir la enfermedad de Crohn, produciéndose por la irritabilidad y los espasmos asociados a ulceración severa y puede ser visto tanto en fases estenóticas como no estenóticas de la enfermedad.

Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

Small intestinal immunopathology following oral infection with tissue cysts of Toxoplasma gondii has been described in C57BL/6 mice. Seven days after infection, mice develop severe small intestinal necrosis and succumb to infection. The immunopathology is mediated by local overproduction of Th1-type cytokines, a so-called "cytokine storm". The immunopathogenesis of this pathology resembles that of inflammatory bowel disease in humans, i.e., Crohn's disease. In this review, we show that the development of intestinal pathology following oral ingestion of T. gondii is not limited to C57BL/6 mice, but frequently occurs in nature. Using a Pubmed search, we identified 70 publications that report the development of gastrointestinal inflammation following infection with T. gondii in 63 animal species. Of these publications, 53 reports are on accidental ingestion of T. gondii in 49 different animal species and 17 reports are on experimental infections in 19 different animal species. Thus, oral infection with T. gondii appears to cause immunopathology in a large number of animal species in addition to mice. This manuscript reviews the common features of small intestinal immunopathology in the animal kingdom and speculates on consequences of this immunopathology for humankind.