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Background and aim Human gut microbiota play an important role in metabolism and host physiology. Perturbations of the gut microbial communities lead to the development of various diseases such as inflammatory bowel disease, celiac disease, allergic diseases, and metabolic diseases. Crohn's disease is a chronic inflammatory bowel disease characterized by periods of remission and relapse. Several studies suggest that intestinal inflammation arises due to an abnormal response of the intestinal immune system to the fecal microbiota. The goal of the study was to evaluate the relative amount of four bacterial groups in fecal samples of Crohn's disease patients and their relation to the inflammatory activity. Methods We studied stool samples of 105 individuals, 54 with Crohn's disease and 51 as a control group. The DNA extracted from the stool samples was subjected to real‐time polymerase chain reaction (qPCR) for quantification of the Bacteroidetes phylum, class Bacilli, and Bifidobacteriaceae and Enterobacteriaceae families. Results We found a significant increase in Bacteroidetes in Crohn's disease samples when compared to the control group (14 650 and 2060 CFU/ng DNA, respectively) (P = 0.014). On the other hand, we observed a significant reduction in Bacilli and Bifidobacteriaceae (13 and 58 CFU/ng DNA, respectively) (P, Gut microbiota is strongly associated with host physiology, and perturbations of the gut microbial communities lead to the development of various diseases. The goal of this study was to evaluate the relative amount of four bacterial groups in fecal samples of patients with Crohn's disease and their relation to the inflammatory activity. We observed that the commensal bacteria were decreased in fecal samples of participants with Crohn´s disease when compared to the control group. There was no relation between the disease localization and/or clinical condition with the microbiota.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche. ispartof: LANCET GASTROENTEROLOGY & HEPATOLOGY vol:7 issue:1 pages:28-37 ispartof: location:Netherlands status: published

Made available in DSpace on 2022-04-29T08:30:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-21 BACKGROUND Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD. AIM To describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil. METHODS This was a prospective, noninterventional study of adult patients with active Crohn’s disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined. RESULTS The study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease. CONCLUSION Although a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting. Department of Internal Medicine Botucatu Medical School at Sao Paulo State University (UNESP) Botucatu Department of Gastroenterology Escola Paulista de Medicina Sao Paulo São Paulo Department of Proctology Kaiser Day Hospital, São Jose do Rio Preto Department of Gastroenterology Faculdade de Medicina do ABC Santo Andre Department of Gastroenterology Faculdade de Medicina, Goiania 74535-170 Department of Gastroenterology CMIP Centro Mineiro de Pesquisa Juiz de Fora Department of Internal Medicine Federal University of Rio de Janeiro Rio de Janeiro Department of Gastroenterology Escola Paulista de Medicina São Paulo Hospital de Clínicas de Porto Alegre Hospital de Clínicas de Porto Alegre Porto Alegre Hospital de Clinicas da Universidade Federal do Paraná Hospital de Clinicas da Universidade Federal do Paraná Gastroenterology Department Hospital Nossa Senhora das Graças Curitiba Department of General Medicine Universidade Federal do Piauí Teresina Gastroenterology Hospital Universitario da Universidade Federal do Piaui Teresina Department of Medicine University Hospital of Federal University of Juiz de Fora, Juiz de Fora, Juiz de Fora Department of Clinical Medicine Universidade Federal de Minas Gerais, Belo Horizonte Hospital de Clinicas da Universidade Federal do Paraná Hospital de Clinicas da Universidade Federal do Paraná, Curitiba Department of Surgery and Anatomy Ribeirao Preto Medical School University of Sao Paulo, Ribeirão Preto Scientific Affairs Takeda Pharmaceuticals Brazil Clinical Research Takeda Pharmaceuticals São Paulo IBD Unit Federal University of Bahia, Salvador Department of Internal Medicine Botucatu Medical School at Sao Paulo State University (UNESP) Botucatu

Made available in DSpace on 2021-06-25T10:51:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-14 BACKGROUND Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce. AIM To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions. METHODS Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables. RESULTS In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%). CONCLUSION In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment. Department of Internal Medicine Federal University of Rio de Janeiro Department of Surgery and Anatomy Ribeirão Preto Medical School University of São Paulo Department of Internal Medicine São Paulo State University (UNESP) Medical School IBD Unit Federal University of Bahia Department of Clinical Medicine Medical School Universidade Federal de Minas Gerais Department of Gastroenterology Escola Paulista de Medicina Hospital de Clinicas Universidade Federal do Parana Department of Proctology Beneficencia Portuguesa Hospital Kaiser Day Hospital Department of Gastroenterology and Hepatology Sciences Hospital de Clínicas Universidade Federal do Rio Grande do Sul Department of Gastroenterology Faculdade de Medicina do ABC Department of General Medicine Gastroenterology Unit University Hospital Federal University of Piaui Department of Gastroenterology Faculdade de Medicina Universidade Federal de Goiás Department of Surgery Botucatu Medical School São Paulo State University (UNESP) Department of Gastroenterology UNIFESP IBD Unit Gastroenterology Department Hospital Nossa Senhora das Graças Department of Proctology Kaiser Hospital Dia Health Sciences Center Epidemiology Unit State University of Piaui Department of Gastroenterology CMIP Centro Mineiro de Pesquisa Scientific Affairs Takeda Pharmaceuticals Brazil Clinical Research Takeda Pharmaceuticals Brazil Department of Medicine University Hospital of Federal University of Juiz de Fora Department of Internal Medicine São Paulo State University (UNESP) Medical School Department of Surgery Botucatu Medical School São Paulo State University (UNESP)

STUDY OBJECTIVES: The pathogenesis of inflammatory bowel disease (IBD) is not well understood, and sleep disorders may be potential triggers for IBD. Thus, an evaluation of the sleep characteristics, fatigue symptoms, and cytokine levels was performed in patients with IBD during periods of active disease and remission. METHODS: A total of 20 participants presenting with Crohn's disease or ulcerative colitis, with active disease (n = 7) or in remission (n = 13), underwent home polysomnography (H-PSG). Pittsburgh Sleep Quality Index (PSQI) and Modified Fatigue Impact Scale (MFIS) were applied, in addition to the evaluation of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) serum levels. Exploratory analysis, t test and Mann-Whitney U test were used. RESULTS: The mean sleep latency in patients with active disease was 133.07 minutes and 106.79 minutes in those in remission. The sleep efficiency and sleep fragmentation in patients with active disease and those in remission were 80.90% and 84.20% (median), and 76.36/min and 69.82/min (mean), respectively, although the H-PSG parameters did not differ between the groups. The PSQI scores indicated poor sleep quality (global score above 5) in all participants with IBD, and the participants with active disease presented more symptoms of fatigue (P = .032). IL-6 and TNF-α average levels were higher in the participants with disease remission, although with a larger dispersion of the data. CONCLUSIONS: No significant difference in the H-PSG characteristics was observed between the patients with IBD with active disease and those in remission; however, the perception of the participants with IBD showed significant effect on the sleep quality and fatigue symptoms. CITATION: Paixão DL, Poyares D, de Paula MS, Duarte JW, Castelo PM, Ambrogini-Júnior O, Miszputen SJ, Oshima CT, Chagas JR, Paiotti AP. Evaluation of home polysomnography findings, quality of sleep, and fatigue in inflammatory bowel disease: a case series. J Clin Sleep Med. 2019;15(1):39–45.

Introdução: A dispepsia funcional é uma síndrome gastrointestinal desafiadora pelos diversos fatores que podem gerá-la e pelos critérios exigidos para diagnosticá-la. Entretanto, é possível entender o perfil epidemiológico e clínico de seus portadores, bem como identificar a influência de algumas condições em suas manifestações. Objetivo: avaliar a prevalência da dispepsia funcional e caracterizar os aspectos epidemiológicos e clínicos. Metodologia: estudo prospectivo, transversal, tipo survey inquérito, com pacientes dispépticos encaminhados ao serviço de endoscopia digestiva alta. A amostra foi composta por 859 indivíduos com diagnóstico clínico de dispepsia, sendo aplicados questionários autoexplicativos: sociodemográfico, Inventário de Ansiedade de Beck, Inquérito de Depressão de Beck e o questionário de ROMA III. Resultados: do total de entrevistados, 36 (4,19%) preencheram os critérios ROMA IV para dispepsia funcional, que engloba duas síndromes clínicas diferentes: a síndrome do desconforto pós-prandial e a síndrome da dor epigástrica. A faixa etária média foi 31,5 anos (19,2-39,7), 23 (63,9%) eram procedentes de Aracaju, 32 (88,8%) do sexo feminino, 21 (60%) solteiros e 19 (54,3%) consideravam-se de cor parda. Foram identificados 19 (52,8%) pacientes portadores de ansiedade e 9 (25%) com depressão. Segundo os critérios, 10 (27,8%) apresentaram síndrome do desconforto pós-prandial, 07 (19,4%) a síndrome da dor epigástrica e 19 (52,8%) os dois subtipos clínicos simultaneamente. Conclusão: a dispepsia funcional foi mais prevalente entre as mulheres, indivíduos solteiros, cor parda e portadores de ansiedade. Não houve significância estatística quanto ao tipo de apresentação clínica, embora a manifestação concomitante dos dois subtipos, tenha sido mais prevalente.

Introdução: Os sintomas dispépticos são frequentemente referidos nas consultas gastroenterológicas. Em boa parte dos doentes é possível reconhecer que alterações emocionais fazem parte dos fatores que desencadeiam ou pioram suas queixas digestivas. Objetivo: avaliar a presença e os níveis de ansiedade em portadores de dispepsia. Metodologia: estudo prospectivo, transversal do tipo survey inquérito, realizado em Aracaju-SE, em pacientes encaminhados para EDA, com diagnóstico clínico de dispepsia/sintomas dispépticos. A amostra foi composta por 859 indivíduos com diagnóstico de dispepsia. Foi aplicado três questionários autoexplicativos: sociodemográfico, Critérios de ROMA III e o Inventário de Ansiedade de Beck. Resultados: Dos 859 entrevistados, 388 (45,1%) foram diagnosticados com ansiedade, sendo 214 (55,1%) ansiedade leve, 112 (28,9%) moderada e 62 (16%) grave. A média de idade dos ansiosos leves, moderados e graves foi de 38 anos, 36,5 anos e 35,5 anos respectivamente. Dos entrevistados, 297 (76,5%) eram mulheres, 207 (53,3%) casados, 204 (52,5%) pardos e 205 (52,8%) com ensino médio completo. Dentre as comorbidades, 71 (18,3%) referiram doença cardiovascular, 80 (20,6%) pulmonar, 186 (47,9%) digestiva, 79 (20,4%) osteomuscular, 256 (66%) transtornos psiquiátricos e 158 (40,7%) usavam medicamentos. A soma sugere queixas concomitantes. De acordo com o ROMA III, 221 (57,3%) referiram dor no peito, 291 (75,2%) azia, 276 (71,5%) empachamento pós prandial e 140 (36,7%) saciedade precoce. Conclusão: Os níveis mais elevados de ansiedade podem se constituir como agravantes para a apresentação e gravidade de sintomas dispépticos.

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Made available in DSpace on 2020-12-12T01:42:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-14 AbbVie Ferring Pharmaceuticals Pfizer Background: Inflammatory bowel diseases (IBD) have been associated with a low quality of life (QoL) and a negative impact on work productivity compared to the general population. Information about disease control, patient-reported outcomes (PROs), treatment patterns and use of healthcare resources is relevant to optimizing IBD management. Aim: To describe QoL and work productivity and activity impairment (WPAI), treatment patterns and use of healthcare resources among IBD patients in Brazil. Methods: A multicenter cross-sectional study included adult outpatients who were previously diagnosed with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). At enrolment, active CD and UC were defined as having a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or calprotectin > 200 μg/g or previous colonoscopy results suggestive of inadequate control (per investigator criteria) and a 9-point partial Mayo score ≥ 5, respectively. The PRO assessment included the QoL questionnaires SF-36 and EQ-5D-5L, the Inflammatory Bowel Disease Questionnaire (IBDQ), and the WPAI questionnaire. Information about healthcare resources and treatment during the previous 3 years was collected from medical records. Chi-square, Fisher's exact and Student's t-/Mann-Whitney U tests were used to compare PROs, treatment patterns and the use of healthcare resources by disease activity (α = 0.05). Results: Of the 407 patients in this study (CD/UC: 64.9%/35.1%, mean age 42.9/45.9 years, 54.2%/56.6% female, 38.3%/37.1% employed), 44.7%/25.2% presented moderate-to-severe CD/UC activity, respectively, at baseline. Expressed in median values for CD/UC, respectively, the SF-36 physical component was 46.6/44.7 and the mental component was 45.2/44.2, the EQ-visual analog scale score was 80.0/70.0, and the IBDQ overall score was 164.0/165.0. Moderate to severe activity, female gender, being unemployed, a lower educational level and lower income were associated with lower QoL (P < 0.05). Median work productivity impairment was 20% and 5% for CD and UC patients, respectively, and activity impairment was 30%, the latter being higher among patients with moderate to severe disease activity compared to patients with mild or no disease activity (75.0% vs 10.0%, P < 0.001). For CD/UC patients, respectively, 25.4%/2.8% had at least one surgery, 38.3%/19.6% were hospitalized, and 70.7%/77.6% changed IBD treatment at least once during the last 3 years. The most common treatments at baseline were biologics (75.3%) and immunosuppressants (70.9%) for CD patients and 5-ASA compounds (77.5%) for UC patients. Conclusion: Moderate to severe IBD activity, especially among CD patients, is associated with a substantial impact on QoL, work productivity impairment and an increased number of IBD surgeries and hospitalizations in Brazil. Department of Surgery and Anatomy Ribeirao Preto Medical School University of Sao Paulo Inflammatory Bowel Disease Center Federal University of Juiz de Fora Hospital de Clinicas da Universidade Federal do Parana Hospital de Clinicas de Porto Alegre Universidade Federal do Piaui Hospital de Clínicas da Universidade Federal do Parana CTI Clinical Trial and Consulting Services CMIP Centro Mineiro de Pesquisa Hospital Nossa Senhora das Gracas Hospital Universitario da Universidade Federal do Piaui Universidade Federal do Rio de Janeiro Universidade do Estado da Bahia Department of Internal Medicine Botucatu Medical School at Sao Paulo State University (UNESP) Instituto Goiano de Gastroenterologia e Endoscopia Digestiva Ltda Kaiser Clinica Escola Paulista de Medicina UNIFESP Disciplina de Gastroenterologia Faculdade de Medicina do ABC Faculdade de Medicina UFMG Takeda Pharmaceuticals Brazil Department of Internal Medicine Botucatu Medical School at Sao Paulo State University (UNESP)

Background Inflammatory bowel disease occurs when luminal antigens from microbiota stimulate the immune system of an intestinal barrier through defects in the tight junctions lead to an exacerbated response in the genetically predisposed individual. It is well known that the consumption of probiotics improves intestinal health. Specifically, the Lactobacillus sp. strains play a key role in the epithelial intestinal barrier, promote mucin secretion, better performance of tight junctions and prevent apoptosis of epithelial cells. This study aimed to evaluate the role of Kefir (Lactobacillus kefiranofaciens) on inflammation of dextran sodium sulphate (DSS)-induced colitis. Methods Forty male Wistar rats were randomised into five groups: Sham; 5% DSS-induced colitis; control Kefir; 5% DSS-induced colitis treated with Kefir; 5% DSS-induced colitis treated with Kefir + 5-ASA (125mg/kg/day) (Ethics Committee on the Use of Animals number 3627290119). The lactic culture of Kefir (Danisco Biolacta, Olstyn, Poland) was administered ad libitum per 6 days. The preparation of the matrix was carried out as follows: whole milk powder was reconstituted to 10% with distilled water and was incubated at 85°C for 15 min using a mechanical shaker. Subsequently, 20 mg freeze-dried Kefir culture was added to 100 ml of the treated milk and fermentation were carried out at 23°C for 16 h. When the desired pH of 4.6 was reached, the fermentation was stopped by cooling the flasks in ice bath and storing them under refrigeration at 4°C until utilisation. The rats were euthanised on day 9. Colonic samples were processed for transmission electron microscope (TEM) and conventional microscopy. Samples were analysed in a TEM EX II 1200 (JEOL, Japan) coupled to a digital camera system GATAN Orius (USA). Histopathological evaluation was performed by a pathologist under a light microscope. Parameters such as inflammation extent, regeneration and crypt damage were graded according to Dieleman et al.3 Statistical analysis was performed by one-way analysis of variance (ANOVA), followed by Tukey’s test using Graph Pad Prism (version 6.0). Results Kefir treatment reduces the severity of DSS-induced colitis evidenced by decreased abdominal discomfort and rectal bleeding. Histologically, there was a significant decreased of colonic damage and preservation of goblet cells (p < 0.0001) compared with DSS-colitis control group (Figure 1). The effect of Kefir was also verified by TEM analysis at the ultrastructural level, demonstrating the tight junctions preserved, decreased of reticulum edema and increased of autophagosomes (Figure 2). Conclusion Kefir promotes autophagy and protects the intestinal barrier against damage caused by DSS.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional condition, which main symptoms of pain, discomfort and abdominal distension, constipation, diarrhea, altered fecal consistency and sensation of incomplete evacuation can be influenced by the presence of dietary fiber and fermentable carbohydrates (FODMAPs). This study aimed to assess the relationship between the quantity of fermentable carbohydrates (FODMAP) and fiber consumed by individuals diagnosed with IBS, and their classification according to the Rome III criteria. METHODS: A transversal study was carried out in the Intestinal Outpatient Clinic of the Gastroenterology Discipline of UNIFESP. The nutrients of interest for the study were: fiber, general carbohydrates and FODMAPs, with intake quantity measured in grams, analyzed through portions consumed. A nutrition log was used, along with a semi-quantitative questionnaire of consumption frequency. RESULTS: The sample included 63 adult patients; 21 with constipated IBS, 21 with diarrhea IBS, and 21 with mixed IBS. Carbohydrate intake was suboptimal in 55.6% of patients in all groups; excessive consumption was identified in 38.1% of the diarrhea group, 14.3% of the mixed group and 38.1% of the constipated group. Low consumption of carbohydrates was found in 28.6% of diarrhea patients and 47.6% of the mixed group. A mean intake of 23 g of fiber per day was identified, lower than recommended. CONCLUSION: The study identified a number of inadequacies in the consumption of different nutrients, excessive carbohydrate intake, especially FODMAPs, identified by the respondents as responsible for a worsening of their conditions. By contrast, other food groups such as meat, eggs and dairy were consumed by the sample population in insufficient quantities. RESUMO CONTEXTO: A síndrome do intestino irritável é um distúrbio funcional crônico, no qual a dieta, principalmente o teor de fibra dietética e presença de carboidratos fermentativos (FODMAPs) podem influenciar nos principais sintomas: dores, desconforto e/ou distensão abdominal, constipação, diarreia, alteração na consistência das fezes, sensação de evacuação incompleta. OBJETIVO: Este estudo teve como objetivo avaliar as quantidades de carboidratos fermentativos (FODMAP) e fibras consumidas por indivíduos com o diagnóstico de síndrome do intestino irritável e relacionar com seu modelo da classificação, segundo os critérios Roma III. MÉTODOS: Estudo transversal, realizado no Ambulatório de Doenças Intestinais da Disciplina de Gastroenterologia/UNIFESP. Os nutrientes de interesse para o estudo foram: fibras, carboidratos em geral e FODMAPs, calculando-se suas quantidades em gramas, analisadas através das porções consumidas. Os instrumentos de pesquisa utilizados: ficha de acompanhamento nutricional e questionário de frequência alimentar semi-quantitativo. RESULTADOS: A amostra incluiu 63 pacientes adultos, com síndrome do intestino irritável constipado (21), diarreico (21) e misto (21). O consumo de carboidratos mostrou-se inadequado em 55,6% dos indivíduos em todos os grupos; os que tinham alto consumo (38,1%) pertenciam ao grupo diarreia, 14,3% ao misto e 38,1 % ao constipado. Baixo consumo deste nutriente foi 28,6% nos casos de diarreia e 47,6% do misto. Observamos uma ingestão média de fibras equivalente à 23 g/dia, nos três grupos, inferior ao recomendado. CONCLUSÃO: O estudo permitiu reconhecer várias inadequações no consumo dos diferentes grupos de alimentos, particularmente excesso de carboidratos, incluindo os classificados como FODMAPs, identificados pelos doentes como responsáveis pela piora das suas queixas. Em contrapartida, nutrientes fundamentais, como carnes, ovos, leite e derivados estiveram referidos em níveis abaixo do recomendado.

The Brazilian Societies of Rheumatology (SBR) and Dermatology (SBD), the Brazilian Federation of Gastroenterology (FBG) and the Brazilian Study Group on Inflammatory Bowel Disease (GEDIIB) gathered a group of their respective specialists on the topic of interest to discuss the most relevant issues regarding the clinical use of biosimilar medicines in Brazil. The main aim of that meeting was to prepare a document with recommendations to guide medical specialists and to help the national regulatory and policy-making agencies as concerns the authorization for marketing biosimilars used in autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, juvenile idiopathic arthritis and ulcerative colitis. In addition to considerations on the typical differences between innovator medicines and biosimilars, the specialists established a set of seven recommendations on regulatory advances related to clinical studies, indication extrapolation, nomenclature, interchangeability, automatic substitution and pharmacovigilance.

ABSTRACT Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohn’s disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.

Reactive oxygen and nitrogen species (ROS/RNS) play a crucial role in inflammatory bowel disease (IBD) exacerbating the chronic inflammatory process. Endogenous and diet antioxidants can neutralize these compounds. The apple is widely consumed, with several antioxidant activity compounds. The present study evaluated the effects of concentrated apple extract (CAE) in acetic acid induced colitis. 29 Wistar male rats were randomized into 5 groups. G1–Sham/saline solution, G2–CAE/control, G3–acetic acid/control, G4–curative- CAE treatment and G5–preventive-CAE treatment. Eight days later, the animals were euthanized and the colonic segment resected for macroscopic and histological analysis. Gene expression was evaluated for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), catalase and copper and zinc superoxide dismutase (CuZnSOD) by quantitative real time PCR, while protein expression was assessed for iNOS, COX-2 and 8-hydroxy-20-deoxyguanosine (8-OHdG) via immunohistochemistry. The groups G3, G4 and G5 had weight loss, while G5 had weight increase at the end of the experiment. The treatment with CAE reduced the macroscopic and microscopic injury, decreased iNOS mRNA expression and increased CuZnSOD mRNA expression in animals with induced acetic acid-colitis. The findings of the present study suggest that CAE treatment exerts an antioxidant role by downregulating iNOS and upregulating CuZnSOD.

Objective: a strong association has been observed between celiac disease, generally its silent clinical form, and autoimmune disorders. A potential correlation with inflammatory bowel disease has also been suggested. Anti-tissue transglutaminase antibodies have been detected in Crohn's disease. We investigated the prevalence of celiac disease in patients with autoimmune diabetes and in Crohn's disease patients and also evaluated the correlation between anti-transglutaminase antibody positivity and the clinical status of these diseases. Methods: anti-tissue transglutaminase and anti-endomysium antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively. Upper digestive endoscopy and duodenal biopsy were indicated for cases with positive serology. Results: anti-transglutaminase antibodies were detected in five diabetic patients (prevalence of 11.1%), only one serum sample was positive for IgG isotypes. Nine of thirty-three patients with Crohn's disease had low positive levels for IgA anti-transglutaminase. Anti-endomysium antibodies were detected only in celiac patients. Celiac disease was confirmed in all diabetic patients submitted to duodenal biopsies who presented both anti-transglutaminase and anti-endomisyum antibodies positivity. In Crohn's disease, its clinical status and the diagnosis of celiac disease were not associated with positive anti-transglutaminase result. Conclusions: the prevalence of celiac disease was high in diabetic patients. Anti-tissue transglutaminase antibodies were sensitive and specific markers of celiac disease in this diabetic group, while these antibodies were of limited value for celiac disease screening in patients with Crohn's disease.

Relatamos um caso de dano hepático em paciente idosa após uso de produtos naturais à base de Hypericum perforatum e copaíba (Copaifera langsdorffii Desf). A hepatotoxicidade do Hypericum perforatum é conhecida por relatos, mas a respeito da copaíba, largamente usada como anti-inflamatório, há apenas dados experimentais na literatura nacional. Essa apresentação visou chamar a atenção para possível efeito tóxico dessa associação, bem como para a recuperação clínica da paciente após interrupção de seu uso. Há uma tendência de suspeitar sobre a ação de medicamentos para justificar a lesão hepática aguda não viral, em razão do grande número de fármacos responsáveis por hepatotoxicidade. A literatura tem publicado experimentos e relatos clínicos em que produtos fitoterápicos, inclusive Hypericum perforatum, são o agente causador dessa agressão, considerados inócuos e utilizados livremente. É preciso lembrar que reações adversas ocorrem também com essas substâncias, merecendo sua investigação na obtenção da anamnese, pela possibilidade de promoverem quadros graves de falência hepática.

Inflammatory bowel disease is relatively frequent in women of childbearing age. Disease management requires greater attention during this clinical condition because of potential risk of maternal-fetal complications. Infliximab has been shown to be safe during pregnancy and lactation, but reports in the literature are scarce. We report two cases of refractory Crohn's disease treated with infliximab with good results, in women. Both patients became pregnant during maintenance regimen and treatment was continued. The literature regarding pregnant patients with inflammatory bowel disease was reviewed.

CONTEXT: Ulcerative colitis is an inflammatory bowel disease involving superficial inflammation of the mucosa of the colon, rectum, and anus, sometimes including the terminal ileum. When in clinical activity, the disease is characterized by various daily evacuations containing blood, mucus and/or pus alternating periods of remission. OBJECTIVE: To compare nutritional parameters (dietary, biochemical and anthropometric) among patients with ulcerative colitis followed up on an outpatient basis over a period of 1 year and during periods of intestinal inflammatory activity and remission. METHODS: Sixty-five patients were studied over a period of 1 year and divided into two groups: group 1 with inflammatory disease activity (n = 24), and group 2 without disease activity (n = 41). Anthropometric measures, biochemical parameters, quantitative food intake, and qualitative food frequency were analyzed. RESULTS: A significant reduction in body mass index and weight and in the intake of energy, proteins, lipids, calcium, iron and phosphorus was observed in the group with inflammatory activity (group 1) when compared to the period of clinical remission. The most affected food groups were cereals, legumes, oils, and fats. In contrast, in group 2 significant differences in triceps and sub scapular skin fold thickness, total protein, hemoglobin and hematocrit were observed between the first and final visit. Calcium and vitamin B6 intake, as well as the consumption of legumes, meat and eggs, and sugar and sweets, was significantly higher than on the first visit. CONCLUSION: Patients with ulcerative colitis followed up on an outpatient basis tend to be well nourished. However, the nutritional aspects studied tend to worsen during the period of inflammatory disease activity.CONTEXTO: A retocolite ulcerativa inespecífica compreende uma das doenças inflamatórias intestinais, com características de inflamação superficial da mucosa do cólon, reto, ânus, podendo incluir o íleo terminal. Caracteriza-se por várias exonerações diárias, com a presença de sangue e/ou pus, cursando em períodos de atividade e remissão inflamatória intestinal. OBJETIVO: Comparar os parâmetros nutricionais (alimentares, bioquímicos e antropométricos) em pacientes com retocolite ulcerativa inespecífica acompanhados em ambulatório, durante a atividade e remissão da doença inflamatória, no período de 1 ano. MÉTODOS: Foram estudados 65 pacientes durante 1 ano e divididos em dois grupos: grupo 1 com atividade inflamatória da doença (n = 24) e grupo 2 sem atividade da doença (n = 41), e analisadas as medidas antropométricas, os exames bioquímicos, o consumo alimentar quantitativo e a frequência alimentar qualitativa. RESULTADOS: O grupo com atividade inflamatória (grupo 1) apresentou redução estatisticamente significante no índice de massa corpórea, peso, no consumo de energia, proteínas, lipídios, cálcio, ferro e fósforo, em relação ao período de remissão clínica. Os grupos alimentares com significado prejuízo foram os cereais, as leguminosas, os óleos e as gorduras. Já no grupo 2, foram observadas alterações com significância estatística na dobra cutânea tricipital e subescapular, nos valores de proteínas totais, hemoglobina e hematócrito da consulta inicial para a final. Encontrou-se consumo de cálcio e vitamina B6, assim como na ingestão do grupo das leguminosas, carnes e ovos, açúcares e doces maiores significativamente do que na consulta inicial. CONCLUSÃO: Pacientes com retocolite ulcerativa inespecífica, acompanhados em ambulatório, tendem a ser bem nutridos, mas na fase de atividade inflamatória da doença, há tendência na piora dos aspectos nutricionais estudados.

Background: An increased number of intraepithelial lymphocytes (IELs) can be the only histological feature in early stages of celiac disease (CD). This is also presented in duodenum of patients with Helicobacter pylori-associated gastritis and in autoimmune diseases. Because CD is frequently associated with type 1 diabetes mellitus, we analyzed the density of IELs in the distal duodenum of non-celiac diabetic patients associated or not with H.pylori infection. Methods: IEL density and the presence of H.pylori were determined in biopsies of the distal duodenum and gastric antrum and body obtained from Brazilian diabetic adolescents who were negative for anti-human tissue transglutaminase and anti-endomysial. The results were compared with the histological findings of gastric and duodenal biopsies obtained from non-diabetic older children and adolescents. Results: H.pylori was detected in 33.3% of diabetic patients and in 56.7% of the control group. No association was observed between the presence of H.pylori and an increased lymphocyte density in the distal duodenum in either group. Diabetic patients presented a duodenal IEL density similar to that of the control group. Lymphocytic gastritis was not identified in any of the biopsies analyzed. Conclusions: The density of IELs in the distal duodenum of diabetic adolescents did not differ from that observed in older children and adolescents without this autoimmune disease. H.pylori infection, which is frequent among adolescents from developing countries, did not modify lymphocyte density in the distal duodenum in the absence of lymphocytic gastritis.

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Some studies suggest that antiinflammatory drugs are a promising alternative for treatment of the disease. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. Wistar rats (n = 25) were randomized into four groups, as follows: Group (1) Sham group: sham induced-colitis rats; Group (2) TNBS group: nontreated induced-colitis rats; Group (3) Lumiracoxib control group; and Group (4) Lumiracoxib-treated induced-colitis rats. Our results showed that rats from groups 2 and 4 presented similar histopathological damage and macroscopic injury in the distal colon as depicted by significant statistically differences (P < 0.01; P < 0.05) compared to the other two groups. Weak expression of COX-2 mRNA was detected in normal colon cells, while higher levels of COX-2 mRNA were detected in group 2 and group 4. Therapy with lumiracoxib reduced COX-2 expression by 20–30%, but it was still higher and statistically significant compared to data obtained from the lumiracoxib control group. Treatment with the selective COX-2 inhibitor lumiracoxib did not reduce inflammation-associated colonic injury in TNBS-induced experimental colitis. Thus, the use of COX-2 inhibitors for treating IBD should be considered with caution and warrants further experimental investigation to elucidate their applicability.

Contexto - A hipolactasia primária é uma condição muito frequente na qual há redução da atividade da lactase na mucosa intestinal. A presença de sintomas abdominais devidos à má absorção da lactose presente em alguns casos caracteriza a intolerância à lactose. Objetivo - Avaliar a eficácia de um produto contendo lactase exógena em comprimidos comparativamente a de um produto comparador com eficácia comprovada em pacientes portadores de intolerância à lactose. Métodos - Estudo multicêntrico, randomizado, de grupos paralelos, com investigador cego, comparativo de não-inferioridade. Cento e vinte e nove (129) pacientes adultos portadores de intolerância à lactose e teste do hidrogênio no ar expirado compatível com o diagnóstico de hipolactasia foram randomizados para receber o produto experimental (Perlatte® - Eurofarma Laboratórios S.A.) ou o produto comparador (Lactaid® - McNeil Nutritionals, EUA), por via oral (um comprimido, três vezes ao dia), durante 42 dias consecutivos. Resultados - Os dados dos 128 pacientes que efetivamente receberam o tratamento do estudo foram avaliados (66 tratados com o produto experimental e 62 com o produto comparador). Os dois grupos se mostraram homogêneos quanto aos dados demográficos e clínicos basais. A média da concentração do hidrogênio expirado aos 90 minutos no teste realizado ao final do tratamento (Dia 42) foi significativamente menor no grupo tratado com o produto experimental (17±18 ppm versus 34±47 ppm na população por protocolo). A diferença entre as médias dos dois grupos foi de -17 ppm (intervalo de confiança de 95% [IC95%]: -31,03; -3,17). O limite superior do IC95% não ultrapassou a margem de não-inferioridade estipulada a priori (7,5 ppm). As análises secundárias de eficácia confirmaram a semelhança entre os tratamentos (populações por protocolo e com intenção de tratamento). Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Objective - Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods - Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte ® - Eurofarma Laboratórios S.A.) or the reference product (Lactaid® - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results - Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. A tolerabilidade foi excelente em ambos os grupos e não houve relato de eventos adversos graves relacionados ao produto. Conclusão - O produto experimental se mostrou não-inferior ao produto comparador, indicando sua eficácia no tratamento substitutivo da lactase endógena em pacientes portadores de intolerância à lactose.

CONTEXT AND OBJECTIVES:Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables.DESIGN AND SETTING:Cross-sectional at a federal university.METHODS:44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated.RESULTS:Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index.CONCLUSIONS:Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index.

Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). Results The calprotectin levels exhibited significant reductions (P = 0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P

Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (PTNF-α and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.

The nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the management of pain and inflammation. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia to symptomatic and complicated ulcers. The mechanism of NSAID action is attributed to the cyclooxygenase (COX) inhibition. New anti-inflammatory drugs have been synthesized, such as selective COX-2 inhibitors, however, these drugs may present side effects, such as modification of the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. A possible association between the use of NSAIDs and the relapse of IBD has been repeatedly suggested. For this reason, many studies are conducted with the use of COX-2 in experimental models. The objective of this review is to describe the role of NSAIDs and COX-2 inhibitors in different experimental models of colitis. We reviewed controlled trials, original articles, case reports and reviews. The role of selective inhibition of COX-2 in the inflammatory process and the course of experimental and human colitis is controversially discussed. In conclusion, the relative role of COX-2 selective inhibitors on human and experimental colitis remains to be explored. Thus, the use of COX-2 inhibitors in IBD should be considered with caution.

Since the introduction of acetylsalicylic acid (aspirin) as the first nonsteroidal antiinflammatory drug (NSAID) in 1897, NSAIDs have been widely used in the management of pain and inflammation (Botting, 2010; Vane et al., 1990; Wallace, 1997). Today, they are classified as traditional nonsteroidal antiinflammatory drugs (tNSAIDs), characterized by differing degrees of antiinflammatory, analgesic and antipyretic activity. tNSAIDs are among the most widely used medicines in the world. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia (10-20%) to symptomatic and complicated ulcers (1-4%) (Scheiman, 2006; Wolfe et al., 1999). The mechanism of tNSAIDs action is attributed to the cyclooxygenase (COX) inhibition (Botting, 2010; Vane, 1971). Cyclooxygenase is a key rate-limiting enzyme that exists in at least two isoforms: COX-1 is observed constitutively expressed in various tissues, whereas COX-2 does not appear to be expressed except at very low levels in most tissues and is rapidly upregulated in response to growth factors and cytokines. More recently, COX-2 has been implicated in several distinct cellular mechanisms, such as angiogenesis, proliferation and the prevention of apoptosis (Dempke et al., 2001). New antiinflammatory drugs have been synthesized, such as selective COX-2 inhibitors (anti-COX-2), however, these drugs may present side effects, such as the ability to modify the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. The precise etiology of IBD, including Crohn s disease (CD) and ulcerative colitis (UC), remains unclear. However, environmental factors, immunological disturbances, genetic influences and the presence of certain chemical mediators (cytokines) have been established as putative participants in the pathogenesis of the disease (Barbieri, 2000; Lashner, 1995; Podolsky, 2002). In the last few decades, the development of experimental models for studying IBD has greatly contributed to enhance understanding of the immunological mechanisms involved, such as changes in the gut epithelial barrier (Colpaert et al, 2001; Shorter et al, 1972). IBD seems to occur when luminal antigens from the bacterial flora stimulate the immune system

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submittedthese mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values inH III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar inboth lines, being not associated with anti-Schistosoma antibody levels. There isan increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same radio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast interms of volume and eosinophil counts in the granulomas, with lesions from H IIImice clearly being larger and containing more of these cells than LIII lesions. Escola Paulista de Medicina Disciplina de Gastroenterologia FIOCRUZ Centro de Pesquisas Gonçalo Muniz Instituto Butantan Laboratório de Imunogenética UNIFESP, EPM, Disciplina de Gastroenterologia SciELO