5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

IL-1β, IL-18, and IL-33 and the receptors IL-1R, IL-18R, ST2, and TLR-2 are potential therapeutic targets that can be modulated to minimize anticancer agent-associated toxicity, optimize cancer treatment dosing, and improve clinical outcomes. In this context, the pathogenesis of mucositis caused by other anticancer agents should be further investigated.

These results suggest an important role of TNF-alpha, IL-1beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

RESUMO -Racional -A doença de Crohn e a retocolite ulcerativa idiopática são consideradas pouco freqüentes nos países em desenvolvimento, sendo escassos os estudos sobre a sua ocorrência no Brasil. Objetivos -Estudar a freqüência de admissão de casos da doença de Crohn e da retocolite ulcerativa inespecífica em um hospital universitário ao longo de 20 anos e descrever características demográficas e clínicas desses casos. Métodos -Calculou-se a freqüência de admissão de casos da doença de Crohn e da retocolite ulcerativa inespecífica de janeiro de 1980 a dezembro de 1999 e analisaram-se todos os casos destas doenças admitidos nos últimos 10 anos desse período. Resultados -No período estudado, registraram-se 257 casos novos, sendo 126 da doença de Crohn e 131 da retocolite ulcerativa inespecífica. A freqüência de admissão de casos de ambas as doenças aumentou de 40 para 61 casos/10.000 atendimentos, do primeiro para o segundo qüinqüênio, com menor crescimento subseqüente, sendo que a doença de Crohn tornou-se, gradualmente, mais freqüente que a retocolite ulcerativa inespecífica. Em ambas as doenças, houve predomínio de casos do gênero feminino, na faixa etária entre 20 e 50 anos, da cor branca, do estado civil casado e de não-tabagistas. Ambas as doenças apresentaram-se com os sintomas digestivos próprios e não houve diferenças entre elas quanto às freqüências de manifestações sistêmicas e extra-intestinais (29,5% vs 23,3%), incluindo as tromboembólicas (5,9% vs 5,5%). Na doença de Crohn, 59,2% dos casos apresentaram complicações (obstrução e/ou perfuração), enquanto que 53,7% dos casos de retocolite ulcerativa inespecífica foram de formas mais graves. Nos casos de doença de Crohn com obstrução, o tabagismo foi significativamente mais freqüente que nas formas não-complicadas. Na retocolite ulcerativa inespecífica, as manifestações sistêmicas e as extra-intestinais, bem como o acometimento de todo o cólon, foram significativamente mais freqüentes nas formas mais graves. Conclusões -Houve aumento da freqüência das doenças inflamatórias intestinais, com a doença de Crohn tornando-se mais comum que a retocolite ulcerativa inespecífica. Tanto uma como outra das afecções, apresentaram-se com as características habituais, destacando-se o predomínio das formas mais graves.DESCRITORES -Doença de Crohn, epidemiologia. Colite ulcerativa, epidemiologia.

3-D anal endosonography enabled measurement of the different anatomical structures of the anal canal and demonstrated its asymmetrical configuration. The shorter anterior EAS and IAS associated with a longer gap could justify the higher incidence of pelvic floor dysfunction in females, especially fecal incontinence and anorectocele with rectal intussusception.

Neurological disorders, especially PN, are common in our Brazilian cohort of IBD patients. They are diverse, multifactorial, and more common in women. Despite the mild phenotype in most cases, attention should be given by the general practitioner and gastroenterologist since they are frequently undiagnosed. Further studies are necessary to confirm these findings in populations with different genetic and nutritional backgrounds.

This study suggests a role of nitric oxide in the pathogenesis of irinotecan-induced intestinal mucositis and also provides evidence for the participation of cytokines on iNOS induction.

Background: Tumour necrosis factor a (TNF-a) is involved in non-steroidal anti-inflammatory drug induced gastropathy. Nitric oxide (NO) is a mediator of gastrointestinal mucosal defence but, paradoxically, it also contributes to mucosal damage. Aims: We optimised the C57BL/6 mouse model of indomethacin induced gastropathy to evaluate the role of TNF-a and inducible nitric oxide synthase (iNOS) generated NO in gastric damage and granulocyte infiltration using tumour necrosis factor receptor 1 (TNF-R12/2) or iNOS (iNOS2/2) deficient mice. Methods: Different doses of indomethacin (2.5, 5, 10, 20 mg/kg) were administered and animals were assessed 6, 12, or 24 hours later. Gastric damage was measured by the sum of all erosions in the gastric mucosa, and gastric granulocyte infiltration was determined by myeloperoxidase (MPO) activity. Other groups of wild-type mice received thalidomide, dexamethasone, fucoidin, L-NAME, or 1400W, and then indomethacin was administered. Additionally, indomethacin was administered to TNF-R12/2 or iNOS2/2. Gastric damage and MPO activity were evaluated 12 hours later. Results: Indomethacin induced dose and time dependent gastric damage and increase in MPO activity in wild-type mice, with the greatest effect at a dose of 10 mg/kg and after 12 hours. Treatment with thalidomide, dexamethasone, or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration, TNF-R12/2 had less gastric damage and MPO activity than controls. Genetic (knockout mice) or pharmacological (1400W and L-NAME) inhibition of iNOS activity reduced indomethacin induced gastric damage, despite no reduction in MPO activity. Conclusion: TNF-a, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. Furthermore, iNOS generated NO is involved in gastric damage induced by indomethacin.