Escherichia coli from Crohn’s disease patient displays virulence features of enteroinvasive (EIEC), enterohemorragic (EHEC), and enteroaggregative (EAEC) pathotypes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Draft genome sequence of shiga toxin-producing Escherichia coli Strain D92/09

Escherichia coli is suspected to be involved with Crohn's disease. Adherence and invasion to epithelial cells are properties commonly observed in these bacteria. Here, we present a draft genome sequence of E. coli D92/09, a multidrug-resistant strain, which besides showing these properties produces Shiga cytotoxin-1 and possibly other toxins.

Inflammatory bowel disease: an overview of immune mechanisms and biological treatments

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Probiotics: the scientific evidence in the context of inflammatory bowel disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Associação entre concentração sérica de vitamina D e alterações da massa muscular esquelética em pacientes com doenças inflamatórias intestinais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de nano e micropartículas de quitosana encapsulando 4-metilesculetina e avaliação no tratamento da doença inflamatória intestinal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Qualidade de vida e capacidade funcional em pacientes com doenças inflamatórias intestinais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tolerance and nutritional therapy of dietary fibre from konjac glucomannan hydrolysates for patients with inflammatory bowel disease (IBD)

Carbohydrates may provide an alternative therapeutic approach for a number of digestive health disorders such as inflammatory bowel disease (IBD). The aim of this work was to characterise the tolerance and efficacy of low and high molecular weight konjac glucomannan hydrolysates within healthy volunteers and patients suffering from IBD and associated gut conditions. These conditions included constipation, Crohn's disease and ulcerative colitis. For general tolerance, fourteen patients participated whilst for the digestive disorder trial, there were twenty. Scores of taste/texture of the product, bowel movement, stool consistency, diarrhoea, existence/absence of blood in the faeces, abdominal pains, flatulence, vomiting, fever, improvement of life style after use, willingness to use in the future and clinician's statements about each patient's conditions before and after use were recorded. The results showed that the hydrolysates were tolerated well for patients with diarrhoea and had a significant improvement on bowel movement, stool consistency, abdominal pain and flatulence after ten days. With respect to effects on IBD, there was a significant health benefit after fourteen days of consumption for bowel movement, stool consistency, diarrhoea, existence/absence of blood in the faeces, abdominal pain, flatulence and vomiting. Most patients declared an improvement of their life style after consuming the hydrolysates. The use of konjac glucomannan hydrolysates as a therapeutic agent or adjunct to standard treatments could prove a successful tool for the treatment of a range of disorders; although large scale studies are required to characterise further the role of the carbohydrates.

Sexualidade e doenças inflamatórias intestinais

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Oral treatment with Hev b 13 ameliorates experimental colitis in mice

Hev b 13 is an allergenic esterase obtained from the rubber tree Hevea brasiliensis, which has been shown recently to induce human mononuclear cells to release interleukin (IL)-10 in vitro. This immunoregulatory cytokine appears to play an important role in preventing inflammation and mucosal damage in animal models of colitis and in Crohn's disease patients. The aim of this study was to evaluate the therapeutic effect of Hev b 13 in mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Two hours following colonic instillation of the haptenizing agent, and daily thereafter for 5 days, Hev b 13 was administered by oral gavage. In mice treated with daily doses of either 0.5 mg/kg or 5.0 mg/kg of Hev b 13, the clinical signs of diarrhoea, rectal prolapse and body weight loss and also histological damage of the distal colon, were reduced significantly, in comparison with water-treated diseased mice. These findings suggest a potent anti-inflammatory activity of Hev b 13; this activity is speculated to be related to its interaction with cells from the immune system.

Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn’s disease

Background Patients with Crohn’s disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores ≥ 6 were considered to have dyspepsia. The control group was composed by 19 age- and sex-matched healthy volunteers. Results Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion Delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

Variazione dei markers di attivata coagulazione indotta dalla terapia infusionale con Infliximab in pazienti affetti da malattie infiammatorie croniche intestinali

INTRODUCTION: A relationship between inflammatory response and coagulation is suggested by many observations. In particular, pro-inflammatory cytokines, such as TNFalpha, promote the activation of coagulation and reduce the production of anticoagulant molecules. It is known that inflammatory bowel diseases show a prothrombotic state and a condition of hypercoagulability. Aim of our study was to evaluate whether anti-TNFalpha therapy induces changes in the levels of coagulation activation markers in IBD patients. MATERIALS AND METHODS: We analyzed 48 plasma samples obtained before and 1 hour after 24 infliximab infusions (5 mg/kg) in 9 IBD patients (5 men and 4 women; mean age: 47.6+17.6 years; 4 Crohn's disease, 4 Ulcerative Colitis,1 Indeterminate Colitis). F1+2 and D-dymer levels were measured in each sample using ELISA methods.The data were statistically analyzed by means of Wilcoxon matched paired test. RESULTS: Median F1+2 levels were markdely reduced 1 hour after anti-TNFα infusion (median pre-infusion levels were 247.0 pmol/L and median post-infusion levels were 185.3 pmol/L) (p<0.002). Median D-dymer levels were also significantly reduced, from 485.2 ng/mL to 427.6 ng/mL (p< 0.001). These modifications were more evident in patients naive for infliximab therapy (p<0.02 for F1+2 and p<0.02 for D-dymer) and in Crohn's disease compared with Ulcerative Colitis patients (p=0.01 for F1+2 and p<0.007 for D-dymer).CONCLUSIONS: Infusion of infliximab significantly reduces the activation of coagulation cascade in IBD patients. This effect is early enough to suggest a direct effect of infliximab on the coagulation cascade and a possible new anti-inflammatory mechanism of action of this molecule.

L'infiammazione intestinale nell'animale sperimentale come modello per lo sviluppo di nuovi farmaci: ruolo della via tachichininergica nelle malattie infiammatorie intestinali

Background: Several lines of evidence showed that inflammation is associated with changes in the expression of tachykinins both in human and animal models. Tachykinins, including substance P (SP), are small peptides expressed in the extrinsic primary afferent nerve fibres and enteric neurons of the gut: they exert their action through three distinct receptors, termed NK1, NK2 and NK3. SP modulates intestinal motility and enteric secretion, acting preferentially through the NK1 receptor. SP neural network and NK1 receptor expression are increased in patients with inflammatory bowel disease, and similar changes were observed in experimental models of inflammation. The 2,4 Dinitrobenzene Sulphonic Acid (DNBS) model of colitis is useful to study innate immunity, non-specific inflammation and wound healing; it has been suggested that the transmural inflammation seen in this model resembles that found in Crohn’s disease and can therefore be used to study what cells and mediators are involved in this type of inflammation. Aim: To test the possible protective effect of the NK1 receptor antagonist SSR140333 on: 1) acute model of intestinal inflammation; 2) reactivation of DNBS-induced colitis in rats. Methods: Acute colitis was induced in male SD rats by intrarectal administration of DNBS (15 mg/rat in 50% ethanol). Reactivation of colitis was induced by intrarectal injections of DNBS on day 28 (7.5 mg/rat in 35% ethanol). Animals were sacrificed on day 6 (acute colitis) and 29 (reactivation of colitis). SSR140333 (10 mg/kg) was administered orally starting from the day before the induction of colitis for 7 days (acute colitis) or seven days before the reactivation of colitis. Colonic damage was assessed by means of macroscopic and microscopic scores, myeloperoxidase activity (MPO) and TNF-α tissue levels. Enzyme immunoassay was used to measure colonic substance P levels. Statistical analysis was performed using analysis of variance (one-way or two-way, as appropriate) with the Bonferroni’s correction for multiple comparisons. Results: DNBS administration impaired body weight gain and markedly increased all inflammatory parameters (p<0.01). Treatment with SSR140333 10 mg/kg significantly counteracted the impairment in body weight gain, decreased macroscopic and histological scores and reduced colonic myeloperoxidase activity (p<0.01). Drug treatment counteracted TNF-α tissue levels and colonic SP concentrations (acute model). Similar results were obtained administering the NK1 receptor antagonist SSR140333 (3 and 10 mg/kg) for 5 days, starting the day after the induction of colitis. Intrarectal administration of DNBS four weeks after the first DNBS administration resulted in reactivation of colitis, with increases in macroscopic and histological damage scores and increase in MPO activity. Preventive treatment with SSR140333 10 mg/kg decreased macroscopic damage score, significantly reduced microscopic damage score but did not affect MPO activity. Conclusions: Treatment with SSR140333 significantly reduced intestinal damage in acute model of intestinal inflammation in rats. The NK1 receptor antagonist SSR140333 was also able to prevent relapse in experimental colitis. These results support the hypothesis of SP involvement in intestinal inflammation and indicate that NK receptor antagonists may have a therapeutic potential in inflammatory bowel disease.

Frauen und AIDS in Tansania /// Arbeitspapiere / Institut für Ethnologie und Afrikastudien ; 60

Mehr als die Hälfte aller HIV-positiven Tansanier sind Frauen. Ihre schwächere gesellschaftliche Stellung ist einer der Faktoren, der dazu beiträgt, dass sie einem erhöhten Infektionsrisiko ausgesetzt sind. Aufgrund geringerer Bildungschancen und einer anhaltenden gesellschaftlichen Idealvorstellung von der Frau als Mutter sind Frauen auch auf dem Arbeitsmarkt benachteiligt. Im Kontext von HIV/AIDS werden afrikanische Frauen häufig als passive Opfer der Epidemie dargestellt und es wird zu selten aufgezeigt, wie sie als Akteure eigene Strategien im Kampf gegen die Krankheit entwickeln. In letzter Zeit gewinnen Frauenorganisationen an Bedeutung, denn viele Frauen wollen ausdrücklich eigenverantwortlich und ohne Männer arbeiten. Eine solche Organisation ist die in meiner Arbeit vorgestellte NGO KIWAMWAKU („Kikundi cha Wanawake Mwanga kupambana na Ukimwi“ – Vereinigung von Frauen aus Mwanga zum Kampf gegen AIDS). Meine Forschung hat gezeigt, dass Frauen ihre gesellschaftliche Stellung durch das Engagement in einer NGO verbessern können. Sie können ein eigenes Einkommen erwirtschaften und nützliche Kenntnisse etwa in der Führung einer Organisation erlangen. Allerdings profitieren nicht alle Beteiligten gleichermaßen. Die drei Leiterinnen der erforschten NGO verfügten über die meisten Vorteile; sie profitierten finanziell, aber auch ideell, denn sie genossen durch ihre Arbeit hohes Ansehen im gesamten Mwanga-Distrikt. Dagegen konnten einige der Klientinnen nur in sehr geringem Maße von Interventionen profitieren. Letztlich bin ich jedoch überzeugt davon, dass durch solche Frauenorganisationen ein wichtiger Prozess angestoßen worden ist, durch den Frauen mittel- oder langfristig eine stärkere Stellung innerhalb der tansanischen Gesellschaft erlangen können, was sich wiederum positiv auf die immer noch steigenden HIV/AIDS-Infektionsraten auswirken kann.