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Chronic refractory pouchitis is a long-term complication after ileal pouch-anal anastomosis and it may be associated with ileal inflammation.To determine the efficacy of infliximab in treatment of chronic refractory pouchitis complicated by ileitis, using a wireless capsule endoscopy.Sixteen patients with chronic refractory pouchitis complicated by ileitis were enrolled. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. Ileitis was documented using wireless capsule endoscopy. Duodenum-jejunum and proximal-middle ileum were evaluated and the presence of small lesions and large lesions were noted. Crohn's disease, intestinal infections were excluded in all patients. Patients were treated with infliximab and clinical response was recorded. Wireless capsule endoscopy was repeated at week 10 and Pouchitis Disease Activity Index score was determined.Ten patients were enrolled and completed the study. Clinical remission was achieved in nine patients. At wireless capsule endoscopy and pouch endoscopy, a complete recovery of lesions was observed in eight patients. One patient presented four small lesions of the ileum at the 6 weeks of treatment and one patient did not show any modification. Clinical and endoscopic remission was maintained in these eight patients at least 6 months.These preliminary results indicate that infliximab may be recommended for the treatment of chronic refractory pouchitis complicated by ileitis.

Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5-15% of patients.To test the hypothesis of a small bowel involvement using wireless capsule endoscopy.This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed.One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers.This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis.

Pouchitis is the major long-term complication after ileal-pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory.To evaluate the efficacy of oral budesonide in inducing remission and improving quality of life in patients with chronic refractory pouchitis.Twenty consecutive patients with active pouchitis, not responding after 1 month of antibiotic treatment were treated with budesonide controlled ileal release 9 mg/day for 8 weeks. Symptomatic, endoscopic and histological evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of Pouchitis Disease Activity Index clinical score ofor = 2, endoscopic score ofor = 1 and total Pouchitis Disease Activity Index score ofor = 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire.Fifteen of 20 patients (75%) achieved remission. The median total Pouchitis Disease Activity Index scores before and after therapy were, respectively, 14 (range 9-16) and 3 (range 2-10) (P0.001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 105 (range 77-175) to 180 (range 85-220) (P0.001).Eight-week treatment with oral budesonide appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment in this open-label study.

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure, and therefore may be effectively treated with topical treatment, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side-effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short-chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy.

Severe colitis is a life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis and intensive treatment and monitoring have all contributed to improved outcome. Since their introduction in 1950s, corticosteroids are the first line therapy for severe active ulcerative colitis (UC). Several prognostic parameters (such as stools movement per day, C-reactive protein, increased amount of intestinal gas or small bowel dilation, hypoalbuminemia, fever etc) help the physician to quickly introduce cyclosporin or to refer the patient to the surgeon. This decision requires a careful evaluation of the patient and a medical /surgical team. Infliximab seems to be a promising drug but more controlled trial are needed.

To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis.In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function.One hundred and seventy-seven patients were enrolled and randomly treated with BDP (n = 90) or 5-ASA (n = 87). Mean DAI score decreased in both treatments groups (P0.0001 vs. baseline for both groups). Clinical remission was achieved in 63.0% of patients in the BDP group vs. 62.5% in the 5-ASA group. A significant DAI score improvement (P0.05) in favour of BDP was observed in patients with extensive disease. Both treatments were well tolerated. Mean plasma cortisol levels were significantly reduced vs. baseline in BDP recipients, but without signs of pituitary-adrenal function depletion.Oral BDP gave an overall treatment result in patients with active ulcerative colitis without signs of systemic side-effects.

Background: The pathogenesis of human ulcerative colitis (UC) is characterized by the presence of IL-13-producing Natural Killer T cells (NKT cells). One major complication of UC is the development of colitis-associated colorectal cancer. In these studies we determined the role of alternatively activated “M2 macrophages” in a new mouse model of colitis-associated carcinogenesis. Further, we verified these results through immunological analysis of surgical specimens obtained from patients with UC-associated colon cancer. Methods: Studies were performed using a mouse model for colitis-associated carcinogenesis based on chronic Oxazolonecolitis in combination with an initial i.p. azoxymethane (AOM) injection in female BALB/c mice. We observed chronic intestinal inflammation lasting for 12 weeks in mice repeatedly administered Oxazolone. Surgical specimens with UC-associated colon cancer were analyzed by flow cytometry and immunohistochemistry. Results: We could show that Oxazolone-colitis was mediated by colonic alpha-galactosyl-ceramide+CD1+ NKT-cells producing IL-13 and therefore resembles the immunological characteristics of human UC. Colon cancer development in this model was dependent on F4/80+CD11bhighGr1low macrophages producing IL-6 and EGF. Those cells inherited phenotypic characteristics of IL-13-stimulated alternativelyactivated “M2 macrophages”. To elucidate the importance of these “M2 macrophages”, we conducted bone marrow chimera studies and demonstrated that innate immune signaling through MyD88 in “M2 macrophages” is the key event for the production of tumor supporting factors like IL-6 and EGF. In surgical specimens obtained from patients with UC-associated colon cancer we verified those experimental findings. We consistently found a dense accumulation of IL-13-producing NKT cells inside the tumors. In addition, in this IL-13-dominated tumor micromilieu CD14+ and CD68+ antigen-presenting cells accumulated intensively and those antigen-presenting cells demonstrated an alternatively activated “M2 phenotype” by the expression of CD163 and CD205. Conclusions: We could demonstrate that in an experimental UC model, as well as in human UC, pathogenic IL-13producing NKT cells accumulate in the tumor micromilieu of UC-associated colon cancers. This immunologic situation inside the tumor microenvironment of mice and men induces tumor promoting M2 macrophages. Therefore M2 macrophages represent a potential target for future therapeutic strategies.

The meta-analyses of published trials have shown topical therapy with 5-aminosalicylic acid (5-ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5-ASA therapy. An alternative to 5-ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5-ASA or new steroids should be treated with oral steroids. Azathioprine or 6-mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried-out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.

The monitoring of patients with ulcerative colitis is easier than in patients with Crohn's disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X-ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response.

Refractoriness to conventional therapy is a common and intriguing problem in Crohn's disease patients. At the present time there is no agreement on its definition and several mechanisms are involved in its determination. Immunosuppressors, such as azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX) are effective drugs for controlling the inflammatory process and avoid chronic glucocorticosteroid treatment and its related side-effects. Recently, the introduction of tumour necrosis factor antibodies (infliximab) has dramatically changed the natural history of Crohn's disease and its therapeutic approach. Several studies have determined the efficacy, mechanisms and safety of infliximab. However, this molecular approach has also left several questions unanswered about the mechanisms of refractoriness, possible concomitant treatments and long-term safety and efficacy.

Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment.To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life.Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0-18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score ofor= 2, endoscopic score ofor= 1 and total score ofor= 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best=32-224).Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8-17) and 3 (range, 1-10), respectively (P0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175 (range, 76-215) with this therapy (P0.0001). The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 35 years; P=0.007), had a longer history of pouchitis (95.5 vs. 26 months; P=0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0-2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs. 12; P=0.13) than those who went into remission. Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8-16) to 9.5 (range, 7-10) (P=0.0078), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127 (range, 76-187) (P=0.039). The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r=0.79, P0.0001), and was significantly related to the patients' overall assessment of satisfaction (P0.0001). No serious side-effects were noted.Four-week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality of life. The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with disease activity.

To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis.In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study.One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups.Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.

Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment.To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis.Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point.67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively.In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission.

The etiology of inflammatory disease is still unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. Reduction of microflora using antibiotics, bowel rest and fecal diversion decreases activity in Crohn's disease and in ulcerative colitis. Several trials have been carried out on the use of antibiotic treatment in patients with active ulcerative colitis with contrasting results. A number of trials have been carried out using Rifaximin, a non-absorbable broad-spectrum antibiotic, confirming the absence of systemic bioavalaibility of the drug even when administered at very high doses and for prolonged periods. It may therefore be useful in treatment of ulcerative colitis and pouchitis, since its absorption through inflamed mucosa is negligible, it maintains a topical action without systemic effects and the lack of resistant bacterial strains may allow prolonged and repeated treatments.

Although 5-aminosalicylic acid (5-ASA) oral compounds are the standard maintenance treatment for ulcerative colitis in remission, some patients cannot use them because of side-effects. Clinical and experimental observations have suggested the potential role of probiotics in inflammatory bowel disease therapy.To evaluate the effects on intestinal microflora and the clinical efficacy of a new probiotic preparation in patients with ulcerative colitis in remission.Twenty patients with ulcerative colitis, intolerant or allergic to 5-ASA, have been treated with a new probiotic preparation (VSL#3, CSL, Milan, Italy) containing 5x10(11) cells/g of 3 strains of bifidobacteria, 4 strains of lactobacilli and 1 strain of Streptococcus salivarius ssp. thermophilus. Two doses of 3 g were administered o.d. for 12 months. Faecal samples for stool culture were obtained from the patients at the beginning of the trial and after 10, 20, 40, 60, 75, 90 days, 12 months and at 15 days after the end of the treatment. The following bacterial groups have been evaluated in the faeces: total aerobic and anaerobic bacteria, enterococci, Streptococcus thermophilus, lactobacilli, bifidobacteria, Bacteroides, clostridia, coliforms. Patients were assessed clinically every two months, and assessed endoscopically at 6 and 12 months or in relapse.Faecal concentrations of Streptococcus salivarius ssp. thermophilus, lactobacilli and bifidobacteria increased significantly in all patients, compared to their basal level, from the 20th day of treatment (P0.05) and remained stable throughout the study. Concentrations of Bacteroides, clostridia, coliforms, total aerobic and anaerobic bacteria did not change significantly during treatment (P = N.S.). Fifteen of 20 treated patients remained in remission during the study, one patient was lost to follow up, while the remaining relapsed. No significant side-effects have been reported.These results show that this probiotic preparation is able to colonize the intestine, and suggest that it may be useful in maintaining the remission in ulcerative colitis patients intolerant or allergic to 5-ASA. Controlled trials are warranted to confirm these preliminary results.

A new mesalazine rectal gel preparation (without propellant gas) has been recently developed to improve topical treatment in distal ulcerative colitis.To evaluate the efficacy, safety and patient tolerability of mesalazine gel enema compared with mesalazine foam enema in the treatment of patients with acute left-sided ulcerative colitis.In a randomized multicentre investigator-blind parallel group trial, 103 patients with mild to moderate left-sided colitis or proctosigmoiditis were randomly allocated to mesalazine 2 g gel enema (n = 50 evaluable patients) and mesalazine 2 g foam enema (n = 53 evaluable patients) for 4 weeks. Clinical symptoms, endoscopic and histological findings were assessed at entry, 2 and 4 weeks. Patients' evaluation of treatment tolerability and acceptability was assessed at 2 and 4 weeks.After 4 weeks of treatment, clinical remission was achieved by 76% of mesalazine gel enema-treated patients and 69% of patients treated with mesalazine foam enema (P = 0.608). Endoscopic remission rates at week 4 were 51 and 52% for the mesalazine gel and foam enemas, respectively (P = 0.925). Histological remission was achieved by 30% of patients in both groups. Patients reported that the new mesalazine gel preparation was significantly better tolerated than the foam enema. Patients in the foam group had significantly more difficulty in retention (25% vs. 6%, P0.05), abdominal bloating (50% vs. 26%, P0.005) and discomfort during administration (48% vs. 26%, P0.05).The new mesalazine gel enema is efficacious and significantly better tolerated than the mesalazine foam enema.

Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease.In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI,or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time.There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096).In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response.

Production of leucocyte migration inhibition factor by peripheral blood leucocytes in response to challenge with gluten fractions has been proposed as a reliable in vitro test for the diagnosis of coeliac disease. We have performed the leucocyte migration inhibition test with two different gluten fractions, GFIII and B2, in untreated and treated coeliac patients, patients with other intestinal diseases (abnormal controls) and healthy controls, and evaluated the sensitivity, specificity and positive and negative predictability of the test for the diagnosis of coeliac disease. Using GFIII as antigen leucocyte migration was significantly inhibited, compared to healthy controls, not only in treated and untreated coeliacs but also in abnormal controls. Using B2 gluten subfraction as antigen only treated coeliacs and abnormal controls differed significantly from healthy controls. The elevated number of abnormal controls showing migration inhibition consistently affected the diagnostic value of the test, which did not vary using B2 subfraction instead of GFIII as antigen. Our study confirms previous observations of gluten sensitization, as detected by leucocyte migration inhibition, in coeliac patients but strongly questions the claim that coeliac disease can be diagnosed on the basis of a positive leucocyte migration inhibition test without the need for intestinal biopsy.

AIM: To elucidate cell proliferation in erosive reflux disease (ERD) and non-erosive reflux disease (NERD), we evaluated markers in squamous epithelial cells. METHODS: Thirty-four consecutive patients with gastroesophageal-reflux-disease-related symptoms (21 NERD and 13 ERD) were evaluated for the enrolment into the study. All patients underwent 24-h pH monitoring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only. RESULTS: Real-time RT-PCR showed that, in patients with ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 (P = 0.011). Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients (2.31 ± 2.87 vs 0.66 ± 1.11). The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%. CONCLUSION: We confirmed reduced epithelial proliferation in ERD compared with NERD patients, and that individuals who develop ERD are characterized by weaker epithelial cell proliferation.

AIM: To profile protein expression in mucosal biopsies from patients with chronic refractory pouchitis following antibiotic or probiotic treatment, using a comparative proteomic approach. METHODS: Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to characterize the changes related to antibiotic therapy in the protein expression profiles of biopsy samples from patients with chronic refractory pouchitis. The same proteomic approach was applied to identify differentially expressed proteins in the non-inflamed pouch before and after probiotic administration. RESULTS: In the first set of 2D gels, 26 different proteins with at least 2-fold changes in their expression levels between the pouchitis condition and antibiotic-induced remission were identified. In the second set of analysis, the comparison between mucosal biopsy proteomes in the normal and probiotic-treated pouch resulted in 17 significantly differently expressed proteins. Of these, 8 exhibited the same pattern of deregulation as in the pouchitis/pouch remission group. CONCLUSION: For the first time, 2D protein maps of mucosal biopsies from patients with ileal pouch-anal anastomosis were provided, and differentially expressed proteins following antibiotic/probiotic treatment were identified.

Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects.To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC.Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters.A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group.BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

AIM: To evaluate the intestinal motility changes evoked by 8 bacterial strains belonging to Bifidobacterium , Lactobacillus and Streptococcus genera within the probiotic preparation VSL#3. METHODS: Ileum and proximal colon segments isolated from guinea-pigs were used as a study model. Entire cells and cell fractions (cell debris, cell wall fraction, cytoplasmatic fraction, proteinaceous and non- proteinaceous cytoplasmatic components) of VSL#3 strains and, as controls, Escherichia coli, Salmonella aboni and Bacillus licheniformis were tested in this in vitro model. RESULTS: Among the bacterial cell fractions tested, only the cytoplasmatic fraction modified intestinal motility. Lactobacillus strains stimulated the contraction of ileum segment, whereas all probiotic strains tested induced proximal colon relaxation response. The non-proteinaceous cytoplasmatic components were responsible for the colon relaxation. CONCLUSION: The results obtained in this study suggest that the proximal colon relaxation activity showed by the probiotic bacteria could be one of the possible mechanisms of action by which probiotics exert their positive effects in regulating intestinal motility.

Many experimental and clinical observations suggest that intestinal microflora plays a potential role in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics or probiotics represents a potentially effective therapeutic option. The available studies do not support the use of antibiotics in ulcerative colitis (UC). Antibiotics are effective in treating septic complications of Crohn's disease (CD) but their use as a primary therapy is more controversial, although this approach is frequently and successfully adopted in clinical practice. There is evidence that probiotic therapy may be effective in the prevention and treatment of mild to moderate UC. In contrast, a lack of successful study data at present precludes the widespread use of probiotics in the treatment of CD. Both antibiotics and probiotics appear to play a beneficial role in the treatment and prevention of pouchitis and further trials are warranted to fully quantify their clinical efficacy.