Age and video capsule endoscopy in obscure gastrointestinal bleeding: a prospective study on hospitalized patients.

BACKGROUND: The influence of aging on video capsule endoscopy (VCE) in obscure gastrointestinal bleeding (OGIB) has never been prospectively assessed. AIMS: To demonstrate if age is a risk factor for incomplete VCE examination in a setting of ongoing hospitalization for OGIB and if it affects the yield of VCE. METHODS: Forty-eight consecutive patients referred to our unit for obscure-overt GI bleeding from March 2007 to September 2009 were prospectively evaluated. Patients were divided into two groups according to their age: ≤65 years (group A) and >65 years (group B). The VCE completion rate and clinically significant findings were studied. RESULTS: The cecum was reached in 73% of patients. There was no difference between the two groups of patients in the VCE completion rate (78% vs. 68%, P=0.4). The overall diagnostic yield was 61%. A significant difference in the diagnostic yield between group A and group B (45% vs. 75%, P=0.04) was shown. Angiodysplasia was diagnosed in 13 out of 24 (54%) patients of group B, whereas mucosal breaks, such as erosions or ulcers, accounted for over a quarter of the group A findings. CONCLUSIONS: Old age is not a risk factor for incomplete VCE examination and it is associated with increased VCE yield.

Characterization of spore forming Bacilli isolated from the human gastrointestinal tract.

AIMS: To isolate and characterize spore-former bacteria able to colonize the human gastrointestinal tract (GIT). METHODS AND RESULTS: A total of 25 spore-formers was isolated from faeces and ileal biopsies of healthy human volunteers and identified at the species level. Physiological analysis was performed to evaluate the ability of the various isolates to form biofilms, to swarm, to produce surfactants and molecules that have antimicrobial activity against selected pathogens. To assess the potential probiotic activity of the isolates, we tested the resistance of cells and spores to simulated gastric conditions, the ability to grow and sporulate in anaerobic conditions and the presence of toxin-encoding genes in their genome. CONCLUSIONS: Spore-formers belonging to various bacterial species have been isolated from the gut of healthy human volunteers. These strains appear to be well adapted to the intestinal environment and we propose them as potential probiotic strains for human use and as oral vaccine vehicles. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge this is the first detailed characterization of spore-forming Bacilli from the human GIT. Our data suggest that the isolated species do not transit, but rather colonize this specific habitat and propose them as probiotic strains for human use.

Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia.

BACKGROUND: Octreotide has shown to be effective against rebleeding from gastrointestinal angiodysplasias, but a long-term daily parenteral administration is recommended. Long-acting octreotide (LAR-OCT) could overcome such a limitation, but it has not been studied extensively. AIM: To investigate the usefulness of long-acting octreotide in the control of chronic bleeding from gastrointestinal angiodysplasias. METHODS: Thirteen patients with chronic gastrointestinal bleeding because of angiodysplasias were enrolled. Diagnosis was made by endoscopy and wireless video capsule. Long-acting octreotide was administered intramuscularly at a dosage of 10 mg/monthly for 1 year. Patients were followed up for a minimum period of 1 year, and haemoglobin levels, blood transfusions, iron supplementation and hospitalizations were recorded 1 year before and after starting long-acting octreotide therapy. RESULTS: Follow-up ranged from 12 to 60 months. Nine of 13 patients (69%) did not need blood transfusions and iron supplementation any longer; a partial improvement was observed in one patient; no effect was found in the others. No side effect was recorded in any patient. CONCLUSIONS: Long-acting octreotide for 1 year may be beneficial as a rescue therapy for controlling chronic bleeding from gastrointestinal angiodysplasias in patients not eligible for surgery. Its monthly administration represents an advantage, which makes such a formulation the choice when a long-term treatment is mandatory.

Transglutaminase in azoxymethane-induced colon cancer in the rat.

A widespread from of transglutaminase, tissue transglutaminase, has been identified in a number of mammalian cell types, both normal and transformed cells; its biological role is not well understood. We investigated the effect of experimentally induced colon cancer on transglutaminase activity in the rat. Azoxymethane (15 mg/kg for six weeks), given by a course of weekly intraperitoneal injections, produces tumors almost exclusively confined to the intestinal tract. Transglutaminase activity was assayed on tissue homogenates both during the period of treatment and, when the cancer had developed, on tumor tissue and on microscopically uninjured adjacent tissue. A transient proliferative phase was present in the intestine during azoxymethane treatment: in this phase we found a coincidentally increased transglutaminase levels. Transglutaminase activity in tumors of both small and large intestine was significantly higher than in adjacent tissue. Immunohistochemistry revealed higher levels of transglutaminase in tumors, mainly localized in the extracellular matrix, than in adjacent tissues, where it was widely distributed. The present study shows that transglutaminase, besides its potential role in intracellular process during early proliferative phase of carcinogenesis, may also play an important role in matrix processing during tumor growth and differentiation.

Pleuropericarditis in a patient with ulcerative colitis in longstanding 5-aminosalicylic acid therapy.

We report a case of pleuropericarditis in a 23-yr-old woman with ulcerative colitis (UC) treated with 5-aminosalicylic acid (5-ASA). In our case we exclude a possible 5-ASA hypersensitivity in view of the longterm complication free treatment and the successful resolution of the case without withdrawal of 5-ASA. A 5-ASA induced lupus-like syndrome was also ruled out by immunoserological investigations. Infectious and endocrinologic causes of pleuropericarditis were also excluded. In conclusion pleuropericarditis must be considered a systemic complication of inflammatory bowel disease (IBD) if adverse reaction to 5-ASA and sulfasalazine as well as other possible pathogenetic factors have been ruled out.

Butyrate, mesalamine, and factor XIII in experimental colitis in the rat: effects on transglutaminase activity.

BACKGROUND/AIMS: Butyrate and factor XIII may improve ulcerative colitis; they also affect tissue and serum transglutaminase levels. We investigated the therapeutic potential of sodium butyrate and factor XIII and the role of transglutaminase during mucosal repair in experimental colitis. METHODS: Rats with induced colitis were treated with sodium butyrate, mesalamine, sodium butyrate plus mesalamine, or saline enemas. Thromboxane B2 was monitored as index of inflammation. In a fifth group, the effectiveness of intravenous Factor XIII was assessed. RESULTS: Sodium butyrate, alone or plus mesalamine, reduced histological activity from 13.7 +/- 1.7 (saline) to 2.5 +/- 1.3 and 2.3 +/- 1.1 (P < 0.01), respectively. Transglutaminase, reduced in the colons of the saline group (783 +/- 157 vs. normal 1800 +/- 192 mU/g; P < 0.01), returned toward normal values in the sodium butyrate or sodium butyrate plus mesalamine groups (1390 +/- 228 and 1226 +/- 172 mU/g, respectively; P < 0.01 vs. saline). Furthermore, sodium butyrate plus mesalamine reduced thromboxane B2 levels by day 5 (0.92 +/- 0.16 vs. saline 1.85 +/- 0.34 ng/mL; P < 0.05). Factor XIII therapy improved the histological picture (2.7 +/- 2.1 vs. saline 13.8 +/- 1.7; P < 0.01) and increased transglutaminase levels both in serum (2.81 +/- 0.11 vs. saline 1.45 +/- 0.09 mU/mL; P < 0.01) and in colon (1503 +/- 127 vs. saline 747 +/- 103). CONCLUSIONS: Sodium butyrate and factor XIII improve colitis, sodium butyrate plus mesalamine reduce early thromboxane B2 synthesis, and transglutaminase(s) plays a role in ulcer healing.

Serum and tissue transglutaminase correlates with the severity of inflammation in induced colitis in the rat.

Simple rat models of acute and chronic colonic inflammation were used to study the behaviour in serum and mucosa of transglutaminase (TG), an enzyme recently found to be reduced in serum of patients with inflammatory bowel disease (IBD) and related to the activity index of the disease. In the first model the intraluminal administration of 400 mM lactic acid in the colon caused an acute inflammation resembling that of florid ulcerative colitis in humans. In the second, intraluminal administration of the hapten 2,4,6-trinitrobenzenesulphonic acid (TNB) (10 or 30 mg) in 0.25 ml of ethanol as a 'barrier breaker' produced a chronic inflammatory disease. The results showed a reduced TG activity in colon of rats in both acute and chronic induced colitis (447 +/- 75 versus 1344 +/- 59 mU/g protein (p less than 0.001) and 484 +/- 59 versus 1204 +/- 75 mU/g protein (p less than 0.001)). This decreased activity was related to the severity of mucosal damage, which was dose-dependent. Moreover, in severe colitis the immunohistochemistry showed a TG location in repairing tissue. Serum TG activity was decreased after TNB administration (1.36 +/- 0.05 versus 3.44 +/- 0.20 mU/ml (p less than 0.001)) but not after lactic acid treatment (3.97 +/- 0.11 versus 3.78 +/- 0.16 mU/ml). In summary, the reduction of TG activity in both tissue and serum when the damage is stabilized reflects the altered morphofunctional integrity of the colon and suggests that serum assay of this enzyme could be a simple marker of intestinal mucosal status in IBD.

Transglutaminase changes in intestinal mucosa after experimental small bowel resection in the rat.

The low serum transglutaminase found in various intestinal disorders (celiac disease and IBD) suggested to us to study the serum and mucosal transglutaminase behaviour in an experimental model of small intestine resection in rats to reduce cellular mass and induce enterocyte hyperproliferation in the proximal part left in continuity. Transglutaminase activity in the intestinal mucosa was significantly higher in resected rats than in control and sham operated animals from days 4 (121 +/- 10 v basal 94 +/- 3 mU/g protein, p < 0.01) to 10 (165 +/- 37 mU/g protein, p < 0.05) after surgery; no significant difference was observed at days 12 and 15 (110 +/- 15 and 105 +/- 23 respectively). Both serum alkaline phosphatase activity (partly produced in enterocytes) and serum transglutaminase were significantly lower in resected rats at each time-point beginning at day 6 (208 +/- 34 v 557 +/- 125 UI and 1.55 +/- 0.11 v 3.78 +/- 0.70 mU/ml, p < 0.001 respectively). These data suggest an involvement of transglutaminase in enterocyte proliferation and confirm the association between reduced intestinal mass and low levels of the enzyme in serum.

Serum transglutaminase in inflammatory bowel diseases.

We evaluated the serum transglutaminase activity in patients with inflammatory bowel diseases (IBD) to correlate its level with clinical status. There were 49 patients with Crohn's disease (CD), 50 with ulcerative colitis (UC), 35 with diseases other than IBD as control group and 42 healthy subjects matched for sex and age. Enzyme activity was significantly lower in both IBD groups than in controls and in normal subjects (p less than 0.001); we found a significant negative correlation between serum transglutaminase (TG) activity and clinical severity of the disease in both IBD patient groups (r = -0.54 in CD, and r = -0.69 in UC). Moreover, in UC and CD patients, a serum TG value lower than 0.80 mU/ml retrospectively proved to predict the need for major surgery and/or total parenteral nutrition. These results suggest that serum TG may prove useful in the management of inflammatory intestinal diseases in predicting clinical outcome.

Human serum transglutaminase and coeliac disease: correlation between serum and mucosal activity in an experimental model of rat small bowel enteropathy.

Transglutaminase (TG) activity is increased in the mucosa of patients with coeliac disease. Among 18 patients with untreated coeliac disease we have found a significant decrease (p less than 0.001) in serum levels of TG activity (0.72 (0.23) mU/ml). There was no significant differences between 16 treated coeliacs (1.24 (0.28) mU/ml) and 30 normal controls (1.63 (0.42) mU/ml). To evaluate the connection between serum and mucosal TG activity we used the experimental model of methotrexate induced acute hypoplastic enteropathy in the rat. Transglutaminase activity was unchanged in serum and mucosa 24 and 48 hours after MTX administration, but increased in mucosa (2.606 (0.95) v basal 0.207 (0.026) mU/mg protein, p less than 0.001) and significantly decreased in serum at 72 hours (2.08 (0.38) v basal 5.56 (1.50) mU/ml, p less than 0.001) during intestinal cell proliferation. Activity of the enzyme in the mucosa and serum returned to baseline levels within 120 hours. This experimental animal model helps to explain the data of TG activity in human intestinal mucosa and serum reported in this study. Results are mean (SD).

Behaviour of transglutaminase activity in intestine of starved and refed rats.

Starvation causes an intestinal mucosa atrophy which is greater in jejunum than in ileum. Hypoplasia is promptly reversed by refeeding. Transglutaminase (TG) has been controversially implicated in cell proliferation and its role in intestine is not defined. We investigate, by the above described model, the behaviour of TG in proximal and distal small bowel as well as in colon of rats after 4 days of starvation and at day 1, 2, 3, 4, 5, 7 and 10 of refeeding. Our results emphasize a significative reduction of TG in small bowel induced by starvation (day 0) and a prompt recovery of the enzyme activity after refeeding; furthermore, in the first intestinal tract TG activity reaches from day 2 to day 5 values which are significantly higher than basal. Four days of starvation do not affect TG in colon. In conclusion, our study demonstrates that in rats high values of TG activity are coincident with the intense proliferative phase in small intestine subsequent to starvation atrophy.

Transglutaminase activity along the rat small bowel and cellular location.

A recent report indicates a relationship between human transglutaminase (TG) jejunal mucosa activity and celiac disease. We investigated the enzyme distribution along six consecutive small bowel segments of mucosa and tested TG activity on brush border membranes obtained from whole mucosa homogenate in Wistar rats. TG activity was significantly present in jejunal mucosa even if mostly detected in the distal part of small intestine. Our study indicates highest enzymatic activity in the subcellular fraction containing organelles and cellular membranes (66.8%) while a 7% activity was associated with the brush border fraction.