5-ASA colonic mucosal concentrations resulting from different pharmaceutical formulations in ulcerative colitis

AIM:To compare the mucosal concentrations of 5-aminosalicylic acid(5-ASA)resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations.METHODS:The study included 130 inflammatory bowel disease(IBD)patients receiving 5-ASA as pH-dependent-release formulations(73 patients),time-dependent-release formulations(11 patients),or pro-drugs(18patients).In addition,28 patients were receiving topical treatment(2-4 g/d)with pH-dependent-release formulations.Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy.The 5-ASA concentrations(ng/mg)were measured in tissue homogenatesusing high-pressure liquid chromatography with electrochemical detection.The t test and Mann-Whitney test,when appropriate,were used for statistical analysis.RESULTS:Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA(51.75±5.72 ng/mg)compared with patients receiving pro-drugs(33.35±5.78 ng/mg,P=0.01)or time-dependent-release formulations(38.24±5.53 ng/mg,P=0.04).Patients with endoscopic remission had significantly higher mucosal concentrations of5-ASA than patients with active disease(60.14±7.95ng/mg vs 35.66±5.68 ng/mg,P=0.02).Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation(67.53±9.22 ng/mg vs 35.53±5.63 ng/mg,P<0.001).Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone(72.33±11.23 ng/mg vs 51.75±5.72 ng/mg,P=0.03).CONCLUSION:IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation,and the highest mean concentration was achieved using pH-dependent-release formulations.

Non-invasive investigation in patients with inflammatory joint disease

Gut inflammation can occur in 30%-60% of patients with spondyloarthropathies.However, the presence of such gut inflammation is underestimated, only 27% of patients with histological evidence of gut inflammation have intestinal symptoms, but subclinical gut inflammation is documented in two-thirds of patients with inflammatory joint disease.There are common genetic and immunological mechanisms behind concomitant inflammation in the joints and intestinal tract.A number of blood tests, e.g.erythrocyte sedimentation rate, orosomucoid, C-reactive protein, and white cell and platelet counts, are probably the most commonly used laboratory markers of inflammatory disease, however, these tests are difficult to interpret in arthropathies associated with gut inflammation, since any increases in their blood levels might be attributable to either the joint disease or to gut inflammation.Consequently, it would be useful to have a marker capable of separately identifying gut inflammation.Fecal proteins, which are indirect markers of neutrophil migration in the gut wall, and intestinal permeability, seem to be ideal for monitoring intestinal inflammation:they are easy to measure non-invasively and are specific for intestinal disease in the absence of gastrointestinal infections.Alongside the traditional markers for characterizing intestinal inflammation, there are also antibodies, in all probability generated by the immune response to microbial antigens and auto-antigens, which have proved useful in establishing the diagnosis and assessing the severity of the condition, as well as the prognosis and the risk of complications.In short, noninvasive investigations on the gut in patients with rheumatic disease may be useful in clinical practice for a preliminary assessment of patients with suspected intestinal disease.

Host-microbiome interaction in Crohn's disease: A familiar or familial issue?

An impaired interaction between the gut and the intestinal microbiome is likely to be the key element in the pathogenesis of Crohn's disease(CD). Family studies have provided invaluable information on CD pathogenesis and on its etiology. Relatives share the same genetic risk of developing the disease as affected subjects. Relatives also exhibit similar features relating to their host-microbiome interaction, namely genetic variants in loci involved in detecting bacteria, a greater seroreactivity to microbial components, and an impaired intestinal permeability. The burden of environmental factors such as cigarette smoking and dysbiosis also seems to be particularly relevant in these genetically predisposed subjects. Diet is emerging as an important factor and could account for the changing epidemiology of CD in recent years. Despite the pivotal role of genetics in the disease's pathogenesis(especially in familial CD), screening tests in healthy relatives cannot be recommended.

Glucose transporter expression in the human colon

AIM To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease(IBD). METHODS Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or rectosigmoidoscopy. Patients diagnosed with ulcerativecolitis(n = 18) or Crohn's disease(n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group(CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, doublelabeled confocal microscopy was used. RESULTS Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive(-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and noninflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels. CONCLUSION Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.

Efficacy of teduglutide in a patient with Crohn’s disease and short bowel syndrome on enteral nutrition:let’s start to think out of the box

Introduction Short bowel syndrome(SBS)is a disorder characterized by malabsorption due to the absence or resection of a long small intestine tract,with an incidence of 2 per million of habitants.In adults,SBS is defined as less than 200 cm without colon and less than 50 cm with residual colon in continuity[1].The causes of SBS in adult patients are different,but the most frequent one(33.3%of the cases)is the need for surgery in patients with Crohn’s disease(CD)[2].