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Background Since their discovery, S100 proteins have been associated with diverse diseases of inflammatory, degenerative, or malignant nature. Due to their participation in inflammation, they have also been studied with regard to inflammatory bowel disease (IBD). Method To provide a review of available literature, a PubMed, MEDLINE, and Embase-based literature search was performed, using all available nomenclature for each member of the S100 protein family, along with the terms inflammatory bowel disease, ulcerative colitis, Crohn’s disease, or indeterminate colitis. Result S100A8/A9, also known as calprotectin, S100A12, or calgranulin C and in a lesser extent S100P, are involved in the pathogenesis, activity, diagnosis, and therapeutic management of IBD. The majority of available literature is focused primarily on S100A8/9, although there is growing evidence on the significance of S100A12. Most studies emphasize the potential merit of S100A8/A9 and S100A12, as markers for differential diagnosis, monitoring of activity, or disease relapse, in IBD. Limitations, regarding the diagnostic utility of these markers, seem to exist and are mainly related to the publication of conflicting results, i.e., for IBD activity, and to the fact that S100A8/A9 and S100A12 are not disease-specific. Conclusions Although the existing data link specific S100 proteins with IBD, there are still several drawbacks in the use of these markers for diagnostic purposes. Thus, it seems that further research is mandatory in order to eliminate the impact of confounding factors but also to detect additional associations between S100 proteins and IBD or novel S100 proteins with a closer correlation with IBD.

Background S100A12, a calcium-binding proinflammatory protein secreted by granulocytes, has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In this study, the utility of serum S100A12, in discriminating IBD from irritable bowel syndrome (IBS), was tested. Methods S100A12 serum levels were determined in 64 patients with ulcerative colitis (UC), 64 with Crohn's disease (CD) and 73 with IBS, by means of an enzyme-linked immunosorbent assay. S100A12 serum levels were evaluated with respect to the levels of known inflammatory markers and patients' characteristics. Results The median values of serum S100A12 levels were 68.2 ng/mL (range: 43.4-147.4) in UC, 70 ng/mL (41.4-169.8) in CD and 43.4 ng/mL (34.4-74.4) in IBS patients. UC and CD patients had significantly higher serum S100A12 levels compared to IBS patients ( P = 0.001 for both comparisons). Moreover, a cut-off for serum S100A12 levels of 54.4 ng/mL could predict both UC and CD with a 66.7% sensitivity and a 64.4% specificity. The area under curve was estimated at 0.67 with a 95% confidence interval of 0.60-0.75 ( P < 0.001). Considering standard activity indices, higher serum S100A12 levels in active compared to inactive IBD were observed, although the recorded difference did not reach statistical significance. C-reactive protein (CRP) and serum amyloid A (SAA) levels, showed a statistically significant positive correlation with S100A12 (r = 0.39, P = 0.001 and r = 0.23, P = 0.02 respectively). Conclusions Increased levels of circulating S100A12 are found in IBD, compared to IBS. When used to distinguish IBD from IBS adult patients, serum S100A12 levels exhibit moderate performance. On the other hand, serum S100A12 may serve as an inflammatory marker in IBD, since it is well correlated with CRP and SAA.

Conservative management of inflammatory bowel disease (IBD) is based on a combination of drugs, including aminosalicylates (ASAs), steroids, antibiotics, immunosuppressives and biologic agents. Although various side effects have been related to treatment regimens, drug-induced nephrotoxicity is rather uncommon. Furthermore, it is often underestimated since renal function deterioration may be attributed to the underlying disease. The nephrotoxicity of ASAs and cyclosporine A seems well established, but recent data have suggested a possible role of biologic agents such as infliximab and adalimubab in renal impairment. The aim of this review is to summarize the nephrotoxic effects of medical treatment as well as to express possible caveats in the administration of novel agents in IBD. Copyright © 2011 S. Karger AG, Basel [PUBLICATION ABSTRACT]

Caveolin-1 (Cav-1) expression has been shown to be associated with tumor growth and resistance to chemotherapy in pancreatic cancer. The primary aim of this study was to explore the significance of Cav-1 expression in pancreatic cancer cells as compared to fibroblasts in relation to cancer cell proliferation and chemoresistance, both in vitro and in vivo, in an immunodeficient mouse model. We also aimed to evaluate the immunohistochemical expression of Cav-1 in the epithelial and stromal component of pancreatic cancer tissue specimens. The immunohistochemical staining of poorly differentiated tissue sections revealed a strong and weak Cav-1 expression in the epithelial tumor cells and stromal fibroblasts, respectively. Conversely, the well-differentiated areas were characterized by a weak epithelial Cav-1 expression. Cav-1 downregulation in cancer cells resulted in an increased proliferation in vitro; however, it had no effect on chemoresistance and growth gain in vivo. By contrast, the decreased expression of Cav-1 in fibroblasts resulted in a growth advantage and the chemo-resistance of cancer cells when they were co-injected into immunodeficient mice to develop mixed fibroblast/cancer cell xenografts. On the whole, the findings of this study suggest that the downregulation of Cav-1 in fibroblasts is associated with an increased tumor proliferation rate in vivo and chemoresistance. Further studies are warranted to explore whether the targeting of Cav-1 in the stroma may represent a novel therapeutic approach in pancreatic cancer.

Background Toll-like receptor ( TLR ) polymorphisms, and especially TLR - 4 Asp299Gly and TLR - 4 Thr399Ile , have been linked with Crohn’s disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. Aims To address these issues, the distribution of TLR - 4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. Methods TLR - 4 Asp299Gly and TLR - 4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti- Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. Results UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents ( P  = 0.002 and P  < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR - 4 compared to those with wild-type alleles ( P  = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 <  P  < 0.05). Despite the mutant TLR - 4 predisposition for UC pancolitis, smoking was associated with more limited disease ( P  < 0.001). Conclusions The presence of TLR - 4 Asp299Gly and TLR - 4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

The best antisecretory treatment after endoscopic hemostasis in patients with ulcer bleeding is still in quest. To compare pantoprazole and somatostatin continuous infusion after endoscopic hemostasis in patients with bleeding peptic ulcers. A total of 164 consecutive patients with a bleeding peptic ulcer, after successful endoscopic hemostasis, were randomly assigned to receive, double blindly, continuous IV infusion of pantoprazole 8 mg/h for 48 h after a bolus of 40 mg (group P) or somatostatin 250 microg/h for 48 h after a bolus of 250 microg (group-S). Twenty-four-hour pH-metry was performed in the last 30 patients in each group. Endoscopy was performed, in case of bleeding nonrecurrence, every 48 h until disappearance of stigmata. Bleeding recurrence: group S 14 patients (17%) versus group P 4 (5%) (P=0.046). In multivariate analysis, bleeding recurrence was 4.57 (CI 1.31-15.91) times more frequent in group S (P=0.02). There was no difference in the need for surgery and mortality. Acid suppression over pH 6: group S 82.9% of the time versus group P 81.5% (P=0.97). Acid suppression over pH 6 for >85% of the time: group S 14 (47%) patients versus group P 17 (57%) (P=0.44). Disappearance of endoscopic stigmata after 48 h: group S 25/68 patients (37%) versus group P 72/78 (92%) (P<0.0001). No major side effects identified in either study group. In patients with a bleeding ulcer, after successful endoscopic hemostasis, despite equipotent acid suppression, pantoprazole continuous infusion was superior to somatostatin to prevent bleeding recurrence and quick disappearance of the endoscopic stigmata. Nevertheless, no differences were seen in the need for surgery and mortality.