Irritable Bowel Syndrome: Alonso C

Alonso C, Santos J. · No affiliation provided · Am J Gastroenterol. · Pubmed #19174802 No free full text.

Abstract: Irritable bowel syndrome remains a bothersome and frustrating disorder that imposes a heavy and growing socio-economic toll on its sufferers, two-thirds of whom are women, and on health care systems. The biomedical community must take a giant step forward into the discipline of women's gastrointestinal health. Efforts and accomplishments, such as the one reported in this month's issue by Cremon et al., are certainly welcome.

Santos J, Alonso C, Vicario M, Ramos L, Lobo B, Malagelada JR. · Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerça Vall d'Hebron & Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Department of Medicine, Barcelona, Spain. · Curr Mol Med. · Pubmed #18537634 No free full text.

Abstract: Inflammatory bowel disease (IBD) and the irritable bowel syndrome (IBS) are common causes of medical consultation and the most frequent diagnosis raised by gastroenterologists. Recent years have witnessed considerable advances in the understanding of the mechanisms involved in the initiation and perpetuation of these chronic and recurrent disorders. However, particularly in IBS, the success of the "bench-to the-bedside medicine" has been rather poor since many affected individuals still experience significant bother and negative impact in their quality of life despite growing investigative and sanitary costs. Besides IBD, several subgroups of IBS patients have been lately identified as carriers of mucosal inflammation throughout the gut. Although multifactorial, life stress has emerged as a critical factor for mucosal inflammation in these conditions. Due to the clinical and biological heterogeneity of IBD and IBS patients, the simplistic hypothesis of a stress-related stepwise progression of gut inflammation may be useful to gain operative knowledge and render better and specific diagnostic markers and improved therapeutic options. Therefore, in this review, we have consciously admitted the possibility of linear evolution of gut inflammation, from the mucosa to the serosa, and assumed a bidirectional progression, from physiological to pathological inflammation. Thus, we have outlined the stress neurocircuitry implicated in the regulation of gut inflammation and the participating pathways (mechanisms, receptors and molecules) and provided with both, evidence and a theoretical-based approach to present and potential drugs that, alone or in combination, might help to prevent, control or regress the stress-induced inflammatory process at different stages.

Santos J, Guilarte M, Alonso C, Malagelada JR. · Digestive Diseases Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, ES-08035 Barcelona, Spain. · Scand J Gastroenterol. · Pubmed #15764142 No free full text.

This publication has no abstract.

Vicario M, Alonso C, Santos J. · Digestive Diseases Research Unit, Institut de Recerca, Department of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. · Gut. · Pubmed #19136518 No free full text.

This publication has no abstract.

Alonso C, Guilarte M, Vicario M, Ramos L, Ramadan Z, Antolín M, Martínez C, Rezzi S, Saperas E, Kochhar S, Santos J, Malagelada JR. · Digestive Diseases Research Unit, Institut de Reçerca, Department of Gastroenterology, Barcelona, Spain. · Gastroenterology. · Pubmed #18455999 No free full text.

Abstract: BACKGROUND & AIMS: Irritable bowel syndrome (IBS), a highly prevalent disorder among women, has been associated with life stress, but the peripheral mechanisms involved remain largely unexplored. METHODS: A 20-cm jejunal segment perfusion was performed in 2 groups of young healthy women, equilibrated by menstrual phase, experiencing either low (LS; n = 13) or moderate background stress (MS; n = 11). Intestinal effluents were collected every 15 minutes, for 30 minutes under basal conditions, and for 1 hour after cold pain stress. Cardiovascular and psychological response, changes in circulating stress and gonadal hormones, and epithelial function (net water flux, albumin output and luminal release of tryptase and alpha-defensins) to cold stress were determined. RESULTS: Cold pain induced a psychological response stronger in the MS than in the LS group, but similar increases in heart rate, blood pressure, adrenocorticotrophic hormone, and cortisol, whereas estradiol and progesterone remained unaltered. Notably, the jejunal epithelium of MS females showed a chloride-related decrease in peak secretory response (Delta[15-0 minutes]: LS, 97.5 [68.4-135.0]; MS, 48.8 [36.6-65.0] microL/min/cm; P < .001) combined with a marked enhancement of albumin permeability (LS(AUC), 6.35 [0.9-9.6]; MS(AUC), 13.97 [8.3-23.1] mg/60 min; P = .008) after cold stress. Epithelial response in both groups was associated with similar increases in luminal tryptase and alpha-defensins release. CONCLUSIONS: Increased exposure to life events determines a defective jejunal epithelial response to incoming stimuli. This abnormal response may represent an initial step in the development of prolonged mucosal dysfunction, a finding that could be linked to enhanced susceptibility for IBS.

Guilarte M, Santos J, de Torres I, Alonso C, Vicario M, Ramos L, Martínez C, Casellas F, Saperas E, Malagelada JR. · Department of Medicine, Hospital Universitari General Vall d'Hebron, 08035 Barcelona, Spain. · Gut. · Pubmed #17005763 No free full text.

Abstract: BACKGROUND: Increased numbers of mast cells and mast cell activation in distal gut segments are associated with symptom onset and severity in irritable bowel syndrome (IBS). Although upper gut symptoms are common, mast cells have not been thoroughly evaluated in proximal gut in IBS patients. METHODS: Jejunal biopsies obtained by Watson's capsule, aspiration of intestinal fluid and one blood sample were obtained in 20 diarrhoea-predominant patients with IBS (D-IBS) and 14 healthy volunteers (H). Psychological stress (Holmes-Rahe Scale) and depression (Beck's Depression Inventory) were evaluated at baseline and food and respiratory allergy excluded. Biopsies were processed for H&E staining and microscopic inflammation assessed by counting intraepithelial lymphocytes. Mast cells in lamina propria were counted by immunohistochemistry with CD117 (c-kit). Tryptase concentration was measured in intestinal fluid and serum. RESULTS: D-IBS patients showed higher psychological stress than healthy volunteers (D-IBS: 203 (SD 114) v H: 112 (SD 99); p = 0.019). Immunohistochemical staining of jejunal mucosa revealed mild increase in intraepithelial CD3+ cells in D-IBS patients (D-IBS: 15.3 (SD 5.5; 95% CI 12.7 to 17.9) v H: 10.3 (SD 3.9; 95% CI 8.0 to 12.5); p = 0.006). Moreover, D-IBS patients showed marked increase in mast cells numbers (D-IBS: 34 (SD 9.3); H: 15.3 (SD 4.4) mast cells/hpf; p<0.001) and higher tryptase concentration in jejunal fluid (D-IBS: 0.45 (SD 0.38); H: 0.09 (SD 0.10) microg/l; p = 0.005). Upper gut symptoms were not associated with gender, mast cell counts, jejunal tryptase or basal stress. CONCLUSION: This jejunal mucosal inflammatory profile may help identify diarrhoea-predominant IBS, a stress-related disorder.