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Editorial A closer look at mucosal inflammation in irritable bowel syndrome: sex- and gender-related disparities--quantity, quality, or both? 2009
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.
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Review Neuropharmacology of stress-induced mucosal inflammation: implications for inflammatory bowel disease and irritable bowel syndrome. 2008
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.
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Review [Stress-mast cell axis and regulation of gut mucosal inflammation: from intestinal health to an irritable bowel] 2007
Ramos L, Vicario M, Santos J. · Unidad de Investigación en Enfermedades Digestivas, Servicio de Aparato Digestivo, Hospital Universitari Vall d'Hebron, Departamento de Medicina, Universitat Autònoma de Barcelona, Barcelona, España. · Med Clin (Barc). · Pubmed #17588364 No free full text.
Abstract: The functional gastrointestinal disorders and the irritable bowel syndrome, in particular, represent one of the commonest causes of medical consultation and the most frequent diagnosis raised by the gastroenterologists. Despite their high prevalence, the aetiology and pathophysiology of these functional digestive disorders remains unclear and specific diagnostic markers and clearly effective therapeutic options are lacking as well. These factors generate an important impairment in the quality of life in these patients and a growing sanitary burden. Recent studies showing the presence of low grade intestinal mucosal inflammation along with mast cell hyperplasia may contribute to the development and perpetuation of visceral hypersensitivity and dismotility patterns and epithelial barrier abnormalities, characteristic of the irritable bowel syndrome. In this article we will review the role of the stress-mast cell axis in the modulation of the gut mucosal inflammation and in the pathophysiology of the irritable bowel syndrome.
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Review Pathogenesis of irritable bowel syndrome: the mast cell connection. 2005
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.
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Article Impaired intestinal molecular tightness in the mucosa of irritable bowel syndrome: what are the mediators? 2009
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.
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Article Maladaptive intestinal epithelial responses to life stress may predispose healthy women to gut mucosal inflammation. 2008
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.
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Article Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. 2007
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.
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Article Prevalence of functional gastrointestinal disorders in women who report domestic violence to the police. 2005
Perona M, Benasayag R, Perelló A, Santos J, Zárate N, Zárate P, Mearin F. · Institute of Functional and Motor Digestive Disorders, Centro Médico Teknon, Barcelona, Spain · Clin Gastroenterol Hepatol. · Pubmed #15880312 No free full text.
Abstract: BACKGROUND & AIMS: Retrospective studies found an association between past sexual, physical, or psychological abuse and functional gastrointestinal disorders (FGIDs). However, there are no studies evaluating such an association concurrently with the ongoing abuse. Our aim was to investigate the prevalence of the main FGIDs, functional dyspepsia and irritable bowel syndrome, in 70 women reporting a situation of domestic violence to the police and to evaluate the level of psychological distress and its relationship with the presence of FGID. METHODS: Through an interview between a social worker and the woman reporting abuse, digestive symptoms, psychological status, and type of abuse were recorded. These data were matched against police records. Functional dyspepsia and irritable bowel syndrome were diagnosed according to Rome II criteria. RESULTS: Seventy-one percent of the women had an FGID: 67% functional dyspepsia, 47% irritable bowel syndrome, and 43% both. In two thirds of the cases, FGID onset occurred simultaneously with or soon after abuse onset. Only 34% of the women had sought medical attention for FGID symptoms. No differences were found between women with or without FGID regarding age and type or duration of abuse; psychological distress tended to be more severe in the group of women with FGIDs. CONCLUSIONS: Most women who suffer domestic violence (reported to the police) have functional dyspepsia and/or irritable bowel syndrome and also have elevated psychological distress. This has important implications, not only for comprehensive health care of women in a situation of abuse, but also for medical treatment of women with FGIDs.
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