Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peptide substance P and its tachykinin receptor, neurokinin-1 (NK1), have been the focus of considerable research for their role in a variety of both central and peripheral diseases. Recent preclinical data, as well as relevant clinical findings, support the potential therapeutic value of NK1 receptor antagonists in centrally mediated disease states, including anxiety and depression. In addition, a separate body of literature supports the use of NK1 receptor antagonists as inhibitors of centrally mediated emetic and cough responses. The role of NK1 receptor antagonists as analgesic agents with potential to treat migraine headache has also been investigated. NK1 receptors are also found in a number of peripheral regions, including the bladder, gastrointestinal tract and bone marrow. Preclinical models have been employed to address the potential therapeutic uses for NK1 receptor antagonists in diseases associated with inflammatory responses, including asthma, irritable bowel syndrome and cystitis of the bladder. Finally, other more recent publications suggest a role for NK1 receptor antagonists as tumour suppressants and haematopoietic agents. These applications for NK1 receptor antagonists are discussed in this review.
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PMID:Potential therapeutic targets for neurokinin-1 receptor antagonists. 1515 33

An increased traffic of circulating CD34+ Hemopoietic Precursors Cells (HPC) is an important feature of systemic allergic inflammation. Bacteria and bacterial products are capable of stimulating the transcription of the maturational cytokines IL12 and IFNs through the activation of Toll-Like-Receptor and the subsequent nuclear translocation of the NF-kappaB factor. In this study the probiotics differentiation/maturational effect potential on CD34+ HPC has been investigated. Fourteen consecutive subjects, 9M and 5F, aged 6-48, with clinical symptoms of asthma and /or conjunctivitis, rhinitis, urticaria, atopic dermatitis, food allergy and irritable bowel syndrome were enrolled. Allergen-specific serum IgE were found in twelve patients. Flow-cytometric measurement of peripheral blood CD34dim/bright HPC values were assessed before and after 30 days of therapy, consisting in the oral administration of one sachet a day of ENDOLAC (UCB Pharma, Turin, Italy). Each sachet contained a mixture of Lactobacillus acidophilus, L. delbrueckii and Streptococcus thermophilus for a total of 1 x 10(9) live bacteria. Circulating CD34+ cell values significantly (p < 0.001) reduced after the treatment. ENDOLAC, thus, may improve the efficacy of the standard treatments of allergic diseases.
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PMID:Probiotics reduce the CD34+ hemopoietic precursor cell increased traffic in allergic subjects. 1518 Mar 51

Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.
Allergy Asthma Proc
PMID:Small bowel of patients with asthma and allergic rhinitis: absence of inflammation despite the presence of major cellular components of allergic inflammation. 1551 May 86

Guanylin, uroguanylin, and the bacterial heat-stable enterotoxin (ST) peptides comprise a new family of cyclic guanosine 3'-5' monophosphate (cGMP)-regulating agonists. The discovery of guanylin and uroguanylin peptides stems from studies of cellular mechanisms underlying a form of secretory diarrhea caused by enteric bacteria. Guanylin, uroguanylin, and microbial ST peptides activate a common apical membrane receptor-guanylate cyclase (R-GC) that elicits large increases in the intestinal secretion of chloride and bicarbonate via the intracellular second messenger, cGMP. Guanylin and uroguanylin were isolated from rat jejunum and opossum urine, respectively. These peptides are endogenous peptide hormones that physiologically regulate R-GC signaling proteins in target cells. Physiological roles for these peptides include the regulation of epithelial cell balance in the intestinal epithelium and modulation of sodium balance through actions in the kidney. The guanylin-uroguanylin-ST peptides are candidate therapeutic agents targeting receptors in the intestine, kidney, and other epithelia. For example, uroguanylin has anti-tumor actions in an animal model for human colon cancer. The ST peptides can be used as diagnostic agents to detect secondary colon cancers by single photon-emitting computed tomography (SPECT) imaging, thus localizing metastatic forms of colon cancer. Other examples of potential therapeutic applications for the guanylin family of cGMP-regulating agonists are: (1) the irritable bowel syndrome (IBS) with constipation, (2) salt-dependent forms of high blood pressure, (3) liver regeneration and repair, and (4) respiratory diseases such as asthma. Competitive pharmacological antagonists of bacterial ST peptides offer a means for treating the diarrhea caused by ST-secreting strains of enteric bacteria.
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PMID:Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics. 1551 84

The epidemiology and health-related quality of life associated with functional gastrointestinal disorders are reviewed, with particular emphasis on irritable bowel syndrome and functional dyspepsia. The literature supports the significant world-wide prevalence of functional gastrointestinal disorders, including irritable bowel syndrome (IBS), functional dyspepsia and chronic constipation. An increased female prevalence has been demonstrated in most studies in patients with IBS and chronic constipation, but not functional dyspepsia. The female to male ratio appears to be greater in the health care-seeking population than in community populations. However, some differences in the reported general prevalence and gender-related prevalence of functional gastrointestinal disorders may be due to cultural factors and study methodology. A significant health care burden is associated with IBS, with increased out-patient services, abdominal and pelvic surgeries, and gastrointestinal- and non-gastrointestinal-related physician visits and health care costs. Health-related quality of life is impacted significantly in patients with functional gastrointestinal disorders, such as functional dyspepsia and IBS, compared with the general healthy population, as well as patients with other chronic medical conditions, such as gastro-oesophageal reflux disease and asthma. Impaired health-related quality of life has been demonstrated, in particular, in patients with moderate to severe disease seen in referral settings. The health-related quality of life appears to improve in treatment responders, or correlates with symptom improvement, with at least some treatment modalities studied in functional gastrointestinal disorders, but further studies are needed. Predictors of health-related quality of life in patients with functional gastrointestinal disorders include psychosocial factors, such as early adverse life events, and symptoms related to visceral perception, e.g. pain and chronic stress. The presence of extra-intestinal symptoms appears to have a major if not greater impact on health care visits, excess health care costs and health-related quality of life in patients with functional gastrointestinal disorders.
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PMID:Review article: epidemiology and quality of life in functional gastrointestinal disorders. 1552 53

The identification of orally active, small molecule antagonists of the alpha4beta1 integrin, VLA-4, could lead to therapeutic agents with utility in a number of clinical settings, including asthma, multiple sclerosis and IBD. Starting from CDR3 sequences conserved among neutralizing alpha4 antibodies, peptides were identified that antagonized VLA-4 mediated adhesion in vitro. Through a series of structural modifications, these peptides evolved into small molecules that exhibited high potency and selectivity for VLA-4 in cell adhesion assays. Finally, through the optimization of physical and pharmacokinetic properties, compounds were identified that exhibited oral activity in animal models of asthma and multiple sclerosis.
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PMID:The identification and optimization of orally efficacious, small molecule VLA-4 antagonists. 1554 38

This paper explores the role of self-management of chronic illness at work, as a predictor for self-disclosure. The study reports findings from a survey sent to all staff at a UK university, of which 610 employees reported managing a chronic illness: arthritis, musculoskeletal pain, diabetes, asthma, migraine, heart disease, irritable bowel syndrome and depression. The study found that discrete self-management factors predicted different levels of disclosure: partial self-disclosure (employees informing line managers about the presence of a chronic illness) and full self-disclosure (employees informing line managers how that chronic illness affected them at work). For partial disclosure, a greater reported experience of chronic illness by employees was positively associated with self-disclosure. For full-disclosure, employees were more likely to report disclosure to line managers if they had already disclosed to colleagues, and if they perceived receiving support from their line managers in relation to their chronic illness as important. Except for academics who were least likely to disclose, occupational groups did not emerge as significant predictors for either partial or full disclosure. Except for diabetes, chronic illness itself was not a significant predictor or barrier to self-disclosure. Our findings suggest that chronically ill employees adopt a disclosure strategy specifically related to different self-management needs of chronic illness at work.
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PMID:Dealing with self-management of chronic illness at work: predictors for self-disclosure. 1562 33

Evidence from clinical trials and experience derived from managing patients with asthma justify a broader role for leukotriene (LT) blockers in asthma management than that recommended by the National Asthma Education and Prevention Program and the NIH Heart, Lung and Blood Institute treatment guidelines. Many published clinical trials, reviews, and case reports have suggested important new applications of LT blockers (ie, montelukast, zafirlukast, pranlukast, and zileuton) in several diseases in which leukotrienes play a pathogenic role. These include paranasal sinus disease, allergic fungal sinusitis, migraine, chronic urticaria, atopic dermatitis, chronic obstructive pulmonary disease, allergic conjunctivitis, mastocytosis, bronchiolitis, idiopathic pulmonary fibrosis, interstitial cystitis, and irritable bowel syndrome. Although double-blind, randomized, placebo-controlled trials are needed to confirm the effects that these drugs may have in these diseases, the aim of this short review is to delineate the future roles that these drugs may have in the management of these conditions.
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PMID:Advances in therapy with antileukotriene drugs. 1564 77

Irritable bowel syndrome (IBS) is one of several functional gastrointestinal disorders commonly encountered in both the clinical setting and the general population. The biopsychosocial model is currently believed to be a more complete explanatory mechanism of IBS symptom genesis and propagation. Gut inflammation and immune activation is one of the biological mechanisms for which evidence is emerging. Experimental parasitic infection of mice bowel resulted in elevated substance P levels and increased expression of cyclooxygenase 2 (COX 2) enzyme, prostaglandin E2, IL-4, IL-5, and IL-13. In IBS patients, increased cellularity and proximity of the inflammatory or immune cells to the nerve trunks of the bowel, elevated interleukin-1beta mRNA expression in mucosal biopsies, and increased inducible nitric oxide synthase and nitrotyrosine elaboration (indicative of lymphocyte activation) were observed. Corticosteroids given after the elimination of an experimentally applied parasite from the bowel of mice resulted in the reversal of persistent gut muscle dysfunction. Selective COX-2 inhibitors attenuated the increased bowel smooth muscle contractility resulting from parasite infection of mice gut. In humans, it has been observed that the relative risk of developing IBS in asthma patients was reduced by 60% by the use of oral steroids. Despite such preclinical and human evidence for the role of inflammation and immune activation in IBS, the efficacy of anti-inflammatory and immunomodulatory agents has not been adequately investigated. Budesonide, a corticosteroid with a high mucosal activity and a low bioavailability, is an anti-inflammatory agent that may be worth investigating for its utility in diarrhea-predominant IBS.
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PMID:Will corticosteroids and other anti-inflammatory agents be effective for diarrhea-predominant irritable bowel syndrome? 1589 25

Altered pain appreciation and autonomic function are hallmarks of Cardiac syndrome X, Irritable bowel syndrome and Reflex sympathetic dystrophy. Both pain appreciation and autonomic function are controlled by the lateral medulla. This hypothesis proposes that lateral medullary ischaemia at a microvascular level is responsible for these syndromes and could also be linked to other conditions where autonomic dysfunction is a major feature such as late-onset asthma, type 2 diabetes and essential hypertension. Autonomic function is controlled by the nucleus tractus solitarius, which acts as the main viscero-afferent nucleus in the brain stem regulating vagal tone. It is particularly susceptible to ischaemia since it is highly metabolically active and lies in a medullary arterial watershed zone. The anatomical route of the vertebral artery through cervical vertebra makes it vulnerable to injury from whiplash with or without any genetic predisposition to atheroma formation. This could make microvascular occlusion commonplace and a plausible explanation for the above syndromes. Ischaemia rather than infarction occurs because of the excellent collateral blood supply in the brainstem. In support of this hypothesis, a new Transcranial doppler ultrasonography arterial signal has been described called small vessel knock, the ultrasound signal of small vessel occlusion. Recent evidence has shown that ultrasound targeting of this signal in the vertebral artery improves clinical symptoms in these syndromes which supports this hypothesis. Two such cases are discussed.
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PMID:Are cardiac syndrome X, irritable bowel syndrome and reflex sympathetic dystrophy examples of lateral medullary ischaemic syndromes? 1589 31


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