Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Spanish Group for the Study of Crohn's Disease and Ulcerative Colitis (GETECCU)

OBJECTIVE: Butyrate enemas may be effective in the treatment of active distal ulcerative colitis. Because colonic fermentation of Plantago ovata seeds (dietary fiber) yields butyrate, the aim of this study was to assess the efficacy and safety of Plantago ovata seeds as compared with mesalamine in maintaining remission in ulcerative colitis. METHODS: An open label, parallel-group, multicenter, randomized clinical trial was conducted. A total of 105 patients with ulcerative colitis who were in remission were randomized into groups to receive oral treatment with Plantago ovata seeds (10 g b.i.d.), mesalamine (500 mg t.i.d.), and Plantago ovata seeds plus mesalamine at the same doses. The primary efficacy outcome was maintenance of remission for 12 months. RESULTS: Of the 105 patients, 102 were included in the final analysis. After 12 months, treatment failure rate was 40% (14 of 35 patients) in the Plantago ovata seed group, 35% (13 of 37) in the mesalamine group, and 30% (nine of 30) in the Plantago ovata plus mesalamine group. Probability of continued remission was similar (Mantel-Cox test, p = 0.67; intent-to-treat analysis). Therapy effects remained unchanged after adjusting for potential confounding variables with a Cox's proportional hazards survival analysis. Three patients were withdrawn because of the development of adverse events consisting of constipation and/or flatulence (Plantago ovata seed group = 1 and Plantago ovata seed plus mesalamine group = 2). A significant increase in fecal butyrate levels (p = 0.018) was observed after Plantago ovata seed administration. CONCLUSIONS: Plantago ovata seeds (dietary fiber) might be as effective as mesalamine to maintain remission in ulcerative colitis.     

Allergy to laxative compound (Plantago ovata seed) among health care professionals.

BACKGROUND: The seeds of Plantago ovata (psyllium, ispaghula) used in the manufacture of bulk laxatives are known to be the cause of occupational allergy (rhinitis, asthma) in health care and pharmaceutical workers. OBJECTIVE: We studied the prevalence of P ovata seed allergy among health care workers in geriatric care homes and compared it with a group of health care professionals not exposed to P ovata seed. Cross reactivity with Plantago lanceolata pollen was also studied. METHODS: Two groups of health professionals were recruited: 58 health care workers from geriatric care homes who were exposed daily to laxatives containing P ovata and 63 nonexposed health care professionals. The prevalence of allergy and sensitization to P ovata seed was determined based on clinical history, skin prick test, and analysis of specific immunoglobulin (Ig) E. IgE immunoblotting was performed to calculate the molecular weights of the P ovata seed allergens. Cross reactivity to P lanceolata pollen was studied by enzyme allergosorbent test (EAST) and immunoblot inhibition techniques. RESULTS: The prevalence of sensitization and clinical allergy to P ovata seed in the exposed group was 13.8% and 8.6%, respectively. No sensitization was observed in the nonexposed group. IgE-binding proteins of 17, 20, 25, 32-34, 54, 73-77, and > 97 kDa were identified. EAST inhibition and immunoblot inhibition demonstrated the existence of cross reactivity between P ovata seed and P lanceolata pollen extracts. CONCLUSIONS: The rate of sensitization to P ovata seed is high among health care workers in geriatric care homes (13.8%). A mild cross reactivity between P ovata seed and P lanceolata pollen was observed.     

Preliminary evaluation of some wild and cultivated plants for snail control in Machakos District, Kenya

Fifty local medicinal, agricultural and wild growing deciduous plants, representing 49 species, 46 genera and 22 families, were screened as water extracts at 1:1000 concentration for molluscicidal activity against Biomphalaria pfeifferi in Machakos District, Kenya. Forty-seven of the 50 (94%) plants and 106 of the 134 (79%) plant materials (roots, stems, leaves, fruits, flowers and seeds) were molluscicidal. The leaves of Pappea capensis (Sapindaceae), Steganotaenia araliacea (Umbelliferae), Zornia setosa subsp. obvata (Papilionaceae) and Terminalia kilimandscharica (Combretaceae), the flower pods of Hyptis pectinata (Labiatae), the seeds of Acacia nilotica (Mimosaceae) and the fruits and roots of Solanum nigrum (Solanaceae) gave 100% kill. Another 15 species produced mortality rates between 53% and 87%. Plants were evaluated for possible use in local snail control programmes by considering their growing characteristics, habitat requirements, toxicity in non-target organisms, abundance in the study area and competing uses.     

The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL

There is accumulating evidence that LDL oxidation is essential for atherogenesis, and that antioxidants that prevent this oxidation may either slow down or prevent atherogenesis. In the present study, we found that Commiphora mukul and its cholesterol-lowering component, guggulsterone, effectively inhibited LDL oxidation mediated by either catalytic copper ions, free radicals generated with the azo compound 2,2'-azobis-(2-amidinopropane)dihydrochloride (AAPH), soybean lipoxygenase enzymatically, or mouse peritoneal macrophages. This inhibition was assessed by the decrease in the following parameters describing LDL oxidation: conjugated dienes, relative electrophoretic mobility (REM), thiobarbituric acid reactive substances, lipid hydroperoxides, oxidation-specific immune epitopes as detected with a monoclonal antibody against oxidized LDL, and the accumulation of LDL derived cholesterol esters in mouse peritoneal macrophages. We concluded that C. mukul and its lipid-lowering component, guggulsterone, significantly inhibit LDL oxidation. The combination of antioxidant and lipid-lowering properties of C. mukul and guggulsterone makes them especially beneficial against atherogenesis.     

Interference of dietary fibres with gastrointestinal enzymes in vitro

Dietary fibres (Plantago ovata seeds, P. ovata husks, wheat bran, alfalfa, pectin, xylan) were incubated in vitro with gastrointestinal enzymes (pepsin, trypsin, chymotrypsin, lipase, alpha-amylase, maltase, lactase) in buffer solutions at concentrations of 1-5% for 10-30 min at 37 degrees C. All fibres induced sometimes pronounced changes in enzyme activity, but the effect of the different fibres on the various enzymes varied individually and was not predictable. Both P. ovata preparations had no (pepsin, trypsin, alpha-amylase) or only stimulating (chymotrypsin, lipase, lactase) actions whereas all other fibres showed inhibiting as well as stimulating influences. Wheat bran induced the most pronounced alterations increasing lipase, maltase and lactase activity and inhibiting alpha-amylase activity. Pectin and xylan were comparable in decreasing lipase and pepsin activity and in increasing chymotrypsin activity but had opposite effects on maltase activity. Alfalfa was able to stimulate lactase and lipase activity but depressed trypsin and alpha-amylase activity. The inactivation of enzymes by dietary fibres can, at least partly, be explained by adsorption to the fibre or by the presence of enzyme inhibitors especially in natural compounds. The reasons for activation processes are unknown. As enzyme activities are decisive for food digestion, the properties of the individual fibres should be carefully considered when used as dietary supplement in physiological or pathological conditions.     

Selective leukocyte apheresis for the treatment of inflammatory bowel disease

The etiology of inflammatory bowel disease (IBD) is not completely understood, thus current therapies have been empirical and directed at treating symptoms rather than addressing the cause. In IBD, the overexpression of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, leads to a persistent intestinal inflammatory response that damages the intestinal mucosa. Recent advances in pharmacologic therapies that target specific cytokines, chemokines, and adhesion molecules have proved successful in alleviating symptoms for some patients. There are 2 selective adsorption apheresis devices that remove leukocytes from whole blood, which are currently available in Japan and Europe-the Cellsorba leukocytapheresis column and the Adacolumn adsorptive extracorporeal granulocyte/monocyte apheresis device. The purported mechanisms of action of these devices have been extensively reviewed and are believed to exert an immunomodulatory and/or anti-inflammatory effect on patients with systemic inflammatory disease. The clinical trials presented here indicate that selective leukocyte apheresis effectively removes activated granulocytes and monocytes/macrophages from peripheral blood while maintaining an excellent safety profile. Despite these findings, large controlled trials of selective leukocyte apheresis in the treatment of IBD are needed to determine the true efficacy of this approach.     

Immunogenicity and mechanisms impairing the response to vaccines in inflammatory bowel disease

Inflammatory bowel disease(IBD) is an immunological disorder that is usually treated with immunosuppressive therapy,potentially leading to increases in vulnerability to infections. Although many infections can be pre-vented by vaccination,vaccination coverage in these patients in clinical practice is insufficient. Therefore,the seroprotection condition should be verified,even for routine vaccines,such as hepatitis B or pneu-mococcus. Response to vaccines in IBD patients is thought to be impaired due to the immunological alterations generated by the disease and to the immunomodulatory treatments. The immunogenicity of hepatitis B,influenza,and pneumococcal vaccines is impaired in IBD patients,whereas the response to papillomavirus vaccine seems similar to that observed in the healthy population. On the other hand,data on the immunogenicity of tetanus vaccine in IBD patients are conflicting. Studies assessing the response to measles-mumps-rubella,varicella,and herpes zoster vaccines in IBD patients are scarce. The cellular and molecular mechanisms responsible for the impairment of the response to vaccination in IBD patients are poorly understood. Studies aiming to assess the response to vaccines in IBD patients and to identify the mechanisms involved in their immunogenicity are warranted. A better understanding of the immune response,specifically to vaccines,in patients with immune-mediated diseases(such as IBD),is crucial when developing vaccines that trigger more potent immunologic responses.     

Helminths as an alternative therapy for intestinal diseases

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity,altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings,such as inflammatory bowel disease(IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies,we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use,but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs,since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease,such as the importance of the specific species of helminths used,appropriate dosing regimens,optimal timing of treatment,the role of host genetics,diet,environment,and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method,especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.     

Interventions of natural and synthetic agents in inflammatory bowel disease,modulation of nitric oxide pathways

Inflammatory bowel disease(IBD) refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI) tract. The elevated levels of nitric oxide(NO) in serum and affected tissues; mainly synthesized by the inducible nitric oxide synthase(i NOS) enzyme; can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation. Various natural and synthetic agents are able to ameliorate GI inflammation and decrease i NOS expression to the extent comparable with some IBD drugs. Thereby, the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway. Electronic databases including Google Scholar and Pub Med were searched from 1980 to May 2018. We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and i NOS expression through the nuclear factor κB(NF-κB) and JAK/STAT signaling pathways. Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms. A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway(i.e.,dexamethasone, pioglitazone, tropisetron) or independent from this pathway(i.e.,nicotine, prednisolone, celecoxib, β-adrenoceptor antagonists). Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.     

Inhibition of nuclear factor-κB by hyaluronan in rheumatoid chondrocytes stimulated with COOH-terminal heparin-binding fibronectin fragment

Abstract

The aim of this study was to examine the inhibitory effect of high molecular weight hyaluronan (HA) on nuclear factor (NF)-κB activation by COOH-terminal heparin-binding fibronectin fragment (HBFN-f) in rheumatoid arthritis (RA) chondrocytes. When RA chondrocytes in monolayer or cartilage explants were cultured with HBFN-f, the fragment stimulated the phosphorylation and nuclear translocation of NF-κB, leading to nitric oxide (NO) production in association with inducible form of NO synthase (iNOS) up-regulation. Inhibition studies with NF-κB inhibitors indicated the requirement of NF-κB for HBFN-f-induced NO production. Pretreatment with 2700?kDa HA resulted in significant suppression of NF-κB activation by HBFN-f. HA also inhibited HBFN-f-stimulated NO production with down-regulation of iNOS. The present study clearly demonstrated that high molecular weight HA suppressed HBFN-f-activated NF-κB in RA chondrocytes. HA could down-regulate the catabolic action of fibronectin fragments like HBFN-f in RA joints as a potent NF-κB inhibitor.     

On the Use of Herbal Medicines in Management of Inflammatory Bowel Diseases: A Systematic Review of Animal and Human Studies

Because of potential adverse events and lack of effectiveness of standard therapies, the use of complementary and alternative medicines (CAM), particularly of herbal therapies, for inflammatory bowel disease (IBD) is increasing. Results from the use of herbal therapies for managing IBD are promising, and no serious adverse events have been reported from them. Herbal therapies show their benefit in managing IBD by different mechanisms such as immune system regulation, antioxidant activity, inhibition of leukotriene B4, inhibition of nuclear factor-kappa B (NF-κB), and antiplatelet activity. In this paper, all reported herbal therapies established in animal IBD models or used for managing human IBD are systematically reviewed and their possible mechanisms of action discussed. Conducting clinical trials with high quality and validity (randomized, double blinded, controlled, on a large number of patients) to obtain more conclusive results about the use of herbal therapies in IBD is recommended.     

Herbal Interventions in Asthma and Allergy

This paper reviews the role of herbal-based medicines in the treatment of asthma and allergic rhinitis. A comprehensive literature search was performed of relevant English-language papers and abstracts were identified through a MEDLINE search and from bibliographies of the identified papers. Papers and studies pertaining to the use of medicinal plants in the treatment of asthma and allergic rhinitis were identified. They were then analyzed according to design, inclusion and exclusion criteria, population studied, variables tested, method of treatment (i.e., specific medicinal plants or herbal combinations), and results. The data have been reviewed and divided on the basis of culture and the effects of medicinal plants in asthma and allergy. A number of studies were found that support the use of some herbal medicines in asthma and allergy. Various derivatives from specific medicinal plants were identified as the antiasthma components and some mechanisms of action were explored. The results show positive effects of these herbs on bronchodilation, pulmonary function tests, and antagonism of asthma mediators such as histamine and platelet activating factor, corticosteroid levels, and clearance of mucus. Improved symptoms were also seen in patients with allergic rhinitis specifically on histamine-induced reactions, e.g., rhinorrhea, sneezing, and itching. From the review, there has been a role for some herbal medicines in the treatment of asthma and allergic rhinitis. Usage of herbal medicines has increased in recent years. Many of these medicinal plants provided relief of symptoms equal to allopathic medicines used. Specific chemical derivatives have been isolated from many of these plant products which act on the mechanisms and mediators that cause asthma and allergies. The amount of research on these products, especially in the United States, is limited. There is a lack of control of quantity and quality of the components in these remedies. Yet, many have fewer side effects than current therapy. Throughout the history of medicine, drugs have been developed from traditional medicine. By continuing to investigate how some of these herbal interventions work, we may be able to find additional effective medicines to treat asthma and allergies.     

Profiling of melatonin in the model tomato (Solanum lycopersicum L.) cultivar Micro-Tom

Abstract:  Melatonin exists in a considerable variety of plant species. However, the physiological roles of melatonin in plants are not well understood. In this study, the distribution and accumulation of melatonin during leaf and fruit development were analyzed in Micro-Tom, a model cultivar of tomato ( Solanum lycopersicum L.). Melatonin was extracted using an acetone–methanol method and measured by enzyme-linked immunosorbent assay. Melatonin was detected in leaves, stems, roots, flowers, fruits, seedlings and seeds in the range of 1.5–66.6 ng/g fresh weight, with seeds containing the highest concentration of melatonin. In fruits and leaves, melatonin concentrations varied depending on the developmental stage, suggesting that melatonin controls some of the processes involved in plant maturation.     

Immunomodulatory therapy for inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have intestinal and extraintestinal symptoms that can greatly impair their quality of life. They must rely on multiple medications with aminosalicylates, corticosteroids, and purine analogues to control these symptoms. Although decades of clinical experience in IBD management has led to optimized approaches for achieving the induction and maintenance of remission, the disease in some patients is still refractory to conventional medical treatment, or the effectiveness of these drugs can be limited by treatment-related side effects. Significant progress in our understanding of the pathogenesis of IBD has yielded several immunomodulatory approaches with novel biological agents or apparatus, such as cyclosporine, cytoprotective agents, infliximab, and leukocytapheresis. Further immunomodulatoy therapy, aiming at the inhibition of molecular and cellular mediators, is anticipated, in parallel with the clarification of im-munoinflammatory pathways in IBD. An additional goal will be to identify factors predictive of response to treatment with each novel immunomodulatory agent or apparatus. This will help provide each patient with optimized and individualized therapy, thereby increasing therapeutic efficacy and reducing possible side effects.     

Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease

Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.     

Increases in free radicals and cytoskeletal protein oxidation and nitration in the colon of patients with inflammatory bowel disease

BACKGROUND: Overproduction of colonic oxidants contributes to mucosal injury in inflammatory bowel disease (IBD) but the mechanisms are unclear. Our recent findings using monolayers of intestinal cells suggest that the mechanism could be oxidant induced damage to cytoskeletal proteins. However, oxidants and oxidative damage have not been well characterised in IBD mucosa. AIMS: To determine whether there are increases in oxidants and in tissue and cytoskeletal protein oxidation in IBD mucosa. METHODS: We measured nitric oxide (NO) and markers of oxidative injury (carbonylation and nitrotyrosination) to tissue and cytoskeletal proteins in colonic mucosa from IBD patients (ulcerative colitis, Crohn's disease, specific colitis) and controls. Outcomes were correlated with IBD severity score. RESULTS: Inflamed mucosa showed the greatest increases in oxidants and oxidative damage. Smaller but still significant increases were seen in normal appearing mucosa of patients with active and inactive IBD. Tissue NO levels correlated with oxidative damage. Actin was markedly (>50%) carbonylated and nitrated in inflamed tissues of active IBD, less so in normal appearing tissues. Tubulin carbonylation occurred in parallel; tubulin nitration was not observed. NO and all measures of oxidative damage in tissue and cytoskeletal proteins in the mucosa correlated with IBD severity. Disruption of the actin cytoarchitecture was primarily within the epithelial cells and paracellular area. CONCLUSIONS: Oxidant levels increase in IBD along with oxidation of tissue and cytoskeletal proteins. Oxidative injury correlated with disease severity but is also present in substantial amounts in normal appearing mucosa of IBD patients, suggesting that oxidative injury does not necessarily lead to tissue injury and is not entirely a consequence of tissue injury. Marked actin oxidation (>50%)-which appears to result from cumulative oxidative damage-was only seen in inflamed mucosa, suggesting that oxidant induced cytoskeletal disruption is required for tissue injury, mucosal disruption, and IBD flare up.     

NF-κB在氧化型低密度脂蛋白引起人脐静脉内皮细胞表达CD40中的作用

目的研究氧化低密度脂蛋白(ox-LDL)对人脐静脉内皮细胞表达分化抗原CD40中核因子κB(NF-κB)的作用,进一步探讨卡托普利可能的抗动脉硬化作用。方法在ox-LDL作用人脐静脉内皮细胞前预先用卡托普利、NF-κB阻断剂(PDTC)、卡托普利+一氧化氮合酶阻断剂(L-NAME)、卡托普利+PDTC作用后,应用流式细胞技术检测细胞表面CD40的表达。结果预先加入卡托普利、PDTC人脐静脉内皮细胞的CD40的表达低于ox-LDL组(P<0.05),卡托普利组内皮细胞CD40的表达值低于卡托普利+PDTC组和卡托普利+NAME组,组间相比差异显著(P<0.001)。结论ox-LDL通过NF-κB途径激活了CD40的表达,卡托普利通过一氧化氮(NO)途径及NF-κB的转录使ox-LDL引起的内皮细胞CD40的表达下降,从而具有抗动脉硬化作用。     

Basic and clinical aspects of osteoporosis in inflammatory bowel disease

Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors （VDRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and ultrasound.DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, whil     

Rectal mucosal nitric oxide in differentiation of inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND & AIMS: Differentiating patients with functional bowel disorders from those with inflammatory bowel disease (IBD) can be difficult. Rectal luminal levels of nitric oxide (NO) are greatly increased in IBD. To further evaluate this disease marker, we compared NO in patients with irritable bowel syndrome (IBS) with those found in patients with active IBD and in healthy control subjects. METHODS: Rectal NO was measured with chemiluminescence technique by using a tonometric balloon method in 28 healthy volunteers, 39 patients with IBS, 86 with IBD (Crohn's disease and ulcerative colitis), and 12 patients with collagenous colitis. In addition, NO was measured before and after a 4-week treatment period in patients with active ulcerative colitis and repeatedly during 2 weeks in healthy volunteers. RESULTS: NO was low in healthy control subjects (median, 45; 25th-75th percentile, 34-64 parts per billion [ppb]), and variations over time were small. In IBS patients NO was slightly increased (150, 53-200 ppb; P < .001), whereas patients with active IBD or collagenous colitis had greatly increased NO levels (3475, 575-8850 ppb, and 9950, 4475-19,750 ppb, respectively; P < .001). With a cutoff level of 250 ppb, NO had a sensitivity of 95% and a specificity of 91% in discriminating between active bowel inflammation and IBS. Rectal NO correlated with disease activity in IBD and collagenous colitis and decreased markedly in IBD patients responding to anti-inflammatory treatment. CONCLUSIONS: Rectal NO is a minimally invasive and rapid tool for discriminating between active bowel inflammation and IBS and a possibly useful add-on for monitoring patients with IBD.