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Sample records for active inflammatory disease

  1. Platelet activity in the pathophysiology of inflammatory bowel diseases.

    PubMed

    Chen, Chunqiu; Li, Yongyu; Yu, Zhen; Liu, Zhanju; Shi, Yanhong; Lewandowska, Urszula; Sobczak, Marta; Fichna, Jakub; Kreis, Martin

    2015-01-01

    Platelets play a crucial role in immune responses. Impaired platelet activation may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and other systems influencing granulocytes, macrophages or endothelial cells. Pharmacological regulation of platelet activation may reduce thromboembolism and limit the interaction of platelets with endothelial and inflammatory cells, in turn weakening the inflammatory responses. In this review we focus on pathophysiological activities of platelets in inflammatory bowel diseases and discuss the studies on currently available anti-platelet therapies in the treatment of gastrointestinal inflammation. Finally, we provide a prospective view to new anti-platelet agents currently under development. PMID:25585124

  2. Cytomegalovirus Infection in Inflammatory Bowel Disease Is Not Associated with Worsening of Intestinal Inflammatory Activity

    PubMed Central

    do Carmo, Alexandre Medeiros; Santos, Fabiana Maria; Ortiz-Agostinho, Carmen Lucia; Nishitokukado, Iêda; Frota, Cintia S.; Gomes, Flavia Ubeda; de Arruda Leite, André Zonetti; Pannuti, Claudio Sérgio; Boas, Lucy Santos Vilas; Teixeira, Magaly Gemio; Sipahi, Aytan Miranda

    2014-01-01

    Background Cytomegalovirus is highly prevalent virus and usually occurs in immunocompromised patients. The pathophysiology and treatment of inflammatory bowel disease often induce a state of immunosuppression. Because this, there are still doubts and controversies about the relationship between inflammatory bowel disease and cytomegalovirus. Aim Evaluate the frequency of cytomegalovirus in patients with inflammatory bowel disease and identify correlations. Methods Patients with inflammatory bowel disease underwent an interview, review of records and collection of blood and fecal samples. The search for cytomegalovirus was performed by IgG and IgM blood serology, by real-time PCR in the blood and by qualitative PCR in feces. Results were correlated with red blood cell levels, C-reactive protein levels, erythrocyte sedimentation rates and fecal calprotectin levels for each patient. Results Among the 400 eligible patients, 249 had Crohn's disease, and 151 had ulcerative colitis. In the group of Crohn's disease, 67 of the patients had moderate or severe disease, but 126 patients presented with active disease, based on the evaluation of the fecal calprotectin. In patients with ulcerative colitis, only 21 patients had moderate disease, but 76 patients presented with active disease, based on the evaluation of the fecal calprotectin. A large majority of patients had positive CMV IgG. Overall, 10 patients had positive CMV IgM, and 9 patients had a positive qualitative detection of CMV DNA by PCR in the feces. All 400 patients returned negative results after the quantitative detection of CMV DNA in blood by real-time PCR. Analyzing the 19 patients with active infections, we only found that such an association occurred with the use of combined therapy (anti-TNF-alpha + azathioprine) Conclusion The findings show that latent cytomegalovirus infections are frequent and active cytomegalovirus infection is rare. We did not find any association between an active infection of CMV

  3. P21-activated kinase in inflammatory and cardiovascular disease

    PubMed Central

    Taglieri, Domenico M.; Ushio-Fukai, Masuko; Monasky, Michelle M.

    2014-01-01

    P-21 activated kinases, or PAKs, are serine–threonine kinases that serve a role in diverse biological functions and organ system diseases. Although PAK signaling has been the focus of many investigations, still our understanding of the role of PAK in inflammation is incomplete. This review consolidates what is known about PAK1 across several cell types, highlighting the role of PAK1 and PAK2 in inflammation in relation to NADPH oxidase activation. This review explores the physiological functions of PAK during inflammation, the role of PAK in several organ diseases with an emphasis on cardiovascular disease, and the PAK signaling pathway, including activators and targets of PAK. Also, we discuss PAK1 as a pharmacological anti-inflammatory target, explore the potentials and the limitations of the current pharmacological tools to regulate PAK1 activity during inflammation, and provide indications for future research. We conclude that a vast amount of evidence supports the idea that PAK is a central molecule in inflammatory signaling, thus making PAK1 itself a promising prospective pharmacological target. PMID:24794532

  4. Linking estrogen receptor β expression with inflammatory bowel disease activity

    PubMed Central

    Pierdominici, Marina; Maselli, Angela; Varano, Barbara; Barbati, Cristiana; Cesaro, Paola; Spada, Cristiano; Zullo, Angelo; Lorenzetti, Roberto; Rosati, Marco; Rainaldi, Gabriella; Limiti, Maria Rosaria; Guidi, Luisa

    2015-01-01

    Crohn disease (CD) and ulcerative colitis (UC) are chronic forms of inflammatory bowel disease (IBD) whose pathogenesis is only poorly understood. Estrogens have a complex role in inflammation and growing evidence suggests that these hormones may impact IBD pathogenesis. Here, we demonstrated a significant reduction (p < 0.05) of estrogen receptor (ER)β expression in peripheral blood T lymphocytes from CD/UC patients with active disease (n = 27) as compared to those in remission (n = 21) and healthy controls (n = 29). Accordingly, in a subgroup of CD/UC patients undergoing to anti-TNF-α therapy and responsive to treatment, ERβ expression was higher (p < 0.01) than that observed in not responsive patients and comparable to that of control subjects. Notably, ERβ expression was markedly decreased in colonic mucosa of CD/UC patients with active disease, reflecting the alterations observed in peripheral blood T cells. ERβ expression inversely correlated with interleukin (IL)-6 serum levels and exogenous exposure of both T lymphocytes and intestinal epithelial cells to this cytokine resulted in ERβ downregulation. These results demonstrate that the ER profile is altered in active IBD patients at both mucosal and systemic levels, at least in part due to IL-6 dysregulation, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of endoscopic disease activity. PMID:26497217

  5. Phospholipase A2 activating protein and idiopathic inflammatory bowel disease.

    PubMed Central

    Peterson, J W; Dickey, W D; Saini, S S; Gourley, W; Klimpel, G R; Chopra, A K

    1996-01-01

    BACKGROUND: Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases (IBD) involving synthesis of eicosanoids from arachidonic acid (AA), which is released from membrane phospholipids by phospholipase A2 (PLA2). A potentially important regulator of the production of these mediators is a protein activator of PLA2, referred to as PLA2 activating protein (PLAP). AIMS: The purpose of this investigation was to discover if PLAP values might be increased in the inflamed intestinal tissue of patients with IBD and in intestinal tissue of mice with colitis. PATIENTS: Biopsy specimens were taken from patients with ulcerative colitis and Crohn's disease undergoing diagnostic colonoscopy, and normal colonic mucosa was obtained from patients without IBD after surgical resection. METHODS: Immunocytochemistry with affinity purified antibodies to PLAP synthetic peptides was used to locate PLAP antigen in sections of intestinal biopsy specimens from IBD patients compared with that of normal intestinal tissue. Northern blot analysis with a murine [32P] labelled plap cDNA probe was performed on RNA extracted from the colons of mice fed dextran sulphate sodium (DSS) and cultured HT-29 cells exposed to lipopolysaccharide (LPS). RESULTS: PLAP antigen was localised predominantly within monocytes and granulocytes in intestinal tissue sections from IBD patients, and additional deposition of extracellular PLAP antigen was associated with blood vessels and oedema fluid in the inflamed tissues. In contrast, tissue sections from normal human intestine were devoid of PLAP reactive antigen, except for some weak cytoplasmic reaction of luminal intestinal epithelial cells. Similarly, colonic tissue from DSS treated mice contained an increased amount of PLAP antigen compared with controls. The stroma of the lamina propria of the colonic mucosa from the DSS treated mice reacted intensely with antibodies to PLAP synthetic peptides, while no reaction was observed with control

  6. Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

    PubMed Central

    Moller, Frederik Trier; Knudsen, Lina; Harbord, Marcus; Satsangi, Jack; Gordon, Hannah; Christiansen, Lene; Christensen, Kaare; Jess, Tine; Andersen, Vibeke

    2016-01-01

    AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 μg/g in 2 participants, and above 50 μg/g in a further 5 participants. CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins. PMID:27275097

  7. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. PMID:23281076

  8. Exercise Decreases Risk of Future Active Disease in Inflammatory Bowel Disease Patients in Remission

    PubMed Central

    Jones, Patricia D.; Kappelman, Michael D.; Martin, Christopher F.; Chen, Wenli; Sandler, Robert S.; Long, Millie D.

    2015-01-01

    Background Although exercise impacts quality of life in patients with inflammatory bowel disease (IBD), little is known about its role in disease activity. Among IBD patients in remission, we aimed to evaluate the association between exercise and subsequent active disease. Methods We performed a prospective study using the Crohn's and Colitis Foundation of America (CCFA) Partners Internet-based cohort of individuals with self-reported IBD. We identified participants in remission, defined as short Crohn's disease activity index (sCDAI) <150 or simple clinical colitis activity index (SCCAI) ≤2. The primary exposure was exercise status, measured using the validated Godin leisure time activity index. The primary study outcome, assessed after six months, was active disease defined using the above disease activity index thresholds. We used bivariate and multivariate analyses to describe the independent association between exercise and risk of active disease. Results We identified 1308 patients with Crohn's Disease (CD) and 549 with ulcerative or indeterminate colitis (UC/IC) in remission, of whom 227(17.4%) with CD and 135 (24.6%) with UC/IC developed active disease after 6 months. Higher exercise level was associated with decreased risk of active disease for CD (adjusted RR 0.72, 95% CI 0.55-0.94) and UC/IC (adjusted RR 0.78, 95% CI 0.54-1.13). Conclusions In patients with CD in remission, those with higher exercise levels were significantly less likely to develop active disease at six months. In patients with UC/IC in remission, patients with higher exercise levels were less likely to develop active disease at six months, however this was not statistically significant. PMID:25723616

  9. Distinct features of circulating microparticles and their relationship with disease activity in inflammatory bowel disease

    PubMed Central

    Voudoukis, Evangelos; Vetsika, Eleni-Kyriaki; Giannakopoulou, Konstantina; Karmiris, Konstantinos; Theodoropoulou, Angeliki; Sfiridaki, Aekaterini; Georgoulias, Vassilis; Paspatis, Gregorios A.; Koutroubakis, Ioannis E.

    2016-01-01

    Background There is evidence that circulating microparticles (MPs) and annexin (+) platelet-derived MPs (PDMPs) are increased in inflammatory bowel disease (IBD). The aim of our study was to characterize the abundance, origin, and annexin V binding of MPs in patients with IBD and correlate them with the disease characteristics. Methods Case-control study of 46 IBD patients (23 Crohn’s disease, 23 ulcerative colitis) and 40 matched healthy controls (HC). MPs were divided according to annexin V binding, their origin was estimated based on specific cell membrane markers in plasma samples and their number was calculated via flow cytometry. Clinical and laboratory activity indices were also analyzed. Results Annexin (-) PDMPs (P=0.0004), total (P=0.04) and annexin (+) monocyte-derived MPs (P=0.02) were increased and annexin (-) total MPs (P=0.0007) were decreased in IBD patients compared to HC. The annexin (+)/(-) ratio of all MP types were significantly elevated in IBD patients compared to HC (P<0.003). IBD patients with active disease displayed elevated total and annexin (+) total MPs, total, annexin (+) and (-) PDMPs compared with those in remission (P<0.05). Annexin (-) PDMPs were considerably increased in IBD patients with active compared to those with inactive disease (P=0.0013). Total and annexin (-) PDMPs were significantly correlated with most of the disease activity indices (P<0.05). Conclusion The majority of circulating MPs, their counterparts and particularly annexin (-) PDMPs are increased in active IBD patients. Annexin (+)/(-) ratio proved to be the most reliable distinctive MP index between HC and IBD patients. PMID:27065731

  10. [Biomarkers for chronic inflammatory diseases].

    PubMed

    Holzinger, D; Föll, D

    2015-12-01

    Inflammatory disorders of childhood, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are a challenge for laboratory diagnostics. Firstly, the classical inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) often inadequately reflect disease activity but on the other hand there are few specific biomarkers that can be helpful in managing these diseases. Acute phase proteins reflect the systemic inflammatory response insufficiently as their increase is only the indirect result of local inflammatory processes. Modern inflammation diagnostics aim to reflect these local processes and to allow precise monitoring of disease activity. Experimental biomarkers, such as S100 proteins can detect subclinical inflammatory activity. In addition, established laboratory parameters exist for JIA [antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP)] and for chronic IBD (fecal calprotectin) that are useful in the treatment of these diseases. PMID:26608264

  11. Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity.

    PubMed

    Boga, Salih; Alkim, Huseyin; Koksal, Ali Riza; Ozagari, Ayse Aysim; Bayram, Mehmet; Tekin Neijmann, Sebnem; Sen, Ilker; Alkim, Canan

    2016-06-01

    ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2-54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding. PMID:27001944

  12. Taurine and inflammatory diseases.

    PubMed

    Marcinkiewicz, Janusz; Kontny, Ewa

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)-halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis. PMID:22810731

  13. Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

    PubMed Central

    Fischbach, W; Becker, W; Mössner, J; Koch, W; Reiners, C

    1987-01-01

    Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors. PMID:3495470

  14. Pelvic Inflammatory Disease

    MedlinePlus

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  15. The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease

    PubMed Central

    Lee, Hye Won; Chung, Sook Hee; Moon, Chang Mo; Che, Xiumei; Kim, Seung Won; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2016-01-01

    Abstract Genetic variants in IL12B, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD. A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay. The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all P <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (P <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (P = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (P = 0.002) and intestinal BD (P = 0.001) but not that of CD. Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients. PMID:27281077

  16. Markers of inflammation, activation of blood platelets and coagulation disorders in inflammatory bowel diseases.

    PubMed

    Matowicka-Karna, Joanna

    2016-01-01

    Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease. It is a group of chronic disorders characterized by inflammation of the gastrointestinal track with unknown etiology. Currently applied biomarkers include CRP, ESR, pANCA, ASCA, and fecal calprotectin. The etiopathogenesis of IBD is multifactorial. In patients with IBD in inflamed alimentary tract mucosa the number of recruited monocytes and activated macrophages which are source of cytokines. In IBD, the exacerbation is accompanied by thrombocytosis. Platelets play a crucial role in the hemostasis and inflammatory response. Selectins, which regulates the hemostasis and inflammatory response, stimulates the secretion of many inflammatory mediators such as β-thromboglobuline, CD40L, fibrinogen, IL-1β, platelet factor-4. In the course of IBD the following changes are observed: an increase in the number of platelets (reactive thrombocytosis), PDW and PCT, reduction in MPV, increased production and excretion of granular content products (P-selectin, GP53, β-TG, PF-4, vWF, fibrinolytic inhibitors). PMID:27117106

  17. Serotonin content of platelets in inflammatory rheumatic diseases. Correlation with clinical activity.

    PubMed

    Zeller, J; Weissbarth, E; Baruth, B; Mielke, H; Deicher, H

    1983-04-01

    Significantly decreased platelet serotonin contents were measured in rheumatoid arthritis, systemic lupus erythematosus (SLE), progressive systemic sclerosis, and mixed connective tissue disease. An inverse relationship between platelet serotonin levels and clinical disease activity was observed in both rheumatoid arthritis and systemic lupus erythematosus. SLE patients with multiple organ involvement showed the lowest platelet serotonin values. No correlation was observed between platelet serotonin contents and nonsteroidal antiinflammatory drug treatment, presence of circulating platelet reactive IgG, or the amount of circulating immune complexes. The results are interpreted as indicating platelet release occurring in vivo during inflammatory episodes of the rheumatic disorders investigated. PMID:6838676

  18. Inflammatory Bowel Disease.

    PubMed

    2016-01-01

    Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed. PMID:26939275

  19. The Case for Increased Physical Activity in Chronic Inflammatory Bowel Disease: A Brief Review.

    PubMed

    Shephard, R J

    2016-06-01

    Regular physical activity reduces the risk of colon cancer, but there is little information on the merits of such activity in the prevention and management of chronic inflammatory bowel disease (CIBD). The present systematic review thus documents current levels of habitual physical activity and aerobic and muscular function in CIBD, and examines the safety, practicality and efficacy of exercise programmes in countering the disease process, correcting functional deficits and enhancing quality of life. A systematic search of the Ovid/Medline database from January 1996 to May 2015 linked the terms physical activity/motor activity/physical fitness/physical training/physical education/training/exercise/exercise therapy with Crohn's disease/colitis/ulcerative colitis/inflammatory bowel disease, supplementing this information by a scanning of reference lists and personal files.12 of 16 published studies show a low level of habitual physical activity in CIBD, with sub-normal values for aerobic power, lean tissue mass and muscular strength. 3 of 4 studies suggest physical activity may reduce the risk of developing IBD, and 11 interventions all note that exercise programmes are well tolerated with some decreases of disease activity, and functional gains leading to an increased health-related quality of life. Moreover, programme compliance rates compare favourably with those seen in the treatment of other chronic conditions. More information on mechanisms is needed, but regular moderate aerobic and/or resistance exercise improves the health status of patients with CIBD both by modulating immune function and by improving physical function. A regular exercise programme should thus become an important component in the management of CIBD. PMID:27116344

  20. Assessment of inflammatory bowel disease activity by technetium 99m phagocyte scanning

    SciTech Connect

    Pullman, W.E.; Sullivan, P.J.; Barratt, P.J.; Lising, J.; Booth, J.A.; Doe, W.F.

    1988-10-01

    Autologous technetium 99m-labeled phagocyte scanning has been used to assess disease activity in inflammatory bowel disease in 51 consecutive patients. Strong correlations were found between the 24-h fecal excretion of isotope and the histologic score of mucosal biopsy specimens (rS = 0.84, p less than 0.001, where rS is Spearman's rank correlation coefficient), and between the 24-h fecal excretion of isotope and a clinical inflammatory bowel disease activity index based on the Crohn's disease activity index (rS = 0.87, p less than 0.001). To develop a clinically useful and objective measure of inflammatory bowel disease activity that did not require a 24-h stool collection, the intensity of bowel uptake on scanning was graded visually from 0 to 4, a ratio of count rates for the region of interest to the iliac crest reference region was calculated, and the rapidity of labeled phagocyte uptake into inflamed bowel was measured as the peak uptake time. Visual grading of disease activity on the scans was validated by comparing it with the ratio of count rates from inflamed bowel regions of interest and those from the iliac crest reference region. The ratio of count rates showed a significant correlation with the clinical disease activity index (r = 0.75, p less than 0.001). The visual scan grade also correlated well with the clinical activity index (r = 0.87, p less than 0.001). Count rates from hourly scans were also used to calculate the time of peak uptake of counts for a given region of interest. There was a strong negative correlation between this peak uptake time and the fecal excretion of isotope (rS = -0.81, p less than 0.001), a clinical activity index (r = -0.60, p less than 0.001), and the histologic score of the mucosal biopsy specimens (r = -0.84, p less than 0.001).

  1. Macrophage Polarization in Inflammatory Diseases

    PubMed Central

    Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

    2014-01-01

    Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases. PMID:24910531

  2. Evolution of Inflammatory Diseases

    PubMed Central

    Okin, Daniel

    2013-01-01

    The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases. PMID:22975004

  3. Nuclear Receptors and Inflammatory Diseases

    PubMed Central

    Wang, Kun; Wan, Yu-Jui Yvonne

    2014-01-01

    It is well known that the steroid hormone glucocorticoid and its nuclear receptor regulate the inflammatory process, a crucial component in the pathophysiological process related to human diseases that include atherosclerosis, obesity and type II diabetes, inflammatory bowel disease, Alzheimer’s disease, multiple sclerosis, and liver tumors. Growing evidence demonstrates that orphan and adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors, liver × receptors, the farnesoid × receptor, NR4As, retinoid × receptors, and the pregnane × receptor, regulate the inflammatory and metabolic profiles in a ligand-dependent or -independent manner in human and animal models. This review summarizes the regulatory roles of these nuclear receptors in the inflammatory process and the underlying mechanisms. PMID:18375823

  4. Ischemic heart disease in systemic inflammatory diseases. An appraisal.

    PubMed

    Gargiulo, Paola; Marsico, Fabio; Parente, Antonio; Paolillo, Stefania; Cecere, Milena; Casaretti, Laura; Pellegrino, Angela Maria; Formisano, Tiziana; Fabiani, Irma; Soricelli, Andrea; Trimarco, Bruno; Perrone-Filardi, Pasquale

    2014-01-01

    Systemic inflammatory diseases are inflammatory syndromes that are associated with increased cardiovascular morbidity and mortality. The link between inflammatory and cardiovascular diseases can be attributed to coexistence of classical risk factors and of inflammatory mechanisms activated in systemic inflammatory diseases and involving the immune system. Yet, clinical implications of these findings are not entirely clear and deeper knowledge and awareness of cardiac involvement in inflammatory diseases are necessary. The aims of this review are to summarize cardiac involvement in systemic inflammatory diseases and to identify areas where evidence is currently lacking that deserve further investigation in the future. PMID:24331863

  5. Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.

    PubMed

    Lampa, Jon; Westman, Marie; Kadetoff, Diana; Agréus, Anna Nordenstedt; Le Maître, Erwan; Gillis-Haegerstrand, Caroline; Andersson, Magnus; Khademi, Mohsen; Corr, Maripat; Christianson, Christina A; Delaney, Ada; Yaksh, Tony L; Kosek, Eva; Svensson, Camilla I

    2012-07-31

    During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments. PMID:22802629

  6. Vitamin D in inflammatory diseases

    PubMed Central

    Wöbke, Thea K.; Sorg, Bernd L.; Steinhilber, Dieter

    2014-01-01

    Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq. PMID:25071589

  7. EFFECT OF PREGNANE XENOBIOTIC RECEPTOR ACTIVATION ON INFLAMMATORY BOWEL DISEASE TREATED WITH RIFAXIMIN.

    PubMed

    Wan, Y C; Li, T; Han, Y-D; Zhang, H-Y; Lin, H; Zhang, B

    2015-01-01

    The causes and pathogenesis of Inflammatory Bowel Disease (IBD) are still not clearly understood. This study aims to prove the important role of rifaximin played in inflammatory reaction caused by abnormity of the intestinal mucosal immune system. Intestinal microflora can greatly promote and maintain the inflammatory reaction of IBD, therefore, antibiotics can be used to treat IBD. Rifaximin is a medicine usually used for local intestinal infection. Many clinical and basic studies have shown that both a single application of rifaximin and the joint application with other medicines could achieve a good efficacy. This paper studied the activation of Pregnane Xenobiotic Receptor (PXR) in treating IBD with rifaximin and analyzed its efficacy in IBD when PXR was involved in the transport of medicine and metabolism. The results prove that rifaximin can not only serve as an anti-microbial drug, but can activate PXR and actually weaken the reaction of IBD. Thus it is safe to say that rifaximin has great potential in treating IBD. PMID:26122229

  8. Measurement of Fractional Exhaled Nitric Oxide as a Marker of Disease Activity in Inflammatory Bowel Disease

    PubMed Central

    Ikonomi, Erkanda; Rothstein, Robin D.; Ehrlich, Adam C.; Friedenberg, Frank K.

    2016-01-01

    Background and Aims Definitive diagnosis of IBD requires endoscopic and pathologic confirmation. These tools are also used to classify disease activity. Our aim was to determine if the fractional exhaled nitric oxide (FeNO) could be utilized to screen for IBD and assess for disease activity. Methods We matched weighted IBD cases and controls from the 2009–2010 NHANES dataset. All subjects underwent measurement of FeNO using standardized techniques. We assessed for potential confounders for FeNO measurement including age, height, and asthma. For IBD subjects, we used the presence of diarrhea, fatigue, and weight loss as a proxy for IBD activity. Laboratory parameters examined to estimate disease activity included anemia (≤ 10 g/dl), iron deficiency (ferritin ≤ 20 ng/ml), hypoalbuminemia (≤ 3.2 g/dl), and CRP (≥ 1.1 mg/dl). Results The weighted sample represented 199,414,901 subjects. The weighted prevalence of IBD was 2,084,895 (1.0%). IBD subjects had nearly the same FeNO level as those without IBD (17.0 ± 16.2 vs. 16.7 ± 14.5 ppb). The odds of a FeNO > 25 ppb was half (OR=0.501; 95% CI 0.497–0.504) for subjects with IBD compared to those without IBD after controlling for confounders. The AUROC curve for FeNO was 0.47 (0.35–0.59). FeNO levels were not higher in patients with laboratory values suggestive of active disease. FeNO levels were higher in IBD patients with diarrhea, rectal urgency, and fatigue but were lower in those with unintentional weight loss. Conclusion Measurement of FeNO does not appear to be useful to screen for IBD or assess disease activity. PMID:27398403

  9. Increasing Patient Activation Could Improve Outcomes for Patients with Inflammatory Bowel Disease.

    PubMed

    Shah, Shawn L; Siegel, Corey A

    2015-12-01

    Inflammatory bowel disease (IBD) is a complex disease process that often requires the integration of skills from various health care providers to adequately meet the needs of patients with IBD. The medical and surgical treatment options for IBD have become more complicated and are frequently a source of angst for both the patient and provider. However, it has become more important than ever to engage patients in navigating the treatment algorithm. Although novel in the IBD world, the concept of patients' becoming more active and effective managers of their care has been well studied in other disease processes such as diabetes mellitus and mental illness. This idea of patient activation refers to a patient understanding his or her role in the care process and having the skill sets and self-reliance necessary to manage his or her own health care. Over the past decade, evidence supporting the role of patient activation in chronic illness has grown, revealing improved health outcomes, enhanced patient experiences, and lower overall costs. Patient activation can be measured, and interventions have been shown to improve levels of activation over time and influence outcomes. A focus on patient activation is very appropriate for patients with IBD because this may potentially serve as a tool for IBD providers to not only improve patient outcomes and experience but also reduce health care costs. PMID:26422517

  10. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease

    PubMed Central

    Zenz, Rainer; Eferl, Robert; Scheinecker, Clemens; Redlich, Kurt; Smolen, Josef; Schonthaler, Helia B; Kenner, Lukas; Tschachler, Erwin; Wagner, Erwin F

    2008-01-01

    Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications. PMID:18226189

  11. Notoginsenoside R1 attenuates experimental inflammatory bowel disease via pregnane X receptor activation.

    PubMed

    Zhang, Jingjing; Ding, Lili; Wang, Baocan; Ren, Gaiyan; Sun, Aning; Deng, Chao; Wei, Xiaohui; Mani, Sridhar; Wang, Zhengtao; Dou, Wei

    2015-02-01

    Notoginsenoside R1 (R1) is the main bioactive component in Panax notoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of R1 on inflammatory bowel disease (IBD). The present study demonstrated that R1 alleviated the severity of dextran sulfate sodium-induced colitis in mice by decreasing the activity of myeloperoxidase, the production of cytokines, the expression of proinflammatory genes, and the phosphorylation of IκB kinase, IκBα, and p65 in the colon. Further studies indicated that R1 dose-dependently activated human/mouse pregnane X receptor (PXR), a known target for decreasing inflammation in IBD, and upregulated the expression of genes involved in xenobiotic metabolism in colorectal cells and the colon. Ligand pocket-filling mutant (S247W/C284W or S247W/C284W/S208W) of the human PXR abrogated the effect of R1 on PXR activation. Time-resolved fluorescence resonance energy transfer PXR competitive binding assay confirmed R1 (ligand) binding affinity. In addition, PXR overexpression inhibited nuclear factor-κB (NF-κB)-luciferase activity, which was potentiated by R1 treatment. PXR knockdown by small interfering RNA demonstrated the necessity of PXR in R1-induced upregulation of the expression of xenobiotic-metabolizing enzymes and downregulation of NF-κB activity. Finally, the anti-inflammatory effect of R1 was confirmed in trinitrobenzene sulfonic acid-induced colitis in mice. These findings suggest that R1 attenuates experimental IBD possibly via the activation of intestinal PXR signaling. PMID:25472953

  12. Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation

    PubMed Central

    Zhang, Jingjing; Ding, Lili; Wang, Baocan; Ren, Gaiyan; Sun, Aning; Deng, Chao; Wei, Xiaohui; Mani, Sridhar

    2015-01-01

    Notoginsenoside R1 (R1) is the main bioactive component in Panax notoginseng, an old herb medicine widely used in Asian countries in the treatment of microcirculatory diseases. However, little is known about the effect of R1 on inflammatory bowel disease (IBD). The present study demonstrated that R1 alleviated the severity of dextran sulfate sodium–induced colitis in mice by decreasing the activity of myeloperoxidase, the production of cytokines, the expression of proinflammatory genes, and the phosphorylation of IκB kinase, IκBα, and p65 in the colon. Further studies indicated that R1 dose-dependently activated human/mouse pregnane X receptor (PXR), a known target for decreasing inflammation in IBD, and upregulated the expression of genes involved in xenobiotic metabolism in colorectal cells and the colon. Ligand pocket–filling mutant (S247W/C284W or S247W/C284W/S208W) of the human PXR abrogated the effect of R1 on PXR activation. Time-resolved fluorescence resonance energy transfer PXR competitive binding assay confirmed R1 (ligand) binding affinity. In addition, PXR overexpression inhibited nuclear factor-κB (NF-κB)–luciferase activity, which was potentiated by R1 treatment. PXR knockdown by small interfering RNA demonstrated the necessity of PXR in R1-induced upregulation of the expression of xenobiotic-metabolizing enzymes and downregulation of NF-κB activity. Finally, the anti-inflammatory effect of R1 was confirmed in trinitrobenzene sulfonic acid–induced colitis in mice. These findings suggest that R1 attenuates experimental IBD possibly via the activation of intestinal PXR signaling. PMID:25472953

  13. Health-related quality of life in adolescents with inflammatory bowel disease depends on disease activity and psychiatric comorbidity.

    PubMed

    Engelmann, G; Erhard, D; Petersen, M; Parzer, P; Schlarb, A A; Resch, F; Brunner, R; Hoffmann, G F; Lenhartz, H; Richterich, A

    2015-04-01

    Adolescent patients with inflammatory bowel disease (IBD) show an increased risk for behavioral and emotional dysfunction. Health-related quality of life (HRQoL) is influenced by medical illnesses, as well as by psychiatric disorders, but for adolescents with IBD, the extent to which HRQoL is influenced by these two factors is unclear. For 47 adolescent IBD patients, we analyzed disease activity, HRQoL and whether or not a psychiatric disorder was present. Disease activity was estimated using pediatric Ulcerative Colitis Activity Index and pediatric Crohn's Disease Activity Index. The IMPACT-III and the EQ-5D were used to measure HRQoL and QoL, respectively. In addition, patient and parent diagnostic interviews were performed. 55.3 % patients fulfilled DSM-IV criteria for one or more psychiatric disorders. In all patients, psychiatric comorbidity together with disease activity contributed to a reduction in quality of life. Adolescents with IBD are at a high risk for clinically relevant emotional or behavioral problems resulting in significantly lower HRQoL. We conclude that accessible, optimally structured psychotherapeutic and/or psychiatric help is needed in adolescent patients with IBD. PMID:24838299

  14. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases.

    PubMed

    Serriari, N-E; Eoche, M; Lamotte, L; Lion, J; Fumery, M; Marcelo, P; Chatelain, D; Barre, A; Nguyen-Khac, E; Lantz, O; Dupas, J-L; Treiner, E

    2014-05-01

    Inflammatory bowel diseases are characterized by a deregulated immune response targeting the gut bacterial flora. Mucosal-associated invariant T (MAIT) cells are major histocompatibility complex (MHC) class Ib-restricted innate-like lymphocytes with anti-bacterial functions. They display an effector/memory phenotype and are found in large numbers in the blood, mucosae and liver. They have also been implicated in inflammatory diseases such as multiple sclerosis. Therefore, we aimed to analyse the possible involvement of MAIT cells in Crohn's disease (CD) and ulcerative colitis (UC). To this end, a phenotypical and functional analysis of MAIT cells isolated from the blood of healthy subjects, CD and UC patients was undertaken. MAIT cells were also quantified in ileal biopsies of CD patients. The frequency of blood MAIT cells was specifically reduced in IBD patients compared with healthy donors, whereas it was dramatically greater in the inflamed versus healthy tissue. MAIT cells were activated as they expressed significantly more the Ki67 antigen, and this was accompanied by phenotypical changes such as increased expression of natural killer (NK)G2D and B and T lymphocyte attenuator (BTLA). Finally, in-vitro-activated MAIT cells from CD and UC patients secreted significantly more interleukin (IL)-17, together with a decreased interferon (IFN)-γ in CD but an increased IL-22 in UC. These data show that MAIT cells are activated in IBD, which results in an increased recruitment towards the inflamed tissues, an altered phenotype and a switch in the pattern of cytokine secretion. This is the first demonstration that MAIT cells are immune players in IBD, whose precise functions in this context need to be addressed. PMID:24450998

  15. Immunoregulatory function of human intestinal mucosa lymphoid cells: evidence for enhanced suppressor cell activity in inflammatory bowel disease.

    PubMed Central

    Fiocchi, C; Youngman, K R; Farmer, R G

    1983-01-01

    Abnormalities in immune regulation at the gut level may be relevant to the pathogenesis of inflammatory bowel disease, but little is known about the immunoregulatory properties of intestinal mononuclear cells. Therefore, we wished to see if lymphoid cells derived from the lamina propria of surgically resected bowel specimens have any modulatory effect upon the immune response of peripheral blood mononuclear cells from patients with ulcerative colitis or Crohn's disease. When autologous peripheral blood and intestinal lamina propria lymphoid cells were mixed at different ratios and cultured in the presence of phytohaemagglutinin, we were able to show that intestinal mononuclear cells had the capacity to modify the mitogenic response of the cultured cells. These intestinal immunoregulatory cells, when obtained from mucosa affected by inflammatory bowel disease, express a significantly enhanced suppressor cell activity as compared with those from non-inflamed control mucosa. Such suppressor cell activity varies with cell concentration and requires cell proliferation, but it is independent of anatomical origin (small vs large bowel), type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease) or immunosuppressive therapy. These findings point to an important functional difference between inflammatory bowel disease and control intestinal mucosa mononuclear cells. The enhanced suppressor activity of lamina propria mononuclear cells may be associated with impairment of cell-mediated immunity at the gut level. This may be related to the pathogenesis of inflammatory bowel disease by leading to defective intestinal immune regulatory events, which may not be detectable at the peripheral level. PMID:6223862

  16. Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

    PubMed Central

    Kwapisz, Lukasz; Mosli, Mahmoud; Chande, Nilesh; Yan, Brian; Beaton, Melanie; Micsko, Jessica; Mennill, Pauline W.; Barnett, William; Bax, Kevin; Ponich, Terry; Howard, John; Tirolese, Anthony; Lannigan, Robert; Gregor, James

    2015-01-01

    Background and Aim: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. Patients and Methods: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver–operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. Results: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. Conclusions: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD. PMID:26655130

  17. Vitamin D and inflammatory diseases

    PubMed Central

    Yin, Kai; Agrawal, Devendra K

    2014-01-01

    Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed. PMID:24971027

  18. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  19. Clinicians’ guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease

    PubMed Central

    Bressler, Brian; Panaccione, Remo; Fedorak, Richard N; Seidman, Ernest G

    2015-01-01

    BACKGROUND: Objective monitoring of the severity of inflammation in patients with inflammatory bowel disease (IBD) is an essential part of disease management. However, repeat endoscopy to define extent and severity of inflammation is not practical. Fecal calprotectin (FC) is a biomarker that can be used as a surrogate test to distinguish inflammatory from noninflammatory gastrointestinal disease. METHODS: A targeted search of the literature regarding FC, focusing primarily on the past three years, was conducted to develop practical clinical guidance on the current utility of FC in the routine management of IBD patients. RESULTS: It is recommended that samples for FC testing be obtained from the first bowel excretion of the day. FC testing should be used as standard of care to accurately confirm inflammation and ‘real-time’ disease activity when a clinician suspects an IBD flare. Although FC is a reliable marker of inflammation, its role in routine monitoring in improving long-term outcomes has not yet been fully assessed. Based on available evidence, the authors suggest the following cut-off values and management strategies: when FC levels are <50 μg/g to 100 μg/g, quiescent disease is likely and therapy should be continued; when FC levels are >100 μg/g to 250 μg/g, inflammation is possible and further testing (eg, colonoscopy) is required to confirm inflammation; and when FC levels are >250 μg/g, active inflammation is likely and strategies to control inflammation should be initiated (eg, optimizing current therapies or switching to an alternative therapy). DISCUSSION: FC is a useful biomarker to accurately assess the degree of inflammation and should be incorporated into the management of patients with IBD. PMID:26125109

  20. Inflammatory bowel disease.

    PubMed

    Szigethy, Eva; McLafferty, Laura; Goyal, Alka

    2010-04-01

    This article reviews the etiology, clinical characteristics, and treatment of inflammatory bowel disease (IBD) and associated psychological sequelae in children and adolescents with this lifelong disease. Pediatric-onset IBD, consisting of Crohn's disease and ulcerative colitis, has significant medical morbidity and in many young persons is also associated with psychological and psychosocial challenges. Depression and anxiety are particularly prevalent and have a multifaceted etiology, including IBD-related factors such as cytokines and steroids used to treat IBD and psychosocial stress. A growing number of empirically supported interventions, such as cognitive behavioral therapy, hypnosis, and educational resources, help youth and their parents cope with IBD as well as the psychological and psychosocial sequelae. While there is convincing evidence that such interventions can help improve anxiety, depression, and health-related quality of life, their effects on IBD severity and course await further study. PMID:20478501

  1. Inflammatory bowel disease.

    PubMed

    Szigethy, Eva; McLafferty, Laura; Goyal, Alka

    2011-08-01

    This article reviews the etiology, clinical characteristics, and treatment of inflammatory bowel disease (IBD) and associated psychological sequelae in children and adolescents with this lifelong disease. Pediatric-onset IBD, consisting of Crohn's disease and ulcerative colitis, has significant medical morbidity and in many young persons is also associated with psychological and psychosocial challenges. Depression and anxiety are particularly prevalent and have a multifaceted etiology, including IBD-related factors such as cytokines and steroids used to treat IBD and psychosocial stress. A growing number of empirically supported interventions, such as cognitive behavioral therapy, hypnosis, and educational resources, help youth and their parents cope with IBD as well as the psychological and psychosocial sequelae. While there is convincing evidence that such interventions can help improve anxiety, depression, and health-related quality of life, their effects on IBD severity and course await further study. PMID:21855713

  2. Inflammatory Bowel Disease

    PubMed Central

    Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S.

    2015-01-01

    Insights into inflammatory bowel disease (IBD) are advancing rapidly owing to immunologic investigations of a plethora of animal models of intestinal inflammation, ground-breaking advances in the interrogation of diseases that are inherited as complex genetic traits, and the development of culture-independent methods to define the composition of the intestinal microbiota. These advances are bringing a deeper understanding to the genetically determined interplay between the commensal microbiota, intestinal epithelial cells, and the immune system and the manner in which this interplay might be modified by relevant environmental factors in the pathogenesis of IBD. This review examines these interactions and, where possible, potential lessons from IBD-directed, biologic therapies that may allow for elucidation of pathways that are central to disease pathogenesis in humans. PMID:20192811

  3. Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion

    SciTech Connect

    Saverymuttu, S.H.; Camilleri, M.; Rees, H.; Lavender, J.P.; Hodgson, H.J.; Chadwick, V.S.

    1986-05-01

    Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease. The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation. We now report a prospective study comparing 111In-granulocyte scanning with endoscopy, histology, and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease. In 52 patients with Crohn's disease or ulcerative colitis, disease extent and severity were assessed macroscopically, histologically, or by scanning using a numerical grading system. Excellent correlations were found between both endoscopy and histology and 111In scans (r = 0.90 (endoscopy) and r = 0.90 (histology) for extent; r = 0.86 and r = 0.91 for disease activity). Severity graded by scanning also showed a close correlation with fecal 111In-granulocyte excretion (r = 0.90). Indium 111-granulocyte scans are a rapid, accurate, noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease.

  4. [Inflammatory Bowel Disease Competence Network].

    PubMed

    Schreiber, Stefan; Hartmann, Heinz; Kruis, Wolfgang; Kucharzik, Torsten; Mudter, Jonas; Siegmund, Britta; Stallmach, Andreas; Witte, Christine; Fitzke, Klaus; Bokemeyer, Bernd

    2016-04-01

    The Inflammatory Bowel Disease Competence Network is a network of more than 500 physicians and scientists from university clinics, hospitals and gastroenterology practices. The focus extends from the two major forms of inflammatory bowel diseases, Crohn's disease and ulcerative colitis, into other chronic inflammatory conditions affecting the intestine, including coeliac disease and microscopic colitis. The network translates basic science discoveries (in particular in the molecular epidemiology research) into innovative diagnostics and therapy. Through its strong networking structures it supports a continuous process to improve quality and standardisation in patient care that is implemented in close interaction with European networks addressing this disease group.Optimisation of patient care based on scientifically proven evidence is a main focus of the network. Therefore, it supports and coordinates translational research and infrastructure projects that investigate aetiology, improvement of diagnostic methods, and development of new or improved use of established therapies. Members participate in various training projects, thus ensuring the rapid transfer of research results into clinical practice.The competence network cooperates with the main patient organisations to engage patients in all levels of activities. The network and the patient organisations have interest in promoting public awareness about the disease entities, because their importance and burden is underestimated in non-specialised medical fields and among the general public. PMID:26968556

  5. Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes

    PubMed Central

    2009-01-01

    Background Research has shown that fecal biomarkers are useful to assess the activity of inflammatory bowel disease (IBD). The aim of the study is: to evaluate the efficacy of the fecal lactoferrin and calprotectin as indicators of inflammatory activity. Findings A total of 78 patients presenting inflammatory bowel disease were evaluated. Blood tests, the Crohn's Disease Activity Index (CDAI), Mayo Disease Activity Index (MDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were used for the clinical and endoscopic evaluation. Two tests were performed on the fecal samples, to check the levels of calprotectin and lactoferrin. The performance of these fecal markers for detection of inflammation with reference to endoscopic and histological inflammatory activity was assessed and calculated sensitivity, specificity, accuracy. A total of 52 patient's samples whose histological evaluations showed inflammation, 49 were lactoferrin-positive, and 40 were calprotectin-positive (p = 0.000). Lactoferrin and calprotectin findings correlated with C-reactive protein in both the CD and UC groups (p = 0.006; p = 0.000), with CDAI values (p = 0.043; 0.010), CDEIS values in DC cases (p = 0,000; 0.000), and with MDAI values in UC cases (p = 0.000). Conclusion Fecal lactoferrin and calprotectin are highly sensitive and specific markers for detecting intestinal inflammation. Levels of fecal calprotectin have a proportional correlation to the degree of inflammation of the intestinal mucosa. PMID:19874614

  6. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging.

    PubMed

    Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

    2016-01-01

    Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit. PMID:27406831

  7. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

    NASA Astrophysics Data System (ADS)

    Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

    2016-07-01

    Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit.

  8. Beyond endoscopic assessment in inflammatory bowel disease: real-time histology of disease activity by non-linear multimodal imaging

    PubMed Central

    Chernavskaia, Olga; Heuke, Sandro; Vieth, Michael; Friedrich, Oliver; Schürmann, Sebastian; Atreya, Raja; Stallmach, Andreas; Neurath, Markus F.; Waldner, Maximilian; Petersen, Iver; Schmitt, Michael; Bocklitz, Thomas; Popp, Jürgen

    2016-01-01

    Assessing disease activity is a prerequisite for an adequate treatment of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis. In addition to endoscopic mucosal healing, histologic remission poses a promising end-point of IBD therapy. However, evaluating histological remission harbors the risk for complications due to the acquisition of biopsies and results in a delay of diagnosis because of tissue processing procedures. In this regard, non-linear multimodal imaging techniques might serve as an unparalleled technique that allows the real-time evaluation of microscopic IBD activity in the endoscopy unit. In this study, tissue sections were investigated using the non-linear multimodal microscopy combination of coherent anti-Stokes Raman scattering (CARS), two-photon excited auto fluorescence (TPEF) and second-harmonic generation (SHG). After the measurement a gold-standard assessment of histological indexes was carried out based on a conventional H&E stain. Subsequently, various geometry and intensity related features were extracted from the multimodal images. An optimized feature set was utilized to predict histological index levels based on a linear classifier. Based on the automated prediction, the diagnosis time interval is decreased. Therefore, non-linear multimodal imaging may provide a real-time diagnosis of IBD activity suited to assist clinical decision making within the endoscopy unit. PMID:27406831

  9. Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease.

    PubMed

    He, Zhangxiu; Si, Yu; Jiang, Tao; Ma, Ruishuang; Zhang, Yan; Cao, Muhua; Li, Tao; Yao, Zhipeng; Zhao, Lu; Fang, Shaohong; Yu, Bo; Dong, Zengxiang; Thatte, Hemant S; Bi, Yayan; Kou, Junjie; Yang, Shufen; Piao, Daxun; Hao, Lirong; Zhou, Jin; Shi, Jialan

    2016-04-01

    Inflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. Wright-Giemsa and immunofluorescence staining demonstrated that the elevated NETs were released by activated IBD neutrophils or by control neutrophils treated with IBD sera obtained from patients with the active disease. MPs and MP-origin cells in IBD groups, especially in active stage, markedly shortened coagulation time and had increased levels of fibrin, thrombin and FXa production as assessed by coagulation function assays. Importantly, we found that on stimulated ECs, PS rich membranes provided binding sites for FXa and FVa, promoting fibrin formation while TNF blockage or IgG depletion attenuated this effect. Treatment of control neutrophils with TNF and isolated IgG from PR3-ANCA-positive active IBD patients also resulted in the release of NETs. Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients. PMID:26660948

  10. Therapeutic Role of Rifaximin in Inflammatory Bowel Disease: Clinical Implication of Human Pregnane X Receptor Activation

    PubMed Central

    Cheng, Jie; Shah, Yatrik M.; Ma, Xiaochao; Pang, Xiaoyan; Tanaka, Toshiya; Kodama, Tatsuhiko; Krausz, Kristopher W.

    2010-01-01

    Human pregnane X receptor (PXR) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a human PXR activator, is in clinical trials for treatment of IBD and has demonstrated efficacy in Crohn's disease and active ulcerative colitis. In the current study, the protective and therapeutic role of rifaximin in IBD and its respective mechanism were investigated. PXR-humanized (hPXR), wild-type, and Pxr-null mice were treated with rifaximin in the dextran sulfate sodium (DSS)-induced and trinitrobenzene sulfonic acid (TNBS)-induced IBD models to determine the protective function of human PXR activation in IBD. The therapeutic role of rifaximin was further evaluated in DSS-treated hPXR and Pxr-null mice. Results demonstrated that preadministration of rifaximin ameliorated the clinical hallmarks of colitis in DSS- and TNBS-treated hPXR mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. In addition, higher survival rates and recovery from colitis symptoms were observed in hPXR mice, but not in Pxr-null mice, when rifaximin was administered after the onset of symptoms. Nuclear factor κB (NF-κB) target genes were markedly down-regulated in hPXR mice by rifaximin treatment. In vitro NF-κB reporter assays demonstrated inhibition of NF-κB activity after rifaximin treatment in colon-derived cell lines expressing hPXR. These findings demonstrated the preventive and therapeutic role of rifaximin on IBD through human PXR-mediated inhibition of the NF-κB signaling cascade, thus suggesting that human PXR may be an effective target for the treatment of IBD. PMID:20627999

  11. Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases

    PubMed Central

    Qian, Feng; Deng, Jing; Wang, Gang; Ye, Richard D.; Christman, John W.

    2016-01-01

    Mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2) is exclusively regulated by p38 MAPK in vivo. Upon activation of p38 MAPK, MK2 binds with p38 MAPK, leading to phosphorylation of TTP, Hsp27, Akt and Cdc25 that are involved in regulation of various essential cellular functions. In this review, we discuss current knowledge about molecular mechanisms of MK2 in regulation of TNF-α production, NADPH oxidase activation, neutrophil migration, and DNA-damage-induced cell cycle arrest which are involved in the molecular pathogenesis of acute lung injury, pulmonary fibrosis, and non-small-cell lung cancer. Collectively current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways is a potential therapeutic strategy for treatment of inflammatory and fibrotic lung diseases and lung cancer. PMID:26119506

  12. Inflammatory bowel disease: Pathogenesis

    PubMed Central

    Zhang, Yi-Zhen; Li, Yong-Yu

    2014-01-01

    Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas. PMID:24415861

  13. Elastic Scattering Spectroscopy as an Optical Marker of Inflammatory Bowel Disease Activity and Subtypes

    PubMed Central

    Rodriguez-Diaz, Eladio; Atkinson, Christopher; Jepeal, Lisa I.; Berg, Adam; Huang, Christopher S.; Cerda, Sandra R.; O’Brien, Michael J.; Bigio, Irving J.; Farraye, Francis A.; Singh, Satish K.

    2016-01-01

    Background In 10% to 15% of individuals, inflammatory bowel disease (IBD) is difficult to classify as ulcerative colitis (UC) or Crohn’s disease (CD). Previous work has demonstrated that probe-based elastic scattering spectroscopy (ESS) can produce spectra, informed by parameters like tissue ultrastructure and hemoglobin content, capable of differentiating pathologies. This study investigates whether ESS is an in vivo optical biomarker for the presence, activity, and type of IBD in the colon. Methods Pilot study, a retrospective data analysis. ESS spectra of endoscopically normal and inflamed colon were obtained from 48 patients with IBD and 46 non-IBD controls. Measurements from patients with IBD were categorized as CD or UC based on clinical diagnosis. Spectra were analyzed using high-dimensional methods. Leave-one-patient-out cross-validation was used to obtain diagnostic performance estimates. Results Patients with IBD were distinguishable from non-IBD controls with a sensitivity of 0.93 and specificity of 0.91 based on readings from endoscopically normal mucosa, and 0.94 and 0.93 from inflamed mucosa. In patients with IBD, histologically normal and inflamed colon were distinguishable with per-class accuracies of 0.83 and 0.89, respectively; histologically normal from inactive inflammation with accuracies of 0.73 and 0.89, respectively; and inactive from active colitis with accuracies of 0.87 and 0.84, respectively. The diagnosis of CD versus UC was made with per-class accuracies of 0.92 and 0.87 in normal and 0.87 and 0.85 in inflamed mucosa, respectively. Conclusions ESS, a simple, low-cost clinically friendly optical biopsy modality, has the potential to enhance the endoscopic assessment of IBD and its activity in real time and may help to distinguish CD from UC. PMID:24798637

  14. Oxidative DNA damage and antioxidant activity in patients with inflammatory bowel disease.

    PubMed

    Dincer, Yildiz; Erzin, Yusuf; Himmetoglu, Solen; Gunes, Kezban Nur; Bal, Kadir; Akcay, Tülay

    2007-07-01

    Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. Endogenous antioxidant enzymes prevent the formation of these harmful products. Oxidative DNA damage and endogenous antioxidant defense were determined in patients with inflammatory bowel disease (IBD). Plasma levels of 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide (NO) and plasma activities of glutathione peroxidase (G-Px) and superoxide dismutase (SOD) were determined in patients with IBD by ELISA and spectrophotometric assay, respectively. Plasma levels of 8-OHdG, SOD, and G-Px activity were found to be increased in the patient group compared to the control group (P < 0.02, P < 0.001, and P < 0.001, respectively), whereas NO was unchanged. 8-OHdG level was found to be weakly correlated with age, NO, and SOD. The results show increased DNA damage in patients with IBD. This may explain the increased risk of developing colon cancer in these patients. PMID:17393334

  15. Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells

    PubMed Central

    Baumgart, D C; Metzke, D; Schmitz, J; Scheffold, A; Sturm, A; Wiedenmann, B; Dignass, A U

    2005-01-01

    Background: Breakdown of tolerance against the commensal microflora is believed to be a major factor in the pathogenesis of inflammatory bowel disease (IBD). Dendritic cells (DC) have been implicated in this process in various animal models, but data on human DC in IBD are very limited. Aim: To characterise plasmacytoid DC (PDC) and myeloid DC (MDC) in patients with active versus inactive IBD and healthy controls. Patients and Methods: Peripheral blood was obtained from 106 patients (Crohn’s disease (CD) n = 49, ulcerative colitis (UC) n = 57) and healthy controls (n = 19). Disease activity was scored using the modified Truelove Witts (MTWSI) for UC and the Harvey Bradshaw severity indices (HBSI) for CD. Four colour flow cytometric analysis was used to identify, enumerate, and phenotype DC. DC from patients with acute flare ups and healthy controls were cultured and stimulated with CpG ODN 2006 or lipopolysaccharide (LPS). Results: IBD patients in remission (PDC UC, 0.39%; CD, 0.35%; MDC-1 UC, 0.23%; CD, 0.22% of PBMC) have slightly lower numbers of circulating DC compared with healthy controls (PDC 0.41%, MDC-1 0.25% of PBMC). In acute flare ups IBD patients experience a significant drop of DC (PDC UC, 0.04%; CD, 0.11%; MDC-1 UC, 0.11%; CD, 0.14% of PBMC) that correlates with disease activity (correlation coefficients: PDC MTWSI, 0.93; HBSI, 0.79; MDC-1 MTWSI, 0.75; HBSI, 0.81). Moreover, both express α4β7 integrin and display an immature phenotype. Freshly isolated PDC and MDC-1 from untreated flaring IBD patients express higher baseline levels of CD86 which increases further in culture and upon stimulation compared with healthy controls. Conclusion: IBD patients lack immature blood DC during flare ups which possibly migrate to the gut. An aberrant response to microbial surrogate stimuli suggests a disturbed interaction with commensals. PMID:15647187

  16. Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Dhillon, Sandeep S; Mastropaolo, Lucas A; Murchie, Ryan; Griffiths, Christopher; Thöni, Cornelia; Elkadri, Abdul; Xu, Wei; Mack, Amanda; Walters, Thomas; Guo, Conghui; Mack, David; Huynh, Hien; Baksh, Shairaz; Silverberg, Mark S; Brumell, John H; Snapper, Scott B; Muise, Aleixo M

    2014-01-01

    OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production. PMID:24430113

  17. Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI.

    PubMed

    Kadayakkara, Deepak K; Ranganathan, Sarangarajan; Young, Won-Bin; Ahrens, Eric T

    2012-04-01

    Macrophages have an important role in the pathogenesis of most chronic inflammatory diseases. A means of non-invasively quantifying macrophage migration would contribute significantly towards our understanding of chronic inflammatory processes and aid the evaluation of novel therapeutic strategies. We describe the use of a perfluorocarbon tracer reagent and in vivo (19)F magnetic resonance imaging (MRI) to quantify macrophage burden longitudinally. We apply these methods to evaluate the severity and three-dimensional distribution of macrophages in a murine model of inflammatory bowel disease (IBD). MRI results were validated by histological analysis, immunofluorescence and quantitative real-time polymerase chain reaction. Selective depletion of macrophages in vivo was also performed, further validating that macrophage accumulation of perfluorocarbon tracers was the basis of (19)F MRI signals observed in the bowel. We tested the effects of two common clinical drugs, dexamethasone and cyclosporine A, on IBD progression. Whereas cyclosporine A provided mild therapeutic effect, unexpectedly dexamethasone enhanced colon inflammation, especially in the descending colon. Overall, (19)F MRI can be used to evaluate early-stage inflammation in IBD and is suitable for evaluating putative therapeutics. Due to its high macrophage specificity and quantitative ability, we envisage (19)F MRI having an important role in evaluating a wide range of chronic inflammatory conditions mediated by macrophages. PMID:22330343

  18. Endothelial Dysfunction in Chronic Inflammatory Diseases

    PubMed Central

    Steyers, Curtis M.; Miller, Francis J.

    2014-01-01

    Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population. PMID:24968272

  19. [Correlation between clinical parameters and quantitative analysis of inflammatory infiltrate. Importance in the diagnosis of active periodontal disease].

    PubMed

    Mendieta Fiter, C

    1989-05-01

    Recent studies have indicated that the destruction in chronic periodontal disease occurs in relatively short periods of time which are followed of prolonged periods of inactivity. These bursts of activity are characterized by an increase in the inflammatory reaction. It has been the purpose of this paper to study the correlation between the clinical measurements of periodontal disease and the histomorphometric quantification of areas of dense inflammatory infiltrate. The results of this study show that the clinical parameters that measure gingival inflammation or loss of periodontal attachment are useful to distinguish pathology from normal (p less than 0.003), but lack sensitivity to detect burst of periodontal disease activity (p greater than 0.05). PMID:2489938

  20. Probiotics and inflammatory bowel diseases

    PubMed Central

    Bai, A‐P; Ouyang, Q

    2006-01-01

    Enteric microflora profiles vary considerably between active inflammatory bowel diseases (IBD) and healthy conditions. Intestinal microflora may partake in the pathogenesis of IBD by one or some ways: specific pathogenic infection induces abnormal intestinal mucosal inflammation; aberrant microflora components trigger the onset of IBD; abnormal host immune response loses normal immune tolerance to luminal components; luminal antigens permeate through the defective mucosal barrier into mucosal lamina propria and induce abnormal inflammatory response. Preliminary studies suggest that administration of probiotics may be benefit for experimental colitis and clinical trials for IBD. Researches have been studying the function of probiotics. Introduction of probiotics can balance the aberrant enteric microflora in IBD patients, and reinforce the various lines of intestinal defence by inhibiting microbial pathogens growth, increasing intestinal epithelial tight junction and permeability, modulating immune response of intestinal epithelia and mucosal immune cells, secreting antimicrobial products, decomposing luminal pathogenic antigens. PMID:16754706

  1. [Inflammatory bowel disease and pregnancy].

    PubMed

    Parfenov, A I

    2012-01-01

    Inflammatory bowel disease (IBD) in pregnant women in their characteristics do not differ from general population, unless they had operations on the pelvic organs. Women with a first pregnancy, regardless of the activity of IBD have an increased risk of adverse pregnancy and high risk births. Most treatment methods are compatible with pregnancy and breastfeeding. Women affected by IBD should discuss their plans for pregnancy with the doctor first in order to know the possible dangers. Every patient in the IBD during pregnancy must be observed by a gastroenterologist, accoucheur and pediatrician to ensure peace of mother and child. PMID:22830229

  2. Impact of inflammatory bowel disease on disability.

    PubMed

    Büsch, Katharina; Sonnenberg, Amnon; Bansback, Nick

    2014-10-01

    Inflammatory bowel disease can impact individuals at a young age, thus compromising their work productivity. Besides the inability to engage in gainful work, the concept of disability also relates to the patients' diminished ability to undertake household and social activities. A literature search was performed of recent literature, and all articles containing information about the impact of inflammatory bowel disease on disability or any work-related outcomes were included. Recent studies suggest that 9 to 19% of inflammatory bowel disease patients suffer from short-term absences from work and 19 to 22% are on long-term disability. Crohn's disease patients reported being more affected by their disease than ulcerative colitis patients. A comparison of results from different studies is difficult due to the lack of consensus on how to define and measure disability. Additional research is needed to better quantify disability in inflammatory bowel disease patients. PMID:25231757

  3. Selenium and inflammatory bowel disease.

    PubMed

    Kudva, Avinash K; Shay, Ashley E; Prabhu, K Sandeep

    2015-07-15

    Dietary intake of the micronutrient selenium is essential for normal immune functions. Selenium is cotranslationally incorporated as the 21st amino acid, selenocysteine, into selenoproteins that function to modulate pathways involved in inflammation. Epidemiological studies have suggested an inverse association between selenium levels and inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis that can potentially progress to colon cancer. However, the underlying mechanisms are not well understood. Here we summarize the current literature on the pathophysiology of IBD, which is multifactorial in origin with unknown etiology. We have focused on a few selenoproteins that mediate gastrointestinal inflammation and activate the host immune response, wherein macrophages play a pivotal role. Changes in cellular oxidative state coupled with altered expression of selenoproteins in macrophages drive the switch from a proinflammatory phenotype to an anti-inflammatory phenotype to efficiently resolve inflammation in the gut and restore epithelial barrier integrity. Such a phenotypic plasticity is accompanied by changes in cytokines, chemokines, and bioactive metabolites, including eicosanoids that not only mitigate inflammation but also partake in restoring gut homeostasis through diverse pathways involving differential regulation of transcription factors such as nuclear factor-κB and peroxisome proliferator-activated receptor-γ. The role of the intestinal microbiome in modulating inflammation and aiding in selenium-dependent resolution of gut injury is highlighted to provide novel insights into the beneficial effects of selenium in IBD. PMID:26045617

  4. Scintigraphic assessment of indium-111-labeled granulocyte splenic pooling: A new approach to inflammatory bowel disease activity

    SciTech Connect

    Loreal, O.; Moisan, A.; Bretagne, J.F.; LeCloirec, J.; Raoul, J.L.; Gastard, J.; Herry, J.Y. )

    1990-09-01

    We have conducted a prospective study into the sensitivity and the specificity of the fall in splenic activity (FSA) as an index of activity in inflammatory bowel disease (IBD). FSA was measured on scintiscans obtained at 3 and 24 hr postinjection of indium-111-labeled granulocytes. One hundred and twenty-two scans were acquired in 96 patients who were divided into six groups: Gr. I = normal volunteers (n = 10); Gr. II = inflammatory rheumatism (n = 10); Gr. III = abscesses (n = 17); Gr. IV = ulcerative colitis (UC: n = 23); Gr. V = colonic Crohn's disease (CCD: n = 22); and Gr. VI = ileal Crohn's disease (ICD: n = 14). FSA for Groups I and II was constantly below 10%, but it was increased in the other four groups (abscesses: 39% +/- 12%; UC: 35% +/- 13.5%; CCD: 23.7% +/- 14.7%; ICD: 21.5% +/- 11.7%). There was a significant correlation between fecal excretion of 111In (FEI) and FSA in patients with IBD (UC: r = 0.71, p less than 0.001; CCD: r = 0.74, p less than 0.001; ICD: r = 0.43, p less than 0.001). FSA was followed in 16 patients with IBD after medical treatment and there was a significant correlation between variations in FSA and in FEI (r = 0.879, p less than 0.001). FSA is a very sensitive although nonspecific index of disease activity in IBD and may replace FEI in the assessment of IBD activity.

  5. Cannabis for inflammatory bowel disease.

    PubMed

    Naftali, Timna; Mechulam, Raphael; Lev, Lihi Bar; Konikoff, Fred M

    2014-01-01

    The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use. PMID:24969296

  6. Pain and Inflammatory Bowel Disease

    PubMed Central

    Bielefeldt, Klaus; Davis, Brian; Binion, David G.

    2010-01-01

    Abdominal pain is a common symptom of inflammatory bowel disease (IBD: Crohn’s disease, ulcerative colitis). Pain may arise from different mechanisms, which can include partial blockage and gut distention as well as severe intestinal inflammation. A majority of patients suffering from acute flares of IBD will experience pain, which will typically improve as disease activity decreases. However, a significant percentage of IBD patients continue experiencing symptoms of pain despite resolving inflammation and achieving what appears to be clinical remission. Current evidence suggests that sensory pathways sensitize during inflammation, leading to persistent changes in afferent neurons and central nervous system pain processing. Such persistent pain is not only a simple result of sensory input. Pain processing and even the activation of sensory pathways is modulated by arousal, emotion, and cognitive factors. Considering the high prevalence of iatrogenic as well as essential neuropsychiatric comorbidities including anxiety and depression in IBD patients, these central modulating factors may significantly contribute to the clinical manifestation of chronic pain. The improved understanding of peripheral and central pain mechanisms is leading to new treatment strategies that view pain as a biopsychosocial problem. Thus, improving the underlying inflammation, decreasing the excitability of sensitized afferent pathways, and altering emotional and/or cognitive functions may be required to more effectively address the difficult and disabling disease manifestations. PMID:19130619

  7. Managing inflammatory bowel disease in adolescent patients.

    PubMed

    Bishop, J; Lemberg, D A; Day, As

    2014-01-01

    Increasing numbers of adolescents are being diagnosed with Crohn's disease or ulcerative colitis, the two main subtypes of inflammatory bowel disease. These young people face many short- and long-term challenges; one or more medical therapies may be required indefinitely; their disease may have great impact, in terms of their schooling and social activities. However, the management of adolescents with one of these incurable conditions needs to encompass more than just medical therapies. Growth, pubertal development, schooling, transition, adherence, and psychological well-being are all important aspects. A multidisciplinary team setting, catering to these components of care, is required to ensure optimal outcomes in adolescents with inflammatory bowel disease. PMID:24729736

  8. Inflammatory Bowel Disease (IBD) and Pregnancy

    MedlinePlus

    ... Inflammatory Bowel Disease? Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). Symptoms include abdominal ... become pregnant? Women with ulcerative colitis and inactive Crohn’s disease are as likely to become pregnant as women ...

  9. Anti-Inflammatory Activity of Fruit Fractions in Vitro, Mediated through Toll-Like Receptor 4 and 2 in the Context of Inflammatory Bowel Disease

    PubMed Central

    Nasef, Noha Ahmed; Mehta, Sunali; Murray, Pamela; Marlow, Gareth; Ferguson, Lynnette R.

    2014-01-01

    Pattern recognition receptors such as Toll-Like Receptor 2 (TLR2) and 4 (TLR4) are important in detecting and responding to stress and bacterial stimuli. Defect or damage in the TLR2 and TLR4 pathways can lead to sustained inflammation, characteristic of inflammatory bowel disease (IBD). The goal of this study was to identify fruit fractions that can be tested further to develop them as complementary therapies for IBD. In order to do this, we identified fruit fractions that mediate their anti-inflammatory response through the TLR4 and TLR2 pathway. Human Embryonic Kidney (HEK)-hTLR4 and hTLR2 cells were stimulated with their respective ligands to induce inflammation. These cells were treated with one of the 12 fractionated fruits and the inflammatory effect measured. 10 of the fruits came up as anti-inflammatory in the hTLR4 assay and nine in the hTLR2 assays. Many of the fruit fractions mediated their anti-inflammatory actions either mainly in their hydrophobic fractions (such as elderberry) or hydrophilic fractions (such as red raspberry), or both. The strongest anti-inflammatory effects were seen for feijoa and blackberry. This study shows that fruits can have multiple fractions eliciting anti-inflammatory effects in a pathway specific manner. This suggests that the compounds found in fruits can act together to produce health benefits by way of reducing inflammation. Exploiting this property of fruits can help develop complimentary therapies for inflammatory diseases. PMID:25415606

  10. IL-18 and Cutaneous Inflammatory Diseases

    PubMed Central

    Lee, Ji hyun; Cho, Dae Ho; Park, Hyun Jeong

    2015-01-01

    Interleukin (IL)-18, an IL-1 family cytokine, is a pleiotropic immune regulator. IL-18 plays a strong proinflammatory role by inducing interferon (IFN)-γ. Previous studies have implicated IL-18 in the pathogenesis of various diseases. However, it is not well understood biologic activities of IL-18 in the diverse skin diseases. Here, we have reviewed the expression and function of IL-18 in skin diseases including inflammatory diseases. This article provides an evidence-based understanding of the role of IL-18 in skin diseases and its relationship with disease activities. PMID:26690141

  11. Pelvic Inflammatory Disease (PID)

    MedlinePlus

    ... sexually transmitted infection (STI) such as gonorrhea or chlamydia, it becomes infected. This can allow bacteria to ... sex with a person who has gonorrhea or chlamydia. These diseases are carried in the semen and ...

  12. Inflammatory Bowel Disease

    MedlinePlus

    ... nutrients . Nutrients include proteins , carbohydrates , fats , vitamins , and minerals . The body needs nutrients for energy and to ... of diarrhea may be treated with fluids and minerals. People with Crohn's disease are sometimes given nutritional ...

  13. Transcriptional dysregulation of inflammatory/immune pathways after active vaccination against Huntington's disease.

    PubMed

    Ramsingh, Arlene I; Manley, Kevin; Rong, Yinghui; Reilly, Andrew; Messer, Anne

    2015-11-01

    Immunotherapy, both active and passive, is increasingly recognized as a powerful approach to a wide range of diseases, including Alzheimer's and Parkinson's. Huntington's disease (HD), an autosomal dominant disorder triggered by misfolding of huntingtin (HTT) protein with an expanded polyglutamine tract, could also benefit from this approach. Individuals can be identified genetically at the earliest stages of disease, and there may be particular benefits to a therapy that can target peripheral tissues in addition to brain. In this active vaccination study, we first examined safety and immunogenicity for a broad series of peptide, protein and DNA plasmid immunization protocols, using fragment (R6/1), and knock-in (zQ175) models. No safety issues were found. The strongest and most uniform immune response was to a combination of three non-overlapping HTT Exon1 coded peptides, conjugated to KLH, delivered with alum adjuvant. An N586-82Q plasmid, delivered via gene gun, also showed ELISA responses, mainly in the zQ175 strain, but with more variability, and less robust responses in HD compared with wild-type controls. Transcriptome profiling of spleens from the triple peptide-immunized cohort showed substantial HD-specific differences including differential activation of genes associated with innate immune responses, absence of negative feedback control of gene expression by regulators, a temporal dysregulation of innate immune responses and transcriptional repression of genes associated with memory T cell responses. These studies highlight critical issues for immunotherapy and HD disease management in general. PMID:26307082

  14. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease.

    PubMed Central

    Mahida, Y R; Wu, K C; Jewell, D P

    1989-01-01

    Macrophages isolated from normal mucosa (greater than 5 cm from tumour) and inflamed mucosa (from patients with inflammatory bowel disease) of colon and ileum were studied for their ability to undergo a respiratory burst as assessed by reduction of nitroblue tetrazolium to formazan. Using phorbol myristate acetate (PMA) and opsonised zymosan as triggers, only a minority (median: 8% for zymosan and 9% for PMA) of macrophages isolated from normal colonic mucosa demonstrated release of oxygen radicals. In contrast, a significantly greater (median: 17% for zymosan and 45% for PMA) proportion of macrophages isolated from inflamed colonic mucosa were able to undergo respiratory burst. Studies with normal and inflamed ileum showed similar results. Stimulation of macrophages isolated from normal colon with interferon-gamma produced only a small increase in the proportion of cells showing release of oxygen radicals. We conclude that the respiratory burst capacity of majority of macrophages isolated from normal colon and ileum is downregulated and a greater proportion of macrophages isolated from inflamed colon and ileum are able to undergo a respiratory burst. Images Fig. 2 PMID:2511088

  15. [The peroxisome-proliferator-activated gamma receptor and chronic inflammatory bowel disease (PPARgamma and IBD)].

    PubMed

    Rousseaux, Christel; Desreumaux, Pierre

    2006-01-01

    PPARgamma has been recently described as being a gene of susceptibility for Intestinal Bowel Diseases (IBD) as NOD2/CARD15 gene. IBD are pathologies due to an abnormal immune response, in genetically predisposed patients, to the bacteria of the intestinal flora. PPARgamma, known for its significant role in adipogenesis, is strongly expressed by the epithelial cells of the colon mucosa. PPARgamma is implicated in the regulation of inflammation. Indeed, agonists of this nuclear receptor decrease strongly the intensity of inflammation during experimental colitis induced by chemical agents. A deficit of PPARgamma in patients with ulcerative colitis has been highlighted, that could in part explain the acute inflammation. In addition, bacteria, including those of the commensal flora, are able to regulate PPARgamma. Toll Like Receptor-4 (TLR-4), responsible for the recognition of bacterial motif as lipopolysaccharide (LPS), is implicated in PPARgamma regulation and its anti-inflammatory properties. All these arguments make of PPARgamma a very interesting therapeutic target for the treatment of IBD. PMID:17151549

  16. New perspectives on basic mechanisms in lung disease. 1. Lung injury, inflammatory mediators, and fibroblast activation in fibrosing alveolitis.

    PubMed Central

    Sheppard, M N; Harrison, N K

    1992-01-01

    It is over 25 years since Scadding first defined the term fibrosing alveolitis. It has since been established that complex mechanisms underlie its pathogenesis, including epithelial and endothelial injury, vascular leakage, production of inflammatory cells and their mediators, and fibroblast activation. Only through a detailed knowledge of how these cellular and molecular events are interlinked will we learn how to combat this disease, which is notoriously resistant to present treatments. So far the only therapeutic advances have been refinements in immunosuppression, and even these treatments are frequently disappointing. We believe that future advances in treatment will come from the development of agents that protect endothelial and epithelial cells from further injury and agents that can inhibit release of inflammatory mediators. A better knowledge of the mechanisms of collagen gene activation and the biochemical pathways of collagen production may also allow the identification of vulnerable sites at which new treatments may be directed. A combined approach to modifying appropriate parts of both the inflammatory component and the fibroblast/collagen component should provide a new stimulus to research. Further epidemiological studies are also needed to identify the environmental causes of lung injury that initiate the cascade of events leading to interstitial fibrosis. Images PMID:1494772

  17. The potential of food protein-derived anti-inflammatory peptides against various chronic inflammatory diseases.

    PubMed

    Majumder, Kaustav; Mine, Yoshinori; Wu, Jianping

    2016-05-01

    Inflammation is considered as one of the major causes for the initiation of various chronic diseases such as asthma, cancer, cardiovascular disease, diabetes, obesity, inflammatory bowel disease, osteoporosis and neurological diseases like Parkinson's disease. Increasing scientific evidence has delineated that inflammatory markers such as TNF-α, IL-1, IL-6, IL-8 and CRP and different transcription factors such as NF-κB and STAT are the major key factors that regulate these inflammatory diseases. Food protein-derived bioactive peptides have been shown to exhibit anti-inflammatory activity by inhibiting or reducing the expression of these inflammatory biomarkers and/or by modulating the activity of these transcription factors. This review aims to discuss various molecular targets and underlying mechanisms of food protein-derived anti-inflammatory peptides and to explore their potential against various chronic inflammatory diseases. © 2015 Society of Chemical Industry. PMID:26711001

  18. MicroRNAs Control Macrophage Formation and Activation: The Inflammatory Link between Obesity and Cardiovascular Diseases

    PubMed Central

    Chang, Richard Cheng-An; Ying, Wei; Bazer, Fuller W.; Zhou, Beiyan

    2014-01-01

    Activation and recruitment of resident macrophages in tissues in response to physiological stress are crucial regulatory processes in promoting the development of obesity-associated metabolic disorders and cardiovascular diseases. Recent studies have provided compelling evidence that microRNAs play important roles in modulating monocyte formation, macrophage maturation, infiltration into tissues and activation. Macrophage-dependent systemic physiological and tissue-specific responses also involve cell-cell interactions between macrophages and host tissue niche cell components, including other tissue-resident immune cell lineages, adipocytes, vascular smooth muscle and others. In this review, we highlight the roles of microRNAs in regulating the development and function of macrophages in the context of obesity, which could provide insights into the pathogenesis of obesity-related metabolic syndrome and cardiovascular diseases. PMID:25014161

  19. Inflammatory Gene Expression Upon TGF-β1-Induced p38 Activation in Primary Dupuytren's Disease Fibroblasts

    PubMed Central

    Bujak, Maro; Ratkaj, Ivana; Markova-Car, Elitza; Jurišić, Davor; Horvatić, Anita; Vučinić, Srđan; Lerga, Jonatan; Baus-Lončar, Mirela; Pavelić, Krešimir; Kraljević Pavelić, Sandra

    2015-01-01

    Objectives: Inflammation is an underlying mechanism behind fibrotic processes and differentiation of cells into myofibroblasts. Presented study therefore provides new data on activation of autoimmune and inflammatory immune response genes that accompany activation of p38 and cell differentiation in primary cells derived from Dupuytren's disease (DD) patients. Methods: Primary non-Dupuytren's disease cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent to diseased tissue obtained from patients diagnosed with the last stage of DD and cultured in vitro. Gene expression, collagen gel contraction assay and analysis of secreted proteins were performed in ND cells treated with TGF-β1 and/or inhibitor of p38 phosphorylation. Results: During differentiation of ND fibroblasts, increased expression of immune response genes PAI-1, TIMP-1, CCL11, and IL-6 was found. These changes were accompanied by increased cell contractility and activation of p38 and its target kinase MK2. Inhibition of p38 phosphorylation reversed these processes in vitro. Conclusions: TGF-β1 induced p38 phosphorylation in ND cells grown from macroscopically unaffected palmar fascia adjacent to diseased tissue from DD patients. This was accompanied by activation of the cytokine genes CCL-11 and IL-6 and secretion of extracellular matrix regulatory proteins PAI-1 and TIMP-1. A combined approach directed toward inflammation and p38 MAPK-mediated processes in DD might be considered for improving management of DD patients and prevention of recurrence. PMID:26697433

  20. Costs in inflammatory bowel diseases

    PubMed Central

    Witczak, Izabela

    2016-01-01

    Variables influencing total direct medical costs in inflammatory bowel diseases include country, diagnosis (generally, patients with Crohn's disease generated higher costs compared with patients with ulcerative colitis), and year since diagnosis. In all studies the mean costs were higher than the median costs, which indicates that a relatively small group of the most severely ill patients significantly affect the total cost of treatment of these diseases. A major component of direct medical costs was attributed to hospitalisation, ranging from 49% to 80% of the total. The costs of surgery constituted 40–61% of inpatient costs. Indirect costs in inflammatory bowel diseases, unappreciated and often underestimated (considered by few authors and as a loss of work), are in fact important and may even exceed direct medical costs. PMID:27110304

  1. Imaging for Inflammatory Bowel Disease.

    PubMed

    Morris, Melanie S; Chu, Daniel I

    2015-12-01

    Multiple imaging modalities exist for inflammatory bowel disease. This article explores the use of plain radiographs, contrast radiologic imaging, computed tomography, MRI, ultrasound, and capsule endoscopy. History, technique, indications for use, limitations, and future directions are discussed for each modality. PMID:26596919

  2. Lipoproteins, inflammatory biomarkers, and cardiovascular imaging in the assessment of atherosclerotic disease activity.

    PubMed

    Vanhecke, Thomas E; Franklin, Barry A; Maciejko, James; Chinnaiyan, Kavitha; McCullough, Peter A

    2009-01-01

    Atherosclerosis is present in about 50% of asymptomatic adults at middle age and in nearly all elderly individuals. The traditional diagnostic and treatment paradigm has addressed risk detection and reduction of binary events, including myocardial infarction (MI), stroke, and cardiovascular death. About 50% of all acute coronary syndromes occur in previously asymptomatic subjects, 90% of whom have modifiable risk factors; yet our current screening approaches fail to prevent the 1.2 million acute cardiovascular events that occur annually in the United States. In a patient with active disease, multiple treatment targets can be approached with a variety of lifestyle changes and medical therapy to render the disease quiescent in theory. A future approach may be interception of atherosclerosis before the identification of theoretical or actual risk of episodic events. This case review highlights use of advanced biomarkers and imaging to assess atherosclerotic disease activity in a 49-year-old asymptomatic woman who presents for evaluation after the death of her father from MI. PMID:19367236

  3. Plasma viscosity in inflammatory bowel disease.

    PubMed Central

    Lobo, A J; Jones, S C; Juby, L D; Axon, A T

    1992-01-01

    AIMS: To assess the relation of plasma viscosity to disease activity in patients with inflammatory bowel disease. METHODS: Crohn's disease (n = 60) and ulcerative colitis (n = 71) were diagnosed on the basis of typical histological or radiological features. Active Crohn's disease was defined as a Crohn's disease activity index of 150 or over. Active ulcerative colitis was defined as a liquid stool passed three times a day or more with blood. Blood samples were assessed for haemoglobin concentration, total white cell count, platelets, plasma viscosity, erythrocyte sedimentation rate, serum albumin, and C-reactive protein. RESULTS: Plasma viscosity was higher in those with active Crohn's disease compared with those with inactive Crohn's disease or active ulcerative colitis. Plasma viscosity correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and platelet count in patients with Crohn's disease. In ulcerative colitis plasma viscosity correlated only with serum C-reactive protein. Plasma viscosity showed a low sensitivity for detecting active Crohn's disease, with 48% of those with active disease having a plasma viscosity within the laboratory reference range. CONCLUSIONS: Plasma viscosity is related to disease activity in Crohn's disease, but is insufficiently sensitive for it to replace erythrocyte sedimentation rate as a measure of the acute phase response in Crohn's disease. PMID:1740516

  4. Inflammatory diseases modelling in zebrafish.

    PubMed

    Morales Fénero, Camila Idelí; Colombo Flores, Alicia Angelina; Câmara, Niels Olsen Saraiva

    2016-02-20

    The ingest of diets with high content of fats and carbohydrates, low or no physical exercise and a stressful routine are part of the everyday lifestyle of most people in the western world. These conditions are triggers for different diseases with complex interactions between the host genetics, the metabolism, the immune system and the microbiota, including inflammatory bowel diseases (IBD), obesity and diabetes. The incidence of these disorders is growing worldwide; therefore, new strategies for its study are needed. Nowadays, the majority of researches are in use of murine models for understand the genetics, physiopathology and interaction between cells and signaling pathways to find therapeutic solutions to these diseases. The zebrafish, a little tropical water fish, shares 70% of our genes and conserves anatomic and physiological characteristics, as well as metabolical pathways, with mammals, and is rising as a new complementary model for the study of metabolic and inflammatory diseases. Its high fecundity, fast development, transparency, versatility and low cost of maintenance makes the zebrafish an interesting option for new researches. In this review, we offer a discussion of the existing genetic and induced zebrafish models of two important Western diseases that have a strong inflammatory component, the IBD and the obesity. PMID:26929916

  5. Inflammatory diseases modelling in zebrafish

    PubMed Central

    Morales Fénero, Camila Idelí; Colombo Flores, Alicia Angelina; Câmara, Niels Olsen Saraiva

    2016-01-01

    The ingest of diets with high content of fats and carbohydrates, low or no physical exercise and a stressful routine are part of the everyday lifestyle of most people in the western world. These conditions are triggers for different diseases with complex interactions between the host genetics, the metabolism, the immune system and the microbiota, including inflammatory bowel diseases (IBD), obesity and diabetes. The incidence of these disorders is growing worldwide; therefore, new strategies for its study are needed. Nowadays, the majority of researches are in use of murine models for understand the genetics, physiopathology and interaction between cells and signaling pathways to find therapeutic solutions to these diseases. The zebrafish, a little tropical water fish, shares 70% of our genes and conserves anatomic and physiological characteristics, as well as metabolical pathways, with mammals, and is rising as a new complementary model for the study of metabolic and inflammatory diseases. Its high fecundity, fast development, transparency, versatility and low cost of maintenance makes the zebrafish an interesting option for new researches. In this review, we offer a discussion of the existing genetic and induced zebrafish models of two important Western diseases that have a strong inflammatory component, the IBD and the obesity. PMID:26929916

  6. Managing pregnancy in inflammatory rheumatological diseases

    PubMed Central

    2011-01-01

    Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications. PMID:21371350

  7. Pelvic Inflammatory Disease (PID) Treatment and Care

    MedlinePlus

    ... Herpes Gonorrhea Hepatitis HIV/AIDS & STDs Human Papillomavirus (HPV) Pelvic Inflammatory Disease ... is pelvic inflammatory disease treated? Several types of antibiotics can cure PID. Antibiotic treatment does not, however, reverse any ...

  8. Diet and Inflammatory Bowel Disease.

    PubMed

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca; Abreu, Maria T

    2015-08-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets-such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet-have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  9. Diet and Inflammatory Bowel Disease

    PubMed Central

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca

    2015-01-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets—such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet—have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  10. Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases.

    PubMed

    Hamon, Yveline; Legowska, Monika; Hervé, Virginie; Dallet-Choisy, Sandrine; Marchand-Adam, Sylvain; Vanderlynden, Lise; Demonte, Michèle; Williams, Rich; Scott, Christopher J; Si-Tahar, Mustapha; Heuzé-Vourc'h, Nathalie; Lalmanach, Gilles; Jenne, Dieter E; Lesner, Adam; Gauthier, Francis; Korkmaz, Brice

    2016-04-15

    The cysteine protease cathepsin C (CatC) activates granule-associated proinflammatory serine proteases in hematopoietic precursor cells. Its early inhibition in the bone marrow is regarded as a new therapeutic strategy for treating proteolysis-driven chronic inflammatory diseases, but its complete inhibition is elusive in vivo Controlling the activity of CatC may be achieved by directly inhibiting its activity with a specific inhibitor or/and by preventing its maturation. We have investigated immunochemically and kinetically the occurrence of CatC and its proform in human hematopoietic precursor cells and in differentiated mature immune cells in lung secretions. The maturation of proCatC obeys a multistep mechanism that can be entirely managed by CatS in neutrophilic precursor cells. CatS inhibition by a cell-permeable inhibitor abrogated the release of the heavy and light chains from proCatC and blocked ∼80% of CatC activity. Under these conditions the activity of neutrophil serine proteases, however, was not abolished in precursor cell cultures. In patients with neutrophilic lung inflammation, mature CatC is found in large amounts in sputa. It is secreted by activated neutrophils as confirmed through lipopolysaccharide administration in a nonhuman primate model. CatS inhibitors currently in clinical trials are expected to decrease the activity of neutrophilic CatC without affecting those of elastase-like serine proteases. PMID:26884336

  11. Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

    PubMed Central

    Lee, Jang Wook; Park, Ji Hoon; Kim, Jeong Wook; Kang, Sang Bum; Koo, Ja Seol; Kim, Young-Ho; Kim, You Sun; Joo, Young Eun; Chang, Sae Kyung

    2016-01-01

    Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB. PMID:27175115

  12. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  13. Outcomes and disease activity measures for assessing treatments in the idiopathic inflammatory myopathies.

    PubMed

    Oddis, Chester V

    2005-04-01

    The assessment and treatment of patients with idiopathic inflammatory myopathy has taken a major step forward over the past few years. Through the efforts of multi-disciplinary international groups of experts interested in the management of patients with myositis, initiatives have led to the development of a core set of outcome measures critical to their assessment. Similarly, the lack of consensus on several issues of clinical trial design has been addressed resulting in the development of a definition of clinical improvement for adult and juvenile patients with inflammatory myopathy using the core set outcomes. The final step in the puzzle of well-designed therapeutic trials in myositis is the determination of consensus guidelines to conduct such trials in adult and pediatric populations of myositis patients. PMID:15760586

  14. Sleep disturbances and inflammatory bowel disease.

    PubMed

    Ali, Tauseef; Orr, William C

    2014-11-01

    With an estimated 70 million Americans suffering, sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many clinical research studies. Sleep is now also considered to be an important environmental and behavioral factor associated with the process of inflammation and the immune system. Increased sleepiness is considered part of the acute phase of response to tissue injury, and sleep loss activates inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Clinical studies in many immune-mediated diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis, have revealed an association of sleep disturbances with disease activity. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. The importance of sleep in inflammatory bowel disease has recently gained attention with some published studies demonstrating the association of sleep disturbances with disease activity, subclinical inflammation, and risk of disease relapse. A comprehensive review of sleep physiology and its association with the immune system is provided here. Experimental and clinical studies exploring this relationship in inflammatory bowel disease are reviewed, and the clinical implications of this relationship and future directions for research are also discussed. PMID:25025716

  15. Coagulation parameters in inflammatory bowel disease

    PubMed Central

    Dolapcioglu, Can; Soylu, Aliye; Kendir, Tulin; Ince, Ali Tuzun; Dolapcioglu, Hatice; Purisa, Sevim; Bolukbas, Cengiz; Sokmen, Haci Mehmet; Dalay, Remzi; Ovunc, Oya

    2014-01-01

    Thromboembolic events represent a major cause of morbidity and mortality in patients with inflammatory bowel disease and they may occur both at the gastrointestinal tract and at extraintestinal sites. This study aimed to examine the alterations in coagulation parameters involved at different steps of hemostasis in patients with Crohn’s disease and ulcerative colitis, in comparison with healthy individuals. Fifty-one patients with inflammatory bowel disease and 26 healthy controls were included in this study. Plasma levels of PT, APTT, AT III, plasminogen, fibrinogen, D-dimer, factor V, factor VIII, protein C, protein S, and APCR were measured and factor V Leiden mutation was examined in both patients and controls. Two patients with ulcerative colitis had a history of previous thromboembolic event. Inflammatory bowel disease was associated with significantly higher levels of fibrinogen, PT, factor V, factor VIII, plasminogen and thrombocyte. Protein S, fibrinogen, plasminogen and thrombocyte levels were associated with disease activity, depending on the type of the disease (Crohn’s disease or ulcerative colitis). The coagulation abnormalities detected in this study seems to be a secondary phenomena resulting from the disease process, which is more likely to be associated with a multitude of factors rather than a single abnormality. PMID:24995109

  16. Fatigue is highly associated with poor health-related quality of life, disability and depression in newly-diagnosed patients with inflammatory bowel disease, independent of disease activity

    PubMed Central

    Cohen, B L; Zoëga, H; Shah, S A; LeLeiko, N; Lidofsky, S; Bright, R; Flowers, N; Law, M; Moniz, H; Merrick, M; Sands, B E

    2014-01-01

    Background Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable. Aim To report prevalence of fatigue in newly diagnosed CD and UC patients and examine its association with health-related quality of life (HRQOL), depression and disability. Methods The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a statewide cohort of newly diagnosed inflammatory bowel disease patients in Rhode Island. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were administered instruments measuring HRQOL, overall disability and work impairment, and depression. Results Fatigue was prevalent in 26.4% of 220 subjects. Cohen's d effect sizes for fatigue were large: Short-Form 36 Health Survey mental health component (CD 1.5, UC 1.4) and physical health component (CD 1.4, UC 1.4), EuroQol-5D valuation of current health state (CD 1.2, UC 1.0), Inflammatory Bowel Disease Questionnaire (CD 1.9, UC 1.6) and Patient Health Questionnaire depression scale (CD 1.8, UC 1.7). Fatigued patients reported more work impairment (Score difference: CD 29.5%, UC 23.8%) and activity impairment (score difference: CD 32.3%, UC 25.7%) on the Work Productivity and Activity Impairment Questionnaire. Fatigue's association with all scores remained highly significant despite controlling for disease activity. Conclusions Fatigue is strongly associated with poor HRQOL, disability and depression similarly in CD and UC even when controlling for disease activity. Fatigue's association with a wide range of patient-reported outcome measures suggests that monitoring fatigue is a simple way to screen for overall disruption in patient life. PMID:24612278

  17. Zinc absorption in inflammatory bowel disease

    SciTech Connect

    Valberg, L.S.; Flanagan, P.R.; Kertesz, A.; Bondy, D.C.

    1986-07-01

    Zinc absorption was measured in 29 patients with inflammatory bowel disease and a wide spectrum of disease activity to determine its relationship to disease activity, general nutritional state, and zinc status. Patients with severe disease requiring either supplementary oral or parenteral nutrition were excluded. The mean 65ZnCl2 absorption, in the patients, determined using a 65Zn and 51Cr stool-counting test, 45 +/- 17% (SD), was significantly lower than the values, 54 +/- 16%, in 30 healthy controls, P less than 0.05. Low 65ZnCl2 absorption was related to undernutrition, but not to disease activity in the absence of undernutrition or to zinc status estimated by leukocyte zinc measurements. Mean plasma zinc or leukocyte zinc concentrations in patients did not differ significantly from controls, and only two patients with moderate disease had leukocyte zinc values below the 5th percentile of normal. In another group of nine patients with inflammatory bowel disease of mild-to-moderate severity and minimal nutritional impairment, 65Zn absorption from an extrinsically labeled turkey test meal was 31 +/- 10% compared to 33 +/- 7% in 17 healthy controls, P greater than 0.1. Thus, impairment in 65ZnCl2 absorption in the patients selected for this study was only evident in undernourished persons with moderate or severe disease activity, but biochemical evidence of zinc deficiency was uncommon, and clinical features of zinc depletion were not encountered.

  18. Managing inflammatory bowel disease in adolescent patients

    PubMed Central

    Bishop, J; Lemberg, DA; Day, AS

    2014-01-01

    Increasing numbers of adolescents are being diagnosed with Crohn’s disease or ulcerative colitis, the two main subtypes of inflammatory bowel disease. These young people face many short- and long-term challenges; one or more medical therapies may be required indefinitely; their disease may have great impact, in terms of their schooling and social activities. However, the management of adolescents with one of these incurable conditions needs to encompass more than just medical therapies. Growth, pubertal development, schooling, transition, adherence, and psychological well-being are all important aspects. A multidisciplinary team setting, catering to these components of care, is required to ensure optimal outcomes in adolescents with inflammatory bowel disease. PMID:24729736

  19. Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases

    PubMed Central

    Das Gupta, Kaustav; Shakespear, Melanie R; Iyer, Abishek; Fairlie, David P; Sweet, Matthew J

    2016-01-01

    Macrophages have central roles in danger detection, inflammation and host defense, and consequently, these cells are intimately linked to most disease processes. Major advances in our understanding of the development and function of macrophages have recently come to light. For example, it is now clear that tissue-resident macrophages can be derived from either blood monocytes or through local proliferation of phagocytes that are originally seeded during embryonic development. Metabolic state has also emerged as a major control point for macrophage activation phenotypes. Herein, we review recent literature linking the histone deacetylase (HDAC) family of enzymes to macrophage development and activation, particularly in relation to these recent developments. There has been considerable interest in potential therapeutic applications for small molecule inhibitors of HDACs (HDACi), not only for cancer, but also for inflammatory and infectious diseases. However, the enormous range of molecular and cellular processes that are controlled by different HDAC enzymes presents a potential stumbling block to clinical development. We therefore present examples of how classical HDACs control macrophage functions, roles of specific HDACs in these processes and approaches for selective targeting of drugs, such as HDACi, to macrophages. Development of selective inhibitors of macrophage-expressed HDACs and/or selective delivery of pan HDACi to macrophages may provide avenues for enhancing efficacy of HDACi in therapeutic applications, while limiting unwanted side effects. PMID:26900475

  20. Genetics of Inflammatory Bowel Diseases.

    PubMed

    McGovern, Dermot P B; Kugathasan, Subra; Cho, Judy H

    2015-10-01

    In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and

  1. Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease.

    PubMed Central

    Okada, Y.; Shimoe, T.; Muguruma, M.; Usumoto, R.; Tsuji, T.; Jinno, K.; Moriwaki, S.; Shin, S.; Hakomori, S.

    1988-01-01

    Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3341453

  2. Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.

    PubMed

    Lapsia, Sameer; Koganti, Siva; Spadaro, Salvatore; Rajapakse, Ramona; Chawla, Anupama; Bhaduri-McIntosh, Sumita

    2016-02-01

    Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. PMID:26307954

  3. Disease Activity in Inflammatory Bowel Disease Is Associated with Increased Risk of Myocardial Infarction, Stroke and Cardiovascular Death – A Danish Nationwide Cohort Study

    PubMed Central

    Kristensen, Søren Lund; Ahlehoff, Ole; Lindhardsen, Jesper; Erichsen, Rune; Jensen, Gunnar Vagn; Torp-Pedersen, Christian; Nielsen, Ole Haagen; Gislason, Gunnar Hilmar; Hansen, Peter Riis

    2013-01-01

    Purpose Chronic inflammatory diseases have been linked to increased risk of atherothrombotic events, but the risk associated with inflammatory bowel disease (IBD) is unclear. We therefore examined the risk of myocardial infarction (MI), stroke, and cardiovascular death in patients with IBD. Methods In a nationwide Danish population-based setting, a cohort of patients with incident IBD between 1996 and 2009 were identified in national registers. Hospitalizations with IBD as primary diagnosis, initiation of biological treatment and dispensed prescriptions of corticosteroids were all used as surrogate markers for disease activity, with flares classified as the first 120 days after diagnosis of IBD, and 120 days after a new corticosteroid prescription, biological treatment or IBD hospitalization, respectively. Continued corticosteroid prescriptions or IBD hospitalizations were defined as persistent activity, and periods free of such events were defined as remissions. Poisson regression was used to examine risk of MI, stroke, and cardiovascular death using a matched population-based comparison cohort as reference Results We identified 20,795 IBD patients with a mean age of 40.3 years that were matched according to age and sex with 199,978 controls. During the study period, there were 365 patients with MI, 454 with stroke, and 778 with cardiovascular death. Patients with IBD had an overall increased risk of MI (rate ratio [RR] 1.17 [95% confidence interval 1.05–1.31]), stroke (RR 1.15 [1.04–1.27], and cardiovascular death (RR 1.35 [1.25–1.45]). During flares and persistent IBD activity the RRs of MI increased to 1.49 (1.16–1.93) and 2.05 (1.58–2.65), the RRs of stroke to 1.53 (1.22–1.92) and 1.55 (1.18–2.04) and for cardiovascular death 2.32 (2.01–2.68) and 2.50 (2.14–2.92). In remission periods, the risk of MI, stroke and cardiovascular death was similar to controls. Conclusion Inflammatory bowel disease is associated with increased risk of MI, stroke

  4. Intestinal Protease-Activated Receptor-2 and Fecal Serine Protease Activity are Increased in Canine Inflammatory Bowel Disease and May Contribute to Intestinal Cytokine Expression

    PubMed Central

    MAEDA, Shingo; OHNO, Koichi; UCHIDA, Kazuyuki; IGARASHI, Hirotaka; GOTO-KOSHINO, Yuko; FUJINO, Yasuhito; TSUJIMOTO, Hajime

    2014-01-01

    ABSTRACT Serine proteases elicit cellular responses via protease-activated receptor-2 (PAR-2) which is known to regulate inflammation and the immune response. Although the gastrointestinal tract is exposed to large amounts of proteolytic enzymes, the role of PAR-2 in canine inflammatory bowel disease (IBD) remains unclear. The objective of this study was to investigate the effects of PAR-2 activation on inflammatory cytokine/chemokine gene expression in canine intestine and the expression of intestinal PAR-2 and fecal serine protease activity in dogs with IBD. Duodenal biopsies from healthy dogs were cultured and treated ex vivo with trypsin or PAR-2 agonist peptide, and inflammatory cytokine/chemokine gene expression in the tissues was then quantified by real-time PCR. PAR-2 mRNA and protein expression levels in the duodenal mucosa were examined by real-time PCR and immunohistochemistry, respectively. Fecal serine protease activity was determined by azocasein assay. In ex vivo-cultured duodenum, trypsin and PAR-2 agonist peptide induced significant up-regulation of mRNA expression levels of interleukin-1 β (IL-1β), IL-8, mucosae-associated epithelial chemokine (MEC) and fractalkine, and this up-regulation was inhibited by a serine protease inhibitor. Duodenal PAR-2 mRNA and protein expression levels were higher in dogs with IBD than in healthy control dogs. Fecal serine protease activity was significantly elevated in dogs with IBD, and the level of activity correlated positively with the clinical severity score. These results suggest that PAR-2 may contribute to the pathogenesis of canine IBD by inducing expression of inflammatory mediators in response to luminal serine proteases. PMID:24829081

  5. Epidemiology and inflammatory bowel diseases

    PubMed Central

    El-Tawil, Ahmed Mahmoud

    2013-01-01

    The role of alcohol in causing or aggravating the pathogenesis of inflammatory bowel disease is unclear. For finding a conclusive answer for this valuable question we conducted this review. Only two studies were identified that successfully fulfilled our inclusive criteria. Usual consumption of alcohol reduced the risk compared with less frequent use (odds ratio = 0.57, 95%CI: 0.37-0.86). Light alcoholic drinking has protective effects against development of ulcerative colitis. But this inverse association disappeared when smoking was included. PMID:23539486

  6. Pneumomediastinum in inflammatory bowel disease

    PubMed Central

    Fenves, Andrew Z.

    2015-01-01

    A 28-year-old man with a history of inflammatory bowel disease (IBD) developed sudden-onset chest pain and dyspnea 9 days after esophagogastroduodenoscopy and colonoscopy. A chest radiograph demonstrated pneumomediastinum tracking along the left heart border. The spontaneous pneumomediastinum was presumed to be a complication of his severe colitis. The severity of our patient's symptoms ultimately necessitated a subtotal colectomy, a decision unrelated to the pneumomediastinum. IBD-associated pneumomediastinum can be attributed to retroperitoneal air leakage from severe colitis and usually resolves with conservative management. PMID:26130885

  7. Immunoregulatory Pathways Involved in Inflammatory Bowel Disease.

    PubMed

    Fonseca-Camarillo, Gabriela; Yamamoto-Furusho, Jesús K

    2015-09-01

    Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The immune response in ulcerative colitis is different from the Crohn's disease. Accumulating evidence suggests that IBD results from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. Several immunoregulatory abnormalities have been reported in patients with IBD, including the ratio of proinflammatory (tumor necrosis factor alpha, IL-6, IL-1-β) to immunoregulatory cytokines (IL-10, TGF-β, IL-35) and selective activation of T-helper (Th) lymphocyte subsets (Th1, Th2, Th9, Th17, and regulatory T cells). The purpose of this review is to show the immunoregulatory pathways (regulatory cells and cytokines) involved in IBD published in recent years. PMID:26111210

  8. Microbiota biodiversity in inflammatory bowel disease

    PubMed Central

    2014-01-01

    Gut microbiota plays a significant role in human health and energy balance, and provides protection against disease states. An altered balance between microbiota and its host (dysbiosis) would appear to contribute to the development of Inflammatory Bowel Disease (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC). CD and UC are chronic inflammatory diseases of the gastrointestinal tes. PMID:24684926

  9. Vitamin D and Inflammatory Bowel Disease

    PubMed Central

    Ardesia, Marco; Ferlazzo, Guido; Fries, Walter

    2015-01-01

    Vitamin D deficiency has been recognized as an environmental risk factor for Crohn's disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn's disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn's disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism. PMID:26000293

  10. Vitamin D and inflammatory bowel disease.

    PubMed

    Ardesia, Marco; Ferlazzo, Guido; Fries, Walter

    2015-01-01

    Vitamin D deficiency has been recognized as an environmental risk factor for Crohn's disease since the early 80s. Initially, this finding was correlated with metabolic bone disease. Low serum 25-hydroxyvitamin D levels have been repeatedly reported in inflammatory bowel diseases together with a relationship between vitamin D status and disease activity. Subsequently, low serum vitamin D levels have been reported in various immune-related diseases pointing to an immunoregulatory role. Indeed, vitamin D and its receptor (VDR) are known to interact with different players of the immune homeostasis by controlling cell proliferation, antigen receptor signalling, and intestinal barrier function. Moreover, 1,25-dihydroxyvitamin D is implicated in NOD2-mediated expression of defensin-β2, the latter known to play a crucial role in the pathogenesis of Crohn's disease (IBD1 gene), and several genetic variants of the vitamin D receptor have been identified as Crohn's disease candidate susceptibility genes. From animal models we have learned that deletion of the VDR gene was associated with a more severe disease. There is a growing body of evidence concerning the therapeutic role of vitamin D/synthetic vitamin D receptor agonists in clinical and experimental models of inflammatory bowel disease far beyond the role of calcium homeostasis and bone metabolism. PMID:26000293

  11. Video capsule endoscopy in inflammatory bowel disease

    PubMed Central

    Collins, Paul D

    2016-01-01

    Video capsule endoscopy (VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has been shown to play a role in monitoring the activity of small bowel Crohn’s disease and can be used to assess the response to anti-inflammatory treatment in Crohn’s disease. For those patients with Crohn’s disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn’s disease. The evolution of colon capsule endoscopy (CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn’s disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn’s disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease. PMID:27499830

  12. Inflammatory and glandular skin disease in pregnancy.

    PubMed

    Yang, Catherine S; Teeple, Mary; Muglia, Jennie; Robinson-Bostom, Leslie

    2016-01-01

    A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. PMID:27265071

  13. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease

    SciTech Connect

    Oppenheimer, D.A.; Jones, H.H.

    1982-12-01

    The case of a 14-year old girl with painful periostitis and ulcerative colitis is reported. The association of chronic inflammatory bowel disease with osteoarthropathy is rare and has previously been reported in eight patients. The periosteal reaction found in association with inflammatory bowel disease is apparently related to a chronic disease course and may cause extreme localized pain.

  14. Adhesion molecules in inflammatory bowel disease.

    PubMed Central

    Jones, S C; Banks, R E; Haidar, A; Gearing, A J; Hemingway, I K; Ibbotson, S H; Dixon, M F; Axon, A T

    1995-01-01

    The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with

  15. MR colonography in inflammatory bowel disease.

    PubMed

    Rimola, Jordi; Ordás, Ingrid

    2014-02-01

    MR colonography has a high diagnostic accuracy for detecting Crohn disease (CD) activity and determining the extent and severity of lesions. In the setting of stricturing CD, MR colonography can provide a detailed map of the lesions, which is useful for clinical decision making. MR colonography can be used as an alternative to conventional colonoscopy in the setting of CD, or as a complementary tool in selected patients with ulcerative colitis. This article reviews the spectrum of MR colonography findings in colonic inflammatory bowel disease and discusses the potential applications and limitations of MR colonography. PMID:24238130

  16. Angiogenesis in Inflammatory Bowel Disease

    PubMed Central

    Alkim, Canan; Alkim, Huseyin; Koksal, Ali Riza; Boga, Salih; Sen, Ilker

    2015-01-01

    Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. PMID:26839731

  17. Relationship between intestinal permeability to ( sup 51 Cr)EDTA and inflammatory activity in asymptomatic patients with Crohn's disease

    SciTech Connect

    Pironi, L.; Miglioli, M.; Ruggeri, E.; Levorato, M.; Dallasta, M.A.; Corbelli, C.; Nibali, M.G.; Barbara, L. )

    1990-05-01

    The relationship between intestinal permeability to an oral dose (100 mu Ci) of (51CR)EDTA and the inflammatory activity of Crohn's disease was studied in 63 adult patients (32 unresected and 31 resected) who underwent 162 evaluations. The results of the (51CR)EDTA test were compared with the serum levels of the acute-phase reactant proteins (APRP) and with the result of the (111In)leukocyte scanning, respectively, as an indirect and direct method to assess intestinal inflammation. In a group of healthy adult controls, the upper normal value for the 24-hr urinary (51CR)EDTA excretion was 3.61 (97.5% percentile) and the mean coefficient of variation was 21%. Sensitivity and specificity of the (51CR)EDTA test in identifying active inflammation expressed by increased serum levels of APRP were, respectively, 97% and 54% in the unresected group and 68% and 52% in the resected group of patients. The low specificity of the test was due to the presence of increased (51CR)EDTA urinary excretion in about half the cases with normal serum levels of APRP. The (111In)leukocyte scanning was performed in a subgroup of 11 patients (three unresected and eight resected) with normal serum levels of APRP, six with increased and five with normal (51CR)EDTA urinary excretion. All six patients with increased intestinal permeability had a positive 111In image of mild to moderate degree of activity. A positive 111In scan was present in two of the five patients with normal permeability; these were two resected patients.

  18. Disease monitoring in inflammatory bowel disease

    PubMed Central

    Chang, Shannon; Malter, Lisa; Hudesman, David

    2015-01-01

    The optimal method for monitoring quiescent disease in patients with Crohn’s disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD. PMID:26523100

  19. The role of methionine metabolism in inflammatory bowel disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methionine (Met) cycle activity is critical for normal cell functions. Met metabolites S-adenosylmethionine (SAM) and methylthioadenosine (MTA) are anti-inflammatory, yet their role in inflammatory bowel disease (IBD) is poorly understood. We hypothesize that active IBD leads to changes in Met metab...

  20. [Treatment of inflammatory bowel diseases].

    PubMed

    Gomollón, Fernando

    2015-09-01

    In addition to immunosuppressive drugs and anti-TNF, there are a number of new options in the treatment of inflammatory bowel diseases. Vedolizumab has been approved by the FDA and EMA and has demonstrated utility both in the treatment of ulcerative colitis (UC) and Crohn's disease (CD), even in anti-TNF refractory patients. Other monoclonal antibodies with different targets such as PF-005447659 (antiMAd-CAM1), ustekinumab (anti-IL23/IL12) or MEDI2070 (anti-IL23) have shown promising results in distinct clinical scenarios. Mongersen (antisense oligonucleotide anti-Smad7) and oznimod (an SP-1 modulator) are new alternatives with proven efficacy in clinical trials in CD and UC, respectively. Some data suggest that faecal microbiota transplantation could be efficacious in individual patients, although controlled data do not show clear differences with placebo. Autologous stem-cell transplantation has shown long-term efficacy in "ultra-refractory" CD. The number of possible treatments is constantly increasing, and future research should focus both on the selection of the most appropriate treatment for any given patient and on comparative trials between options. PMID:26520192

  1. Anti-inflammatory Activity.

    PubMed

    2016-01-01

    Inflammation is the body's first response to infection or injury and is critical for both innate and adaptive immunity. It can be considered as part of the complex biological response of vascular tissues to harmful stimuli such as pathogens, damaged cells, or irritants. The search for natural compounds and phytoconstituents that are able to interfere with these mechanisms by preventing a prolonged inflammation could be useful for human health. Here, the anti-inflammatory properties of plant-based drugs are put together with both in vitro and acute (carrageenan, egg albumin and croton oil) and chronic (cotton pellet) in vivo models. PMID:26939273

  2. Fecal calprotectin in inflammatory bowel disease.

    PubMed

    Walsham, Natalie E; Sherwood, Roy A

    2016-01-01

    Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn's disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD. PMID:26869808

  3. Fecal calprotectin in inflammatory bowel disease

    PubMed Central

    Walsham, Natalie E; Sherwood, Roy A

    2016-01-01

    Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn’s disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD. PMID:26869808

  4. Biologic therapy for inflammatory bowel disease.

    PubMed

    Ardizzone, Sandro; Bianchi Porro, Gabriele

    2005-01-01

    Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved

  5. Caring for Women with Inflammatory Bowel Disease.

    PubMed

    Feagins, Linda A; Kane, Sunanda V

    2016-06-01

    Ulcerative colitis and Crohn disease are chronic inflammatory diseases with typical onset in early adulthood. These diseases, therefore, can affect a woman throughout the many stages of her life, including menstruation, sexuality, pregnancy, and menopause. Unique health issues face women during these stages and can affect the course of their inflammatory bowel disease as well as treatment strategies and health maintenance. This article covers the non-pregnancy-related issues that are important in caring for women with inflammatory bowel disease. The topics of pregnancy and fertility are covered in a separate review. PMID:27261900

  6. Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and anti-inflammatory activity in murine disease models.

    PubMed

    Man, Mao-Qiang; Shi, Yuejun; Man, Mona; Lee, Seung Hun; Demerjian, Marianne; Chang, Sandra; Feingold, Kenneth R; Elias, Peter M

    2008-08-01

    While psoriasis is one of the most common skin disorders in humans, effective, safe and inexpensive treatments are still largely unavailable. Chinese herbal medicine (CHM) has been used for centuries for treating psoriasis and several reports claim that systemic administration of one such CHM, Tuhuai, mainly composed of flos sophorae, smilax glabra roxb and licorice, is effective in psoriasis. However, the mechanisms by which this CHM improves psoriasis are not yet clear. Two universal features of psoriasis are epidermal hyperplasia and inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia and/or inflammation are widely used to treat psoriasis. Here, we investigated whether topical applications of Tuhuai extract exhibit anti-proliferative and anti-inflammatory activities in two murine models of inflammatory dermatoses. To assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal barrier function twice-daily for 4 days in normal hairless mice followed by topical applications of either 1% Tuhuai extract or Vehicle to both flanks immediately after each barrier perturbation. Changes in epidermal proliferation and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and acute allergic contact dermatitis (oxazolone) models were used. Whereas topical Tuhuai extract did not alter epidermal proliferation or induce irritation in normal skin, it both reduced epidermal hyperplasia in the epidermal hyperproliferative model, and reduced inflammation in both irritant and allergic contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative and anti-inflammatory properties in a variety of human models of inflammatory dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive therapeutic alternative for the treatment of inflammatory dermatoses, including psoriasis. PMID:18341576

  7. Pharmacogenetics of inflammatory bowel disease.

    PubMed

    Mascheretti, Silvia; Croucher, Peter J P; Schreiber, Stefan

    2004-06-01

    The therapeutic efficacy and toxicity of many commonly employed drugs show interindividual variations that relate to several factors, including genetic variability in drug-metabolizing enzymes, transporters or targets. The study of the genetic determinants influencing interindividual variations in drug response is known as pharmacogenetics. The ability to identify, through preliminary genetic screening, the patients most likely to respond positively to a medication should facilitate the best choice of treatment for each patient; drugs likely to exhibit low efficacy or to give negative side-effects can be avoided. Among the medications used for inflammatory bowel disease, the best studied pharmacogenetically is azathioprine. The hematopoietic toxicity of azathioprine is due to single nucleotide polymorphisms in the thiopurine S-methyltransferase enzyme. Additionally, likely gene targets have been investigated to predict the response to glucocorticoids and infliximab, a monoclonal antibody against tumour necrosis factor that induces remission in approximately 30-40% of patients. However, no genetic predictor of response has been identified in either case. PMID:15157830

  8. Gut microbiota and inflammatory bowel disease.

    PubMed

    Hammer, Heinz F

    2011-01-01

    Bacteria play an important role in the pathogenesis of inflammatory bowel disease (IBD), its complications and its symptoms. Antibiotics can decrease tissue invasion and eliminate aggressive bacterial species. They are used in IBD to treat infective complications and for altering bacterial flora, which may result in specific anti-inflammatory effects. In addition, suppression of bacterial metabolic activities or direct effects of antibiotics on intestinal structures and functions may result in symptoms which cannot be differentiated from symptoms caused by inflammation. Although current clinical trials do not fulfill criteria of evidence-based treatment, a few placebo- or standard treatment-controlled studies suggest that metronidazole and ciprofloxacin are effective in Crohn's colitis and ileocolitis, perianal fistulae and pouchitis. Administration of probiotics, prebiotics and synbiotics can restore a predominance of beneficial species. However, beneficial effects of probiotics in IBD are modest, strain-specific and limited to certain manifestations of disease and duration of use of the probiotic. For probiotics there is reasonable evidence of efficacy in relapse prevention in chronic pouchitis and ulcerative colitis, and suggestive evidence for postoperative prevention in pouchitis. Therapeutic manipulation of the intestinal flora offers considerable promise for treating IBD, but must be supported by large controlled therapeutic trials before widespread clinical acceptance. These agents may become a component of treating IBD in combination with traditional anti-inflammatory and immunosuppressive agents. Probiotic strategies, based on metagenomic or metabonomic analyses, and new classes of probiotics might play an important role in the future management of IBD. PMID:22179210

  9. Management of Inflammatory Bowel Disease During Pregnancy.

    PubMed

    Bar-Gil Shitrit, Ariella; Grisaru-Granovsky, Sorina; Ben Ya'acov, Ami; Goldin, Eran

    2016-08-01

    Inflammatory bowel disease (IBD) usually affects women during their reproductive years and many concerns arise among these young patients. Pre-pregnancy consultation with a multi-disciplinary team is very important. The team should make patients aware of the critical importance of ensuring that conception occurs during a period of disease remission. Conception during an IBD flare-up results in disease activity or even exacerbates disease in two-thirds of women. Exacerbation of the disease is associated with increased frequency of maternal and fetal complications. Drug therapy constitutes a considerable source of patient anxiety but most drugs used for treating IBD are considered safe. Therefore, continuing pharmacological therapy during pregnancy is necessary to maintain disease control. Optimization of pre-conception nutritional status and smoking cessation are also emphasized. The general guideline for most patients, except for active perianal disease patients, is to aim for vaginal delivery in the absence of obstetric contraindications. Consistent, ongoing follow-up, as detailed in this review, should allay the anxieties and fears surrounding continuing immunosuppressive drugs during pregnancy, allowing each patient to attain the optimal conditions for achieving her goal of holding a healthy baby. PMID:27068171

  10. Skin Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Huang, Brian L.; Chandra, Stephanie; Shih, David Quan

    2012-01-01

    Inflammatory bowel disease (IBD) is a disease that affects the intestinal tract via an inflammatory process. Patients who suffer from IBD often have diseases that affect multiple other organ systems as well. These are called extraintestinal manifestations and can be just as, if not more debilitating than the intestinal inflammation itself. The skin is one of the most commonly affected organ systems in patients who suffer from IBD. The scientific literature suggests that a disturbance of the equilibrium between host defense and tolerance, and the subsequent over-activity of certain immune pathways are responsible for the cutaneous disorders seen so frequently in IBD patients. The purpose of this review article is to give an overview of the types of skin diseases that are typically seen with IBD and their respective pathogenesis, proposed mechanisms, and treatments. These cutaneous disorders can manifest as metastatic lesions, reactive processes to the intestinal inflammation, complications of IBD itself, or side effects from IBD treatments; these can be associated with IBD via genetic linkage, common autoimmune processes, or other mechanisms that will be discussed in this article. Ultimately, it is important for healthcare providers to understand that skin manifestations should always be checked and evaluated for in patients with IBD. Furthermore, skin disorders can predate gastrointestinal symptoms and thus may serve as important clinical indicators leading physicians to earlier diagnosis of IBD. PMID:22347192

  11. Hansen's disease in association with immune reconstitution inflammatory syndrome

    PubMed Central

    George, Anju; Vidyadharan, Suja

    2016-01-01

    Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy. PMID:26955584

  12. Hansen's disease in association with immune reconstitution inflammatory syndrome.

    PubMed

    George, Anju; Vidyadharan, Suja

    2016-01-01

    Immune reconstitution inflammatory syndrome is characterized by a paradoxical worsening of an existing infection or disease process, soon after initiation of highly active antiretroviral therapy. The first case of leprosy presenting as immune reconstitution inflammatory syndrome was published in 2003. Here we report a case of Hansen's disease borderline tuberculoid presenting with type 1 lepra reaction 5 months after initiation of highly active antiretroviral therapy. PMID:26955584

  13. Role of scintigraphy in inflammatory bowel disease

    PubMed Central

    Stathaki, Maria I; Koukouraki, Sophia I; Karkavitsas, Nikolaos S; Koutroubakis, Ioannis E

    2009-01-01

    The diagnosis of inflammatory bowel disease (IBD) depends on direct endoscopic visualization of the colonic and ileal mucosa and the histological study of the obtained samples. Radiological and scintigraphic methods are mainly used as an adjunct to endoscopy. In this review, we focus on the diagnostic potential of nuclear medicine procedures. The value of all radiotracers is described with special reference to those with greater experience and more satisfactory results. Tc-99m hexamethylpropylene amine oxime white blood cells remain a widely acceptable scintigraphic method for the diagnosis of IBD, as well as for the evaluation of disease extension and severity. Recently, pentavalent Tc-99m dimercaptosuccinic acid has been recommended as an accurate variant and a complementary technique to endoscopy for the follow-up and assessment of disease activity. Positron emission tomography alone or with computed tomography using fluorine-18 fluorodeoxyglucose appears to be a promising method of measuring inflammation in IBD patients. PMID:19522018

  14. Inflammatory bowel disease and coronary artery disease.

    PubMed

    Sappati Biyyani, Raja Shekhar R; Fahmy, Nabil M; Baum, Elizabeth; Nelson, Karl M; King, James F

    2009-01-01

    Chronic inflammation with the presence of excess serum acute-phase proteins, cytokines and cell adhesion molecules is increasingly being implicated in atherosclerosis. The association between inflammatory bowel disease (IBD) and coronary artery disease (CAD) is unstudied. This is a preliminary, thesis-generating cross-sectional study aimed at evaluating the presence of traditional atherosclerotic risk factors in patients with IBD and CAD compared with the control population. The medical records of 42 consecutive IBD patients with CAD from 1999 to 2005 (27 men) were reviewed for the Framingham risk factors. The Framingham risk score (FRS) is calculated based on age, sex, hypertension, diabetes and hyperlipidemia. FRS of patients with IBD and CAD was compared with the FRS of 137 age- and sex-matched (102 men) consecutive patients with CAD (controls). When the Framingham risk score adjusted for group and gender with age as a covariate, the adjusted total FRS score was higher in patients with CAD alone (10.0 [3.75]) as compared to those with; IBD and CAD: (8.1 [3.47]; p = 0.001). FRS is lower in cases (patients with IBD and CAD) when compared with the controls (CAD alone). PMID:19529899

  15. A Low Dose of Fermented Soy Germ Alleviates Gut Barrier Injury, Hyperalgesia and Faecal Protease Activity in a Rat Model of Inflammatory Bowel Disease

    PubMed Central

    Moussa, Lara; Bézirard, Valérie; Salvador-Cartier, Christel; Bacquié, Valérie; Lencina, Corinne; Lévêque, Mathilde; Braniste, Viorica; Ménard, Sandrine

    2012-01-01

    Pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF), IL-1β and TNF-α predominate in inflammatory bowel diseases (IBD) and TNBS colitis. Increased levels of serine proteases activating protease-activated receptor 2 (PAR-2) are found in the lumen and colonic tissue of IBD patients. PAR-2 activity and pro-inflammatory cytokines impair epithelial barrier, facilitating the uptake of luminal aggressors that perpetuate inflammation and visceral pain. Soy extracts contain phytoestrogens (isoflavones) and serine protease inhibitors namely Bowman-Birk Inhibitors (BBI). Since estrogens exhibit anti-inflammatory and epithelial barrier enhancing properties, and that a BBI concentrate improves ulcerative colitis, we aimed to evaluate if a fermented soy germ extract (FSG) with standardized isoflavone profile and stable BBI content exert cumulative or synergistic protection based on protease inhibition and estrogen receptor (ER)-ligand activity in colitic rats. Female rats received orally for 15 d either vehicle or FSG with or without an ER antagonist ICI 182.780 before TNBS intracolonic instillation. Macroscopic and microscopic damages, myeloperoxidase activity, cytokine levels, intestinal paracellular permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression were assessed 24 h, 3 d and 5 d post-TNBS. FSG treatment improved the severity of colitis, by decreasing the TNBS-induced rise in gut permeability, visceral sensitivity, faecal proteolytic activity and PAR-2 expression at all post-TNBS points. All FSG effects were reversed by the ICI 182.780 except the decrease in faecal proteolytic activity and PAR-2 expression. In conclusion, the anti-inflammatory properties of FSG treatment result from two distinct but synergic pathways i.e an ER-ligand and a PAR-2 mediated pathway, providing rationale for potential use as adjuvant therapy in IBD. PMID:23166707

  16. Macrophage Targeted Theranostics as Personalized Nanomedicine Strategies for Inflammatory Diseases

    PubMed Central

    Patel, Sravan Kumar; Janjic, Jelena M.

    2015-01-01

    Inflammatory disease management poses challenges due to the complexity of inflammation and inherent patient variability, thereby necessitating patient-specific therapeutic interventions. Theranostics, which integrate therapeutic and imaging functionalities, can be used for simultaneous imaging and treatment of inflammatory diseases. Theranostics could facilitate assessment of safety, toxicity and real-time therapeutic efficacy leading to personalized treatment strategies. Macrophages are an important cellular component of inflammatory diseases, participating in varied roles of disease exacerbation and resolution. The inherent phagocytic nature, abundance and disease homing properties of macrophages can be targeted for imaging and therapeutic purposes. This review discusses the utility of theranostics in macrophage ablation, phenotype modulation and inhibition of their inflammatory activity leading to resolution of inflammation in several diseases. PMID:25553105

  17. [Coexistence of coeliac disease and inflammatory bowel disease in children].

    PubMed

    Krawiec, Paulina; Pawłowska-Kamieniak, Agnieszka; Pac-Kożuchowska, Elżbieta; Mroczkowska-Juchkiewcz, Agnieszka; Kominek, Katarzyna

    2016-01-01

    Coeliac disease and inflammatory bowel disease are chronic inflammatory conditions of gastrointestinal tract with complex aetiology with genetic, environmental and immunological factors contributing to its pathogenesis. It was noted that immune-mediated disorders often coexist. There is well-known association between coeliac disease and type 1 diabetes and ulcerative colitis and primary sclerosing cholangitis. However, growing body of literature suggests the association between coeliac disease and inflammatory bowel disease, particularly ulcerative colitis. This is an extremely rare problem in paediatric gastroenterology. To date there have been reported several cases of children with coexisting coeliac disease and inflammatory bowel disease. Herewith we present review of current literature on coexistence of coeliac disease and inflammatory bowel disease in children. PMID:26891438

  18. Medicinal plants used in treatment of inflammatory skin diseases

    PubMed Central

    2013-01-01

    Skin is an organ providing contact with the environment and protecting the human body from unfavourable external factors. Skin inflammation, reflected adversely in its functioning and appearance, also unfavourably affects the psyche, the condition of which is important during treatment of chronic skin diseases. The use of plants in treatment of inflammatory skin diseases results from their influence on different stages of inflammation. The paper presents results of the study regarding the anti-inflammatory activity of the plant raw material related to its influence on skin. The mechanism of action, therapeutic indications and side effects of medicinal plants used for treatment of inflammatory diseases of the skin are described. PMID:24278070

  19. PPAR Regulation of Inflammatory Signaling in CNS Diseases

    PubMed Central

    Bright, John J.; Kanakasabai, Saravanan; Chearwae, Wanida; Chakraborty, Sharmistha

    2008-01-01

    Central nervous system (CNS) is an immune privileged site, nevertheless inflammation associates with many CNS diseases. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that regulate immune and inflammatory responses. Specific ligands for PPARα, γ, and δ isoforms have proven effective in the animal models of multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, and trauma/stroke, suggesting their use in the treatment of neuroinflammatory diseases. The activation of NF-κB and Jak-Stat signaling pathways and secretion of inflammatory cytokines are critical in the pathogenesis of CNS diseases. Interestingly, PPAR agonists mitigate CNS disease by modulating inflammatory signaling network in immune cells. In this manuscript, we review the current knowledge on how PPARs regulate neuroinflammatory signaling networks in CNS diseases. PMID:18670616

  20. Extraintestinal Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Schoepfer, Alain; Scharl, Michael; Lakatos, Peter L.; Navarini, Alexander; Rogler, Gerhard

    2015-01-01

    Abstract: Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD. PMID:26154136

  1. Extraintestinal Manifestations of Inflammatory Bowel Disease.

    PubMed

    Vavricka, Stephan R; Schoepfer, Alain; Scharl, Michael; Lakatos, Peter L; Navarini, Alexander; Rogler, Gerhard

    2015-08-01

    Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD. PMID:26154136

  2. Use of thiopurines in inflammatory bowel disease.

    PubMed

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen; Rogler, Gerhard

    2013-02-21

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine and thioguanine. We will briefly summarize dose recommendations, indications for thiopurine therapy and side effects which are relevant in clinical practice. We discuss some currently debated topics, including the combination of azathioprine and allopurinol, switching of thiopurine therapy in case of side effects, the use of azathioprine in pregnancy, the infection risk using thiopurines and the evidence when to stop thiopurines. Excellent reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail. PMID:23467510

  3. [Fecal Calprotectin in Inflammatory Bowel Disease].

    PubMed

    Lee, Jun

    2016-05-25

    Inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis comprise conditions characterized by chronic, relapsing immune activation and inflammation within the gastrointestinal tract. Objective estimation of intestinal inflammation is the mainstay in the diagnosis and observation of IBD, but is primarily dependent on expensive and invasive procedures such as endoscopy. Therefore, a simple, noninvasive, inexpensive, and accurate test would be extremely important in clinical practice. Fecal calprotectin is a calcium-containing protein released into the lumen that is excreted in feces during acute and chronic inflammation. It is well-researched, noninvasive, and has high sensitivity and specificity for identification of inflammation in IBD. This review will focus on the use of fecal calprotectin to help diagnose, monitor, and determine treatment in IBD. PMID:27206433

  4. Pelvic inflammatory disease among female recruit trainees, active component, U.S. Armed Forces, 2002-2012.

    PubMed

    Rohrbeck, Patricia

    2013-09-01

    Pelvic inflammatory disease (PID) is a bacterial infection causing an inflammatory reaction in the upper genital tract. It can be treated with antibiotics, but since it is often asymptomatic, women often delay seeking health care, which may result in long-term sequelae such as infertility. Among 161,501 female recruits who began basic training between January 2002 and December 2011, 1,750 (1.1%) met the surveillance case definition for PID during the 12 months following completion of their basic military training. The overall incidence rate (11.2 per 1,000 person-years) showed a stable trend during the surveillance period, with the exception of a decline for females accessed in 2011. The unadjusted rates were higher among women who were not screened for chlamydia during basic training. Compared to their respective counterparts, rates were higher in service women aged 17-20, of black, non-Hispanic race/ethnicity, married, in the Army, and who had a chlamydia diagnosis after basic training. The lowest rates were among women 25 years and older, other race/ethnicity, and in the Coast Guard. The findings in this report may warrant further evaluation of the long-term impact of chlamydia screening programs for recruit trainees on PID and PID-related sequelae among service women. PMID:24093960

  5. Sphingolipid metabolites in inflammatory disease

    PubMed Central

    Maceyka, Michael; Spiegel, Sarah

    2015-01-01

    Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes. Progress in our understanding of sphingolipid metabolism, state-of-the-art sphingolipidomic approaches and animal models have generated a large body of evidence demonstrating that sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate, are signalling molecules that regulate a diverse range of cellular processes that are important in immunity, inflammation and inflammatory disorders. Recent insights into the molecular mechanisms of action of sphingolipid metabolites and new perspectives on their roles in regulating chronic inflammation have been reported. The knowledge gained in this emerging field will aid in the development of new therapeutic options for inflammatory disorders. PMID:24899305

  6. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease*

    PubMed Central

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; de Freitas, Thaís Helena Proença; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  7. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.

    PubMed

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; Freitas, Thaís Helena Proença de; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  8. The Role of Fecal Calprotectin in Investigating Inflammatory Bowel Diseases

    PubMed Central

    Erbayrak, Mustafa; Turkay, Cansel; Eraslan, Elife; Cetinkaya, Hulya; Kasapoglu, Benan; Bektas, Mehmet

    2009-01-01

    INTRODUCTION: Invasive and non-invasive tests can be used to evaluate the activity of inflammatory bowel diseases. OBJECTIVE: The aim of the present study was to investigate the role of fecal calprotectin in evaluating inflammatory bowel disease activity and the correlation of fecal calprotectin with the erythrocyte sedimentation rate and C reactive protein values in inflammatory bowel disease. METHOD: Sixty-five patients affected with inflammatory bowel disease were enrolled. Twenty outpatients diagnosed with inflammatory bowel disease comprised the control group. RESULTS: In the present study, all patients in the control group had an fecal calprotectin value lower than the cut-off point (50 mg/kg). CONCLUSION: In conclusion, fecal calprotectin was found to be strongly associated with colorectal inflammation indicating organic disease. Fecal calprotectin is a simple and non-invasive method for assessing excretion of macrophages into the gut lumen. Fecal calprotectin values can be used to evaluate the response to treatment, to screen asymptomatic patients, and to predict inflammatory bowel disease relapses. PMID:19488608

  9. Biologic concentration testing in inflammatory bowel disease.

    PubMed

    Vaughn, Byron P; Sandborn, William J; Cheifetz, Adam S

    2015-06-01

    Anti-TNF medications have revolutionized the care of patients with inflammatory bowel disease. However, despite an initial robust effect, loss of response is common and long-term results are disappointing. Much of this lack of durability may be due to inadequate dose optimization, and recent studies suggest a correlation between serum drug concentrations and clinical outcomes. Currently, in clinical practice, measurement of drug concentrations and antibodies to drug are typically performed only when a patient presents with active inflammatory bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF ("reactive" setting). However, proactive monitoring of anti-TNF concentrations with titration to a therapeutic window (i.e., therapeutic concentration monitoring) represents a new strategy with many potential clinical benefits including prevention of immunogenicity, less need for IFX rescue therapy, and greater durability of IFX treatment. This review will cover the salient features of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach for the use of anti-TNF concentration testing in both the reactive and proactive settings. PMID:25590953

  10. Iron deficiency anemia in inflammatory bowel disease

    PubMed Central

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-01-01

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  11. Iron deficiency anemia in inflammatory bowel disease.

    PubMed

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-08-15

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  12. Allopurinol enhances the activity of hypoxanthine-guanine phosphoribosyltransferase in inflammatory bowel disease patients during low-dose thiopurine therapy: preliminary data of an ongoing series.

    PubMed

    Seinen, Margien L; de Boer, Nanne K H; Smid, Kees; van Asseldonk, Dirk P; Bouma, Gerd; van Bodegraven, Adriaan A; Peters, Godefridus J

    2011-12-01

    Thiopurines are crucial in the treatment of inflammatory bowel disease. The phenotype of pivotal metabolic enzymes determines whether thioguanine nucleotides (6-TGN) are generated in clinically sufficiently high levels. The first step in activation of thiopurine prodrugs to 6-TGN is catalysis by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Often, patients exhibit a clinically unfavorable metabolism, leading to discontinuation of conventional thiopurine therapy. The combination of allopurinol and low-dose thiopurine therapy may optimize this variant metabolism, presumably by affecting enzyme activities. We performed a prospective pharmacodynamic study to determine the effect of combination therapy on the activity of HGPRT. The activity of HGPRT and 6-TGN concentrations was measured in red blood cells during thiopurine monotherapy and after 4 weeks of combination therapy. The activity of HGPRT was also measured after 12 weeks of combination therapy. From the results, we conclude that combination therapy increases the activity of HGPRT and subsequently 6-TGN concentrations. PMID:22132961

  13. Inflammatory Bowel Disease and Nutrition

    MedlinePlus

    ... rcom ing any disease, especially inflammatory bowel disease (IBD). There can be many causes of inadequate nutrition in children and adolescents with IBD. First, a child’s appetite may decrease during a “ ...

  14. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

    PubMed Central

    Polizzotto, Mark N.; Uldrick, Thomas S.; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some

  15. Quality Improvement in Inflammatory Bowel Disease

    PubMed Central

    Siegel, Corey A.

    2013-01-01

    Chronic illnesses such as inflammatory bowel disease (IBD) present a unique opportunity to define and improve the quality of care. Processes of care can be complex, and outcomes of care may vary across different healthcare delivery settings. Patients with IBD are managed over long periods of time and often by the same physician within a single care delivery system. Both patients with Crohn’s disease and ulcerative colitis have variable courses of disease progression that require changes in therapy over time. These factors necessitate multiple areas of potential assessment and improvement of processes and outcomes of care. A current initiative is the development of quality measures. The American Gastroenterological Association has developed accountability measures for the Physician Quality Reporting System, and the Crohn’s and Colitis Foundation of America has developed a set of top 10 recommended processes and outcomes of measurement for high-quality care of patients with IBD. In addition, the pediatric ImproveCareNow collaborative network has collected improvement data from dozens of pediatric centers over the past 5 years and has demonstrated improvement in overall disease activity in their cohort through iterative quality improvement processes. Future directions for quality indicators for adults with IBD will involve implementation of quality-measure reporting, both for purposes of reimbursement as well as improvement of care. These strategies will need to be closely monitored to evaluate the effect of improvement programs on outcomes. PMID:23943663

  16. New pharmaceuticals in inflammatory bowel disease

    PubMed Central

    Łodyga, Michał; Eder, Piotr; Bartnik, Witold; Gonciarz, Maciej; Kłopocka, Maria; Linke, Krzysztof; Małecka-Panas, Ewa; Radwan, Piotr

    2015-01-01

    This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment. PMID:26557934

  17. Inflammatory bowel disease in ankylosing spondylitis

    PubMed Central

    Jayson, M. I. V.; Salmon, P. R.; Harrison, W. J.

    1970-01-01

    Routine detailed gastroenterological investigations were performed in a series of 47 ankylosing spondylitics. Evidence of chronic inflammatory bowel disease was found in eight patients, a prevalence of 17%. Unsuspected bowel disease was found in the absence of symptoms in three of these patients. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5430378

  18. Pharmacogenetics of thiopurines in inflammatory bowel disease.

    PubMed

    Derijks, Luc J J; Wong, Dennis R

    2010-01-01

    Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the genetic polymorphisms of genes encoding for glutathione S-tranferases, xanthine oxidase, thiopurine S-methyltransferase, inosine triphosphate pyrophosphatase, hypoxanthine phosphoribosyltransferase, inosine monophosphate dehydrogenase and multidrug resistance proteins. Pharmacogenetic knowledge in this field has increased dramatically and is still rapidly increasing, but the translation into practical guidelines with tailored advices will cost much effort in the near future. PMID:20205660

  19. Expression of CCL20 and Its Corresponding Receptor CCR6 Is Enhanced in Active Inflammatory Bowel Disease, and TLR3 Mediates CCL20 Expression in Colonic Epithelial Cells

    PubMed Central

    Skovdahl, Helene Kolstad; Granlund, Atle van Beelen; Østvik, Ann Elisabet; Bruland, Torunn; Bakke, Ingunn; Torp, Sverre Helge; Damås, Jan Kristian; Sandvik, Arne Kristian

    2015-01-01

    Background The chemokine CCL20 and its receptor CCR6 are putative drug targets in inflammatory bowel disease, and CCL20 is a novel IBD predilection gene. Previous findings on the CCL20 response in these diseases are divergent. This study was undertaken to examine CCL20 and CCR6 during active and inactive disease, and mechanisms for CCL20 regulation by the innate immune system. As TLR3 has recently emerged as a possible mediator of CCL20 production, we hypothesised that this TLR plays an important role in enterocytic CCL20 production. Methods A large microarray study on colonic pinch biopsies from active and inactive ulcerative colitis and Crohn’s disease provided background information. CCL20 and CCR6 were localized and their expression levels assessed in biopsies using in situ hybridization and immunohistochemistry. Regulation of CCL20 was studied in the HT29 cell line using a panel of pattern recognition receptor ligands followed by a TLR3 siRNA assay. Results CCL20 and CCR6 mRNA abundances were increased during active inflammation (CCL20 5.4-fold in ulcerative colitis and 4.2-fold in Crohn’s disease; CCR6 1.8 and 2.0, respectively). CCL20 and CCR6 mRNA positive immune cells in lamina propria were more numerous, and CCL20 immunoreactivity increased massively in the epithelial cells during active inflammation for both diseases. TLR3 stimulation potently induced upregulation and release of CCL20 from HT29 cells, and TLR3 silencing reduced CCL20 mRNA and protein levels. Conclusions The CCL20-CCR6 axis is involved during active inflammation in both ulcerative colitis and Crohn’s disease. The epithelial cells seem particularly involved in the CCL20 response, and results from this study strongly suggest that the innate immune system is important for activation of the epithelium, especially through TLR3. PMID:26536229

  20. Inflammatory Cutaneous Diseases in Renal Transplant Recipients

    PubMed Central

    Savoia, Paola; Cavaliere, Giovanni; Zavattaro, Elisa; Veronese, Federica; Fava, Paolo

    2016-01-01

    Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols. PMID:27548160

  1. Inflammatory markers in coronary artery disease.

    PubMed

    Ikonomidis, Ignatios; Michalakeas, Christos A; Parissis, John; Paraskevaidis, Ioannis; Ntai, Konstantina; Papadakis, Ioannis; Anastasiou-Nana, Maria; Lekakis, John

    2012-01-01

    Coronary artery disease (CAD) is one of the most common manifestations of atherosclerosis. Inflammation is considered one of the major processes that contribute to atherogenesis. Inflammation plays an important role not only on the initiation and progression of atherosclerosis but also on plaque rupture, an event that leads to acute vascular events. Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, and inflammatory biomarkers express different parts of the atherogenic process, regarding the initiation and progression of atherosclerosis or the destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers may prove to be useful in the detection, staging, and prognosis of patients with CAD. Furthermore, the fact that inflammatory processes are essential steps in the course of the disease offers future therapeutic targets for the interruption of the atherogenic process or for the management of acute events. PMID:22628054

  2. Pelvic Inflammatory Disease (For Teens)

    MedlinePlus

    ... of the fallopian tubes, uterus, or ovaries. Most girls with PID develop it after getting a sexually transmitted disease (STD) , such as chlamydia or gonorrhea. Girls who have sex with different partners or don' ...

  3. Information for patients about inflammatory bowel disease.

    PubMed

    Mansfield, J C; Tanner, A R; Bramble, M G

    1997-01-01

    In inflammatory bowel disease it is important that patients understand their condition since this helps to improve long-term management of the disease. The aim of this study was to assess the information given to patients with inflammatory bowel disease about their condition, its treatment and the National Association for Colitis and Crohn's disease. Two surveys were performed, using anonymous questionnaires. One was of all association members in north-east England, the other was a sample of patients attending medical outpatients. The surveys showed that more patients heard of the National Association for Colitis and Crohn's disease from the media than from medical sources. Of patients seen in medical clinics, 75% would welcome more information about their disease. In four of the six participating centres less than half the patients had been told about the existence of a patients' association. There was considerable variation in the instructions on what action to take in the event of a relapse. These findings suggest that the opportunity offered by out-patient clinics to educate and inform patients is often wasted. Clinicians often neglect to mention the National Association for Colitis and Crohn's disease, especially to patients with long-standing disease. A higher priority should be given to providing patients with appropriate information on inflammatory bowel disease. Three simple audit standards for the organisation of outpatient clinic information are proposed. PMID:9131520

  4. Probiotics for inflammatory bowel disease: a critical appraisal.

    PubMed

    Sans, Miquel

    2009-01-01

    The notion that the intestinal microbiota plays a key role for the development of intestinal inflammation, initially based on a series of clinical observations both in human inflammatory bowel disease and experimental colitis, has been reinforced by a growing body of evidence demonstrating that the abnormal recognition of bacterial and other microbiota antigens by the innate immune system is one of the earliest events in the pathogenesis of inflammatory bowel disease. In keeping with our present knowledge of inflammatory bowel disease pathophysiology, the search for therapeutic approaches aimed at modifying the composition of the intestinal microbiota to obtain new, more targeted treatments for inflammatory bowel disease that are basically free of side effects has been a subject of intense research activity. Probiotics are defined as live organisms capable of conferring health benefits beyond their nutritional properties. Numerous micro-organisms have been evaluated to induce or maintain remission, or both, in ulcerative colitis, Crohn's disease and pouchitis. Overall, probiotics have successfully demonstrated some efficacy in some inflammatory bowel disease scenarios. However, a critical review of the available scientific literature shows that: (1) in spite of great expectations, reflected by a high number of review and editorial articles in top journals, the number of published, well-designed clinical trials using probiotics in inflammatory bowel disease is small, often with few patients; (2) the range of microbial agents makes it particularly difficult to draw global conclusions; (3) the quality of the evidence on the efficacy of probiotics in pouchitis is clearly better than that in ulcerative colitis, while there is virtually no evidence of probiotic efficacy in Crohn's disease. The appropriate selection of probiotic agents combined with convincing clinical trials will determine whether probiotics can jump from promise to reality in inflammatory bowel disease

  5. Management of arthropathy in inflammatory bowel diseases

    PubMed Central

    Manguso, Francesco; Vitiello, Maria; Iervolino, Salvatore; Di Minno, Matteo Nicola Dario

    2015-01-01

    The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory to conventional therapy and in patients with associated articular manifestations. The treatment of peripheral involvement and/or enthesitis and/or dactylitis is based on local steroid injections, while sulfasalazine and/or low doses of systemic steroids may be useful in case of inadequate response to intra-articular steroids. Sulfasalazine induces only a little improvement in peripheral arthritis. Immunomodulators such as methotrexate, azathioprine, cyclosporine and leflunomide show their efficacy in some patients with peripheral arthritis and other extra-intestinal components. TNF-α inhibitors should be considered the first-line therapeutic approach when moderate-to-severe luminal Crohn’s disease or ulcerative colitis is associated with polyarthritis. The aim of this review is to provide a fair summary of current treatment options for the arthritis associated with IBD. PMID:25729557

  6. Update on Janus kinase antagonists in inflammatory bowel disease.

    PubMed

    Boland, Brigid S; Sandborn, William J; Chang, John T

    2014-09-01

    Janus kinase (JAK) inhibitors have emerged as a novel orally administered small-molecule therapy for the treatment of ulcerative colitis and possibly Crohn disease. These molecules are designed to selectively target the activity of specific JAKs and to offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease. PMID:25110261

  7. Inflammatory bowel diseases and reproductive health.

    PubMed

    Kokoszko-Bilska, Agnieszka; Sobkiewicz, Slawomir; Fichna, Jakub

    2016-08-01

    Inflammatory bowel diseases (IBD) constitute a group of chronic intestinal diseases, including Crohn's disease and ulcerative colitis, which typically involve patients of reproductive age and may influence several features of human reproduction. There are many concerns regarding the interactions between the course of IBD, applied treatment (pharmacological or surgical), and fertility, reproductive outcomes, and also neonatal outcomes. To review the literature describing fertility in IBD patients (separately for female and male), and possible infertility treatment in this group of patients, a PubMed search for English only publications (articles and/or abstracts) was conducted. Initially, the titles of publications and their abstracts were screened, and the most appropriate articles were selected and reviewed. Overall, in patients with quiescent IBD, fertility is almost identical to the general population, but particular subgroups of patients (with active disease, on pharmacological treatment, and after pelvic or abdominal surgery) may be affected by reduced fertility. Additionally, patients with IBD have fewer children than the general population, mainly as a result of voluntary childlessness. The main objectives for successful reproductive outcomes in IBD patients are proper guidance and also optimal treatment for achieving and maintaining disease remission. Recently, the European Evidence-Based Consensus on Reproduction and Pregnancy in IBD (the European Crohn's and Colitis Organization Guidelines) has been established to optimize preconceptional counseling and to promote an appropriate clinical management for patients planning to conceive. However, further studies are needed regarding the preservation of fertility in IBD patients and introduction of optimal infertility treatment in this group of patients. PMID:27117378

  8. Mesenchymal stem cells and inflammatory lung diseases.

    PubMed

    Iyer, S S; Co, C; Rojas, M

    2009-03-01

    Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lung diseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lung diseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lung diseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lung diseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury. PMID:19352305

  9. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. PMID:27589705

  10. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

  11. The role of psychological stress in inflammatory bowel disease.

    PubMed

    Mawdsley, Joel E; Rampton, David S

    2006-01-01

    Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the gastrointestinal tract whose natural history is one of periods of remission and relapse. The aetiology is complex and reflects an interaction between genes and environment. Psychological stress has long been reported by both doctors and patients as worsening disease activity in IBD. Prospective studies of the relationship between disease relapse and adverse life events have produced conflicting results, in part due to the inherent difficulties of such studies. However, several more recent analyses have suggested that both adverse life events and chronic perceived stress can contribute to disease relapse. There is also an increasing body of evidence to suggest that experimental stress can increase mucosal inflammation both in patients with IBD and in animal models of colitis. Despite this increase in understanding the pro-inflammatory effects of stress in IBD, thus far only a few limited studies have examined stress reduction as a therapeutic modality. PMID:17709955

  12. Chronic Inflammatory Diseases: Progress and Prospect with Herbal Medicine.

    PubMed

    Ghosh, Nilanjan; Ali, Asif; Ghosh, Rituparna; Das, Shaileyee; Mandal, Subhash C; Pal, Mahadeb

    2016-01-01

    Diseases associated with chronic inflammatory pathology claim a major share of worldwide deaths each year. A principal reason behind the huge number of casualties is associated with mild or unnoticed symptoms for long period of time since the outset, and that specific treatment options for these diseases have not yet emerged. Current anti-inflammatory drugs essentially have become ineffective for long term protection from these diseases as they also interfere with essential cellular pathways and associated toxicities. Notably, recent studies with a number of phytochemicals have shown promising results. These compounds isolated from various medicinal plants express their anti-inflammatory activities by down regulating expression of several crucial pro-inflammatory mediators. These are mostly antioxidants; inhibit induction of key transcription factors like nuclear factor kappa B (NF-κB) that are responsible for expression of proinflammatory mediators, and other growth regulators. Definitely, some of these compounds have the potential to be developed into new therapeutic agents to better control inflammation associated diseases in near future. This review summarizes recent findings on the molecular mechanisms through which various inflammatory activities are linked to disease progression and a group of natural products that have shown promise in controlling these processes. PMID:26561064

  13. Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD) Children in Relation to Growth and Disease Activity

    PubMed Central

    Martin, Francois-Pierre; Ezri, Jessica; Cominetti, Ornella; Da Silva, Laeticia; Kussmann, Martin; Godin, Jean-Philippe; Nydegger, Andreas

    2016-01-01

    Background: Growth failure and delayed puberty are well known features of children and adolescents with inflammatory bowel disease (IBD), in addition to the chronic course of the disease. Urinary metabonomics was applied in order to better understand metabolic changes between healthy and IBD children. Methods: 21 Pediatric patients with IBD (mean age 14.8 years, 8 males) were enrolled from the Pediatric Gastroenterology Outpatient Clinic over two years. Clinical and biological data were collected at baseline, 6, and 12 months. 27 healthy children (mean age 12.9 years, 16 males) were assessed at baseline. Urine samples were collected at each visit and subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy. Results: Using 1H NMR metabonomics, we determined that urine metabolic profiles of IBD children differ significantly from healthy controls. Metabolic differences include central energy metabolism, amino acid, and gut microbial metabolic pathways. The analysis described that combined urinary urea and phenylacetylglutamine—two readouts of nitrogen metabolism—may be relevant to monitor metabolic status in the course of disease. Conclusion: Non-invasive sampling of urine followed by metabonomic profiling can elucidate and monitor the metabolic status of children in relation to disease status. Further developments of omic-approaches in pediatric research might deliver novel nutritional and metabolic hypotheses. PMID:27529220

  14. Management of Musculoskeletal Manifestations in Inflammatory Bowel Disease

    PubMed Central

    Sheth, Tejas; Pitchumoni, C. S.; Das, Kiron M.

    2015-01-01

    Musculoskeletal manifestations are the most common extraintestinal manifestations in inflammatory bowel diseases. Some appendicular manifestations are independent of gut inflammation and are treated with standard anti-inflammatory strategies. On the other hand, axial involvement is linked to gut inflammatory activity; hence, there is a considerable amount of treatment overlap. Biological therapies have revolutionized management of inflammatory bowel diseases as well as of associated articular manifestations. Newer mechanisms driving gut associated arthropathy have surfaced in the past decade and have enhanced our interests in novel treatment targets. Introduction of biosimilar molecules is expected in the US market in the near future and will provide an opportunity for considerable cost savings on healthcare. A multidisciplinary approach involving a gastroenterologist, rheumatologist, and physical therapist is ideal for these patients. PMID:26170832

  15. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease.

    PubMed

    Orel, Rok; Kamhi Trop, Tina

    2014-09-01

    It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn's disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment. PMID:25206258

  16. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease

    PubMed Central

    Orel, Rok; Kamhi Trop, Tina

    2014-01-01

    It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment. PMID:25206258

  17. Structural brain lesions in inflammatory bowel disease

    PubMed Central

    Dolapcioglu, Can; Dolapcioglu, Hatice

    2015-01-01

    Central nervous system (CNS) complications or manifestations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic mechanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mechanisms. A direct causal relationship between inflammatory bowel disease (IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebrovascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment. PMID:26600970

  18. Mechanisms of Pediatric Inflammatory Bowel Disease.

    PubMed

    Peloquin, Joanna M; Goel, Gautam; Villablanca, Eduardo J; Xavier, Ramnik J

    2016-05-20

    Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, is characterized by chronic intestinal inflammation due to a complex interaction of genetic determinants, disruption of mucosal barriers, aberrant inflammatory signals, loss of tolerance, and environmental triggers. Importantly, the incidence of pediatric IBD is rising, particularly in children younger than 10 years. In this review, we discuss the clinical presentation of these patients and highlight environmental exposures that may affect disease risk, particularly among people with a background genetic risk. With regard to both children and adults, we review advancements in understanding the intestinal epithelium, the mucosal immune system, and the resident microbiota, describing how dysfunction at any level can lead to diseases like IBD. We conclude with future directions for applying advances in IBD genetics to better understand pathogenesis and develop therapeutics targeting key pathogenic nodes. PMID:27168239

  19. Infertility in men with inflammatory bowel disease

    PubMed Central

    Shin, Takeshi; Okada, Hiroshi

    2016-01-01

    Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms “IBD AND male infertility”, “Crohn’s disease AND male infertility”, “ulcerative colitis AND male infertility”. References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options. PMID:27602237

  20. Infertility in men with inflammatory bowel disease.

    PubMed

    Shin, Takeshi; Okada, Hiroshi

    2016-08-01

    Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms "IBD AND male infertility", "Crohn's disease AND male infertility", "ulcerative colitis AND male infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options. PMID:27602237

  1. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  2. Inflammatory Bowel Disease: School Nurse Management

    ERIC Educational Resources Information Center

    Kitto, Lisa

    2010-01-01

    Initial symptoms and diagnosis of inflammatory bowel disease (IBD) usually occur between 10 and 20 years of age, although younger cases are reported. The complicated nature of IBD diagnosis and treatment can interfere with physical and emotional development that normally occurs in school-age children and adolescents. The school nurse should be…

  3. Endothelium-platelet interactions in inflammatory lung disease.

    PubMed

    Tabuchi, Arata; Kuebler, Wolfgang M

    2008-01-01

    In addition to their established role in hemostasis, recent studies have identified platelets as key regulators of inflammatory reactions. Upon activation, platelets interact with both endothelial cells and circulating leukocytes. By receptor-mediated activation of interacting cell types and by release of mitogenic, pro-inflammatory and -coagulatory mediators, platelets contribute crucially to the initiation and propagation of pathological conditions and processes such as inflammatory bowel disease or atherosclerosis. In inflammatory lung disease, platelets play a critical role in the recruitment of neutrophils, eosinophils and lymphocytes as shown in experimental models of acute lung injury and allergic airway inflammation. Circulating platelet-leukocyte aggregates have been detected in patients with allergic asthma and cystic fibrosis, and in experimental lung injury. Here, we discuss the molecular mechanisms regulating the interaction of platelets with leukocytes, endothelial cells, and the subendothelial matrix with special regard to platelet kinetics in pulmonary microvessels and the putative role of platelets in inflammatory lung disorders. In light of the existing data from experimental and clinical studies it is conceivable that platelet adhesion molecules and platelet mediators provide promising targets for novel therapeutic strategies in inflammatory lung diseases. PMID:18625343

  4. Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

    PubMed Central

    Landy, Jonathan; Ronde, Emma; English, Nick; Clark, Sue K; Hart, Ailsa L; Knight, Stella C; Ciclitira, Paul J; Al-Hassi, Hafid Omar

    2016-01-01

    Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. PMID:27003989

  5. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

    PubMed Central

    2011-01-01

    More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors. PMID:21304099

  6. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  7. Diarrhea in chronic inflammatory bowel diseases.

    PubMed

    Wenzl, Heimo H

    2012-09-01

    Diarrhea is a common clinical feature of inflammatory bowel diseases and may be accompanied by abdominal pain, urgency, and fecal incontinence. The pathophysiology of diarrhea in these diseases is complex, but defective absorption of salt and water by the inflamed bowel is the most important mechanism involved. In addition to inflammation secondary to the disease, diarrhea may arise from a variety of other conditions. It is important to differentiate the pathophysiologic mechanisms involved in the diarrhea in the individual patient to provide the appropriate therapy. This article reviews microscopic colitis, ulcerative colitis, and Crohn's disease, focusing on diarrhea. PMID:22917170

  8. Pancreatic disorders in inflammatory bowel disease.

    PubMed

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-08-15

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  9. Proctectomy for inflammatory bowel disease.

    PubMed

    Bauer, J J; Gelernt, I M; Salk, B A; Kreel, I

    1986-01-01

    Between July 1973 and October 1984, we performed proctectomy either as part of a primary proctocolectomy or as a secondary staged procedure in 388 patients with ulcerative colitis and in 39 patients with Crohn's disease. The proctectomies were performed using a two-team synchronous approach. An intersphincteric or perimuscular technique was employed. All perineal wounds were closed and drained by suction drainage and the pelvic peritoneum was closed in all cases. Two patients died in the early postoperative period, one from a pulmonary embolus and one from sepsis. Three patients had to be reexplored for postoperative hemorrhage, in all cases from a branch of the superior hemorrhoidal artery. Postoperative perineal hematoma developed in two patients and perineal abscess developed in four patients which necessitated opening of the perineal skin wound. Nonhealing of the perineal wound occurred in 3 of 388 patients with ulcerative colitis and in 5 of 39 patients with Crohn's disease. No perineal dehiscence or hernias were seen. Postoperatively, one man was permanently impotent and two had prolonged but temporary impotence. Three patients had retrograde ejaculation at last follow-up. PMID:3484910

  10. Microbiota and Pelvic Inflammatory Disease

    PubMed Central

    Sharma, Harsha; Tal, Reshef; Clark, Natalie A.; Segars, James H.

    2014-01-01

    Female genital tract microbiota play a crucial role in maintaining health. Disequilibrium of the microbiota has been associated with increased risk of pelvic infections. In recent years, culture-independent molecular techniques have expanded understanding of the composition of genital microbiota and the dynamic nature of the microbiota. There is evidence that upper genital tract may not be sterile and may harbor microflora in the physiologic state. The isolation of bacterial vaginosis-associated organisms in women with genital infections establishes a link between pelvic infections and abnormal vaginal flora. With the understanding of the composition of the microbiota in healthy and diseased states, the next logical step is to identify the function of the newly identified microbes. This knowledge will further expand our understanding of the causation of pelvic infections, which may lead to more effective prevention and treatment strategies. PMID:24390920

  11. The etiology of pelvic inflammatory disease.

    PubMed

    Keith, L; Berger, G S

    1984-05-01

    The etiology of pelvic inflammatory disease (PID) is speculated upon based on reported incidence and epidemiological studies. In Western society, the incidence of PID (annual) is 1% among women aged 15-34 years and 2% in the high risk group of women aged 15-24 years. The annual incidence in the US is higher, at least 2% among fecund sexually active women aged 13-44 years. The medical consequences of PID are infertility, ectopic pregnancy, and chronic pelvic pain. Causative agents include Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis and various other aerobic and anaerobic microorganisms; however, the natural genital flora of females is so varied that determining actual causative agents is difficult. some case-control studies have determined risk factors for PID; these include particularly current or prior use of IUD, prior pelvic surgery, sexual activity (including number of partners), race, and prior PID acute infection. PID is not a sexually transmitted disease, but rather is classified as sexually derived. Use of barrier methods and oral contraceptives protects against PID. IUD use greatly increases the risk of PID, probably because of the avenue the device provides for organisms to ascend from the lower to the upper genital tract. The role of males in PID etiology is currently the subject of much discussion. It is theorized that the mechanical action of penis insertion in intercourse helps to move causative agents to the upper genital region; also, semen may carry vaginal flora through the cervical opening into the uterus and tubes. Menstruation and PID are closely associated, perhaps because the cervix dilates during bleedings. Research areas include: determination of role of sexual activity (and number of partners) in PID etiology; evaluation of events of menstruation that are predisposing; evaluation of relationship between bacteriosperma and lower and upper genital infections; relationship of particular contraceptive methods to PID

  12. Dry Eye: an Inflammatory Ocular Disease

    PubMed Central

    Hessen, Michelle; Akpek, Esen Karamursel

    2014-01-01

    Keratoconjunctivitis sicca, or dry eye, is a common ocular disease prompting millions of individuals to seek ophthalmological care. Regardless of the underlying etiology, dry eye has been shown to be associated with abnormalities in the pre-corneal tear film and subsequent inflammatory changes in the entire ocular surface including the adnexa, conjunctiva and cornea. Since the recognition of the role of inflammation in dry eye, a number of novel treatments have been investigated designed to inhibit various inflammatory pathways. Current medications that are used, including cyclosporine A, corticosteroids, tacrolimus, tetracycline derivatives and autologous serum, have been effective for management of dry eye and lead to measurable clinical improvement. PMID:25279127

  13. Associations of MICA Polymorphisms with Inflammatory Rheumatic Diseases

    PubMed Central

    Wang, Qingwen; Zhou, Xiaodong

    2015-01-01

    Inflammatory rheumatic diseases are characterized by inflammation resulting from the immune dysregulation that usually attacks joints, skin and internal organs. Many of them are considered as complex disease that may be predisposed by multiple genes and/or genetic loci, and triggered by environmental factors such as microbiome and cellular stress. The major histocompatibility complex class I chain-related gene A (MICA) is a highly polymorphic gene that encodes protein variants expressed under cellular stress conditions, and these MICA variants play important roles in immune activation and surveillance. Recently, accumulating evidences from both genetic and functional studies have suggested that MICA polymorphisms may be associated with various rheumatic diseases, and the expression of MICA variants may attribute to the altered immune responses in the diseases. The objective of this review is to discuss potential genetic associations and pathological relevance of MICA in inflammatory rheumatic diseases that may help us to understand pathogenesis contributing to the development of these diseases. PMID:26862354

  14. Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

    PubMed Central

    Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

    2015-01-01

    Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

  15. New serological biomarkers of inflammatory bowel disease

    PubMed Central

    Li, Xuhang; Conklin, Laurie; Alex, Philip

    2008-01-01

    Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Σ) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (ΣMan3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (ΣMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn’s disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and β-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)’s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically useful

  16. Impairment of the ABCA1 and SR-BI-mediated cholesterol efflux pathways and HDL anti-inflammatory activity in Alzheimer's disease.

    PubMed

    Khalil, Abdelouahed; Berrougui, Hicham; Pawelec, Graham; Fulop, Tamas

    2012-01-01

    The aim of our study was to investigate the effect of Alzheimer's disease (AD) on the cholesterol efflux capacity and anti-inflammatory activity of HDL. HDL and apoA-I were isolated from 20 healthy subjects and from 39 AD patients. Our results showed that serum- and HDL-mediated cholesterol efflux is significantly impaired in AD patients. This impairment of serum and HDL cholesterol efflux capacity was significantly inversely correlated to the AD severity as evaluated by MMSE scores. Results obtained from SR-BI-enriched Fu5AH and ABCA1-enriched J774 cells revealed that AD impaired the interaction of HDL and apoA-I with both the ABCA1 transporter and SR-BI receptor. Purified apoA-I from AD patients also failed to remove free excess cholesterol from ABCA1-enriched J774 macrophages. Interestingly, the decrease in plasma α-tocopherol content and the increase in MDA formation and HDL relative electrophoretic mobility indicated that AD patients had higher levels of oxidative stress. The anti-inflammatory activity of HDL was also significantly lower in AD patients as measured by the level of ICAM-1 expression. In conclusion, our study provides evidence for the first time that the functionality of HDL is impaired in AD and that this alteration might be caused by AD-associated oxidative stress and inflammation. PMID:22178419

  17. Polymicrobial synergy and dysbiosis in inflammatory disease

    PubMed Central

    Lamont, Richard J.; Hajishengallis, George

    2014-01-01

    Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy among metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases. PMID:25498392

  18. Inflammatory Diseases of the Teeth and Jaws.

    PubMed

    Zohrabian, Vahe M; Abrahams, James J

    2015-10-01

    The teeth are unique in that they provide a direct pathway for spread of infection into surrounding osseous and soft tissue structures. Periodontal disease is the most common cause of tooth loss worldwide, referring to infection of the supporting structures of the tooth, principally the gingiva, periodontal ligament, cementum, and alveolar bone. Periapical disease refers to an infectious or inflammatory process centered at the root apex of the tooth, usually occurring when deep caries infect the pulp chamber and root canals. We review the pathogenesis, clinical features, and radiographic findings (emphasis on computed tomography) in periodontal and periapical disease. PMID:26589697

  19. Chronic Inflammatory Diseases and Endothelial Dysfunction

    PubMed Central

    Castellon, Xavier; Bogdanova, Vera

    2016-01-01

    Chronic inflammatory diseases are associated with increases in cardiovascular diseases (CVD) and subclinical atherosclerosis as well as early-stage endothelial dysfunction screening using the FMD method (Flow Mediated Dilation). This phenomenon, referred to as accelerated pathological remodeling of arterial wall, could be attributed to traditional risk factors associated with atherosclerosis. Several new non-invasive techniques have been used to study arterial wall’s structural and functional alterations. These techniques (based of Radio Frequency, RF) allow for an assessment of artery age through calculations of intima-media thickness (RF- QIMT), pulse wave rate (RF- QAS) and endothelial dysfunction degree (FMD). The inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors, result of the major consequences of oxidative stress and RAS (Renin Angiotensin System) imbalance associated with the deleterious effect of known risk factors that lead to the alteration of the arterial wall. Inflammation plays a key role in all stages of the formation of vascular lesions maintained and exacerbated by the risk factors. The consequence of chronic inflammation is endothelial dysfunction that sets in and we can define it as an integrated marker of the damage to arterial walls by classic risk factors. The atherosclerosis, which develops among these patients, is the main cause for cardiovascular morbi-mortality and uncontrolled chronic biological inflammation, which quickly favors endothelial dysfunction. These inflammatory and autoimmune diseases should now be considered as new cardiovascular risk factors. PMID:26815098

  20. Developmental origins of inflammatory and immune diseases.

    PubMed

    Chen, Ting; Liu, Han-Xiao; Yan, Hui-Yi; Wu, Dong-Mei; Ping, Jie

    2016-08-01

    Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic-pituitary-adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention. PMID:27226490

  1. Occult spondyloarthritis in inflammatory bowel disease.

    PubMed

    Bandinelli, Francesca; Manetti, Mirko; Ibba-Manneschi, Lidia

    2016-02-01

    Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients. PMID:26354428

  2. Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation.

    PubMed

    Planagumà, A; Domènech, T; Pont, M; Calama, E; García-González, V; López, R; Aulí, M; López, M; Fonquerna, S; Ramos, I; de Alba, J; Nueda, A; Prats, N; Segarra, V; Miralpeix, M; Lehner, M D

    2015-10-01

    Neutrophil infiltration and activation in the lung are important pathophysiological features in COPD, severe asthma and bronchiectasis mostly mediated by CXCL8 and CXCL1 via CXCR1 and CXCR2. No thorough study to date has been performed to compare the anti-inflammatory effect profile of dual CXCR1/2 vs. selective CXCR2 antagonists in relevant human neutrophil assays and pulmonary inflammation models. Dual CXCR1/2 (SCH527123, diaminocyclobutandione-1) and selective CXCR2 (SB265610, thiopyrimidine-1) antagonist activity and receptor residence time were determined by [(35)S]GTPγS binding in human (h)- and guinea pig (gp)-CXCR1 and CXCR2 overexpressing membranes. h-neutrophil chemotaxis, degranulation and ROS production were established using CXCL8 or CXCL1 to evaluate dual CXCR1/2- or selective CXCR2-dependent activities. LPS-induced lung inflammation in gp was selected to assess in vivo potency. Dual CXCR1/2 antagonists blocked both CXCL8 and CXCL1-induced h-neutrophil functions and [(35)S]GTPγS binding. In contrary, selective CXCR2 antagonists displayed significantly reduced potency in CXCL8 -mediated h-neutrophil responses despite being active in CXCR2 assays. Upon LPS challenge in gp, administration of SCH527123 inhibited the increase of neutrophils in BALF, modestly reduced blood neutrophils and induced minor neutrophil accumulation in bone marrow. Differentiation of CXCR1/2 vs. CXCR2 antagonists could not be extended to in vivo due to differences in CXCR1 receptor homology between h and gp. Dual CXCR1/2 therapy may represent a promising anti-inflammatory treatment for respiratory diseases reducing more effectively neutrophil migration and activation in the lung than a CXCR2 selective treatment. However, the in vivo confirmation of this claim is still missing due to species differences in CXCR1. PMID:26271598

  3. Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.

    PubMed

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia. PMID:25760987

  4. Preventive Effects of a Fermented Dairy Product against Alzheimer’s Disease and Identification of a Novel Oleamide with Enhanced Microglial Phagocytosis and Anti-Inflammatory Activity

    PubMed Central

    Ano, Yasuhisa; Ozawa, Makiko; Kutsukake, Toshiko; Sugiyama, Shinya; Uchida, Kazuyuki; Yoshida, Aruto; Nakayama, Hiroyuki

    2015-01-01

    Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer’s disease and to identify the responsible component. Here, in a mouse model of Alzheimer’s disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer’s disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia. PMID:25760987

  5. Inflammatory bowel disease: clinics and pathology. Do inflammatory bowel disease and periodontal disease have similar immunopathogeneses?

    PubMed

    Brandtzaeg, P

    2001-08-01

    Inflammatory bowel disease (IBD) comprises two chronic, tissue-destructive, clinical entities Crohn disease (CD) and ulcerative colitis (UC) both apparently caused by immunological overreaction (hypersensitivity) to commensal gut bacteria. Under normal conditions the intestinal immune system shows a down-regulating tone ('oral tolerance') against dietary antigens and the indigenous microbiota. This local homeostasis is disturbed in IBD, leading to hyperactivation of T helper 1 (Th1) cells with abundant secretion of interferon-gamma and tumor necrosis factor (TNF) and production of IgG antibodies against commensal bacteria. In addition, UC includes genetically determined autoimmunity, particularly IgG1-mediated cytotoxic epithelial attack. Breaching of the epithelium is the best-defined event underlying abrogation of oral tolerance, but immune deviation caused by cytokines fiom irritated epithelial cells or subepithelial elements (for example, mast cells, natural killer cells, macrophages) may also be involved. Endogenous infection with local hypersensitivity likewise causes periodontal disease, reflecting 'frustrated' immune elimination mechanisms entertained by antigens from dental plaque. Altogether, perturbation of a tightly controlled cytokine network, with abnormal crosstalk between several cell types, apparently explains the progressive immunopathology of chronic inflammatory mucosal diseases in general. This adverse development will be influenced by numerous immunity genes, the dosage and potential pathogeniciy of commensal bacteria, general health, nutritional status, and psychological factors. Several targets for new therapy have tentatively been identified to block immunopathological mechanisms in IBD, and inhibition of TNF has a striking beneficial effect in CD, supporting a central role of this cytokine. PMID:11570527

  6. Sleep Loss Activates Cellular Inflammatory Signaling

    PubMed Central

    Irwin, Michael R.; Wang, Minge; Ribeiro, Denise; Cho, Hyong Jin; Olmstead, Richard; Breen, Elizabeth Crabb; Martinez-Maza, Otoniel; Cole, Steve

    2008-01-01

    Background Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF) -κB, a transcription factor that serves a critical role in the inflammatory signaling cascade. Methods In 14 healthy adults (7 females; 7 males), peripheral blood mononuclear cell NF-κB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 23:00 h to 03:00 h), and recovery sleep. Results In the morning after a night of sleep loss, mononuclear cell NF-κB activation was significantly greater compared with morning levels following uninterrupted baseline or recovery sleep, in which the response was found in females but not in males. Conclusions These results identify NF-κB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease. PMID:18561896

  7. Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics.

    PubMed

    Osiri, Manathip; Wongpiyabovorn, Jongkonnee; Sattayasomboon, Youwanuch; Thammacharoenrach, Niramol

    2016-07-01

    The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-γ, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-α in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA. PMID:27188857

  8. Xanthine Oxidase Activity Is Associated with Risk Factors for Cardiovascular Disease and Inflammatory and Oxidative Status Markers in Metabolic Syndrome: Effects of a Single Exercise Session

    PubMed Central

    Feoli, Ana Maria Pandolfo; Macagnan, Fabrício Edler; Piovesan, Carla Haas; Bodanese, Luiz Carlos; Siqueira, Ionara Rodrigues

    2014-01-01

    Objective. The main goal of the present study was to investigate the xanthine oxidase (XO) activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. Materials/Methods. A case-control study (9 healthy and 8 MS volunteers) was performed to measure XO, superoxide dismutase (SOD), glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP) content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Results. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Conclusions. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome. PMID:24967004

  9. Environment and the inflammatory bowel diseases.

    PubMed

    Frolkis, Alexandra; Dieleman, Levinus A; Barkema, Herman W; Panaccione, Remo; Ghosh, Subrata; Fedorak, Richard N; Madsen, Karen; Kaplan, Gilaad G

    2013-03-01

    Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breastfeeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology. PMID:23516681

  10. Surgical strategies in paediatric inflammatory bowel disease

    PubMed Central

    Baillie, Colin T; Smith, Jennifer A

    2015-01-01

    Inflammatory bowel disease (IBD) comprises two distinct but related chronic relapsing inflammatory conditions affecting different parts of the gastrointestinal tract. Crohn’s disease is characterised by a patchy transmural inflammation affecting both small and large bowel segments with several distinct phenotypic presentations. Ulcerative colitis classically presents as mucosal inflammation of the rectosigmoid (distal colitis), variably extending in a contiguous manner more proximally through the colon but not beyond the caecum (pancolitis). This article highlights aspects of the presentation, diagnosis, and management of IBD that have relevance for paediatric practice with particular emphasis on surgical considerations. Since 25% of IBD cases present in childhood or teenage years, the unique considerations and challenges of paediatric management should be widely appreciated. Conversely, we argue that the organizational separation of the paediatric and adult healthcare worlds has often resulted in late adoption of new approaches particularly in paediatric surgical practice. PMID:26034347

  11. Extraluminal factors contributing to inflammatory bowel disease

    PubMed Central

    Batra, Arvind; Stroh, Thorsten; Siegmund, Britta

    2011-01-01

    Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease (IBD). The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors, which together result in dysregulation of the mucosal immune system. Thus, the majority of previous studies have focused on the immune response within the intestinal wall. The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process, namely the mesenteric fat tissue, the lymphatics and the microvasculature. Broadening our view across the intestinal wall will not only facilitate our understanding of the disease, but will also us to identify future therapeutic targets. PMID:21350706

  12. Xanthogranulomatous cystitis associated with inflammatory bowel disease

    PubMed Central

    Chung, Doreen E.; Carr, Lesley K.; Sugar, Linda; Hladunewich, Michelle; Deane, Leslie A.

    2010-01-01

    Xanthogranulomatous inflammation is a benign condition characterized by the presence of multinucleated giant cells, chronic inflammatory cells and lipid-laden macrophages, known as xanthoma cells. Only 22 cases of xanthogranulomatous cystitis (XGC) have been reported in the Japanese and English literature. In this report, we describe the twenty-third case of XGC and the third case associated with inflammatory bowel disease (IBD). A 50-year-old woman with quiescent Crohn’s disease was incidentally found to have a bladder mass on ultrasound. The lesion was resected through a transurethral approach. Pathology demonstrated XGC. At 3 months post-resection, there was no evidence of recurrence adjacent to the previous resection scar. PMID:20694091

  13. Role of Diet in Inflammatory Bowel Disease.

    PubMed

    Ruemmele, Frank M

    2016-01-01

    The incidence of inflammatory bowel disease (IBD) is steadily in the rise in Western as well as in developing countries paralleling the increase of westernized diets, characterized by high protein and fat as well as excessive sugar intake, with less vegetables and fiber. An interesting hypothesis is that environmental (food-) triggered changes of the intestinal microbiome might cause a proinflammatory state preceding the development of IBD. Indeed, an intact intestinal epithelial barrier assuring a normal bacterial clearance of the intestinal surface is crucial to guarantee intestinal homeostasis. Any factors affecting the epithelial barrier function directly or indirectly may impact on this homeostasis, as well as any changes of the intestinal microbial composition. It is intriguing to learn that some frequently used food components impact on the quality of the intestinal barrier, as well as on the composition of the intestinal microbiome. This highlights the close interaction between living conditions, hygiene, food habits and food quality with the bacterial composition of the intestinal microbiome and the activation status of the intestinal immune system. There is clear evidence that nutritional therapy is highly successful in the treatment of Crohn's disease (CD). Exclusive enteral nutrition is well established as induction therapy of CD. New diets, such as a CD exclusion diet or defined diets (specific carbohydrate diets, FODMAP diet, Paleolithic diet) are being discussed as treatment options for IBD. Well-designed clinical trials in IBD are urgently required to define the precise role of each of these diets in the prevention or management of IBD. Up to now, the role of diet in IBD is highly undermined by lay and anecdotal reports without sufficient scientific proof. PMID:27355913

  14. Serologic celiac disease in patients with inflammatory bowel disease

    PubMed Central

    Tavakkoli, Hamid; Haghdani, Saeid; Adilipour, Haiedeh; Daghaghzadeh, Hamed; Minakari, Mohammad; Adibi, Peyman; Ahmadi, Khalil; Emami, Mohammah Hasan

    2012-01-01

    Background: There is an association of celiac disease (CD) with several gastrointestinal illnesses. We aimed to determine the prevalence of CD in patients with inflammatory bowel disease (IBD) to evaluate the value of the routine serological tests for CD in these patients. Materials and Methods: patients with IBD underwent screening test for CD. The screening test was based on IgA anti-tTG antibody evaluated by ELISA method and IgA EMA (endomysial antibody) measured by the indirect immunofluorescence method. Fisher exact and chi-square and t tests were used for data analysis. Results: the study was conducted on 100 patients, with a mean age of 34.74 ± 12.03 (SD) years. The mean simplified Crohn's disease activity index was 90 ± 17 (SE) and the mean colitis activity index was 3.46± 0.96 (SE). Seventeen patients (17%) had IgA anti-tTG antibody levels above the cutoff point (> 20). Thirty-two patients were positive for IgA EMA. IgA EMA was positive in nine IgA anti-tTG positive patients (three patients with Crohn's Disease and six ones with ulcerative colitis). Then, the prevalence of serologic CD was 9% that was higher than that of general population. A significant correlation was found between the results of IgA EMA and those of IgA anti-tTG (P=0.001) whereas Fisher exact test revealed significant difference between frequency distribution of positive and negative results of IgA EMA and IgA anti-tTG in patients with ulcerative colitis and Crohn's disease (P=0). Conclusion: the prevalence of serologic CD in general population in Iran has been reported to be 0.6–0.96%. Then, its prevalence in our sample size was about ten times more than that in general population. PMID:23264789

  15. Nutritional concerns in pediatric inflammatory bowel disease

    PubMed Central

    2016-01-01

    The pathophysiology and fundamental etiologic mechanism of inflammatory bowel disease (IBD) is not well understood even though therapeutic regimens and drugs are rapidly evolutionary. IBD has complicated connections with genetic, immunologic, gut microbial, environmental, and nutritional factors. It is not clearly well known to the physicians how to feed, what nutrients are more helpful, and what food to be avoided. This review discusses the issues of growth and important nutritional concerns in the management of IBD in childhood. PMID:27462352

  16. Biologic targeting in the treatment of inflammatory bowel diseases

    PubMed Central

    Bosani, Matteo; Ardizzone, Sandro; Porro, Gabriele Bianchi

    2009-01-01

    The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of “controlled” inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-α], interferon-gamma [IFN-γ], interleukin-1 [IL-1], IL-6, IL-12 and anti-inflammatory cytokines IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may therefore be a logical target for inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-κB), and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn’s disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn’s disease. Therapeutics agents to inhibit leukocyte trafficking

  17. Biologic targeting in the treatment of inflammatory bowel diseases.

    PubMed

    Bosani, Matteo; Ardizzone, Sandro; Porro, Gabriele Bianchi

    2009-01-01

    The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which nonspecifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Under normal situations, the intestinal mucosa is in a state of "controlled" inflammation regulated by a delicate balance of proinflammatory (tumor necrosis factor [TNF-alpha], interferon-gamma [IFN-gamma], interleukin-1 [IL-1], IL-6, IL-12 and anti-inflammatory cytokines IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may therefore be a logical target for inflammatory bowel disease therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-kappaB), and other miscellaneous therapies are being evaluated as potential therapies for the treatment of inflammatory bowel disease. In this context, infliximab and adalimumab are currently the only biologic agents approved in Europe for the treatment of inflammatory Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP571, certolizumab pegol, etanercept, onercept. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanism involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutics agents to inhibit leukocyte trafficking

  18. The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities.

    PubMed

    Choi, Jae Sue; Islam, Md Nurul; Ali, Md Yousof; Kim, Young Myeong; Park, Hye Jin; Sohn, Hee Sook; Jung, Hyun Ah

    2014-10-01

    To investigate the effect of C-glycosylation at different positions of luteolin, the structure-activity relationships of luteolin and a pair of isomeric C-glycosylated derivatives orientin and isoorientin, were evaluated. We investigated the effects of C-glycosylation on the antioxidant, anti-Alzheimer's disease (AD), anti-diabetic and anti-inflammatory effects of luteolin and its two C-glycosides via in vitro assays of peroxynitrite (ONOO(-)), total reactive oxygen species (ROS), nitric oxide (NO), 1,1-diphenyl-2-picrylhydraxyl (DPPH), aldose reductase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor cleaving enzyme 1 (BACE1), and cellular assays of NO production and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Of the three compounds, isoorientin showed the highest scavenging activity against DPPH, NO, and ONOO(-), while luteolin was the most potent inhibitor of ROS generation. In addition, luteolin showed the most potent anti-AD activity as determined by its inhibition of AChE, BChE, and BACE1. With respect to anti-diabetic effects, luteolin exerted the strongest inhibitory activity against PTP1B and rat lens aldose reductase. Luteolin also inhibited NO production and iNOS protein expression in LPS-stimulated macrophages, while orientin and isoorientin were inactive at the same concentrations. The effects of C-glycosylation at different positions of luteolin may be closely linked to the intensity and modulation of antioxidant, anti-AD, anti-diabetic, and anti-inflammatory effects of luteolin and its C-glycosylated derivatives. PMID:24988985

  19. Non-invasive investigation of inflammatory bowel disease

    PubMed Central

    Tibble, JA; Bjarnason, I

    2001-01-01

    The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn’s disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn’s disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4-day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated. PMID:11819811

  20. Inflammatory Bowel Disease: Changing Associations to Mechanisms.

    PubMed

    Click, Benjamin; Whitcomb, David C

    2016-01-01

    Managing the health of individual patients suffering from complex disorders is a challenge and is costly. Inflammatory bowel disease (IBD) is a prototypic complex disorder of the small and large intestines. Susceptibility is complex, severity is variable, and response to treatment is unpredictable. Di Narzo et al. (Clin Transl Gastroenterol 7: e177; doi:10.1038/ctg.2016.34) bring diverse teams of physicians and scientists together to break down the mechanisms of IBD by linking pathogenic genetic variants with altered gene expression in specific cell types causing IBD. Framing new findings in the context of other complex diseases provides a roadmap for predictive medicine. PMID:27607898

  1. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    PubMed Central

    Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

    2013-01-01

    Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

  2. Update of fecal markers of inflammation in inflammatory bowel disease.

    PubMed

    Judd, Thomas A; Day, Andrew S; Lemberg, Daniel A; Turner, Dan; Leach, Steven T

    2011-10-01

    The diagnosis, prognosis, and assessment of disease activity of inflammatory bowel disease (IBD) require investigating clinical, radiological, and histological criteria, as well as serum inflammatory markers. However, a range of fecal inflammatory markers now appears to have the potential to greatly assist in these processes. Calprotectin, a prominent neutrophil protein, was identified two decades ago as a potentially revolutionary marker for IBD. Following this discovery, numerous additional markers, including S100A12, lactoferrin, and M2-pyruvate kinase, have also been suggested as novel markers of IBD. In the present study, we provide an up-to-date review of fecal markers of IBD, and further, provide a novel analysis of each of these fecal markers in severe ulcerative colitis and compare their expression pattern in contrast to calprotectin. PMID:21777275

  3. Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

    PubMed Central

    O'Sullivan, Shane; Gilmer, John F.

    2015-01-01

    Matrix metalloproteinases (MMPs) are known to be upregulated in inflammatory bowel disease (IBD) and other inflammatory conditions, but while their involvement is clear, their role in many settings has yet to be determined. Studies of the involvement of MMPs in IBD since 2006 have revealed an array of immune and stromal cells which release the proteases in response to inflammatory cytokines and growth factors. Through digestion of the extracellular matrix and cleavage of bioactive proteins, a huge diversity of roles have been revealed for the MMPs in IBD, where they have been shown to regulate epithelial barrier function, immune response, angiogenesis, fibrosis, and wound healing. For this reason, MMPs have been recognised as potential biomarkers for disease activity in IBD and inhibition remains a huge area of interest. This review describes new roles of MMPs in the pathophysiology of IBD and suggests future directions for the development of treatment strategies in this condition. PMID:25948887

  4. Pulmonary manifestations of inflammatory bowel disease

    PubMed Central

    Majewski, Sebastian

    2015-01-01

    Bronchopulmonary signs and symptoms are examples of variable extraintestinal manifestations of the inflammatory bowel diseases (IBD). These complications of Crohn's disease (CD) and ulcerative colitis (UC) seem to be underrecognized by both pulmonary physicians and gastroenterologists. The objective of the present review was to gather and summarize information on this particular matter, on the basis of available up-to-date literature. Tracheobronchial involvement is the most prevalent respiratory presentation, whereas IBD-related interstitial lung disease is less frequent. Latent and asymptomatic pulmonary involvement is not unusual. Differential diagnosis should always consider infections (mainly tuberculosis) and drug-induced lung pathology. The common link between intestinal disease and lung pathology is unknown, but many hypotheses have been proposed. It is speculated that environmental pollution, common immunological mechanisms and predisposing genetic factors may play a role. PMID:26788078

  5. Pulmonary manifestations of inflammatory bowel disease.

    PubMed

    Majewski, Sebastian; Piotrowski, Wojciech

    2015-12-10

    Bronchopulmonary signs and symptoms are examples of variable extraintestinal manifestations of the inflammatory bowel diseases (IBD). These complications of Crohn's disease (CD) and ulcerative colitis (UC) seem to be underrecognized by both pulmonary physicians and gastroenterologists. The objective of the present review was to gather and summarize information on this particular matter, on the basis of available up-to-date literature. Tracheobronchial involvement is the most prevalent respiratory presentation, whereas IBD-related interstitial lung disease is less frequent. Latent and asymptomatic pulmonary involvement is not unusual. Differential diagnosis should always consider infections (mainly tuberculosis) and drug-induced lung pathology. The common link between intestinal disease and lung pathology is unknown, but many hypotheses have been proposed. It is speculated that environmental pollution, common immunological mechanisms and predisposing genetic factors may play a role. PMID:26788078

  6. The Role of Physical Exercise in Inflammatory Bowel Disease

    PubMed Central

    Bilski, Jan; Brzozowski, Bartosz; Mazur-Bialy, Agnieszka; Sliwowski, Zbigniew; Brzozowski, Tomasz

    2014-01-01

    We reviewed and analyzed the relationship between physical exercise and inflammatory bowel disease (IBD) which covers a group of chronic, relapsing, and remitting intestinal disorders including Crohn's disease (CD) and ulcerative colitis. The etiology of IBD likely involves a combination of genetic predisposition and environmental risk factors. Physical training has been suggested to be protective against the onset of IBD, but there are inconsistencies in the findings of the published literature. Hypertrophy of the mesenteric white adipose tissue (mWAT) is recognized as a characteristic feature of CD, but its importance for the perpetuation of onset of this intestinal disease is unknown. Adipocytes synthesize proinflammatory and anti-inflammatory cytokines. Hypertrophy of mWAT could play a role as a barrier to the inflammatory process, but recent data suggest that deregulation of adipokine secretion is involved in the pathogenesis of CD. Adipocytokines and macrophage mediators perpetuate the intestinal inflammatory process, leading to mucosal ulcerations along the mesenteric border, a typical feature of CD. Contracting skeletal muscles release biologically active myokines, known to exert the direct anti-inflammatory effects, and inhibit the release of proinflammatory mediators from visceral fat. Further research is required to confirm these observations and establish exercise regimes for IBD patients. PMID:24877092

  7. Role of antibiotics for treatment of inflammatory bowel disease

    PubMed Central

    Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

    2016-01-01

    Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn’s disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms

  8. Role of antibiotics for treatment of inflammatory bowel disease.

    PubMed

    Nitzan, Orna; Elias, Mazen; Peretz, Avi; Saliba, Walid

    2016-01-21

    Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms

  9. Environmental triggers for inflammatory bowel disease.

    PubMed

    Ananthakrishnan, Ashwin N

    2013-01-01

    Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis (UC)] are chronic immunologically mediated diseases that are due to a dysregulated immune response to intestinal flora in a genetically susceptible host. Despite advances in genetics, the likelihood of occurrence of disease remains incompletely explained and there appears to be a strong role for the environment in mediating risk of disease. Smoking remains the most widely studied and replicated risk factor, contributing to increased risk and severity of CD while conferring protection against UC. Recent data has suggested novel risk factors. Lower plasma vitamin D is associated with an increased risk of Crohn's disease, and vitamin D supplementation may prevent relapse of disease. Several medications including oral contraceptives, post-menopausal hormone replacement, aspirin, NSAIDs, and antibiotics may increase risk of CD or UC with the mechanisms of effect remaining inadequately defined. There is continuing evidence that depression and psychosocial stress may play a role in the pathogenesis of both CD and UC, while at the same time also increasing risk for disease flares. There is also a growing understanding of the role of diet on IBD, in particular through its effect on the microbiome. Animal protein intake and n-6 fatty acids may increase risk of UC while n-3 fatty acids and dietary fiber may confer protection. The effect of diet on established disease remains poorly studied. There is need for routine measurement of a spectrum of environmental exposures in prospective studies to further our understanding. PMID:23250702

  10. Oral pathology in inflammatory bowel disease

    PubMed Central

    Muhvić-Urek, Miranda; Tomac-Stojmenović, Marija; Mijandrušić-Sinčić, Brankica

    2016-01-01

    The incidence of inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine. PMID:27433081

  11. Oral pathology in inflammatory bowel disease.

    PubMed

    Muhvić-Urek, Miranda; Tomac-Stojmenović, Marija; Mijandrušić-Sinčić, Brankica

    2016-07-01

    The incidence of inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine. PMID:27433081

  12. Metabolomics – A novel window into inflammatory disease

    PubMed Central

    Fitzpatrick, Martin; Young, Stephen P

    2015-01-01

    Inflammation is an important component of normal responses to infection and injury. However, chronic activation of the immune system, perhaps due to aberrant responses to normal stimuli, can lead to the establishment of a chronic inflammatory state. Such inflammatory conditions are often debilitating, and are associated with a number of important co-morbidities including cardiovascular disease. Resting non-proliferative tissues have distinctive metabolic activities and requirements, which differ considerably from those in infiltrating immune cells, which are undergoing proliferation and differentiation. Immune responses in tissues may therefore be modulated by the relative abundance of substrates in the inflamed site. In turn immune cell activity can feed back and affect metabolic behaviour of the tissues, as most clearly demonstrated in cachexia - the loss of cellular mass driven by tumour necrosis factor-alpha (TNF-α) a key mediator of the inflammatory response. Here we discuss the potential for metabolomic analysis to clarify the interactions between inflammation and metabolic changes underlying many diseases. We suggest that an increased understanding of the interaction between inflammation and cellular metabolism, energy substrate use, tissue breakdown markers, the microbiome and drug metabolites, may provide novel insight into the regulation of inflammatory diseases. PMID:23348753

  13. Use of biosimilars in inflammatory bowel disease: Statements of the Italian Group for Inflammatory Bowel Disease.

    PubMed

    Annese, Vito; Vecchi, Maurizio

    2014-11-01

    The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost "copies" of these drugs produced by competitor companies-referred to as biosimilars-are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease. PMID:25139379

  14. Oral manifestation in inflammatory bowel disease: A review

    PubMed Central

    Lankarani, Kamran B; Sivandzadeh, Gholam Reza; Hassanpour, Shima

    2013-01-01

    Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis, not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity. These oral manifestations may assist in the diagnosis and the monitoring of disease activity, whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups. Indurated tag-like lesions, cobblestoning, and mucogingivitis are the most common specific oral findings encountered in CD cases. Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differential diagnosis, side effects of drugs, infections, nutritional deficiencies, and other inflammatory conditions should also be considered. Treatment usually involves managing the underlying intestinal disease. In severe cases with local symptoms, topical and/or systemic steroids and immunosuppressive drugs might be used. PMID:24379574

  15. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity

    PubMed Central

    Rahmani, Arshad H; Aly, Salah M; Ali, Habeeb; Babiker, Ali Y; Srikar, Sauda; khan, Amjad A

    2014-01-01

    The current mode of treatment of various diseases based on synthetic drugs is expensive, alters genetic and metabolic pathways and also shows adverse side effects. Thus, safe and effective approach is needed to prevent the diseases development and progression. In this vista, Natural products are good remedy in the treatment/management of diseases and they are affordable and effective without any adverse effects. Dates are main fruit in the Arabian Peninsula and are considered to be one of the most significant commercial crops and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that constituents of dates act as potent antioxidant, anti-tumour as well as anti-inflammatory, provide a suitable alternative therapy in various diseases cure. In this review, dates fruits has medicinal value are summarized in terms of therapeutic implications in the diseases control through anti-oxidant, anti-inflammatory, anti-tumour and ant-diabetic effect. PMID:24753740

  16. Can Probiotics Cure Inflammatory Bowel Diseases?

    PubMed

    Korada, Siva Kumar; Yarla, Nagendra Sastry; Bishayee, Anupam; Aliev, Gjumrakch; Aruna Lakshmi, K; Arunasree, M K; Dananajaya, B L; Mishra, Vijendra

    2016-01-01

    Gastrointestinal (GI) disorders, especially microbial dysbiosis play role in several GI ailments such as irritable bowel syndrome, colorectal cancer, inflammatory bowel diseases, and antibiotic-associated diarrhoea. Role of inflammatory bowel disease (IBD) is multifactorial as it involves loss of maintaining intestinal epithelial barrier integrity, increased release of pro-inflammatory molecules, and microbial dysbiosis in gut microflora. Some specific pathogens also play a key role in the IBD development. The origin and causation are still in unfathomable condition and the exact root cause is unknown. Recently probiotic studies have been gaining importance because of their positive responses in their IBD experimental results. According to joint Food and Agricultural Organisation/World Health Organisation working group, probiotics are defined as live microorganisms which when administered in adequate amount confer health benefit on the host. These live beneficial microorganisms are considered helpful in improving gut colonization and perseverance thereby improves prophylactic effect. In the direction of IBD research, a number of studies are needed to standardize its methodology and its applicability on human usage. The particular review presents an overview of gut microflora and its impact on host health, types of IBD and existing therapies to treat this disorder, mechanism of several probiotic actions, role of probiotics in IBD prevention with their supporting evidences. PMID:26648465

  17. Inflammatory bowel disease imaging: Current practice and future directions

    PubMed Central

    Kilcoyne, Aoife; Kaplan, Jess L; Gee, Michael S

    2016-01-01

    The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn’s disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities. PMID:26811637

  18. Latent tuberculosis screening tests and active tuberculosis infection rates in Turkish inflammatory bowel disease patients under anti-tumor necrosis factor therapy

    PubMed Central

    Çekiç, Cem; Aslan, Fatih; Vatansever, Sezgin; Topal, Firdevs; Yüksel, Elif Sarıtaş; Alper, Emrah; Dallı, Ayşe; Ünsal, Belkıs

    2015-01-01

    Background Tumor necrosis factor (TNF)-α inhibitors increase the risk of tuberculosis (TB). The objective of the present study was to determine the rate of active TB infection in inflammatory bowel disease (IBD) patients receiving anti-TNF therapy and to determine the results of their latent TB infection (LTBI) screening tests during the follow up. Methods This is a retrospective observational study of IBD patients receiving anti-TNF therapy. Tuberculin skin test (TST), interferon-γ release assay (IGRA), and chest radiography were used to determine LTBI. Active TB infection rate during anti-TNF treatment was determined. Results Seventy-six IBD patients (25 with ulcerative colitis, 51 with Crohn’s disease; 53 male; mean age 42.0±12.4 years) were included. Forty-four (57.9%) patients received infliximab and 32 (42.1%) adalimumab. Their median duration of anti-TNF therapy was 15 months. Forty-five (59.2%) patients had LTBI and received isoniazid (INH) prophylaxis. During the follow-up period, active TB was identified in 3 (4.7%) patients who were not receiving INH prophylaxis. There was a moderate concordance between the TST and the IGRA (kappa coefficient 0.44, 95% CI 0.24-0.76). Patients with or without immunosuppressive therapy did not differ significantly with respect to TST (P=0.318) and IGRA (P=0.157). Conclusion IBD patients receiving anti-TNF therapy and prophylactic INH have a decreased risk of developing active TB infection. However, despite LTBI screening, the risk of developing active TB infection persists. PMID:25831138

  19. Neutrophilic dermatoses and inflammatory bowel diseases.

    PubMed

    Marzano, A V; Menicanti, C; Crosti, C; Trevisan, V

    2013-04-01

    Pyoderma gangrenosum (PG) and Sweet's Syndrome (SS) are inflammatory skin diseases caused by the accumulation of neutrophils in the skin and, rarely, in internal organs, which led to coining the term of neutrophilic dermatoses (ND) to define these conditions. Recently, ND have been included among the autoinflammatory diseases, which are forms due to mutations of genes regulating the innate immune responses. Both PG and SS are frequently associated with inflammatory bowel diseases (IBD), a group of chronic intestinal disorders which comprises ulcerative colitis and Crohn's disease and whose pathogenesis involves both the innate and adaptive immunity in genetically prone individuals. Patients with IBD develop PG in 1-3% of cases, while SS is rarer. PG presents with deep erythematous-to-violaceous painful ulcers with undermined borders, but bullous, pustular, and vegetative variants can also occur. SS, also known as acute febrile neutrophilic dermatosis, is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions and a diffuse neutrophilic dermal infiltrate. In this review that will be focused on PG and SS, we will describe also the aseptic abscesses syndrome, a new entity within the spectrum of ND which frequently occurs in association with IBD and is characterized by deep abscesses mainly involving the spleen and skin and by polymorphic cutaneous manifestations including PG- and SS-like lesions. PMID:23588144

  20. Intestinal barrier in inflammatory bowel disease

    PubMed Central

    Antoni, Lena; Nuding, Sabine; Wehkamp, Jan; Stange, Eduard F

    2014-01-01

    A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis. PMID:24574793

  1. Enteroscopy in small intestinal inflammatory diseases.

    PubMed

    Gay, G J; Delmotte, J S

    1999-01-01

    The development of new semilong enteroscopes, videopush enteroscope (VPE), has modified the diagnostic and therapeutic approach to inflammatory intestinal diseases owing to the biopsy and therapeutic capacities. In Crohn's Disease, VPE is useful in nonusual clinical presentations: occult intestinal bleeding and in the treatment by dilatation of jejunal and ileal strictures. In atrophic coeliac disease (ACD) VPE is mandatory each time oesogastroduodenoscopy biopsies are noninformative in order to obtain pathologic jejunal biopsis. In addition, in refractory ACD and in the case of jejunal blood loss ACD, VPE is mandatory in the search for ulcerative jejunitis and lymphoma. The management of chronic diarrhea of the adult, classic endoscopy remains the gold standard procedure and is carried out first but in patients with negative results, VPE can proceed immediately. Good results can only be obtained if VPE is performed by endoscopist who is highly interested in this field of investigation. PMID:9834320

  2. Therapeutic innovations in inflammatory bowel diseases.

    PubMed

    Vanhove, W; Nys, K; Vermeire, S

    2016-01-01

    Inflammatory bowel disease (IBD) is a spectrum of complex multifactorial immune disorders characterized by chronic inflammation of the gut. Significant advances have been made in unraveling the pathogenesis of this disease spectrum, which have spurred the discovery of new therapeutic targets and strategies. In this review, we highlight the emerging new classes of IBD therapeutics under clinical evaluation and their method of action, including JAK inhibitors, anti-SMAD7 oligonucleotides, and cell-based therapies. Moreover, we discuss how an approach based on unique molecular insights in a given patient will, in the future, lead to a truly individualized/tailored disease management, starting at diagnosis, aiding in prognosis, and resulting in a personalized therapeutic approach. PMID:26509246

  3. [Hormonal changes in inflammatory bowel disease].

    PubMed

    Kollerová, Jana; Koller, Tomáš; Hlavatý, Tibor; Payer, Juraj

    2015-12-01

    Inflammatory bowel disease is often accompanied by extraintestinal manifestations due to a common autoimmune etiopathogenesis, chronic systemic inflammation, frequent nutrition deficits, and the treatment. Endocrine system changes belong to manifestations too. Interaction is mutual, Crohn's disease and ulcerative colitis cause functional and morphological changes of endocrine tissues. On the other hand the endocrine disorders negatively influence the course of bowel disease. In the article we analyze correlation of IBD with gonadal hormone production and fertility, with adrenal function, with the function and morphology of the thyroid, with growth hormone production and growth disorders in children, and with bone mineral density reduction. This topic is not studied enough and needs more analysis and clarification. PMID:27124970

  4. Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

    PubMed Central

    Biasi, Fiorella; Leonarduzzi, Gabriella; Oteiza, Patricia I.

    2013-01-01

    Abstract Oxidative stress is thought to play a key role in the development of intestinal damage in inflammatory bowel disease (IBD), because of its primary involvement in intestinal cells' aberrant immune and inflammatory responses to dietary antigens and to the commensal bacteria. During the active disease phase, activated leukocytes generate not only a wide spectrum of pro-inflammatory cytokines, but also excess oxidative reactions, which markedly alter the redox equilibrium within the gut mucosa, and maintain inflammation by inducing redox-sensitive signaling pathways and transcription factors. Moreover, several inflammatory molecules generate further oxidation products, leading to a self-sustaining and auto-amplifying vicious circle, which eventually impairs the gut barrier. The current treatment of IBD consists of long-term conventional anti-inflammatory therapy and often leads to drug refractoriness or intolerance, limiting patients' quality of life. Immune modulators or anti-tumor necrosis factor α antibodies have recently been used, but all carry the risk of significant side effects and a poor treatment response. Recent developments in molecular medicine point to the possibility of treating the oxidative stress associated with IBD, by designing a proper supplementation of specific lipids to induce local production of anti-inflammatory derivatives, as well as by developing biological therapies that target selective molecules (i.e., nuclear factor-κB, NADPH oxidase, prohibitins, or inflammasomes) involved in redox signaling. The clinical significance of oxidative stress in IBD is now becoming clear, and may soon lead to important new therapeutic options to lessen intestinal damage in this disease. Antioxid. Redox Signal. 19, 1711–1747. PMID:23305298

  5. Inflammatory Bowel “Cardiac” Disease: Point Prevalence of Atrial Fibrillation in Inflammatory Bowel Disease Population

    PubMed Central

    Pattanshetty, Deepak J.; Anna, Kiran; Gajulapalli, Rama D.; Sappati-Biyyani, RajaShekhar R.

    2015-01-01

    Background/Aim: Proinflammatory markers such as interleukin (IL)-6 have been closely associated with atrial fibrillation (AF). These markers are characteristically elevated in chronic inflammatory bowel disease (IBD) and positively correlate with disease activity. Although IBD and AF have similar pathogenesis, there have been very limited studies looking at their association. The aim of this study is to determine the prevalence of AF in patients with IBD. Patients and Methods: Medical records of patients with biopsy proven IBD (n = 203, both in and outpatient) were retrospectively reviewed. One hundred and forty-one IBD patients with documentary evidence of electrocardiograms (ECG's) were included. The “Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA)” study, a large cross-sectional study (n = 1.89 million) done to evaluate the prevalence of AF among the US population, was our control population. All ECGs available till December 2010 for each IBD patient were reviewed carefully for evidence of AF. We studied the prevalence of AF among IBD population and compared it to that of control (ATRIA) population. Results: The prevalence of AF was significantly higher among IBD patients compared with the ATRIA study patients (11.3% vs 0.9%, P < 0.0001). Additionally, the IBD patient population were much younger compared with the controls (64.4 ± 10.7 vs 71.2 ± 12.2, P = 0.02). Conclusion: AF has an overall higher prevalence across all age groups in IBD compared with the subjects of ATRIA study, which could be due to the chronic inflammatory state of IBD. Further studies are needed to study the association in detail. PMID:26458861

  6. Purinergic signaling in inflammatory renal disease

    PubMed Central

    Arulkumaran, Nishkantha; Turner, Clare M.; Sixma, Marije L.; Singer, Mervyn; Unwin, Robert; Tam, Frederick W. K.

    2013-01-01

    Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signaling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signaling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive) role of purinergic signaling. We discuss the role of extracellular nucleotides in adaptation to ischemic renal injury and in the pathogenesis of inflammatory renal disease. PMID:23908631

  7. Fecal Microbiota Transplantation for Inflammatory Bowel Disease

    PubMed Central

    Lopez, Joanna

    2016-01-01

    The gut bacterial microbiome, particularly its role in disease and inflammation, has gained international attention with the successful use of fecal microbiota transplantation (FMT) in the treatment of Clostridium difficile infection. This success has led to studies exploring the role of FMT in other conditions, including inflammatory bowel disease (IBD). Both Crohn’s disease and ulcerative colitis are chronic inflammatory conditions of the gastrointestinal system that have multifactorial etiologies. A shift in gut microbial composition in genetically susceptible individuals, an altered immune system, and environmental factors are all hypothesized to have a role in the pathogenesis of IBD. While numerous case reports and cohort studies have described the use of FMT in patients with IBD over the last 2 decades, the development of new sequencing techniques and results from 2 recent randomized, controlled trials have allowed for a better understanding of the relationship between the microbiome and the human host. However, despite these efforts, knowledge remains limited and the role of FMT in the management of IBD remains uncertain. Further investigation is necessary before FMT joins the current armamentarium of treatment options in clinical practice. PMID:27493597

  8. Enteral nutrition in inflammatory bowel disease.

    PubMed Central

    Gassull, M A; Abad, A; Cabré, E; González-Huix, F; Giné, J J; Dolz, C

    1986-01-01

    To assess the effect of the addition of enteral tube feeding with polymeric diets to the standard treatment of acute attacks of inflammatory bowel disease a total of 43 patients admitted to hospital (23 with Crohn's disease and 20 with ulcerative colitis) were studied retrospectively. Total enteral nutrition was given to 26 as the sole nutritional supply and to 17 in conjunction with a normal ward diet, when appropriate, according to the severity of attack (control group). Nutritional state was assessed and classified in all patients at admission and at the end of the study, by measuring the triceps skinfold thickness, mid arm muscle circumference, and serum albumin concentration as representative of body fat, muscle protein, and visceral protein, respectively. At admission the three nutritional variables were not statistically different between the groups. There was a significantly positive effect on mid arm muscle circumference in patients on total enteral nutrition compared with the control group, but there was no effect on either triceps skinfold thickness or serum albumin concentration. The percentage of subjects requiring intravenous albumin infusion, however, was significantly less in the group fed enterally than in the control group. In addition, fewer patients in the group fed enterally required surgical treatment compared with the control group, despite the fact that one of the criteria for starting enteral nutritional support was the expectancy that surgery would be needed. Total enteral nutrition was well tolerated and no major side effects arose during its use in patients with acute exacerbations of inflammatory bowel disease. PMID:3098646

  9. Fecal Microbiota Transplantation for Inflammatory Bowel Disease.

    PubMed

    Lopez, Joanna; Grinspan, Ari

    2016-06-01

    The gut bacterial microbiome, particularly its role in disease and inflammation, has gained international attention with the successful use of fecal microbiota transplantation (FMT) in the treatment of Clostridium difficile infection. This success has led to studies exploring the role of FMT in other conditions, including inflammatory bowel disease (IBD). Both Crohn's disease and ulcerative colitis are chronic inflammatory conditions of the gastrointestinal system that have multifactorial etiologies. A shift in gut microbial composition in genetically susceptible individuals, an altered immune system, and environmental factors are all hypothesized to have a role in the pathogenesis of IBD. While numerous case reports and cohort studies have described the use of FMT in patients with IBD over the last 2 decades, the development of new sequencing techniques and results from 2 recent randomized, controlled trials have allowed for a better understanding of the relationship between the microbiome and the human host. However, despite these efforts, knowledge remains limited and the role of FMT in the management of IBD remains uncertain. Further investigation is necessary before FMT joins the current armamentarium of treatment options in clinical practice. PMID:27493597

  10. In Vivo Inhibition of RIPK2 Kinase Alleviates Inflammatory Disease*

    PubMed Central

    Tigno-Aranjuez, Justine T.; Benderitter, Pascal; Rombouts, Frederik; Deroose, Frederik; Bai, XiaoDong; Mattioli, Benedetta; Cominelli, Fabio; Pizarro, Theresa T.; Hoflack, Jan; Abbott, Derek W.

    2014-01-01

    The RIPK2 kinase transduces signaling downstream of the intracellular peptidoglycan sensors NOD1 and NOD2 to promote a productive inflammatory response. However, excessive NOD2 signaling has been associated with numerous diseases, including inflammatory bowel disease (IBD), sarcoidosis and inflammatory arthritis, making pharmacologic inhibition of RIPK2 an appealing strategy. In this work, we report the generation, identification, and evaluation of novel RIPK2 specific inhibitors. These compounds potently inhibit the RIPK2 tyrosine kinase activity in in vitro biochemical assays and cellular assays, as well as effectively reduce RIPK2-mediated effects in an in vivo peritonitis model. In conjunction with the development of these inhibitors, we have also defined a panel of genes whose expression is regulated by RIPK2 kinase activity. Such RIPK2 activation markers may serve as a useful tool for predicting settings likely to benefit from RIPK2 inhibition. Using these markers and the FDA-approved RIPK2 inhibitor Gefitinib, we show that pharmacologic RIPK2 inhibition drastically improves disease in a spontaneous model of Crohn Disease-like ileitis. Furthermore, using novel RIPK2-specific inhibitors, we show that cellular recruitment is inhibited in an in vivo peritonitis model. Altogether, the data presented in this work provides a strong rationale for further development and optimization of RIPK2-targeted pharmaceuticals and diagnostics. PMID:25213858

  11. Spontaneous and transgenic rodent models of inflammatory bowel disease

    PubMed Central

    Jurjus, Abdo

    2015-01-01

    Inflammatory Bowel Disease (IBD) is a multifactorial disorder with many different putative influences mediating disease onset, severity, progression and diminution. Spontaneous natural IBD is classically expressed as Crohn's Disease (CD) and Ulcerative Colitis (UC) commonly found in primates; lymphoplasmocytic enteritis, eosinophilic gastritis and colitis, and ulcerative colitis with neuronal hyperplasia in dogs; and colitis in horses. Spontaneous inflammatory bowel disease has been noted in a number of rodent models which differ in genetic strain background, induced mutation, microbiota influences and immunopathogenic pathways. Histological lesions in Crohn's Disease feature noncaseating granulomatous inflammation while UC lesions typically exhibit ulceration, lamina propria inflammatory infiltrates and lack of granuloma development. Intestinal inflammation caused by CD and UC is also associated with increased incidence of intestinal neoplasia. Transgenic murine models have determined underlying etiological influences and appropriate therapeutic targets in IBD. This literature review will discuss current opinion and findings in spontaneous IBD, highlight selected transgenic rodent models of IBD and discuss their respective pathogenic mechanisms. It is very important to provide accommodation of induced putative deficits in activities of daily living and to assess discomfort and pain levels in the face of significant morbidity and/or mortality in these models. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis, and evaluating ways in which they influence disease expression represent potential investigative approaches with the greatest potential for new discoveries. PMID:26155200

  12. Proper Use of Inflammatory Bowel Disease Drugs during Pregnancy.

    PubMed

    Kanis, S L; van der Woude, C J

    2016-01-01

    Crohn's disease and ulcerative colitis, referred to as inflammatory bowel disease (IBD), are chronic, relapsing conditions. Patients are often diagnosed at a reproductive age, and therefore questions about fertility and reproductions often arise. Preconceptional counseling is the most important aspect in the management of IBD patients with a pregnancy wish. Patients should be counseled on the influence of IBD and IBD drugs on pregnancy. Most drugs are not related to adverse outcome while used during pregnancy. Active disease is related to adverse outcomes; therefore, it is of utmost importance to strive for remission before conception and during pregnancy. PMID:27548630

  13. [Recommendations for the diagnosis and treatment of latent and active tuberculosis in patients with inflammatory joint diseases treated with tumour necrosis factor alpha inhibitors].

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2006-01-01

    The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-alpha) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test. PMID:17094335

  14. Environmental risk factors for inflammatory bowel disease.

    PubMed

    Molodecky, Natalie A; Kaplan, Gilaad G

    2010-05-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD. PMID:20567592

  15. Management of inflammatory bowel disease in pregnancy

    PubMed Central

    Smith, M A; Sanderson, J D

    2010-01-01

    Inflammatory bowel disease (IBD) affects body image, relationships, family planning, fertility and pregnancy outcomes. However, the common misconception that IBD is a contraindication, or serious concern, in pregnancy is essentially a myth. Most patients with IBD can expect to have uneventful pregnancies. We present an overview of the management of IBD during pregnancy, including management in those planning pregnancy, the suitability of relevant medication during pregnancy and breast feeding, investigation and monitoring of IBD during pregnancy, surgical management and considerations relating to delivery. While there are some definite alterations required in the management of IBD during pregnancy, management is essentially unchanged. With close attention to aspects such as nutrition and smoking cessation, and optimal disease control in the run-up to and during pregnancy, we have an opportunity to help our patients with IBD achieve good pregnancy outcomes.

  16. GENETICS AND PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

    PubMed Central

    Liu, Ta-Chiang; Stappenbeck, Thaddeus S.

    2016-01-01

    We are currently in an exciting time where our understanding of genetic underpinnings of inflammatory bowel disease (IBD) has undergone a revolution, based in large part by novel genotyping and sequencing technologies. With >160 susceptible loci identified for IBD, the goals now are to understand at a fundamental level, the function of these susceptibility alleles. Clinical relevance of how these susceptible genes shape the development of IBD is also a high priority. The main challenge is to understand how the environment and microbiome play a role in triggering disease in genetically susceptible individual, as the interactions may be complex. To advance the field, novel in vitro and mouse models that are designed to interrogate complex genetics and be able to functionally test hypotheses are needed. Ultimately, the goal of genetics studies will be to translate genetics to the patients with IBD and improve their care. PMID:26907531

  17. Inflammatory bowel disease pathogenesis: where are we?

    PubMed

    Fiocchi, Claudio

    2015-03-01

    Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. PMID:25827798

  18. Genetics and Pathogenesis of Inflammatory Bowel Disease.

    PubMed

    Liu, Ta-Chiang; Stappenbeck, Thaddeus S

    2016-05-23

    We are currently in an exciting time when our understanding of genetic underpinnings of inflammatory bowel disease (IBD) has undergone a revolution, based in large part on novel genotyping and sequencing technologies. With >160 susceptible loci identified for IBD, the goal is now to understand at a fundamental level the function of these susceptibility alleles. Determining the clinical relevance of how these susceptible genes shape the development of IBD is also a high priority. The main challenge is to understand how the environment and microbiome play a role in triggering disease in genetically susceptible individuals, as the interactions may be complex. To advance the field, novel in vitro and mouse models that are designed to interrogate complex genetics and functionally test hypotheses are needed. Ultimately, the goal of genetics studies will be to translate genetics to patients with IBD and improve their care. PMID:26907531

  19. Ascomycins: promising agents for the treatment of inflammatory skin diseases.

    PubMed

    Paul, C; Graeber, M; Stuetz, A

    2000-01-01

    Ascomycin derivatives represent a novel class of anti-inflammatory macrolactams currently under development for the treatment of skin diseases. The main biological effect of ascomycins is an inhibition of the synthesis of both Th1 and Th2-type cytokines in target cells. Several compounds are being developed with SDZ ASM 981 being at the most advanced stage. It has high anti-inflammatory activity in animal models of skin inflammation and does not induce skin atrophy. Topical application of SDZ ASM 981 was shown to be effective in atopic dermatitis (AD), allergic contact dermatitis and also in psoriasis under semi-occlusive conditions. In patients with AD, SDZ ASM 981 cream led to consistently low systemic exposure even when applied on large areas of skin. SDZ ASM 981 overcomes the drawbacks of current topical therapies of inflammatory skin diseases as its safety profile is better than that of topical corticosteroids. Studies continue to investigate its efficacy and safety in the treatment of inflammatory skin diseases. PMID:11060661

  20. Correlations between Psoriasis and Inflammatory Bowel Diseases

    PubMed Central

    Skroza, Nevena; Proietti, Ilaria; La Viola, Giorgio; Bernardini, Nicoletta; Nicolucci, Francesca; Tolino, Ersilia; Zuber, Sara; Soccodato, Valentina; Potenza, Concetta

    2013-01-01

    For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis. PMID:23971052

  1. Bacterial flora in inflammatory bowel disease.

    PubMed

    Marteau, Philippe

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) involves an interaction between host susceptibility (which is partly genetically determined), mucosal immunity and the intestinal milieu. Micro-organisms have physiological effects on mucosal structure, epithelial turnover, the intestinal immune cells and, thus, on many intestinal functions. Toll-like receptors and nucleotide oligomerisation-binding domain proteins in host cells recognise specific bacterial molecules and modify the immune response. Human studies have repeatedly shown that the microbiota of patients with IBD differs from that of controls and is unstable, both in the intestinal lumen and at the surface of the mucosa. A single pathogen has not been identified, but potentially pro-inflammatory micro-organisms have been found in samples from IBD patients more often than from healthy controls. These include Mycobacterium paratuberculosis, and enteroadherent and invasive Escherichia coli in Crohn's disease (CD). Ecological descriptions of the microbiota present in patients with IBD (either in the faeces or adherent to the mucosa) have repeatedly reported a decrease in usually dominant bacteria, especially those from the dominant phylum Firmicutes. A decrease in the biodiversity of Firmicutes has been observed in CD, while a recent study has shown that a decrease in Firmicutes, especially Faecalibacterium prausnitzii, was associated with CD and the post-operative recurrence of CD lesions in the ileum. Taken together, these results suggest that dysbiosis, or an imbalance within the (dominant) intestinal microbiota, may favour IBD. PMID:20203504

  2. Epithelial Transport in Inflammatory Bowel Diseases

    PubMed Central

    Ghishan, Fayez K.; Kiela, Pawel R.

    2014-01-01

    The epithelium of the gastrointestinal tract is one of the most versatile tissues in the organism, responsible for providing a tight barrier between dietary and bacterial antigens and the mucosal and systemic immune system, while maintaining efficient digestive and absorptive processes to ensure adequate nutrient and energy supply. Inflammatory Bowel Diseases (IBD; Crohn’s disease and ulcerative colitis) are associated with a breakdown of both functions, which in some cases are clearly interrelated. In this updated literature review, we focus on the effects of intestinal inflammation and the associated immune mediators on selected aspects of the transepithelial transport of macro- and micronutrients. The mechanisms responsible for nutritional deficiencies are not always clear and could be related to decreased intake, malabsorption and excess losses. We summarize the known causes of nutrient deficiencies and the mechanism of IBD-associated diarrhea. We also overview the consequences of impaired epithelial transport, which infrequently transcend its primary purpose to affect the gut microbial ecology and epithelial integrity. While some of those regulatory mechanisms are relatively well established, more work needs to be done to determine how inflammatory cytokines can alter the transport process of nutrients across the gastrointestinal and renal epithelia. PMID:24691115

  3. Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases.

    PubMed

    Park, Mi Hee; Jo, MiRan; Kim, Yu Ri; Lee, Chong-Kil; Hong, Jin Tae

    2016-07-01

    Peroxiredoxins (PRDXs) are antioxidant enzymes, known to catalyze peroxide reduction to balance cellular hydrogen peroxide (H2O2) levels, which are essential for cell signaling and metabolism and act as a regulator of redox signaling. Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Early studies demonstrated that PRDXs regulates cell growth, metabolism and immune regulation and therefore involved in the pathologic regulator or protectant of several cancers, neurodegenerative diseases and inflammatory diseases. Oxidative stress and antioxidant systems are important regulators of redox signaling regulated diseases. In addition, thiol-based redox systems through peroxiredoxins have been demonstrated to regulate several redox-dependent process related diseases. In this review article, we will discuss recent findings regarding PRDXs in the development of diseases and further discuss therapeutic approaches targeting PRDXs. Moreover, we will suggest that PRDXs could be targets of several diseases and the therapeutic agents for targeting PRDXs may have potential beneficial effects for the treatment of cancers, neurodegenerative diseases and inflammatory diseases. Future research should open new avenues for the design of novel therapeutic approaches targeting PRDXs. PMID:27130805

  4. Non-Inflammatory Destructive Periodontal Disease

    PubMed Central

    José Ricardo Kina; Yumi Umeda Suzuki, Thaís; Fumico Umeda Kina, Eunice; Kina, Juliana; Kina, Mônica

    2016-01-01

    Background: Non-Inflammatory Destructive Periodontal Disease (NIDPD), is a severe destructive periodontal disease, that is characterized by the attachment loss and alveolar bone loss, without signs of the gingival inflammation, and the periodontal pocket development. Objective: Despite the fact that various cases of NIDPD have been reported; their etiology and disease evolution is still indefinite, and therefore, are open for discussion. Method: An NIDPD case was studied in order to demonstrate features of the disease, and discuss the possible etiology and treatment. Results: In this clinical case, the etiology of NIDPD seems to be an association of endogenous opportunist bacteria with anatomical aspects, occlusion pattern, emotional stress and mouth breathing condition. Conclusion: In spite of all cases described in the literature are comparable and may have similar etiology as related in this clinical case, additional research is needed to identify and clarify the role of the etiologic factors which determine the disease. PMID:27053968

  5. Mitochondrial dysfunction in inflammatory bowel disease

    PubMed Central

    Novak, Elizabeth A.; Mollen, Kevin P.

    2015-01-01

    Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD. PMID:26484345

  6. Expression of Toll-like receptor-3 is enhanced in active inflammatory bowel disease and mediates the excessive release of lipocalin 2

    PubMed Central

    Østvik, A E; Granlund, A v B; Torp, S H; Flatberg, A; Beisvåg, V; Waldum, H L; Flo, T H; Espevik, T; Damås, J K; Sandvik, A K

    2013-01-01

    Anti-microbial peptides might influence the pathogenesis and course of inflammatory bowel disease (IBD). We sought to clarify the role of the anti-microbial glycoprotein lipocalin 2 (LCN2) in the colon by determining its localization and regulation in IBD. Following a microarray gene expression study of colonic biopsies from a large IBD population (n = 133), LCN2 was localized using immunohistochemistry and in-situ hybridization. Moreover, we examined the regulation of LCN2 in HT-29 cells with a panel of pattern recognition receptors (PRRs) and sought evidence by immunohistochemistry that the most relevant PRR, the Toll-like receptor (TLR)-3, was indeed expressed in colonic epithelium in IBD. LCN2 was among the 10 most up-regulated genes in both active ulcerative colitis (UCa) and active Crohn's disease (CDa) versus healthy controls. LCN2 protein was found in both epithelial cells and infiltrating neutrophils, while mRNA synthesis was located solely to epithelial cells, indicating that de-novo synthesis and thus regulation of LCN2 as measured in the gene expression analysis takes place in the mucosal epithelial cells. LCN2 is a putative biomarker in faeces for intestinal inflammation, different from calprotectin due to its epithelial site of synthesis. LCN2 release from the colonic epithelial cell line HT-29 was enhanced by both interleukin (IL)-1β and the TLR-3 ligand poly(I:C), and TLR-3 was shown to be expressed constitutively in colonic epithelial cells and markedly increased during inflammation. PMID:23668802

  7. Alteration in T lymphocyte subpopulations in inflammatory bowel disease.

    PubMed Central

    Victorino, R M; Hodgson, H J

    1980-01-01

    Peripheral blood mononuclear cells from thirty-one patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease) were analysed for the proportions and absolute numbers of total T cells, and for the T cell subpopulations carrying Fc receptors for either IgM (Tmu cells) or IgG (T gamma cells). Twenty-six control subjects were studied simultaneously. Total T cell numbers were normal in patients with inflammatory bowel disease but there was a marked reduction in the proportion and absolute numbers of Tmu cells in patients, whether their disease was active or in remission. T gamma cells were normal. Simultaneous assessment of lymphocyte response to mitogens in vitro was performed in a group of patients. Responses to phytohaemagglutinin, concanavalin A and pokeweed mitogen were decreased and a positive correlation was found between the number of circulating Tmu cells and the responses to mitogens in vitro. These studies demonstrate that despite the presence of normal numbers of total T cells in inflammatory bowel disease, there is a marked imbalance in T cell subpopulations that correlates with mitogen responsiveness. This imbalance provides a possible cellular basis for the defect in cell-mediated immunity seen in these patients. PMID:6969150

  8. Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer.

    PubMed

    Connelly, Margery A; Gruppen, Eke G; Otvos, James D; Dullaart, Robin P F

    2016-08-01

    The physiological function initially attributed to the oligosaccharide moieties or glycans on inflammatory glycoproteins was to improve protein stability. However, it is now clear that glycans play a prominent role in glycoprotein structure and function and in some cases contribute to disease states. In fact, glycan processing contributes to pathogenicity not only in autoimmune disorders but also in atherosclerotic cardiovascular disease, diabetes and malignancy. While most clinical laboratory tests measure circulating levels of inflammatory proteins, newly developed diagnostic and prognostic tests are harvesting the information that can be gleaned by measuring the amount or structure of the attached glycans, which may be unique to individuals as well as various diseases. As such, these newer glycan-based tests may provide future means for more personalized approaches to patient stratification and improved patient care. Here we will discuss recent progress in high-throughput laboratory methods for glycomics (i.e. the study of glycan structures) and glycoprotein quantification by methods such as mass spectrometry and nuclear magnetic resonance spectroscopy. We will also review the clinical utility of glycoprotein and glycan measurements in the prediction of common low-grade inflammatory disorders including cardiovascular disease, diabetes and cancer, as well as for monitoring autoimmune disease activity. PMID:27312321

  9. Immunization status in children with inflammatory bowel disease.

    PubMed

    Longuet, Romain; Willot, Stephanie; Giniès, Jean-Louis; Pélatan, Cecile; Breton, Estelle; Segura, Jean-François; Bridoux, Laure; Le Henaff, Gaelle; Cagnard, Benoit; Jobert, Agathe; Cardonna, Joël; Grimal, Isabelle; Balençon, Martine; Darviot, Estelle; Delaperrière, Nadège; Caldari, Dominique; Piloquet, Hugues; Dabadie, Alain

    2014-05-01

    Inflammatory bowel diseases have an increased risk of infections due to immunosuppressive therapies. To report the immunization status according to previous recommendations and the reasons explaining a delay, a questionnaire was filled in by the pediatric gastroenterologist, concerning outpatients, in six tertiary centers and five local hospitals, in a study, from May to November 2011. One hundred and sixty-five questionnaires were collected, of which 106 Crohn's diseases, 41 ulcerative colitis, and 17 indeterminate colitis. Sex ratio was 87:78 M/F. Median age was 14.4 years old (4.2-20.0). One hundred and nine patients (66 %) were receiving or had received an immunosuppressive therapy (azathioprine, infliximab, methotrexate, or prednisone). Vaccines were up to date according to the vaccine schedule of French recommendations in 24 % of cases and according to the recommendations for inflammatory bowel disease in 4 % of cases. Coverage by vaccine was the following: diphtheria-tetanus-poliomyelitis 87 %, hepatitis B 38 %, pneumococcus 32 %, and influenza 22 %. Immunization delay causes were as follows: absence of proposal 58 %, patient refusal 41 %, fear of side effects 33 %, and fear of disease activation 5 %. Therefore, immunization coverage is insufficient in children with inflammatory bowel disease, due to simple omission or to refusal. A collaboration with the attending physicians and a targeted information are necessary. PMID:24305728

  10. Activation of human inflammatory cells by secreted phospholipases A2.

    PubMed

    Triggiani, Massimo; Granata, Francescopaolo; Frattini, Annunziata; Marone, Gianni

    2006-11-01

    Secreted phospholipases A(2) (sPLA(2)s) are enzymes detected in serum and biological fluids of patients with various inflammatory, autoimmune and allergic disorders. Different isoforms of sPLA(2)s are expressed and released by human inflammatory cells, such as neutrophils, eosinophils, T cells, monocytes, macrophages and mast cells. sPLA(2)s generate arachidonic acid and lysophospholipids thus contributing to the production of bioactive lipid mediators in inflammatory cells. However, sPLA(2)s also activate human inflammatory cells by mechanisms unrelated to their enzymatic activity. Several human and non-human sPLA(2)s induce degranulation of mast cells, neutrophils and eosinophils and activate exocytosis in macrophages. In addition some, but not all, sPLA(2) isoforms promote cytokine and chemokine production from macrophages, neutrophils, eosinophils, monocytes and endothelial cells. These effects are primarily mediated by binding of sPLA(2)s to specific membrane targets (heparan sulfate proteoglycans, M-type, N-type or mannose receptors) expressed on effector cells. Thus, sPLA(2)s may play an important role in the initiation and amplification of inflammatory reactions by at least two mechanisms: production of lipid mediators and direct activation of inflammatory cells. Selective inhibitors of sPLA(2)-enzymatic activity and specific antagonists of sPLA(2) receptors are current being tested for pharmacological treatment of inflammatory and autoimmune diseases. PMID:16952481

  11. Inflammatory Cytokines in Vascular Dysfunction and Vascular Disease

    PubMed Central

    Sprague, Alexander H.; Khalil, Raouf A.

    2009-01-01

    The vascular inflammatory response involves complex interaction between inflammatory cells (neutrophils, lymphocytes, monocytes, macrophages), endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM). Vascular injury is associated with increased expression of adhesion molecules by ECs and recruitment of inflammatory cells, growth factors, and cytokines, with consequent effects on ECs, VSMCs and ECM. Cytokines include tumor necrosis factors, interleukins, lymphokines, monokines, interferons, colony stimulating factors, and transforming growth factors. Cytokines are produced by macrophages, T cells and monocytes, as well as platelets, ECs and VSMCs. Circulating cytokines interact with specific receptors on various cell types and activate JAK-STAT, NF-κB, and Smad signaling pathways leading to an inflammatory response involving cell adhesion, permeability and apoptosis. Cytokines also interact with mitochondria to increasie the production of reactive oxygen species. Cytokine-induced activation of these pathways in ECs modifies the production/activity of vasodilatory mediators such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, and bradykinin, as well as vasoconstrictive mediators such as endothelin and angiotensin II. Cytokines interact with VSMCs to activate Ca2+, protein kinase C, Rho-Kinase, and MAPK pathways, which promote cell growth and migration, and VSM reactivity. Cytokines also interact with integrins and matrix metalloproteinases (MMPs) and modify ECM composition. Persistent increases in cytokines are associated with vascular dysfunction and vascular disease such as atherosclerosis, abdominal aortic aneurysm, varicose veins and hypertension. Genetic and pharmacological tools to decrease the production of cytokines or to diminish their effects using cytokine antagonists could provide new approaches in the management of inflammatory vascular disease. PMID:19413999

  12. Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir

    PubMed Central

    HIRANO, Toshio

    2010-01-01

    In this review, the author discusses the research that led to the identification and characterization of interleukin 6 (IL-6), including his own experience isolating IL-6, and the roles this cytokine has on autoimmune and inflammatory diseases. The cDNAs encoding B-cell stimulatory factor 2 (BSF-2), interferon (IFN)-β2 and a 26-kDa protein were independently cloned in 1986, which in turn led to the identification of each. To resolve the confusing nomenclature, these identical molecules were named IL-6. Characterization of IL-6 revealed a multifunctional cytokine that is involved in not only immune responses but also hematopoiesis, inflammation, and bone metabolism. Moreover, IL-6 makes significant contributions to such autoimmune and inflammatory diseases as rheumatoid arthritis (RA). IL-6 activates both the STAT3 and SHP2/Gab/MAPK signaling pathways via the gp130 signal transducer. F759 mice, which contain a single amino-acid substitution in gp130 (Y759F) and show enhanced STAT3 activation, spontaneously develop a RA-like arthritis as they age. F759 arthritis is dependent on CD4+ T cells, IL-6, and IL-17A, and is enhanced by the pX gene product from human T cell leukemia virus 1 (HTLV-1). Arthritis development in these mice requires that the F759 mutation is present in nonhematopoietic cells, but not in immune cells, highlighting the important role of the interaction between nonimmune tissues and the immune system in this disease. Furthermore, this interaction is mediated by the IL-6 amplifier through STAT3 and NF-κB. Ultimately, this model may represent a general etiologic process underlying other autoimmune and inflammatory diseases. More importantly, the understanding of IL-6 has paved the way for new therapeutic approaches for RA and other autoimmune and inflammatory diseases. PMID:20689230

  13. Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappaB target gene expression.

    PubMed

    Shah, Yatrik M; Ma, Xiaochao; Morimura, Keiichirou; Kim, Insook; Gonzalez, Frank J

    2007-04-01

    Pregnane X receptor (PXR) expression was shown to be protective in inflammatory bowel disease (IBD). However, the mechanism by which PXR provides protection remains unclear. Wild-type and Pxr-null mice were treated with the PXR agonist pregnenolone-16alpha-carbonitrile or vehicle and administered 2.5% dextran sulfate sodium (DSS) in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis. In vivo intestinal permeability assays and proinflammatory cytokine analysis were performed. PXR agonist-treated mice were protected from DSS-induced colitis compared with vehicle-treated mice, as defined by body weight loss, diarrhea, rectal bleeding, colon length, and histology. Pregnenolone-16alpha-carbonitrile did not decrease the severity of IBD in Pxr-null mice. PXR agonist treatment did not increase epithelial barrier function but did decrease mRNA expression of several NF-kappaB target genes in a PXR-dependent manner. The present study clearly demonstrates a protective role for PXR agonist in DSS-induced IBD. The data suggest that PXR-mediated repression of NF-kappaB target genes in the colon is a critical mechanism by which PXR activation decreases the susceptibility of mice to DSS-induced IBD. PMID:17170021

  14. Antileukotrienes in upper airway inflammatory diseases.

    PubMed

    Cingi, Cemal; Muluk, Nuray Bayar; Ipci, Kagan; Şahin, Ethem

    2015-11-01

    Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature survey. Data on LTs, antileukotrienes, and antileukotrienes in chronic rhinosinusitis and nasal polyps, asthma, and allergic rhinitis are presented. Antileukotriene drugs are classified into two groups: CysLT receptor antagonists (zafirlukast, pranlukast, and montelukast) and LT synthesis inhibitors (5-lipoxygenase inhibitors such as zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have important proinflammatory and profibrotic effects that contribute to the extensive hyperplastic rhinosinusitis and nasal polyposis (NP) that characterise these disorders. Patients who receive zafirlukast or zileuton tend to show objective improvements in, or at least stabilisation of, NP. Montelukast treatment may lead to clinical subjective improvement in NP. Montelukast treatment after sinus surgery can lead to a significant reduction in eosinophilic cationic protein levels in serum, with a beneficial effect on nasal and pulmonary symptoms and less impact in NP. Combined inhaled corticosteroids and long-acting β-agonists treatments are most effective for preventing exacerbations among paediatric asthma patients. Treatments with medium- or high-dose inhaled corticosteroids, combined inhaled corticosteroids and LT receptor antagonists, and low-dose inhaled corticosteroids have been reported to be equally effective. Antileukotrienes have also been reported to be effective for allergic

  15. Preventing infective complications in inflammatory bowel disease

    PubMed Central

    Mill, Justine; Lawrance, Ian C

    2014-01-01

    Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician’s tailored use of justified therapies, and the patients’ education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections. PMID:25110408

  16. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors: March 2008 update.

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment. PMID:18344925

  17. Recommendations for the diagnosis and treatment of latent and active tuberculosis in inflammatory joint diseases candidates for therapy with tumor necrosis factor alpha inhibitors - March 2008 update.

    PubMed

    Fonseca, João Eurico; Lucas, Helena; Canhão, Helena; Duarte, Raquel; Santos, Maria José; Villar, Miguel; Faustino, Augusto; Raymundo, Elena

    2008-01-01

    The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFα) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFα therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFα therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFα therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn's complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions, ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-α therapy, even in the presence of a negative test, after risk / benefit assessment. Rev Port Pneumol 2007; XIV (2): 271-283. PMID:25966834

  18. The role of antimicrobial peptides in chronic inflammatory skin diseases

    PubMed Central

    Majewski, Sławomir

    2016-01-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases. PMID:26985172

  19. The role of antimicrobial peptides in chronic inflammatory skin diseases.

    PubMed

    Marcinkiewicz, Małgorzata; Majewski, Sławomir

    2016-02-01

    Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases. PMID:26985172

  20. Light and sound - emerging imaging techniques for inflammatory bowel disease

    PubMed Central

    Knieling, Ferdinand; Waldner, Maximilian J

    2016-01-01

    Patients with inflammatory bowel disease are known to have a high demand of recurrent evaluation for therapy and disease activity. Further, the risk of developing cancer during the disease progression is increasing from year to year. New, mostly non-radiant, quick to perform and quantitative methods are challenging, conventional endoscopy with biopsy as gold standard. Especially, new physical imaging approaches utilizing light and sound waves have facilitated the development of advanced functional and molecular modalities. Besides these advantages they hold the promise to predict personalized therapeutic responses and to spare frequent invasive procedures. Within this article we highlight their potential for initial diagnosis, assessment of disease activity and surveillance of cancer development in established techniques and recent advances such as wide-view full-spectrum endoscopy, chromoendoscopy, autofluorescence endoscopy, endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, molecular imaging endoscopy, B-mode and Doppler ultrasound, contrast-enhanced ultrasound, ultrasound molecular imaging, and elastography. PMID:27433080

  1. Light and sound - emerging imaging techniques for inflammatory bowel disease.

    PubMed

    Knieling, Ferdinand; Waldner, Maximilian J

    2016-07-01

    Patients with inflammatory bowel disease are known to have a high demand of recurrent evaluation for therapy and disease activity. Further, the risk of developing cancer during the disease progression is increasing from year to year. New, mostly non-radiant, quick to perform and quantitative methods are challenging, conventional endoscopy with biopsy as gold standard. Especially, new physical imaging approaches utilizing light and sound waves have facilitated the development of advanced functional and molecular modalities. Besides these advantages they hold the promise to predict personalized therapeutic responses and to spare frequent invasive procedures. Within this article we highlight their potential for initial diagnosis, assessment of disease activity and surveillance of cancer development in established techniques and recent advances such as wide-view full-spectrum endoscopy, chromoendoscopy, autofluorescence endoscopy, endocytoscopy, confocal laser endoscopy, multiphoton endoscopy, molecular imaging endoscopy, B-mode and Doppler ultrasound, contrast-enhanced ultrasound, ultrasound molecular imaging, and elastography. PMID:27433080

  2. The Role of CLCA Proteins in Inflammatory Airway Disease

    PubMed Central

    Patel, Anand C.; Brett, Tom J.; Holtzman, Michael J.

    2014-01-01

    Inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) exhibit stereotyped traits that are variably expressed in each person. In experimental mouse models of chronic lung disease, these individual disease traits can be genetically segregated and thereby linked to distinct determinants. Functional genomic analysis indicates that at least one of these traits, mucous cell metaplasia, depends on members of the calcium-activated chloride channel (CLCA) gene family. Here we review advances in the biochemistry of the CLCA family and the evidence of a role for CLCA family members in the development of mucous cell metaplasia and possibly airway hyperreactivity in experimental models and in humans. Based on this information, we develop the model that CLCA proteins are not integral membrane proteins with ion channel function, but instead are secreted signaling molecules that specifically regulate airway target cells in healthy and disease conditions. PMID:18954282

  3. Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease

    PubMed Central

    Hotamisligil, Gökhan S.

    2010-01-01

    The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions. Failure of the ER's adaptive capacity results in activation of the unfolded protein response (UPR), which intersects with many different inflammatory and stress signaling pathways. These pathways are also critical in chronic metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. The ER and related signaling networks are emerging as a potential site for the intersection of inflammation and metabolic disease. PMID:20303879

  4. [Systemic inflammatory rheumatic diseases competence network].

    PubMed

    Rufenach, C; Burmester, G-R; Zeidler, H; Radbruch, A

    2004-04-01

    The foundation of the competence network for rheumatology, which is funded by the "Bundesministerium für Bildung und Forschung" (BMBF) since 1999, succeeded to create a unique research structure in Germany: medical doctors and scientists from six university rheumatology centres (Berlin, Düsseldorf, Erlangen, Freiburg, Hannover und Lübeck/Bad Bramstedt) work closely together with scientists doing basic research at the Deutsches Rheuma-Forschungszentrum (DRFZ), with rheumatological hospitals, reha-clinics, and rheumatologists. Jointly they are searching for causes of systemic inflammatory rheumatic diseases and try to improve therapies-nationwide and with an interdisciplinary approach. The primary objective of this collaboration is to transfer new scientific insights more rapidly in order to improve methods for diagnosis and patients treatment. PMID:14999386

  5. Flavonoids in Inflammatory Bowel Disease: A Review.

    PubMed

    Vezza, Teresa; Rodríguez-Nogales, Alba; Algieri, Francesca; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Galvez, Julio

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients' life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects. PMID:27070642

  6. Diagnostic imaging in pediatric renal inflammatory disease

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Schroeder, B.A.; Starshak, R.J.

    1986-08-15

    Some form of imaging procedure should be used to document the presence of infection of the upper urinary tract in troublesome cases in children. During the past several years, sonography, nuclear radiology, and computed tomography (CT) have had a significant influence on renal imaging. The purpose of this article is to reevaluate the noninvasive imaging procedures that can be used to diagnose pediatric renal inflammatory disease and to assess the relative value of each modality in the various types of renal infection. The authors will not discuss the radiologic evaluation of the child who has had a previous renal infection, in whom cortical scarring or reflux nephropathy is a possibility; these are different clinical problems and require different diagnostic evaluation.

  7. Doppler ultrasound studies in pelvic inflammatory disease.

    PubMed

    Tinkanen, H; Kujansuu, E

    1992-01-01

    Ten women with tubo-ovarian abscess caused by pelvic inflammatory disease (PID) were investigated by transvaginal Doppler ultrasound during the acute and healing phases of the infection. The pulsatility index (PI) of the uterine arteries was measured and compared with the values obtained from 19 healthy women. Each control patient was investigated three times during a single menstrual cycle. In PID patients, the PI values were significantly lower than in controls in the same phase of the menstrual cycle. When C-reactive protein was > 50, the PI values were lowest and reverted to normal values when the infection subsided. In a case of chronic infection, the PI did not rise to normal despite normal infection parameters. Doppler ultrasound seems to offer a new method of assessing PID. PMID:1487185

  8. Diagnostic Evaluation of Pelvic Inflammatory Disease

    PubMed Central

    Soper, David E.

    1994-01-01

    Pelvic inflammatory disease (PID) is a serious public health and reproductive health problem in the United States. An early and accurate diagnosis of PID is extremely important for the effective management of the acute illness and for the prevention of long-term sequelae. The diagnosis of PID is difficult, with considerable numbers of false-positive and false-negative diagnoses. An abnormal vaginal discharge or evidence of lower genital tract infection is an important and predictive finding that is often underemphasized and overlooked. This paper reviews the clinical diagnosis and supportive laboratory tests for the diagnosis of PID and outlines an appropriate diagnostic plan for the clinician and the researcher. PMID:18475365

  9. Case Report: Inflammatory Bowel Disease and Thrombosis.

    PubMed

    Maneval, Rhonda E; Clemence, Bonnie J

    2016-01-01

    Patients with inflammatory bowel disease (IBD) have a greater risk for developing venous thromboembolism (VTE). Patients admitted to the hospital with IBD flares often require insertion of long-term venous access devices, such as peripherally inserted central catheters (PICCs), to provide access for medications, blood draws, fluid management, and nutrition. PICCs have been associated with an increased risk for upper extremity deep vein thrombosis. In this case study analysis, 2 patients with IBD and PICCs who developed VTE are examined. The case report includes a thorough discussion of medical history, symptomology, PICC insertion, and events leading to VTE development. A review of acquired risk factors for IBD patients and a comparison of risk factors that predisposed each to VTE are explored. These cases highlight the need for nurses and physicians to heighten surveillance and engage in proactive strategies to prevent VTE in this population of patients. PMID:27074991

  10. Colorectal Cancer in Inflammatory Bowel Disease

    PubMed Central

    Potack, Jonathan

    2008-01-01

    Patients with long-standing inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC). CRC risk increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and severity of inflammation of the colon. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid. To reduce CRC mortality in IBD, colonoscopic surveillance remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia. PMID:20485613

  11. Neurological disorders and inflammatory bowel diseases

    PubMed Central

    Casella, Giovanni; Tontini, Gian Eugenio; Bassotti, Gabrio; Pastorelli, Luca; Villanacci, Vincenzo; Spina, Luisa; Baldini, Vittorio; Vecchi, Maurizio

    2014-01-01

    Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms. PMID:25083051

  12. Flavonoids in Inflammatory Bowel Disease: A Review

    PubMed Central

    Vezza, Teresa; Rodríguez-Nogales, Alba; Algieri, Francesca; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Galvez, Julio

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects. PMID:27070642

  13. [Progress in PDE4 targeted therapy for inflammatory diseases].

    PubMed

    Song, Shun-de; Tang, Hui-fang

    2014-05-01

    cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases. PMID:24998661

  14. Anti-inflammatory activity of cationic lipids.

    PubMed

    Filion, M C; Phillips, N C

    1997-10-01

    1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. 2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha). 3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. 4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70-95%). 5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. 6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its

  15. Inflammatory bowel disease and celiac disease: Overlaps and differences

    PubMed Central

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-01-01

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults. PMID:24803796

  16. Dendritic cells in inflammatory sinonasal diseases.

    PubMed

    Cao, P-P; Shi, L-L; Xu, K; Yao, Y; Liu, Z

    2016-07-01

    Dendritic cells (DCs) are critical in linking the innate and adaptive immune responses, which have been implicated in the pathogenesis of many immune and inflammatory diseases as well as the development of tumours. The role of DCs in the pathophysiology of lung diseases has been widely studied. However, the phenotype, subset and function of DCs in upper airways under physiological or pathological conditions remain largely undefined. Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two important upper airway diseases with a high worldwide prevalence. Aberrant innate and adaptive immune responses have been considered to play an important role in the pathogenesis of AR and CRS. To this end, understanding the function of DCs in shaping the immune responses in sinonasal mucosa is critical in exploring the pathogenic mechanisms underlying AR and CRS as well as in developing novel therapeutic strategies. This review summarizes the phenotype, subset, function and regulation of DCs in sinonasal mucosa, particularly in the setting of AR and CRS. Furthermore, this review discusses the perspectives for future research and potential clinical utility focusing on DC pathways in the context of AR and CRS. PMID:27159777

  17. The Intestinal Microbiota in Inflammatory Bowel Disease.

    PubMed

    Becker, Christoph; Neurath, Markus F; Wirtz, Stefan

    2015-01-01

    The intestinal microbiota has important metabolic and host-protective functions. Conversely to these beneficial functions, the intestinal microbiota is thought to play a central role in the etiopathogenesis of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), a chronic inflammation of the gut mucosa. Genetic screens and studies in experimental mouse models have clearly demonstrated that IBD can develop due to excessive translocation of bacteria into the bowel wall or dysregulated handling of bacteria in genetically susceptible hosts. In healthy individuals, the microbiota is efficiently separated from the mucosal immune system of the gut by the gut barrier, a single layer of highly specialized epithelial cells, some of which are equipped with innate immune functions to prevent or control access of bacterial antigens to the mucosal immune cells. It is currently unclear whether the composition of the microbial flora or individual bacterial strains or pathogens induces or supports the pathogenesis of IBD. Further research will be necessary to carefully dissect the contribution of individual bacterial species to this disease and to ascertain whether specific modulation of the intestinal microbiome may represent a valuable further option for future therapeutic strategies. PMID:26323629

  18. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

    PubMed Central

    Lee, In-Ah; Kamba, Alan; Low, Daren; Mizoguchi, Emiko

    2014-01-01

    Family 18 chitinases have a binding capacity with chitin, a polymer of N-acetylglucosamine. Recent studies strongly suggested that chitinase 3-like 1 (CHI3L1, also known as YKL-40) and acidic mammalian chitinase, the two major members of family 18 chitinases, play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD), bronchial asthma and several other inflammatory disorders. Based on the data from high-throughput screening, it has been found that three methylxanthine derivatives, caffeine, theophylline, and pentoxifylline, have competitive inhibitory effects against a fungal family 18 chitinase by specifically interacting with conserved tryptophans in the active site of this protein. Methylxanthine derivatives are also known as adenosine receptor antagonists, phosphodiesterase inhibitors and histone deacetylase inducers. Anti-inflammatory effects of methylxanthine derivatives have been well-documented in the literature. For example, a beneficial link between coffee or caffeine consumption and type 2 diabetes as well as liver cirrhosis has been reported. Furthermore, theophylline has a long history of being used as a bronchodilator in asthma therapy, and pentoxifylline has an immuno-modulating effect for peripheral vascular disease. However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells. In this review article we will examine the above possibility and summarize the biological significance of methylxanthine derivatives in intestinal epithelial cells. We hope that this study will provide a rationale for the development of methylxanthine derivatives, in particular caffeine, -based anti-inflammatory therapeutics in the field of IBD and IBD-associated carcinogenesis. PMID:24574789

  19. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    PubMed

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  20. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    PubMed Central

    Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  1. [Sweet's syndrome. Its association with chronic inflammatory bowel disease].

    PubMed

    Calvo Catalá, J; González Pérez, J A; Febrer Bosch, I; Oliver Mas, V; Herrera Ballester, A

    1990-07-01

    Sweet's syndrome, or febrile neutrophilic dermatosis, is a disease first described by Sweet R.D. in 1964 as a dermatologic disease. Subsequently, it has been associated to several disease. One of those rarely describe is the association to chronic intestinal inflammatory disease. We reviewed the cases studied in our hospital since 1980 and found two cases associated to chronic intestinal inflammatory disease. We recommend the carrying out of gastrointestinal studies in patients afflicted by Sweet's syndrome to detect its association. PMID:2103250

  2. Intrinsic Self-DNA Triggers Inflammatory Disease Dependent on STING

    PubMed Central

    Ahn, Jeonghyun; Ruiz, Phillip; Barber, Glen N.

    2016-01-01

    Inflammatory diseases such as Aicardi–Goutières syndrome and severe systemic lupus erythematosus are generally lethal disorders that have been traced to defects in the exonuclease TREX1 (DNase III). Mice lacking TREX1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the stimulator of IFN genes (STING) pathway. In this study, we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into TREX1−/− mice. TREX1−/− macrophages did not exhibit significant augmented ability to produce proinflammatory cytokines compared with normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies. PMID:25261479

  3. Transition of Care in Inflammatory Bowel Disease

    PubMed Central

    Abraham, Bincy P

    2014-01-01

    The management of patients with chronic conditions, such as inflammatory bowel disease (IBD), requires specific attention and careful planning during the transition from pediatric to adult care. Early education about the transition process and the acquisition of self-management skills are crucial to fostering independent adolescents and young adults who have the knowledge and tools to manage life with a chronic disease. A growing body of literature describes the challenges and barriers to providing adolescent and transition care. Potential barriers to effective transition include the following: differences between adult- and pediatric-onset IBD; patients’ lack of developmental maturity and readiness, self-efficacy, and knowledge of the disease; poor adherence to therapy; adolescent anxiety and depression; differences between pediatric and adult IBD care; and parental and provider reluctance to transition. Despite our ability to identify barriers and challenges, there remain significant gaps in our knowledge about how they should be addressed. Outcomes data on adolescents with IBD are limited, and there are even fewer data on how the transition of care affects long-term treatment and outcomes. More research is needed to truly understand the best way to facilitate care during transition and improve outcomes. Current research and transition guidelines acknowledge that providing support and guidance to patients and their families and establishing clear goals can ultimately equip patients with the skills needed to cope with a chronic disease as adults and can improve their long-term care. This paper provides an overview of the transition from pediatric to adult IBD care, a discussion of challenges and barriers, and recommendations and resources that can help patients, parents, and providers navigate this important process.

  4. EPA- and DHA-derived resolvins' actions in inflammatory bowel disease.

    PubMed

    Schwanke, Raquel Cristina; Marcon, Rodrigo; Bento, Allisson Freire; Calixto, João B

    2016-08-15

    Inflammatory bowel diseases are chronic diseases divided into two major forms, ulcerative colitis and Crohn's disease, which are both associated with a chronic inflammatory condition of the gastrointestinal tract. Recent studies have shown that the resolution of inflammatory conditions is a biosynthetically active process where new pro-resolution lipid mediators derived from omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), such as E- and D-series resolvins, protectins, and macrophage mediator in resolving inflammation (maresins), have potent anti-inflammatory activity and serve as specialised mediators that play an important role in the resolution of inflammation. Recent studies have also shown the role of resolvins in referred hyperalgesia associated with different inflammatory processes, such as the visceral pain caused by inflammatory bowel disease. There are many reports describing the principal effects of EPA- and DHA-derived mediators in experimental models of inflammatory bowel diseases. This review focuses on the recent studies on the important role played by pro-resolution lipid mediators in controlling the inflammatory process associated with inflammatory bowel diseases. PMID:26325092

  5. Inflammatory Lung Disease in Rett Syndrome

    PubMed Central

    De Felice, Claudio; Rossi, Marcello; Chisci, Glauco; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Iacona, Ingrid; Cortelazzo, Alessio; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease. PMID:24757286

  6. Campylobacter concisus and inflammatory bowel disease

    PubMed Central

    Zhang, Li; Lee, Hoyul; Grimm, Michael C; Riordan, Stephen M; Day, Andrew S; Lemberg, Daniel A

    2014-01-01

    Investigation of the possible role of Campylobacter concisus (C. concisus) in inflammatory bowel disease (IBD) is an emerging research area. Despite the association found between C. concisus and IBD, it has been difficult to explain how C. concisus, a bacterium that is commonly present in the human oral cavity, may contribute to the development of enteric diseases. The evidence presented in this review shows that some C. concisus strains in the oral cavity acquired zonula occludens toxin (zot) gene from a virus (prophage) and that C. concisus Zot shares conserved motifs with both Vibrio cholerae Zot receptor binding domain and human zonulin receptor binding domain. Both Vibrio cholerae Zot and human zonulin are known to increase intestinal permeability by affecting the tight junctions. Increased intestinal permeability is a feature of IBD. Based on these data, we propose that a primary barrier function defect caused by C. concisus Zot is a mechanism by which zot-positive C. concisus strains may trigger the onset and relapse of IBD. PMID:24574800

  7. Campylobacter concisus and inflammatory bowel disease.

    PubMed

    Zhang, Li; Lee, Hoyul; Grimm, Michael C; Riordan, Stephen M; Day, Andrew S; Lemberg, Daniel A

    2014-02-01

    Investigation of the possible role of Campylobacter concisus (C. concisus) in inflammatory bowel disease (IBD) is an emerging research area. Despite the association found between C. concisus and IBD, it has been difficult to explain how C. concisus, a bacterium that is commonly present in the human oral cavity, may contribute to the development of enteric diseases. The evidence presented in this review shows that some C. concisus strains in the oral cavity acquired zonula occludens toxin (zot) gene from a virus (prophage) and that C. concisus Zot shares conserved motifs with both Vibrio cholerae Zot receptor binding domain and human zonulin receptor binding domain. Both Vibrio cholerae Zot and human zonulin are known to increase intestinal permeability by affecting the tight junctions. Increased intestinal permeability is a feature of IBD. Based on these data, we propose that a primary barrier function defect caused by C. concisus Zot is a mechanism by which zot-positive C. concisus strains may trigger the onset and relapse of IBD. PMID:24574800

  8. Placental inflammation is not increased in inflammatory bowel disease

    PubMed Central

    Taleban, Sasha; Gundogan, Fusun; Chien, Edward K.; Degli-Esposti, Silvia; Saha, Sumona

    2015-01-01

    Background Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls. Methods Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn’s disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery. Results Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32). Conclusions Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes. PMID:26423206

  9. Oral Inflammatory Diseases and Systemic Inflammation: Role of the Macrophage

    PubMed Central

    Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.

    2012-01-01

    Inflammation is a complex reaction to injurious agents and includes vascular responses, migration, and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated, and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation. PMID:22623923

  10. Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD): Analysis of Transplantation Outcome and IBD Activity in a Large Single Center Cohort

    PubMed Central

    Schnitzler, Fabian; Friedrich, Matthias; Stallhofer, Johannes; Schönermarck, Ulf; Fischereder, Michael; Habicht, Antje; Karbalai, Nazanin; Wolf, Christiane; Angelberger, Marianne; Olszak, Torsten; Beigel, Florian; Tillack, Cornelia; Göke, Burkhard; Zachoval, Reinhart; Denk, Gerald; Guba, Markus; Rust, Christian; Grüner, Norbert; Brand, Stephan

    2015-01-01

    Background Currently, limited data of the outcome of inflammatory bowel disease (IBD) in patients after solid organ transplantation (SOT) are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort. Methods Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment. Results 4.74% of patients with ulcerative colitis (UC) and 0.84% of patients with Crohn’s disease (CD) underwent SOT (p = 2.69 x 10−6, UC vs. CD). 77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal transplantation and one patient (3.2%) heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26–84.06). Four patients (13.0%) needed anti-TNF therapy after SOT (response rate 75%). Conclusions SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated. PMID:26288187

  11. Rheumatic manifestations of inflammatory bowel disease.

    PubMed

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-11-28

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy. PMID:19938189

  12. Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis

    PubMed Central

    Lu, Chao; Yang, Jun; Yu, Weilai; Li, Dejian; Xiang, Zun; Lin, Yiming; Yu, Chaohui

    2015-01-01

    Background There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD). Aim To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD. Methods We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs). Results Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09–0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15–0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48–2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13–3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index≥150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence. Conclusion Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study. PMID:26172950

  13. Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Delongui, Francieli; Alfieri, Daniela Frizon; Lozovoy, Marcell Alysson Batisti; Amin, Ricardo Braga; Dichi, Isaias; Simão, Andréa Name Colado

    2016-01-01

    The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92. PMID:27340510

  14. Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis

    PubMed Central

    Loddo, Italia; Romano, Claudio

    2015-01-01

    Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although etiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota, and immune response are involved in the pathogenesis. Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD) have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to <10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci. Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early-onset IBD (before 5 years) or very early onset IBD (before 2 years). Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, ~50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice. The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is an emerging field, and

  15. New developments in the pharmacotherapy of inflammatory bowel disease.

    PubMed

    Harting, J W

    1992-08-21

    In this article the clinical features and aetiology of inflammatory bowel diseases are described and current pharmacotherapeutic possibilities are explored. Also reviewed are recent developments and future prospects for the pharmacotherapy of inflammatory bowel diseases, including aminosalicylates, corticosteroids, immunosuppressants, lipoxygenase inhibitors, fish oil, sucralfate, bismuth compounds, free radical scavengers, (hydroxy)chloroquine, sodium cromoglycate and methotrexate. PMID:1437510

  16. MPNs as Inflammatory Diseases: The Evidence, Consequences, and Perspectives

    PubMed Central

    Hasselbalch, Hans Carl; Bjørn, Mads Emil

    2015-01-01

    In recent years the evidence is increasing that chronic inflammation may be an important driving force for clonal evolution and disease progression in the Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Abnormal expression and activity of a number of proinflammatory cytokines are associated with MPNs, in particular MF, in which immune dysregulation is pronounced as evidenced by dysregulation of several immune and inflammation genes. In addition, chronic inflammation has been suggested to contribute to the development of premature atherosclerosis and may drive the development of other cancers in MPNs, both nonhematologic and hematologic. The MPN population has a substantial inflammation-mediated comorbidity burden. This review describes the evidence for considering the MPNs as inflammatory diseases, A Human Inflammation Model of Cancer Development, and the role of cytokines in disease initiation and progression. The consequences of this model are discussed, including the increased risk of second cancers and other inflammation-mediated diseases, emphasizing the urgent need for rethinking our therapeutic approach. Early intervention with interferon-alpha2, which as monotherapy has been shown to be able to induce minimal residual disease, in combination with potent anti-inflammatory agents such as JAK-inhibitors is foreseen as the most promising new treatment modality in the years to come. PMID:26604428

  17. Inflammatory networks in ageing, age-related diseases and longevity.

    PubMed

    Vasto, Sonya; Candore, Giuseppina; Balistreri, Carmela Rita; Caruso, Marco; Colonna-Romano, Giuseppina; Grimaldi, Maria Paola; Listi, Florinda; Nuzzo, Domenico; Lio, Domenico; Caruso, Calogero

    2007-01-01

    Inflammation is considered a response set by the tissues in response to injury elicited by trauma or infection. It is a complex network of molecular and cellular interactions that facilitates a return to physiological homeostasis and tissue repair. The individual response against infection and trauma is also determined by gene variability. Ageing is accompanied by chronic low-grade inflammation state clearly showed by 2-4-fold increase in serum levels of inflammatory mediators. A wide range of factors has been claimed to contribute to this state; however, the most important role seems to be played by the chronic antigenic stress, which affects immune system thorough out life with a progressive activation of macrophages and related cells. This pro-inflammatory status, interacting with the genetic background, potentially triggers the onset of age-related inflammatory diseases as atherosclerosis. Thus, the analysis of polymorphisms of the genes that are key nodes of the natural immunity response might clarify the patho-physiology of age-related inflammatory diseases as atherosclerosis. On the other hand, centenarians are characterized by marked delay or escape from age-associated diseases that, on average, cause mortality at earlier ages. In addition, centenarian offspring have increased likelihood of surviving to 100 years and show a reduced prevalence of age-associated diseases, as cardiovascular disease (CVD) and less prevalence of cardiovascular risk factors. So, genes involved in CVD may play an opposite role in human longevity. Thus, the model of centenarians can be used to understand the role of these genes in successful and unsuccessful ageing. Accordingly, we report the results of several studies in which the frequencies of pro-inflammatory alleles were significantly higher in patients affected by infarction and lower in centenarians whereas age-related controls displayed intermediate values. These findings point to a strong relationship between the genetics

  18. Inflammatory Bowel Disease in Australasian Children and Adolescents

    PubMed Central

    Day, A. S.; Lemberg, D. A.; Gearry, R. B.

    2014-01-01

    Many reports indicate increasing rates of inflammatory bowel disease, with data also showing changing patterns of this chronic disease in children and adolescents. This review focuses upon the available data of the epidemiology of inflammatory bowel disease in children and adolescents in Australia and New Zealand (collectively termed Australasia). Recent data show high incidence of IBD (especially Crohn disease) in this area and indicate rising rates of IBD in children and adolescents. PMID:24799892

  19. Inflammatory bowel disease in australasian children and adolescents.

    PubMed

    Day, A S; Lemberg, D A; Gearry, R B

    2014-01-01

    Many reports indicate increasing rates of inflammatory bowel disease, with data also showing changing patterns of this chronic disease in children and adolescents. This review focuses upon the available data of the epidemiology of inflammatory bowel disease in children and adolescents in Australia and New Zealand (collectively termed Australasia). Recent data show high incidence of IBD (especially Crohn disease) in this area and indicate rising rates of IBD in children and adolescents. PMID:24799892

  20. Nanocarriers in therapy of infectious and inflammatory diseases

    NASA Astrophysics Data System (ADS)

    Ikoba, Ufuoma; Peng, Haisheng; Li, Haichun; Miller, Cathy; Yu, Chenxu; Wang, Qun

    2015-02-01

    Nanotechnology is a growing science that has applications in various areas of medicine. The composition of nanocarriers for drug delivery is critical to guarantee high therapeutic performance when targeting specific host sites. Applications of nanotechnology are prevalent in the diagnosis and treatment of infectious and inflammatory diseases. This review summarizes recent advancements in the application of nanotechnology to the therapy of infectious and inflammatory diseases. The major focus is on the design and fabrication of various nanomaterials, characteristics and physicochemical properties of drug-loaded nanocarriers, and the use of these nanoscale drug delivery systems in treating infectious and inflammatory diseases, such as AIDS, hepatitis, tuberculosis, melanoma, and representative inflammatory diseases. Clinical trials and future perspective of the use of nanocarriers are also discussed in detail. We hope that such a review will be valuable to researchers who are exploring nanoscale drug delivery systems for the treatment of specific infectious and inflammatory diseases.

  1. Complement, a target for therapy in inflammatory and degenerative diseases.

    PubMed

    Morgan, B Paul; Harris, Claire L

    2015-12-01

    The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies. PMID:26493766

  2. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications.

    PubMed

    Cibor, Dorota; Domagala-Rodacka, Renata; Rodacki, Tomasz; Jurczyszyn, Artur; Mach, Tomasz; Owczarek, Danuta

    2016-01-21

    Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases. PMID:26811647

  3. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications

    PubMed Central

    Cibor, Dorota; Domagala-Rodacka, Renata; Rodacki, Tomasz; Jurczyszyn, Artur; Mach, Tomasz; Owczarek, Danuta

    2016-01-01

    Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases. PMID:26811647

  4. Neuroendocrine host factors and inflammatory disease susceptibility.

    PubMed Central

    Ligier, S; Sternberg, E M

    1999-01-01

    The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. PMID:10502534

  5. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease.

    PubMed

    Sreedhar, Remya; Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Watanabe, Kenichi

    2016-05-01

    Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD. PMID:26995272

  6. The treatment of pelvic inflammatory disease.

    PubMed

    Rees, E

    1980-12-01

    The treatment of pelvic inflammatory disease depends upon the etiology of the condition. Pelvic infection (PI) after parturition and abortion, gynecologic surgery, and a variety of invasive procedures is commonly associated with the isolation of anaerobic and aerobic flora of the vagina. The factors which influence the choice of antimicrobial treatment and the role of Bacteroides fragilis and Escherichia coli are discussed. Sexually transmissible agents of importance are Neisseria gonorrhoeae and Chlamydia trachomatis. Pelvic infections associated with these pathogens require antibiotics which exert an optimum effect against them. Examination and treatment of the sexual partner(s) are important. The possible role of the anaerobic and aerobic vaginal flora as opportunistic secondary pathogens is discussed. Developments in the surgical treatment of the sequelae of PID are reviewed. The results of treatment of uncomplicated gonorrhea in 262 women are reported. C. trachomatis was isolated from 53% of women before treatment. After treatment, PI developed in 11 women who had been given penicillin and in one woman who had been given tetracycline (P = 0.0071). It is suggested that recognition and treatment of postgonococcal cervicitis in women treated for uncomplicated gonorrhea with penicillin might provide one form of preventive treatment for nongonococcal PI. PMID:6894059

  7. Mouth cancer in inflammatory bowel diseases.

    PubMed

    Giagkou, E; Christodoulou, D K; Katsanos, K H

    2016-05-01

    Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic. PMID:26671147

  8. Elderly patients and inflammatory bowel disease.

    PubMed

    Nimmons, Danielle; Limdi, Jimmy K

    2016-02-01

    The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; loco-motor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management. PMID:26855812

  9. Elderly patients and inflammatory bowel disease

    PubMed Central

    Nimmons, Danielle; Limdi, Jimmy K

    2016-01-01

    The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; loco-motor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management. PMID:26855812

  10. Longitudinal study of circulating protein biomarkers in inflammatory bowel disease

    PubMed Central

    Viennois, Emilie; Baker, Mark T.; Xiao, Bo; Wang, Lixin; Laroui, Hamed; Merlin, Didier

    2014-01-01

    Inflammatory bowel diseases (IBD) are chronic and progressive inflammatory disorders of the gastrointestinal tract. In IBD, protein serological biomarkers could be relevant tools for assessing disease activity, performing early-stage diagnosis and managing the treatment. Using the interleukin-10 knockout (IL-10−/−) mouse, a model that develops a time-dependent IBD-like disorder that predominates in the colon; we performed longitudinal studies of circulating protein biomarkers in IBD. Circulating protein profiles in serum samples collected from 30-, 93-, and 135-day-old IL-10−/− mice were investigated using two-dimensional differential gel electrophoresis and MALDI TOF/TOF tandem mass spectrometry. A total of 15 different proteins were identified and confirmed by ELISA and Western blot to be differentially accumulated in serum samples from mid- to late-stage IL-10−/− mice compared to early non-inflamed IL-10−/− mice. The use of another model of colitis and an extra-intestinal inflammation model validated this biomarker panel and demonstrated that comprised some global inflammatory markers, some intestinal inflammation-specific markers and some chronic intestinal inflammation markers. Statistical analyses using misclassification error rate charts validated the use of these identified proteins as powerful biomarkers of colitis. Unlike standard biomarker screening studies, our analyses identified a panel of proteins that allowed the definition of protein signatures that reflect colitis status. PMID:25230104

  11. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    PubMed

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  12. Inflammatory bowel disease in children of middle eastern descent.

    PubMed

    Naidoo, Christina Mai Ying; Leach, Steven T; Day, Andrew S; Lemberg, Daniel A

    2014-01-01

    Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course. PMID:24987422

  13. Inflammatory Bowel Disease in Children of Middle Eastern Descent

    PubMed Central

    Naidoo, Christina Mai Ying; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.

    2014-01-01

    Increasing rates of inflammatory bowel disease (IBD) are now seen in populations where it was once uncommon. The pattern of IBD in children of Middle Eastern descent in Australia has never been reported. This study aimed to investigate the burden of IBD in children of Middle Eastern descent at the Sydney Children's Hospital, Randwick (SCHR). The SCHR IBD database was used to identify patients of self-reported Middle Eastern ethnicity diagnosed between 1987 and 2011. Demographic, diagnosis, and management data was collected for all Middle Eastern children and an age and gender matched non-Middle Eastern IBD control group. Twenty-four patients of Middle Eastern descent were identified. Middle Eastern Crohn's disease patients had higher disease activity at diagnosis, higher use of thiopurines, and less restricted colonic disease than controls. Although there were limitations with this dataset, we estimated a higher prevalence of IBD in Middle Eastern children and they had a different disease phenotype and behavior compared to the control group, with less disease restricted to the colon and likely a more active disease course. PMID:24987422

  14. Natural products and anti-inflammatory activity.

    PubMed

    Yuan, Gaofeng; Wahlqvist, Mark L; He, Guoqing; Yang, Min; Li, Duo

    2006-01-01

    The aim of this review paper was to summarise some commonly available natural products and their anti-inflammatory activity. We have collected data from MEDLINE, Current Contents and scientific journals, which included 92 publications. There are numerous natural products detailed in this literature; however we have summarized a few of the most commonly available and potent ones. In this paper, the natural products with anti-inflammatory activity including curcumin, parthenolide, cucurbitacins, 1,8-cineole, pseudopterosins, lyprinol, bromelain, flavonoids, saponins, marine sponge natural products and Boswellia serrata gum resin were reviewed. Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Further studies are being conducted to investigate the mechanism of action, metabolism, safety and long term side effect of these natural products, as well as interactions between these natural products with food and drug components. PMID:16672197

  15. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  16. Advances in nutritional therapy in inflammatory bowel diseases: Review.

    PubMed

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-21

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  17. Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease.

    PubMed

    Foster, Meika; Samman, Samir

    2012-07-01

    In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

  18. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases.

    PubMed

    Tran, Thanh-Huyen; Mattheolabakis, George; Aldawsari, Hibah; Amiji, Mansoor

    2015-09-01

    Cell secreted exosomes (30-100nm vesicles) play a major role in intercellular communication due to their ability to transfer proteins and nucleic acids from one cell to another. Depending on the originating cell type and the cargo, exosomes can have immunosuppressive or immunostimulatory effects, which have potential application as immunotherapies for cancer and autoimmune diseases. Cellular components shed from tumor cells or antigen presenting cells (APCs), such as dendritic cells, macrophages and B cells, have been shown to be efficiently packaged in exosomes. In this review, we focus on the application of exosomes as nanocarriers and immunological agents for cancer and autoimmune immunotherapy. APC-derived exosomes demonstrate effective therapeutic efficacy for the treatment of cancer and experimental autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition to their intrinsic immunomodulating activity, exosomes have many advantages over conventional nanocarriers for drug and gene delivery. PMID:25842185

  19. New endoscopic imaging techniques in surveillance of inflammatory bowel disease.

    PubMed

    Gabbani, Tommaso; Manetti, Natalia; Bonanomi, Andrea Giovanni; Annese, Antonio Luca; Annese, Vito

    2015-03-16

    Endoscopy plays a crucial role in the management of inflammatory bowel disease (IBD). Advances imaging techniques allow visualization of mucosal details, tissue characteristics and cellular alteration. In particular chromoendoscopy, magnification endoscopy, confocal laser endomicroscopy and endocytoscopy seem to have the possibility to radically modify the approach to surveillance and decision making. Dye-based chromoendoscopy (DBC) and magnification chromoendoscopy improve detection of dysplasia, and evaluation of inflammatory activity and extension of ulcerative colitis and are thus considered the standard of care. Dye-less chromoendoscopy could probably replace conventional DBC for surveillance. Narrow band imaging and i-scan have shown to improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. This technology is best used in conjunction with chromoendoscopy, narrow-band imaging, or autofluorescence because of its minute scanning area. This combination is useful for appropriate tissue classification of mucosal lesions already detected by standard or optically enhanced endoscopy. The best combination for IBD surveillance appear to be chromoendoscopy for identification of areas of suspicion, with further examination with CLE to detect intraepithelial neoplasia. However cost, availability, and experience are still an issue. PMID:25789093

  20. New endoscopic imaging techniques in surveillance of inflammatory bowel disease

    PubMed Central

    Gabbani, Tommaso; Manetti, Natalia; Bonanomi, Andrea Giovanni; Annese, Antonio Luca; Annese, Vito

    2015-01-01

    Endoscopy plays a crucial role in the management of inflammatory bowel disease (IBD). Advances imaging techniques allow visualization of mucosal details, tissue characteristics and cellular alteration. In particular chromoendoscopy, magnification endoscopy, confocal laser endomicroscopy and endocytoscopy seem to have the possibility to radically modify the approach to surveillance and decision making. Dye-based chromoendoscopy (DBC) and magnification chromoendoscopy improve detection of dysplasia, and evaluation of inflammatory activity and extension of ulcerative colitis and are thus considered the standard of care. Dye-less chromoendoscopy could probably replace conventional DBC for surveillance. Narrow band imaging and i-scan have shown to improve activity and extent assessment in comparison to white-light endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions in surveillance colonoscopy and predict neoplastic and inflammatory changes with high accuracy compared to histology. This technology is best used in conjunction with chromoendoscopy, narrow-band imaging, or autofluorescence because of its minute scanning area. This combination is useful for appropriate tissue classification of mucosal lesions already detected by standard or optically enhanced endoscopy. The best combination for IBD surveillance appear to be chromoendoscopy for identification of areas of suspicion, with further examination with CLE to detect intraepithelial neoplasia. However cost, availability, and experience are still an issue. PMID:25789093

  1. Astrocyte pathology in Alexander disease causes a marked inflammatory environment.

    PubMed

    Olabarria, Markel; Putilina, Maria; Riemer, Ellen C; Goldman, James E

    2015-10-01

    Astrocytes and microglia are commonly involved in a wide variety of CNS pathologies. However, they are typically involved in a secondary response in which many cell types are affected simultaneously and therefore it is difficult to know their contributions to the pathology. Here, we show that pathological astrocytes in a mouse model of Alexander disease (AxD; GFAP (Tg);Gfap (+/R236H)) cause a pronounced immune response. We have studied the inflammatory response in the hippocampus and spinal cord of these mice and have found marked microglial activation, which follows that of astrocytes in a spatial pathological progression, as shown by increased levels of Iba1 and microglial cell (Iba1+) density. RNA sequencing and subsequent gene ontology (GO) analysis revealed that a majority of the most upregulated genes in GFAP (Tg);Gfap (+/R236H) mice are directly associated with immune function and that cytokine and chemokine GO attributes represent nearly a third of the total immune attributes. Cytokine and chemokine analysis showed CXCL10 and CCL2 to be the most and earliest increased molecules, showing concentrations as high as EAE or stroke models. CXCL10 was localized exclusively to astrocytes while CCL2 was also present in microglia. Despite the high levels of CXCL10 and CCL2, T cell infiltration was mild and no B cells were found. Thus, mutations in GFAP are sufficient to trigger a profound inflammatory response. The cellular stress caused by the accumulation of GFAP likely leads to the production of inflammatory molecules and microglial activation. Examination of human AxD CNS tissues also revealed microglial activation and T cell infiltrates. Therefore, the inflammatory environment may play an important role in producing the neuronal dysfunction and seizures of AxD. PMID:26296699

  2. Nutritional aspect of pediatric inflammatory bowel disease: its clinical importance

    PubMed Central

    Kim, Seung

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. The incidence of the disease is rapidly increasing worldwide, and a number of patients are diagnosed during their childhood or adolescence. Aside from controlling the gastrointestinal symptoms, nutritional aspects such as growth, bone mineral density, anemia, micronutrient deficiency, hair loss, and diet should also be closely monitored and managed by the pediatric IBD team especially since the patients are in the development phase. PMID:26576179

  3. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.

    PubMed

    Yao, Xin; Huang, Jiaqi; Zhong, Haihong; Shen, Nan; Faggioni, Raffaella; Fung, Michael; Yao, Yihong

    2014-02-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine with significant functions in the regulation of the immune system. As a potent pro-inflammatory cytokine, IL-6 plays a pivotal role in host defense against pathogens and acute stress. However, increased or deregulated expression of IL-6 significantly contributes to the pathogenesis of various human diseases. Numerous preclinical and clinical studies have revealed the pathological roles of the IL-6 pathway in inflammation, autoimmunity, and cancer. Based on the rich body of studies on biological activities of IL-6 and its pathological roles, therapeutic strategies targeting the IL-6 pathway are in development for cancers, inflammatory and autoimmune diseases. Several anti-IL-6/IL-6 receptor monoclonal antibodies developed for targeted therapy have demonstrated promising results in both preclinical studies and clinical trials. Tocilizumab, an anti-IL-6 receptor antibody, is effective in the treatment of various autoimmune and inflammatory conditions notably rheumatoid arthritis. It is the only IL-6 pathway targeting agent approved by the regulatory agencies for clinical use. Siltuximab, an anti-IL-6 antibody, has been shown to have potential benefits treating various human cancers either as a single agent or in combination with other chemotherapy drugs. Several other anti-IL-6-based therapies are also under clinical development for various diseases. IL-6 antagonism has been shown to be a potential therapy for these disorders refractory to conventional drugs. New strategies, such as combination of IL-6 blockade with inhibition of other signaling pathways, may further improve IL-6-targeted immunotherapy of human diseases. PMID:24076269

  4. The intestinal microbiota in inflammatory bowel diseases.

    PubMed

    Sartor, R Balfour

    2014-01-01

    Abundant clinical and experimental evidence supports a role for resident microbiota in Crohn's disease and pouchitis, and probably in ulcerative colitis (UC). These disorders occur in areas of highest bacterial concentrations. Pouchitis and Crohn's colitis respond to antibiotics, while pouchitis and UC can be treated with probiotics. Serologic markers recognizing intestinal bacteria and yeast are present in the majority of Crohn's disease patients and may predict disease aggressiveness. Abnormal profiles of fecal and mucosally associated enteric bacteria (dysbiosis) occur in Crohn's disease, UC, pouchitis and experimental enterocolitis, with a proliferation of aggressive species that promote experimental colitis and a corresponding decrease in protective bacterial subsets. Many of these protective bacteria produce short-chain fatty acids, including butyrate, that promote epithelial barrier function, inhibit effector immune responses and induce regulatory T cell subsets. Furthermore, certain Clostridia species stimulate regulatory T cells that can inhibit intestinal inflammation. Animal models of chronic, immune-mediated enterocolitis convincingly demonstrate that enteric resident bacteria stimulate effector immune cells in susceptible hosts and that a subset of enteric bacteria has particularly aggressive activities, with host and bacterial specificity. Recent studies suggest parallel and perhaps complementary roles for enteric viruses, which have only very recently been identified. PMID:25227293

  5. Challenges in pediatric inflammatory bowel disease.

    PubMed

    Bousvaros, Athos; Sylvester, Francisco; Kugathasan, Subra; Szigethy, Eva; Fiocchi, Claudio; Colletti, Richard; Otley, Anthony; Amre, Devendra; Ferry, George; Czinn, Steven J; Splawski, Judy B; Oliva-Hemker, Maria; Hyams, Jeffrey S; Faubion, William A; Kirschner, Barbara S; Dubinsky, Marla C

    2006-09-01

    It is estimated that of the >1 million individuals in the United States with inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that begins in childhood affects the individual at a critical period of growth and development. Children with Crohn's disease and ulcerative colitis may experience complications such as growth failure, school absence, and depression. In addition, because children with IBD have fewer environmental confounders such as smoking, children may be an excellent population to study microbial and immune interactions. Despite these opportunities, the discipline of pediatric IBD investigation is still in its infancy. In September of 2005, a group of investigators with expertise in pediatric IBD met in Boston (Massachusetts) to review the current status of childhood IBD research and to develop research priorities that warranted funding from the Crohn's and Colitis Foundation of America. The group included pediatricians, internists, basic scientists, clinical investigators, and members of the administrative staff and board of the Crohn's and Colitis Foundation of America. The research needs in respective areas were outlined by the heads of 10 focus groups, each with expertise in their respective fields (genetics, psychosocial issues, epidemiology, microbiology, immunology, quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and clinical trials). Before the conference, heads of the research focus groups developed their proposals with experts in the field. At the end of the conference, members of the focus groups and members of the steering committee rated the proposed areas of study in terms of feasibility and importance. It was recommended that the Crohn's and Colitis Foundation of America focus its initial efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and skeletal development, the genetics of early-onset IBD, the development of quality improvement interventions to standardize

  6. [Update on the use of PET radiopharmaceuticals in inflammatory disease].

    PubMed

    Martínez-Rodríguez, I; Carril, J M

    2013-01-01

    The use of molecular imaging with PET/CT technology using different radiotracers, especially the (18)F-FDG is currently spreading beyond the area of oncology, the most interest being placed on inflammatory and infectious diseases. This article presents a review of its contribution in different inflammatory conditions in the context of structural and conventional nuclear medicine imaging. Special emphasis is placed on the more significant diseases such as large-vessel vasculitis, sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of the atheroma plaque. PMID:24028819

  7. Iron deficiency: the hidden miscreant in inflammatory bowel disease.

    PubMed

    Allocca, Mariangela; Fiorino, Gionata; Danese, Silvio

    2014-01-01

    Iron deficiency (ID) and anemia of chronic diseases (ACD) are the most common causes of anemia in inflammatory bowel disease (IBD), and frequently coexist. In these circumstances, detection of ID may be difficult as inflammation influences the parameters of iron metabolism. The prevalence of iron deficiency anemia (IDA) ranges between 36% and 76% in this population of patients. Anemia may impair physical condition, quality of life (QOL), and cognitive function, negatively affecting almost every aspect of daily life. Furthermore, it may be one of the causes of death in IBD. Consequently, iron replacement therapy should be initiated as soon as ID or IDA is detected, together with the treatment of underlying inflammation. Oral iron therapy is a simple and cheap treatment, but often is poorly tolerated and may worsen the intestinal damage. Moreover, in inflammatory states, duodenal iron absorption is blocked by a cytokine-mediated mechanism. Consequently, intravenous iron therapy is preferred in the presence of severe anemia, intolerance or lack of response to oral iron, and moderately to severely active disease. Recently, new intravenous iron compounds (iron carboxymaltose, iron isomaltoside 1000, ferumoxytol) have become available. Iron carboxymaltose has been shown to be safe and effective in IBD patients with IDA. Furthermore, it allows for rapid administration of high single doses, saving time and costs. If proven to be efficacious and well tolerated, it may become the standard therapy in the near future. PMID:25213175

  8. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer's Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation.

    PubMed

    Tyagi, Ethika; Fiorelli, Tina; Norden, Michelle; Padmanabhan, Jaya

    2013-01-01

    The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer's disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD. Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice. Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons. In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1 β (IL-1 β ) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes. It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1 β injection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK). We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation. These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD. PMID:24175110

  9. The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease

    PubMed Central

    Keane, Michael P; Strieter, Robert M

    2002-01-01

    The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance. PMID:11806840

  10. Fertility and Contraception in Women With Inflammatory Bowel Disease.

    PubMed

    Martin, Jason; Kane, Sunanda V; Feagins, Linda A

    2016-02-01

    Inflammatory bowel disease (IBD) carries a high burden in women during their reproductive years, and family planning issues are often a significant cause of concern. Fertility is normal in women with nonsurgically treated ulcerative colitis and similar or slightly reduced in women with Crohn's disease. Women who undergo ileal pouch anastomosis have reduced fertility. Fertility is likely worsened by disease activity but unaffected by medications used to treat IBD. Infertile patients with IBD respond as well as non-IBD patients to in vitro fertilization (IVF). Despite normal fertility, patients with IBD have fewer children due to concerns regarding infertility, disease inheritance, congenital abnormalities, and disease-related sexual dysfunction. Patients rarely discuss these issues with a physician. When discussion does occur, it may lead to changes in decision-making. Contraceptives are an important part of family planning, particularly during times of high disease activity. All forms of contraceptives are acceptable in patients with IBD, although there are specific considerations. The risks of combined oral contraceptives outweigh the benefits in patients with active disease and patients with prior or high risk for thromboembolism. Oral contraceptives and IBD are independently associated with an increased risk for thromboembolism, although it is not known whether this effect is compounding. Depot medroxyprogesterone acetate injection should be avoided in patients with or at risk for osteopenia. Intrauterine devices and implants are the most effective form of contraception and should be a first-line recommendation. The use of oral contraceptives is associated with the development of IBD, although there is no increased risk of disease relapse with the use of any form of contraceptive. PMID:27182211

  11. Fertility and Contraception in Women With Inflammatory Bowel Disease

    PubMed Central

    Martin, Jason; Kane, Sunanda V.

    2016-01-01

    Inflammatory bowel disease (IBD) carries a high burden in women during their reproductive years, and family planning issues are often a significant cause of concern. Fertility is normal in women with nonsurgically treated ulcerative colitis and similar or slightly reduced in women with Crohn’s disease. Women who undergo ileal pouch anastomosis have reduced fertility. Fertility is likely worsened by disease activity but unaffected by medications used to treat IBD. Infertile patients with IBD respond as well as non-IBD patients to in vitro fertilization (IVF). Despite normal fertility, patients with IBD have fewer children due to concerns regarding infertility, disease inheritance, congenital abnormalities, and disease-related sexual dysfunction. Patients rarely discuss these issues with a physician. When discussion does occur, it may lead to changes in decision-making. Contraceptives are an important part of family planning, particularly during times of high disease activity. All forms of contraceptives are acceptable in patients with IBD, although there are specific considerations. The risks of combined oral contraceptives outweigh the benefits in patients with active disease and patients with prior or high risk for thromboembolism. Oral contraceptives and IBD are independently associated with an increased risk for thromboembolism, although it is not known whether this effect is compounding. Depot medroxyprogesterone acetate injection should be avoided in patients with or at risk for osteopenia. Intrauterine devices and implants are the most effective form of contraception and should be a first-line recommendation. The use of oral contraceptives is associated with the development of IBD, although there is no increased risk of disease relapse with the use of any form of contraceptive. PMID:27182211

  12. Epithelial expression of interleukin-37b in inflammatory bowel disease.

    PubMed

    Imaeda, H; Takahashi, K; Fujimoto, T; Kasumi, E; Ban, H; Bamba, S; Sonoda, H; Shimizu, T; Fujiyama, Y; Andoh, A

    2013-06-01

    Interleukin (IL)-37 is a member of the IL-1 cytokine family. We investigated IL-37b expression in the inflamed mucosa of inflammatory bowel disease (IBD) patients. Furthermore, we analysed IL-37b expression in human colonic epithelial cells. The human colonic epithelial cell line T84 and human colonic subepithelial myofibroblasts (SEMFs) were used. IL-37b expression in the IBD mucosa was evaluated by immunohistochemistry. IL-37b mRNA and protein expression were determined by real time-polymerase chain reaction (PCR) and Western blotting, respectively. IL-37b was not detected in the normal colonic mucosa. In the inflamed mucosa of IBD patients, epithelial IL-37b expression was increased markedly. In ulcerative colitis (UC) and Crohn's disease (CD) patients, IL-37b expression was enhanced in the affected mucosa. In the intestinal epithelial cell line T84, the expression of IL-37b mRNA and protein was enhanced by tumour necrosis factor (TNF)-α. This IL-37b induction by TNF-α was mediated by nuclear factor (NF)-κB and activator protein (AP)-1 activation. Furthermore, IL-37b inhibited TNF-α-induced interferon-γ-inducible protein (IP)-10 expression significantly in human colonic SEMFs. Epithelial IL-37b expression was increased in IBD patients, especially UC patients. IL-37b may be involved in the pathophysiology of IBD as an anti-inflammatory cytokine and an inhibitor of both innate and acquired immune responses. PMID:23600829

  13. Mucosal healing in inflammatory bowel diseases: a systematic review.

    PubMed

    Neurath, Markus F; Travis, Simon P L

    2012-11-01

    Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted. PMID:22842618

  14. Helminth products as a potential therapeutic strategy for inflammatory diseases.

    PubMed

    Soares, Maria Fernanda de Macedo; Araújo, Claudia A

    2008-06-01

    Helminths secrete several molecules that can modulate the immune responses, favoring their evasion and perpetuate their survival in the host. These molecules interfere with antigen presentation, cell proliferation and activation, antibody production, cause cell death, and stimulate regulatory responses. Here, we focus on some helminth products and address their immunomodulatory effects in the host immune system and, also, we describe some anti-inflammatory properties of an Ascaris suum-derived immunomodulatory molecule, named PAS-1. This protein is a 200-kDa molecule isolated by affinity chromatography using MAIP-1 (monoclonal antibody which recognizes PAS-1), coupled to Sepharose 4B. It suppresses the inflammatory responses in murine models of delayed-type hypersensitivity, lung allergic inflammation and LPS-induced inflammation into air pouches. PAS-1 also stimulates the secretion of regulatory cytokines such as IL-10 and TGF-beta and primes IFN-gamma-secreting CD8+ and IL-10/ TGF-beta-secreting CD4+CD25+ cell clones that avoid the lung inflammation. Thus, this protein is a potent immunomodulatory component that may be used for therapeutic interventions in inflammatory diseases. PMID:18691141

  15. Therapeutic potential of traditional chinese medicine on inflammatory diseases.

    PubMed

    Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

    2013-07-01

    Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation-induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review. PMID:24716170

  16. Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.

    PubMed

    Passos, Lívia Silva Araújo; Villani, Fernanda Nobre Amaral; Magalhães, Luísa Mourão Dias; Gollob, Kenneth J; Antonelli, Lis Ribeiro do Vale; Nunes, Maria Carmo Pereira; Dutra, Walderez Ornelas

    2016-09-15

    The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. PMID:27368347

  17. Nutritional impact of inflammatory bowel diseases on children and adolescents☆

    PubMed Central

    dos Santos, Gilton Marques; Silva, Luciana Rodrigues; Santana, Genoile Oliveira

    2014-01-01

    OBJECTIVE: To perform a sistematiy review of the literature about the nutritional impact of inflammatory bowel diseases in children and adolescents. DATA SOURCES: A systematic review was performed using PubMed/MEDLINE, LILACS and SciELO databases, with inclusion of articles in Portuguese and in English with original data, that analyzed nutritional aspects of inflammatory bowel diseases in children and adolescents. The initial search used the terms "inflammatory bowel diseases" and "children" or "adolescents" and "nutritional evaluation" or "nutrition deficiency". The selection of studies was initially performed by reading the titles and abstracts. Review studies and those withouth data for pediatric patients were excluded. Subsequently, the full reading of the articles considered relevant was performed. RESULTS: 237 studies were identified, and 12 of them were selected according to the inclusion criteria. None of them was performed in South America. During the analysis of the studies, it was observed that nutritional characteristics of patients with inflammatory bowel disease may be altered; the main reports were related to malnutrition, growth stunting, delayed puberty and vitamin D deficiency. CONCLUSION: There are nutritional consequences of inflammatory bowel diseases in children and adolescents, mainly growth stunting, slower pubertal development, underweight and vitamin deficiencies. Nutritional impairments were more significant in patients with Crohn's disease; overweight and obesity were more common in patients with ulcerative rectocolitis. A detailed nutritional assessment should be performed periodically in children and adolescents with inflammatory bowel disease. PMID:25511006

  18. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

    PubMed Central

    Moro, Kazuki; Nagahashi, Masayuki; Ramanathan, Rajesh; Takabe, Kazuaki; Wakai, Toshifumi

    2016-01-01

    Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers. PMID:27458590

  19. Rifaximin in the treatment of inflammatory bowel disease

    PubMed Central

    Guslandi, Mario

    2011-01-01

    The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases (IBD), hence the rationale for the use of antibiotics in the treatment of those disorders. Antibiotics, however, may induce untoward effects, especially during long-term therapy. Rifaximin α polymer is an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects. Rifaximin has provided promising results in inducing remission of Crohn’s disease (up to 69% in open studies and significantly higher rates than placebo in double blind trials) and ulcerative colitis (76% in open studies and significantly higher rates than placebo in controlled studies) and might also have a role in maintaining remission of ulcerative colitis and pouchitis. The potential therapeutic activity of rifaximin in IBD deserves to be further investigated and confirmed in larger, controlled studies. The optimal dosage still needs to be better defined. PMID:22180705

  20. Rifaximin in the treatment of inflammatory bowel disease.

    PubMed

    Guslandi, Mario

    2011-11-14

    The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases (IBD), hence the rationale for the use of antibiotics in the treatment of those disorders. Antibiotics, however, may induce untoward effects, especially during long-term therapy. Rifaximin α polymer is an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects. Rifaximin has provided promising results in inducing remission of Crohn's disease (up to 69% in open studies and significantly higher rates than placebo in double blind trials) and ulcerative colitis (76% in open studies and significantly higher rates than placebo in controlled studies) and might also have a role in maintaining remission of ulcerative colitis and pouchitis. The potential therapeutic activity of rifaximin in IBD deserves to be further investigated and confirmed in larger, controlled studies. The optimal dosage still needs to be better defined. PMID:22180705

  1. [The relationship between selenium and gastrointestinal inflammatory diseases].

    PubMed

    Nagy, Dániel Tamás; Fülesdi, Béla; Hallay, Judit

    2013-10-13

    The cell-membrane toxicity of reactive oxygen and nitrogen species (RONS) plays an increasing role in the pathomechanism of gastrointestinal tract diseases. Trace elements are important parts of antioxidant protecting system, especially the selenium (Se), which, in the form of glutathione peroxidase contributes to the immunity of the gut (GALT). Due to the absorptional disorders and consequent malnutrition observed in the course of inflammatory bowel diseases (IBD) an important role is associated with nutritional therapy, including energy-, protein- and trace element-support. Human studies show, that IBD is mostly accompanied by lower serum Se concentrations, reduced antoxidant and increased proinflammatory activity. Adequate Se-replacement may reduce the severity of organ failure and infections, but not mortality. However, it is encouraging that in animal studies obvious preventive effect of Se has been found on IBD and chronic inflammation induced colon cancer . PMID:24095913

  2. Trait emotional intelligence and inflammatory diseases.

    PubMed

    Costa, Sebastiano; Petrides, K V; Tillmann, Taavi

    2014-01-01

    Researchers have become increasingly interested in the psychological aspects of inflammatory disorders. Within this line of research, the present study compares the trait emotional intelligence (trait EI) profiles of 827 individuals with various inflammatory conditions (rheumatoid arthritis [RA], ankylosing spondylitis, multiple sclerosis, and RA plus one comorbidity) against 496 healthy controls. Global trait EI scores did not show significant differences between these groups, although some differences were observed when comparisons were carried out against alternative control groups. Significant differences were found on the trait EI factors of Well-being (where the healthy group scored higher than the RA group) and Sociability (where the healthy group scored higher than both the RA group and the RA plus one comorbidity group). The discussion centers on the multifarious links and interplay between emotions and inflammatory conditions. PMID:23725416

  3. Antisense approach to inflammatory bowel disease: prospects and challenges.

    PubMed

    Marafini, Irene; Di Fusco, Davide; Calabrese, Emma; Sedda, Silvia; Pallone, Francesco; Monteleone, Giovanni

    2015-05-01

    Despite the great success of anti-tumour necrosis factor-based therapies, the treatment of Crohn's disease (CD) and ulcerative colitis (UC) still remains a challenge for clinicians, as these drugs are not effective in all patients, their efficacy may wane with time, and their use can increase the risk of adverse events and be associated with the development of new immune-mediated diseases. Therefore, new therapeutic targets are currently being investigated both in pre-clinical studies and in clinical trials. Among the technologies used to build new therapeutic compounds, the antisense oligonucleotide (ASO) approach is slowly gaining space in the field of inflammatory bowel diseases (IBDs), and three ASOs have been investigated in clinical trials. Systemic administration of alicaforsen targeting intercellular adhesion molecule-1, a protein involved in the recruitment of leukocytes to inflamed intestine, was not effective in CD, even though the same compound was of benefit when given as an enema to UC patients. DIMS0150, targeting nuclear factor (NF) κB-p65, a transcription factor that promotes pro-inflammatory responses, was very promising in pre-clinical studies and is currently being tested in clinical trials. Oral mongersen, targeting Smad7, an intracellular protein that inhibits transforming growth factor (TGF)-β1 activity, was safe and well tolerated by CD patients, and the results of a phase II clinical trial showed the efficacy of the drug in inducing clinical remission in patients with active disease. In this leading article, we review the rationale and the clinical data available regarding these three agents, and we discuss the challenge of using ASOs in IBD. PMID:25911184

  4. Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

    PubMed

    Agca, R; Heslinga, S C; van Halm, V P; Nurmohamed, M T

    2016-05-15

    Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care. PMID:26888573

  5. Clostridium difficile infection in patients with inflammatory bowel disease

    PubMed Central

    Biesiada, Grażyna; Perucki, William; Mach, Tomasz

    2014-01-01

    Clostridium difficile is a bacterium widely distributed in the human environment. In the last decade the incidence and severity of Clostridium difficile infection has grown, particularly in Europe and North America, making it one of the more common nosocomial infections. A group particularly susceptible to Clostridium difficile infection are patients with inflammatory bowel disease, especially those with involvement of the colon. This paper presents relevant data on Clostridium difficile infections in inflammatory bowel disease patients, including epidemiology, pathogenesis, diagnosis and treatment. PMID:25097707

  6. Toward an antifibrotic therapy for inflammatory bowel disease

    PubMed Central

    2016-01-01

    Fibrosis in inflammatory bowel disease (IBD) is a largely unresolved clinical problem. Despite recent advances in anti-inflammatory therapies over the last few decades, the occurrence of intestinal strictures in Crohn’s disease patients has not significantly changed. No antifibrotic therapies are available. This journal supplement will address novel mechanisms of intestinal fibrosis, biomarker and imaging techniques and is intended to provide a roadmap toward antifibrotic therapies in IBD. PMID:27536358

  7. Toward an antifibrotic therapy for inflammatory bowel disease.

    PubMed

    Rieder, Florian

    2016-08-01

    Fibrosis in inflammatory bowel disease (IBD) is a largely unresolved clinical problem. Despite recent advances in anti-inflammatory therapies over the last few decades, the occurrence of intestinal strictures in Crohn's disease patients has not significantly changed. No antifibrotic therapies are available. This journal supplement will address novel mechanisms of intestinal fibrosis, biomarker and imaging techniques and is intended to provide a roadmap toward antifibrotic therapies in IBD. PMID:27536358

  8. Self-Care Among Patients With Inflammatory Bowel Disease

    PubMed Central

    Yngman-Uhlin, Pia; Hjortswang, Henrik; Riegel, Barbara; Stjernman, Henrik; Hollman Frisman, Gunilla

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology. The disease occurs early in life and the burden of symptoms is significant. Patients need to perform self-care to handle their symptoms, but knowledge about what kind of self-care patients do is limited and these individuals need to learn how to manage the symptoms that arise. The aim of this study was to explore self-care among patients with IBD. Twenty adult patients with IBD, 25–66 years of age, were interviewed. Data were analyzed by performing a qualitative content analysis. Four categories with 10 subcategories emerged from the analysis of the interviews. The self-care patients perform consists of symptom recognition (subcategories: physiological sensations and psychological sensations), handling of symptoms (subcategories: adapting the diet, using medical treatment, stress management, and using complementary alternative medicine), planning life (subcategories: planning for when to do activities and when to refrain from activities), and seeking new options (subcategories: seeking knowledge and personal contacts). Self-care consists of symptom recognition, handling life through planning, and accommodating the existing situation with the ultimate goal of maintaining well-being. Being one step ahead facilitates living with IBD. A decision to actively participate in care of a chronic illness is a prerequisite for self-care. Healthcare professionals must consider patients' potential for and desire for self-care when giving advice on self-care activities. Doing so may help people better cope with IBD. PMID:26166423

  9. Physical Fitness in Adolescence and Subsequent Inflammatory Bowel Disease Risk

    PubMed Central

    Melinder, Carren; Hiyoshi, Ayako; Hussein, Oula; Halfvarson, Jonas; Ekbom, Anders; Montgomery, Scott

    2015-01-01

    OBJECTIVES: Physical fitness may reduce systemic inflammation levels relevant to the risk of symptomatic Crohn's disease (CD) and ulcerative colitis (UC); we assessed if fitness in adolescence is associated with subsequent inflammatory bowel disease (IBD) risk, independent of markers of risk and prodromal disease activity. METHODS: Swedish registers provided information on a cohort of 240,984 men (after exclusions) who underwent military conscription assessments in late adolescence (1969–1976). Follow-up started at least 4 years after the conscription assessment until 31 December 2009 (up to age 57 years). Cox's regression assessed the association of physical fitness with CD (n=986) and UC (n=1,878) in separate models, with adjustment including: socioeconomic conditions in childhood; physical fitness, height, body mass index, and erythrocyte sedimentation rate (ESR) in adolescence; and subsequent diagnoses of IBD. RESULTS: Low fitness was associated with a raised risk of IBD, with unadjusted hazard ratios (and 95% confidence intervals) of 1.62 (1.31–2.00) for CD and 1.36 (1.17–1.59) for UC. The results were attenuated by adjustment, particularly for markers of prodromal disease activity to 1.32 (1.05–1.66) and 1.25 (1.06–1.48), respectively. Raised ESR in adolescence was associated with increased risks for subsequent CD (5.95 (4.47–7.92)) and UC (1.92 (1.46–2.52)). CONCLUSIONS: The inverse association of physical fitness with IBD risk is consistent with a protective role for exercise. However, evidence of disease activity before diagnosis was already present in adolescence, suggesting that some or all of the association between fitness and IBD may be due to prodromal disease activity reducing exercise capacity and therefore fitness. PMID:26540026

  10. Bacterial Intestinal Superinfections in Inflammatory Bowel Diseases Beyond Clostridum difficile.

    PubMed

    Lobatón, Triana; Domènech, Eugeni

    2016-07-01

    Besides genetics and environmental factors, intestinal microbiota seem to play a major role in the pathogenesis of inflammatory bowel diseases. For many decades, it has been said that some enteropathogens may even trigger both inflammatory bowel disease development and disease flares. For this reason, stool testing had been performed in inflammatory bowel disease flares but current guidelines only recommend to rule out Clostridium difficile infection and there is no clear advice for other enteropathogens given that the scarce available evidence points at a low prevalence of this sort of intestinal superinfections with no clear impact on disease course. The present article reviews the current knowledge about the role of bacterial enteropathogens on disease pathogenesis and flares beyond C. difficile. PMID:27104824

  11. Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases

    PubMed Central

    Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

    2013-01-01

    Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation–induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review. PMID:24716170

  12. Etiology and pathophysiology of inflammatory bowel disease--environmental factors.

    PubMed

    Andus, T; Gross, V

    2000-01-01

    Environmental factors play an important role in the pathophysiology of inflammatory bowel disease. There is a strong and consistent association between smoking and Crohn's disease, and between nonsmoking and ulcerative colitis. Despite extensive research, the exact pathophysiological mechanisms for these associations remain unclear. In spite of this, some clinical trials with nicotine-patches showed beneficial effects for the treatment of ulcerative colitis. Associations of Crohn's disease and ulcerative colitis with other environmental factors are weaker like the association with use of oral contraceptives or those less well investigated such as the association with childhood hygiene. Most studies suggesting a potential pathogenetic role of Mycobacterium paratuberculosis or an effect of tuberculostatic therapy in Crohn's disease could not be reproduced by others. Perinatal or childhood infections by viruses like measles are heavily debated, but not proven to be causal for inflammatory bowel disease. Coagulation disorders have been described as protecting from inflammatory bowel disease, suggesting hypercoagulability to be a pathogenetic factor. Some studies described that appendectomy may prevent the onset of ulcerative colitis in man and mice. Other environmental factors such as hydrogen sulfide, tonsillectomy, diet, blood transfusions, and Listeria also require confirmation. There are, however, convincing data from genetic animal models and twin studies that environmental factors as the intestinal bacterial flora interact with susceptible hosts to cause inflammatory bowel disease. Inflammatory bowel diseases have multifactorial etiologies, which require a differentiated approach for treatment and prevention. PMID:10690583

  13. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    PubMed

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. PMID:24781339

  14. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems

    PubMed Central

    Hartman, Kira G.; Bortner, James D.; Falk, Gary W.; Ginsberg, Gregory G.; Jhala, Nirag; Yu, Jian; Martín, Martín G.; Rustgi, Anil K.; Lynch, John P.

    2014-01-01

    Gastrointestinal (GI) illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammation are a common element of many GI diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett’s esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. PMID:24781339

  15. Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases.

    PubMed

    Bar-Or, Amit; Hintzen, Rogier Q; Dale, Russell C; Rostasy, Kevin; Brück, Wolfgang; Chitnis, Tanuja

    2016-08-30

    Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatric-onset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. PMID:27572856

  16. Gene therapy for lung inflammatory diseases: not so far away?

    PubMed Central

    Sallenave, J. M.; Porteous, D. J.; Haslett, C.

    1997-01-01

    The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses-- for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease. 


 PMID:9337837

  17. Gene therapy for lung inflammatory diseases: not so far away?

    PubMed

    Sallenave, J M; Porteous, D J; Haslett, C

    1997-08-01

    The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease. PMID:9337837

  18. Central Endoscopy Reading in Inflammatory Bowel Diseases.

    PubMed

    Panés, Julián; Feagan, Brian G; Hussain, Fez; Levesque, Barrett G; Travis, Simon P

    2016-09-01

    Endoscopic assessment of the presence and severity of endoscopic lesions has become an essential part of clinical trials in ulcerative colitis and Crohn's disease, for both patient eligibility and outcome measures. Variability in lesion interpretation between and within observers and the potential bias of local investigators in patient assessment have long been recognized. This variability can be reduced, although not completely removed, by independent evaluation of the examinations by experienced off-site (central) readers, properly trained in regard to lesion definition and identification, that should be removed from direct patient contact and blinded to any other clinical or study data. Adding endoscopic demonstration of active disease to eligibility criteria has the potential to reduce placebo response rates, whereas in outcome assessment it has the potential to provide a more precise estimation of the treatment effect, increasing the efficiency of the study. Central endoscopy reading is still at the beginning of its development, and the paradigms of central reading need refinement in terms of the number of readers, the process by which a final score is assigned, the selection and sequence of central readers, and the endoscopic indices of choice. PMID:27604978

  19. Inflammatory Bowel Disease Patients' Participation, Attitude and Preferences Toward Exercise.

    PubMed

    Chae, J; Yang, H I; Kim, B; Park, S J; Jeon, J Y

    2016-07-01

    The purpose of the study was to investigate the level of exercise participation in patients with inflammatory bowel disease (IBD) and to investigate their intention, attitude and preference toward exercise. The data of 158 IBD patients that participated in a self-administered survey at Severance Hospital between March 2013 and November 2013 were included in this cross sectional and descriptive analysis. Questionnaires included 3 sections to determine the IBD patient's current exercise participation, attitude toward exercise, and exercise preferences. This study investigated IBD patients both collectively, and according to their specific disease: Crohn's disease (CD) (n=62), Ulcerative colitis (UC) (n=73) and intestinal Behçet's disease (BD) (n=23). IBD patients currently participate in 103 min/week of exercise including mild, moderate and strenuous intensity, with BD patients being the least active, followed by CD, and UC being most active. The majority of IBD patients found exercise to be pleasant (57.7%), beneficial (80.5%), sensible (71.8%), uplifting (61%) and good (70.5%), and 44.4% found exercise to be enjoyable. This study shows the IBD patients' participation, attitude and preferences toward exercise and provides much needed information for the development of evidence based exercise programs that are specific to IBD. PMID:27191208

  20. Preclinical inflammatory rheumatic diseases: an overview and relevant nomenclature.

    PubMed

    Raza, Karim; Gerlag, Danielle M

    2014-11-01

    Chronic inflammatory and autoimmune conditions result from an interplay between genetic and environmental factors culminating in the phenotypes of established disease. The transition from health to established disease is relatively well understood in rheumatoid arthritis (RA), which provides an exemplar for other diseases. This article addresses terminologies to describe the phases of disease leading to RA, disease initiation and the point from which disease duration should be timed, the future research agenda suggested by this approach to the definition of phases of disease, and the importance of capturing the patient perspective in research into the earliest phases of disease. PMID:25437278

  1. Porous antioxidant polymer microparticles as therapeutic systems for the airway inflammatory diseases.

    PubMed

    Jeong, Dahee; Kang, Changsun; Jung, Eunkyeong; Yoo, Donghyuck; Wu, Dongmei; Lee, Dongwon

    2016-07-10

    Inhaling steroidal anti-inflammatory drugs is the most common treatment for airway inflammatory diseases such as asthma. However, frequent steroid administration causes adverse side effects. Therefore, the successful clinical translation of numerous steroidal drugs greatly needs pulmonary drug delivery systems which are formulated from biocompatible and non-immunogenic polymers. We have recently developed a new family of biodegradable polymer, vanillyl alcohol-containing copolyoxalate (PVAX) which is able to scavenge hydrogen peroxide and exert potent antioxidant and anti-inflammatory activity. In this work, we report the therapeutic potential of porous PVAX microparticles which encapsulate dexamethasone (DEX) as a therapeutic system for airway inflammatory diseases. PVAX microparticles themselves reduced oxidative stress and suppressed the expression of pro-inflammatory tumor necrosis factor-alpha and inducible nitric oxide synthase in the lung of ovalbumin-challenged asthmatic mice. However, DEX-loaded porous PVAX microparticles showed significantly enhanced therapeutic effects than PVAX microparticles, suggesting the synergistic effects of PVAX with DEX. In addition, PVAX microparticles showed no inflammatory responses to lung tissues. Given their excellent biocompatibility and intrinsic antioxidant and anti-inflammatory activity, PVAX microparticles hold tremendous potential as therapeutic systems for the treatment of airway inflammatory diseases such as asthma. PMID:27151077

  2. Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches

    PubMed Central

    Park, Mi Hee; Hong, Jin Tae

    2016-01-01

    Nuclear factor-κB (NF-κB) is a transcription factor that plays a crucial role in various biological processes, including immune response, inflammation, cell growth and survival, and development. NF-κB is critical for human health, and aberrant NF-κB activation contributes to development of various autoimmune, inflammatory and malignant disorders including rheumatoid arthritis, atherosclerosis, inflammatory bowel diseases, multiple sclerosis and malignant tumors. Thus, inhibiting NF-κB signaling has potential therapeutic applications in cancer and inflammatory diseases. PMID:27043634

  3. Diabetic Retinopathy: Vascular and Inflammatory Disease

    PubMed Central

    Semeraro, F.; Cancarini, A.; dell'Omo, R.; Rezzola, S.; Romano, M. R.; Costagliola, C.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID:26137497

  4. Cannabidiol in inflammatory bowel diseases: a brief overview.

    PubMed

    Esposito, Giuseppe; Filippis, Daniele De; Cirillo, Carla; Iuvone, Teresa; Capoccia, Elena; Scuderi, Caterina; Steardo, Antonio; Cuomo, Rosario; Steardo, Luca

    2013-05-01

    This minireview highlights the importance of cannabidiol (CBD) as a promising drug for the therapy of inflammatory bowel diseases (IBD). Actual pharmacological treatments for IBD should be enlarged toward the search for low-toxicityand low-cost drugs that may be given alone or in combination with the conventional anti-IBD drugs to increase their efficacy in the therapy of relapsing forms of colitis. In the past, Cannabis preparations have been considered new promising pharmacological tools in view of their anti-inflammatory role in IBD as well as other gut disturbances. However, their use in the clinical therapy has been strongly limited by their psychotropic effects. CBD is a very promising compound since it shares the typical cannabinoid beneficial effects on gut lacking any psychotropic effects. For years, its activity has been enigmatic for gastroenterologists and pharmacologists, but now it is evident that this compound may interact at extra-cannabinoid system receptor sites, such as peroxisome proliferator-activated receptor-gamma. This strategic interaction makes CBD as a potential candidate for the development of a new class of anti-IBD drugs. PMID:22815234

  5. Diagnostic Accuracy of CT Enterography for Active Inflammatory Terminal Ileal Crohn Disease: Comparison of Full-Dose and Half-Dose Images Reconstructed with FBP and Half-Dose Images with SAFIRE.

    PubMed

    Gandhi, Namita S; Baker, Mark E; Goenka, Ajit H; Bullen, Jennifer A; Obuchowski, Nancy A; Remer, Erick M; Coppa, Christopher P; Einstein, David; Feldman, Myra K; Kanmaniraja, Devaraju; Purysko, Andrei S; Vahdat, Noushin; Primak, Andrew N; Karim, Wadih; Herts, Brian R

    2016-08-01

    Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all

  6. Anti-inflammatory effects of antidepressants: possibilities for preventives against Alzheimer's disease.

    PubMed

    Hashioka, Sadayuki; McGeer, Patrick L; Monji, Akira; Kanba, Shigenobu

    2009-03-01

    Increasing evidence of pro-inflammatory mediator expression in major depressions indicate that inflammatory changes may play a role. If this is true, the efficacy of antidepressants may be partially attributable to suppression of inflammation. Various types of antidepressants can suppress serum and plasma levels of pro-inflammatory mediators in patients with major depression. Therefore they can inhibit the production of pro-inflammatory mediators by immune cells. These include glial cells, which are the main sources and targets of cytokines in the brain. This review summarizes the evidence showing that antidepressants have an anti-inflammatory potential. The putative mechanisms are also discussed. Because of the anti-inflammatory effects of antidepressants, they might also act as preventives for neurodegenerative dementias including Alzheimer's disease, where the pathogenesis involves chronic inflammation associated with activated microglia. PMID:20021334

  7. [Inflammatory bowel disease and bone decreased bone mineral density].

    PubMed

    Hisamatsu, Tadakazu; Wada, Yasuyo; Kanai, Takanori

    2015-11-01

    Metabolic bone diseases such as osteopenia and osteoporosis increase the risk of bone fracture that negatively affects quality of life of individuals. Patients with inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD), have been shown to be at increased risk of decreased bone mineral density, however frequency of metabolic bone disease in IBD and identified risk factors are varied among reports. PMID:26503868

  8. Inflammatory bowel disease: is it a primary immunodeficiency?

    PubMed

    Glocker, Erik; Grimbacher, Bodo

    2012-01-01

    Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn's disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system. PMID:21997382

  9. Vaccinations in patients with immune-mediated inflammatory diseases

    PubMed Central

    Rahier, Jean-François; Moutschen, Michel; Van Gompel, Alfons; Van Ranst, Marc; Louis, Edouard; Segaert, Siegfried; Masson, Pierre

    2010-01-01

    Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals. PMID:20591834

  10. Inflammatory bowel disease: An increased risk factor for neurologic complications

    PubMed Central

    Morís, Germán

    2014-01-01

    Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn’s disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity. PMID:24574797

  11. Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases.

    PubMed

    Zhong, Zhenyu; Sanchez-Lopez, Elsa; Karin, Michael

    2016-01-01

    Loss of homeostasis, as a result of pathogen invasion or self imbalance, causes tissue damage and inflammation. In addition to its well-established role in promoting clearance of pathogens or cell corpses, inflammation is also key to drive tissue repair and regeneration. Conserved from flies to humans, a transient, well-balanced inflammatory response is critical for restoration of tissue homeostasis after damage. The absence of such a response can result in failure of tissue repair, leading to the development of devastating immunopathologies and degenerative diseases. Studies in the past decade collectively suggest that a malfunction of NLRP3 inflammasome, a key tissue damage sensor, is a dominant driver of various autoinflammatory and autoimmune diseases, including gout, rheumatoid arthritis, and lupus. It is therefore crucial to understand the biology and regulation of NLRP3 inflammasome and determine its affect in the context of various diseases. Of note, various studies suggest that autophagy, a cellular waste removal and rejuvenation process, serves an important role as a macrophage-intrinsic negative regulator of NLRP3 inflammasome. Here, we review recent advances in understanding how autophagy regulates NLRP3 inflammasome activity and discuss the implications of this regulation on the pathogenesis of autoinflammatory and autoimmune diseases. PMID:27586797

  12. Inflammatory bowel disease alters intestinal bile acid transporter expression.

    PubMed

    Jahnel, Jörg; Fickert, Peter; Hauer, Almuthe C; Högenauer, Christoph; Avian, Alexander; Trauner, Michael

    2014-09-01

    The enterohepatic circulation of bile acids (BAs) critically depends on absorption of BA in the terminal ileum and colon, which can be affected by inflammatory bowel disease (IBD). Diarrhea in IBD is believed to result in part from BA malabsorption (BAM). We explored whether IBD alters mRNA expression of key intestinal BA transporters, BA detoxifying systems, and nuclear receptors that regulate BA transport and detoxification. Using real-time polymerase chain reaction, mucosal biopsy specimens from the terminal ileum in Crohn's disease (CD) patients and from the descending colon in ulcerative colitis (UC) patients were assessed for mRNA expression. Levels were compared with healthy controls. The main ileal BA uptake transporter, the apical sodium dependent bile acid transporter, was downregulated in active CD and UC and in CD in remission. Other significant changes such as repression of breast cancer-related protein and sulphotransferase 2A1 were seen only during active disease. In UC, pancolitis (but not exclusively left-sided colitis) was associated with altered expression of major BA transporters [multidrug resistance-associated protein 3 (MRP3), MRP4, multidrug resistance gene 1, organic solute transporter α/β] and nuclear receptors (pregnane X receptor, vitamin D receptor) in the descending colon. UC pancolitis leads to broad changes and CD ileitis to selective changes in intestinal BA transporter expression. Early medical manipulation of intestinal BA transporters may help prevent BAM. PMID:24965812

  13. Inflammatory bowel disease related innate immunity and adaptive immunity

    PubMed Central

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn’s disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD. PMID:27398134

  14. Extra intestinal manifestations and complications in inflammatory bowel disease.

    PubMed

    Marineaţă, Anca; Rezuş, Elena; Mihai, Cătălina; Prelipcean, Cristina Cijevschi

    2014-01-01

    Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), doesn't affect only the intestinal tract, but also involve other organs such as: eyes, skin, joints, liver and biliary tracts, kidneys, lungs, vascular system. It is difficult to differentiate the true extraintestinal manifestations from secondary extraintestinal complications. The pathogenetic autoimmune mechanisms include genetic susceptibility, antigenic display of autoantigen, aberrant self-recognition and immunopathogenetic autoantibodies against organ-specific cellular antigens shared by colon and extra-colonic organs. An important role is owned by microbes due to molecular mimicry. This paper reviews the frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. PMID:25076688

  15. Systemic therapies for inflammatory eye disease: Past, Present and Future

    PubMed Central

    2013-01-01

    In this review we consider the current evidence base for treatments in inflammatory eye disease, and in particular uveitis, from a historical perspective. We consider the challenges that have traditionally hindered progress in inflammatory eye disease including small target populations, heterogeneous disease groups, poorly defined phenotypes, diagnostic inconsistency, subjective outcome measures, specific issues around visual acuity as an outcome measure and low commercial interest. Strategies to address these issues are considered de novo and with reference to recent advances outside of ophthalmology and highlight the promise for ocular inflammation. Progress in these specialties has included the development of thriving clinical-trial cultures, public-private partnerships, pathogenetic- and structure-led drug design, efficient drug development pipelines, and biomarker-defined treatment protocols enabling personalization of medicine. Although there are challenges, these are exciting opportunities as we seek to develop safe and effective treatments for patients with inflammatory eye disease. PMID:23617902

  16. Vaccines and recommendations for their use in inflammatory bowel disease

    PubMed Central

    Sánchez-Tembleque, María Dolores; Corella, Carmen; Pérez-Calle, Jose L

    2013-01-01

    The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocom-promised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine. PMID:23538680

  17. Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease

    PubMed Central

    Lee, Ji Min; Lee, Kang-Moon

    2016-01-01

    Patients with inflammatory bowel disease have significantly increased in recent decades in Korea. Intestinal tuberculosis (ITB) and intestinal Behcet’s disease (BD), which should be differentiated from Crohn’s disease (CD), are more frequent in Korea than in the West. Thus, the accurate diagnosis of these inflammatory diseases is problematic in Korea and clinicians should fully understand their clinical and endoscopic characteristics. Ulcerative colitis mostly presents with rectal inflammation and continuous lesions, while CD presents with discontinuous inflammatory lesions and frequently involves the ileocecal area. Involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps are more frequently seen in ITB than in CD. A few ulcers with discrete margins are a typical endoscopic finding of intestinal BD. However, the differential diagnosis is difficult in many clinical situations because typical endoscopic findings are not always observed. Therefore, clinicians should also consider symptoms and laboratory, pathological, and radiological findings, in addition to endoscopic findings. PMID:27484813

  18. Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor

    PubMed Central

    Glocker, Erik-Oliver; Kotlarz, Daniel; Boztug, Kaan; Gertz, E. Michael; Schäffer, Alejandro A.; Noyan, Fatih; Perro, Mario; Diestelhorst, Jana; Allroth, Anna; Murugan, Dhaarini; Hätscher, Nadine; Pfeifer, Dietmar; Sykora, Karl-Walter; Sauer, Martin; Kreipe, Hans; Lacher, Martin; Nustede, Rainer; Woellner, Cristina; Baumann, Ulrich; Salzer, Ulrich; Koletzko, Sibylle; Shah, Neil; Segal, Anthony W.; Sauerbrey, Axel; Buderus, Stephan; Snapper, Scott B.; Grimbacher, Bodo; Klein, Christoph

    2009-01-01

    BACKGROUND The molecular cause of inflammatory bowel disease is largely unknown. METHODS We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients’ peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. RESULTS In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10–induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor α and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10–dependent “negative feedback” regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful. CONCLUSIONS Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient. PMID:19890111

  19. Management of stress in inflammatory bowel disease: a therapeutic option?

    PubMed

    Goodhand, James R; Wahed, Mahmood; Rampton, David S

    2009-12-01

    There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of, inflammatory bowel disease (IBD). Unfortunately, owing to methodological difficulties inherent in undertaking appropriately targeted and blinded trials, there are limited high-quality data regarding the effects on IBD of interventions aimed to ameliorate stress and mood disorders. Nevertheless, patients want psychological intervention as well as conventional medical strategies. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there are no strong data as of yet to indicate that stress management has a beneficial effect on the activity or course of IBD. As yet, which, when and how interventions targeted at psychological stress and mood disturbances should be offered to individual patients with IBD is not clear. PMID:19929586

  20. Next-Generation Therapeutics for Inflammatory Bowel Disease.

    PubMed

    Dulai, Parambir S; Sandborn, William J

    2016-09-01

    Tumor necrosis factor (TNF) antagonists are the cornerstone of therapy for moderately to severely active inflammatory bowel disease (IBD). Although our understanding of pharmacokinetics, pharmacodynamics, and treatment optimization for these agents has evolved considerably over the past decade, a substantial majority of individuals fail to respond or lose response to TNF-antagonists over time. A need therefore remains for efficacious treatment options in these patients. Alternative immunological targets have now been identified, and several novel therapeutic agents are in development for IBD. In this review article, we discuss these novel therapeutic agents, with a particular focus on those demonstrated to be efficacious in phase 2 and 3 clinical trials. We further discuss considerations to be made when integrating these agents into routine practice over the next decade. PMID:27461274

  1. The Roles of Vitamin D and Its Analogs in Inflammatory Diseases.

    PubMed

    Lin, Zongtao; Li, Wei

    2016-01-01

    The discovery of nonclassical actions, other than mineral homeostasis, of 1α,25- dihydroxyvitamin D3 (1,25D3) has expanded its applications. Among these, its anti-inflammation activity has drawn more and more attention of researchers to investigate its role in regulating the progression of inflammatory diseases. The expression of many inflammation-related genes is regulated by 1,25D3 through vitamin D receptor (VDR) in a large variety of cells including immune cells such as, but not limited to, macrophages, dendritic cells, T helper cells, and B cells. Studies of 1,25D3 in these immune cells have shown both direct and indirect immunomodulatory activities affecting innate and adaptive immune responses. Moreover, 1,25D3 can also exert its anti-inflammation effects through regulating the biosynthesis of pro-inflammatory molecules in the prostaglandin pathway or through nuclear factor kappa light-chain-enhancer of activated B cells (NFκB) by affecting cytokine production and inflammatory responses. These actions of 1,25D3 may explain the associations between vitamin D levels and inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, asthma, type 1 diabetes, and systemic lupus erythematosus. Although several analogs of 1,25D3 have shown potent immunomodulatory or anti-inflammatory activity on immune cell cultures or in animal models, no vitamin D analog has been used in clinical research to treat inflammatory diseases. Here, we review the relationship between vitamin D analogs and inflammation based on observations of immune cells, prostaglandin and NFκB pathways, as well as common inflammatory diseases. PMID:26369816

  2. Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

    PubMed Central

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Kappo, Abidemi Paul

    2015-01-01

    Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance. PMID:25850012

  3. Exploring inflammatory disease drug effects on neutrophil function.

    PubMed

    Wu, Xiaojie; Kim, Donghyuk; Young, Ashlyn T; Haynes, Christy L

    2014-08-21

    Neutrophils are critical inflammatory cells; thus, it is important to characterize the effects of drugs on neutrophil function in the context of inflammatory diseases. Herein, chemically guided neutrophil migration, known as chemotaxis, is studied in the context of drug treatment at the single cell level using a microfluidic platform, complemented by cell viability assays and calcium imaging. Three representative drugs known to inhibit surface receptor expression, signaling enzyme activity, and the elevation of intracellular Ca(2+) levels, each playing a significant role in neutrophil chemotactic pathways, are used to examine the in vitro drug effects on cellular behaviors. The microfluidic device establishes a stable concentration gradient of chemokines across a cell culture chamber so that neutrophil migration can be monitored under various drug-exposure conditions. Different time- and concentration-dependent regulatory effects were observed by comparing the motility, polarization, and effectiveness of neutrophil chemotaxis in response to the three drugs. Viability assays revealed distinct drug capabilities in reducing neutrophil viability while calcium imaging clarified the role of Ca(2+) in the neutrophil chemotaxis. This study provides mechanistic insight into the drug effects on neutrophil function, facilitating comparison of current and potential pharmaceutical approaches. PMID:24946254

  4. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease.

    PubMed

    García-Lafuente, Ana; Guillamón, Eva; Villares, Ana; Rostagno, Mauricio A; Martínez, José Alfredo

    2009-09-01

    Chronic inflammation is being shown to be increasingly involved in the onset and development of several pathological disturbances such as arteriosclerosis, obesity, diabetes, neurodegenerative diseases and even cancer. Treatment for chronic inflammatory disorders has not been solved, and there is an urgent need to find new and safe anti-inflammatory compounds. Flavonoids belong to a group of natural substances occurring normally in the diet that exhibit a variety of beneficial effects on health. The anti-inflammatory properties of flavonoids have been studied recently, in order to establish and characterize their potential utility as therapeutic agents in the treatment of inflammatory diseases. Several mechanisms of action have been proposed to explain in vivo flavonoid anti-inflammatory actions, such as antioxidant activity, inhibition of eicosanoid generating enzymes or the modulation of the production of proinflammatory molecules. Recent studies have also shown that some flavonoids are modulators of proinflammatory gene expression, thus leading to the attenuation of the inflammatory response. However, much work remains to be done in order to achieve definitive conclusions about their potential usefulness. This review summarizes the known mechanisms involved in the anti-inflammatory activity of flavonoids and the implications of these effects on the protection against cancer and cardiovascular disease. PMID:19381780

  5. Progress and frustration in inflammatory bowel disease.

    PubMed Central

    Brooke, B. N.

    1980-01-01

    Advances -- and lack of them -- in our understanding of the aetiology, nature, and treatment of ulcerative colitis and Crohn's disease during the past 30 years are reviewed with special reference to personal experience. PMID:7002013

  6. Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease.

    PubMed

    Kruidenier, Laurens; Kuiper, Ineke; Van Duijn, Wim; Mieremet-Ooms, Marij A C; van Hogezand, Ruud A; Lamers, Cornelis B H W; Verspaget, Hein W

    2003-09-01

    Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of

  7. [Drug delivery strategies for targeted treatment of inflammatory bowel disease].

    PubMed

    Lautenschläger, C; Schmidt, C; Lange, K; Stallmach, A

    2015-03-01

    Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive agents, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Present treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. The development of novel disease-targeted drug delivery strategies is preferable for a more effective therapy and thus demonstrates the potential to address unmet medical needs. This review gives an overview about drug delivery strategies for the treatment of IBD. Therefore, established intestine-targeting strategies for a selective drug release into the diseased part of the gastrointestinal tract will be presented, including prodrugs, and dosage forms with pH-/time-dependent drug release. Furthermore future-oriented disease-targeting strategies for a selective drug release into the intestinal inflammation will be described, including micro-/nanosized synthetic and biologic drug carriers. This novel therapeutic approach may enable a more effective anti-inflammatory treatment of IBD with reduced risks of adverse reactions. PMID:25723326

  8. Herbal and plant therapy in patients with inflammatory bowel disease

    PubMed Central

    Triantafyllidi, Aikaterini; Xanthos, Theodoros; Papalois, Apostolos; Triantafillidis, John K.

    2015-01-01

    The use of herbal therapy in inflammatory bowel disease (IBD) is increasing worldwide. The aim of this study was to review the literature on the efficacy of herbal therapy in IBD patients. Studies on herbal therapy for IBD published in Medline and Embase were reviewed, and response to treatment and remission rates were recorded. Although the number of the relevant clinical studies is relatively small, it can be assumed that the efficacy of herbal therapies in IBD is promising. The most important clinical trials conducted so far refer to the use of mastic gum, tormentil extracts, wormwood herb, aloe vera, triticum aestivum, germinated barley foodstuff, and boswellia serrata. In ulcerative colitis, aloe vera gel, triticum aestivum, andrographis paniculata extract and topical Xilei-san were superior to placebo in inducing remission or clinical response, and curcumin was superior to placebo in maintaining remission; boswellia serrata gum resin and plantago ovata seeds were as effective as mesalazine, whereas oenothera biennis had similar relapse rates as ω-3 fatty acids in the treatment of ulcerative colitis. In Crohn’s disease, mastic gum, Artemisia absinthium, and Tripterygium wilfordii were superior to placebo in inducing remission and preventing clinical postoperative recurrence, respectively. Herbal therapies exert their therapeutic benefit by different mechanisms including immune regulation, antioxidant activity, inhibition of leukotriene B4 and nuclear factor-kappa B, and antiplatelet activity. Large, double-blind clinical studies assessing the most commonly used natural substances should urgently be conducted. PMID:25830661

  9. Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

    PubMed Central

    Sung, Nak Yoon

    2015-01-01

    Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation. PMID:26330757

  10. Tumor Necrosis Factor-alpha Converting Enzyme: Implications for Ocular Inflammatory Diseases

    PubMed Central

    Ramana, Kota V

    2010-01-01

    Tumor necrosis factor-alpha (TNF-α) –converting enzyme (TACE), a member of the family of metalloproteinase disintegrin proteins, is responsible for the conversion of inactive TNF-α precursor from to active mature form. TNF-α is a pleiotropic cytokine that contributes to cellular immunity and inflammatory response in wide range of inflammatory pathologies. Although a large number of studies indicate the use of TACE inhibitors, which prevents processing of TNF-α as potential therapeutic drugs for the treatment of inflammatory diseases including rheumatoid arthritis, Crohn’s disease and cancer, very few studies indicate its use in ocular pathologies. It is still not clearly understood how the TACE-mediated shedding of cytokines and growth factors in various ocular tissues plays a critical role in the cytotoxic signals causing tissue dysfunction and damage leading to blindness. Regulation of TACE activity is likely to have wide implications for ocular immunology and inflammatory diseases. Specifically, since anti-TNF-α therapies have been used to prevent ocular inflammatory complications, the use of TACE inhibitors could be a novel therapeutic approach for ocular inflammatory diseases especially uveitis. PMID:20303413

  11. AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

    PubMed

    King, Tanya S; Russe, Otto Quintus; Möser, Christine V; Ferreirós, Nerea; Kynast, Katharina L; Knothe, Claudia; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-09-01

    AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties. PMID:26049010

  12. Current stage in inflammatory bowel disease: What is next?

    PubMed Central

    Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

    2015-01-01

    In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

  13. Intestinal permeability to 99mTc-diethylenetriaminopentaacetic acid in inflammatory bowel disease

    SciTech Connect

    Casellas, F.; Aguade, S.; Soriano, B.; Accarino, A.; Molero, J.; Guarner, L.

    1986-09-01

    Intestinal permeability in inflammatory bowel disease and its relation to periods of disease activity has been investigated by measuring the urinary excretion of DTPA labeled with 99mTc. Urine excretion in 10 control subjects was 2.7 +/- 1% of the test dose. Twelve patients with ulcerative colitis excreted 5.08 +/- 1.6% in remission, 10.61 +/- 2% during periods of mild activity, 19.41 +/- 0.9% during moderate activity, and 15.41 +/- 6.3% with severe activity. Sixteen patients with Crohn's disease excreted 5.7 +/- 1.9% in remission, 8.47 +/- 2.8% during mild activity of the disease, and 14.29 +/- 5.8% during moderate activity. No differences were observed between ulcerative colitis and Crohn's disease, or between ileal and colonic forms of Crohn's disease. Excretion in remission was significantly greater than in control subjects and there was a correlation between excretion and disease activity. In serial determinations done in seven patients we found that urine excretion of the test substance correlated with disease activity. We also studied DTPA excretion in 10 cases with gastric or duodenal ulcer (2.28 +/- 1.4%), six cases of acute gastroenteritis (4.87 +/- 3.1%) and nine cases with other intestinal diseases (3.6 +/- 1.1%). In all these cases, DTPA excretion was lower than in inflammatory bowel disease. Our results show that the urinary excretion of DTPA is a simple test that measures accurately the degree of activity of inflammatory bowel disease. The test is useful in Crohn's disease as well as in ulcerative colitis, and detects intestinal permeability abnormalities even in clinical remission. Significantly lower excretions are found in other intestinal diseases. The test may be recommended as a screening test for use in clinical practice.

  14. Data management of an inflammatory bowel disease registry.

    PubMed

    Reed, J F; Moser, K A; Faust, L A; Mills, S

    1992-06-01

    The history and etiology of inflammatory bowel disease which is characterized by two major disease processes: ulcerative colitis and Crohn's disease, remain unknown. Research is focussing on seven major areas of genetic, environmental and physiologic factors that apparently relate to this disease. Based on this background, a population based Inflammatory Bowel Disease Registry was established in 1987 in the Lehigh Valley area of southeastern Pennsylvania. Consent forms, patient data forms and protocols for operation and implementation were developed, and databases were designed to accommodate demographic, basic history, follow-up and relative history data. The databases were correlated with an IBD registry ID number which both enabled relational analyses and ensured confidentiality of data information. The registry continues to grow, providing feedback for both continued medical research and supportive information for IBD patients and their physicians. PMID:1402437

  15. [Inflammatory spinal disease: Spondyloarthritis: Importance of imaging].

    PubMed

    Schueller-Weidekamm, C

    2015-04-01

    Conventional radiography of the pelvis and lumbar spine is the method of choice for the initial evaluation of spondyloarthritis (SpA). Sacroiliitis is classified according to the modified New York grading criteria; however, to improve the early diagnosis of SpA, magnetic resonance imaging (MRI) should be performed as MRI enables the detection of early inflammation, such as subchondral bone marrow edema of the sacroiliac joints (SIJ), which defines sacroiliitis. Sacroiliitis and HLA-B27 are considered to be equivalent criteria for the diagnosis of SpA. In equivocal findings in the SIJ, an evaluation of the whole spine might be helpful because involvement of the thoracic and lumbar spine, shiny corner sign (Romanus lesions) and spondylodiscitis (Andersson lesions), as well as inflammation of the pedicles, zygoapophyseal joints and longitudinal ligaments, are typical findings in SpA. The prevalence of seronegative SpA is higher than has been previously assumed. Imaging in SpA plays an important role in selecting patients with inflammatory back pain and thus, helping to prevent irreversible changes through adequate early treatment. PMID:25784132

  16. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-04-18

    Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

  17. Microflora in inflammatory bowel diseases: a pediatric perspective.

    PubMed

    Bruzzese, Eugenia; Canani, Roberto Berni; De Marco, Giulio; Guarino, Alfredo

    2004-07-01

    Several lines of evidence link inflammatory bowel diseases to modifications of intestinal microflora. Epidemiologic and clinical data suggest a triggering role for select agents in ulcerative colitis and in Crohn disease. Experimental evidence indicates that intestinal microorganisms are needed for developing intestinal inflammation in IL-10 knockout mice, and this is associated with an increased number of adherent clostridia and a decrease of lactobacilli and bifidobacteria. It may be hypothesized that a host-agent-specific relationship leads to an abnormal immune response, which may be genetically driven in select inflammatory bowel diseases. However, different from adults, the pattern of intestinal microflora undergoes profound changes during the early stage of life, contributing to the development of the immune system. A close relationship exists between microbiologic and immunologic imprinting. The microbiologic imprinting in neonates may be modified using bacterial probiotics that colonize the intestine, modify the immune response, and decrease the risk for atopy. Probiotics may decrease the recurrences of inflammatory bowel diseases. Preliminary evidence of intestinal antiinflammatory effects has been detected in children with cystic fibrosis. Overall these data provide the rationale to investigate the interaction between intestinal microflora and the local and general immune response in children with, or at risk for, inflammatory bowel diseases. This approach may be a key for understanding the pathophysiology of intestinal inflammation and may disclose novel strategies to educate better the immune system, particularly during its developmental stage. PMID:15220668

  18. Anti-selectin therapy for the treatment of inflammatory diseases.

    PubMed

    Rossi, Barbara; Constantin, Gabriela

    2008-06-01

    Leukocyte migration into the tissues represents a key process in the pathogenesis of inflammatory diseases. Data obtained in clinical trials have convincingly shown that inhibition of leukocyte migration into the target organs represents an effective therapeutic approach for diseases in which inflammation has a noxious effect. Leukocyte tethering and rolling are the earliest steps of leukocyte adhesion cascade in inflamed vessels. Selectins are type I transmembrane glycoproteins that bind sialylated carbohydrate structures in a calcium-dependent manner and are involved in the tethering and rolling of leukocytes under physiological and pathological conditions. Three selectins have been identified: L-, P- and E-selectin. Current understanding of the glycosylation-dependent selectin function reveals a complex role for selectins and their ligands during inflammatory diseases. Among selectin ligands, mucin P-selectin glycoprotein ligand-1 (PSGL-1) binds all three selectins and has a well-documented role in organ targeting during inflammation in animal models. However, although inhibition of selectins and their ligands in animal models of inflammatory diseases has proven the validity of this approach in vivo, only a limited number of anti-selectin drugs have been tested in humans. Recent results obtained in clinical trials for asthma and psoriasis show that, although very challenging, the development of selectin antagonists holds concrete promise for the therapy of inflammatory diseases. PMID:18691137

  19. Pathogenic Th cell subsets in chronic inflammatory diseases.

    PubMed

    Kumagai, Jin; Hirahara, Kiyoshi; Nakayama, Toshinori

    2016-01-01

      CD4(+) T cells play central roles to appropriate protection against pathogens. While, they can also be pathogenic driving inflammatory diseases. Besides the classical model of differentiation of T helper 1 (Th1) and Th2 cells, various CD4(+) T cell subsets, including Th17, Th9, T follicular helper (Tfh) and T regulatory (Treg) cells, have been recognized recently. In this review, we will focus on how these various CD4(+) T cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. We will also discuss various unique subpopulations of T helper cells that have been identified. Recent advancement of the basic immunological research revealed that T helper cells are plastic than we imagined. So, we will focus on the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T helper cell subsets. These latest finding regarding T helper cell subsets has pushed us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the conventional Th1/Th2 balance. Toward this end, we put forward another model, "the pathogenic Th population disease induction model", as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID:27212597

  20. Inflammatory targets of therapy in sickle cell disease.

    PubMed

    Owusu-Ansah, Amma; Ihunnah, Chibueze A; Walker, Aisha L; Ofori-Acquah, Solomon F

    2016-01-01

    Sickle cell disease (SCD) is a monogenic globin disorder characterized by the production of a structurally abnormal hemoglobin (Hb) variant Hb S, which causes severe hemolytic anemia, episodic painful vaso-occlusion, and ultimately end-organ damage. The primary disease pathophysiology is intracellular Hb S polymerization and consequent sickling of erythrocytes. It has become evident for more than several decades that a more complex disease process contributes to the myriad of clinical complications seen in patients with SCD with inflammation playing a central role. Drugs targeting specific inflammatory pathways therefore offer an attractive therapeutic strategy to ameliorate many of the clinical events in SCD. In addition, they are useful tools to dissect the molecular and cellular mechanisms that promote individual clinical events and for developing improved therapeutics to address more challenging clinical dilemmas such as refractoriness to opioids or hyperalgesia. Here, we discuss the prospect of targeting multiple inflammatory pathways implicated in the pathogenesis of SCD with a focus on new therapeutics, striving to link the actions of the anti-inflammatory agents to a defined pathobiology, and specific clinical manifestations of SCD. We also review the anti-inflammatory attributes and the cognate inflammatory targets of hydroxyurea, the only Food and Drug Administration-approved drug for SCD. PMID:26226206

  1. Reproductive tract inflammatory disease in postpartum dairy cows.

    PubMed

    LeBlanc, S J

    2014-05-01

    Up to half of dairy cows are affected by at least one of metritis, purulent vaginal discharge, endometritis or cervicitis in the postpartum period. These conditions result from inadequate immune response to bacterial infection (failure to clear pathogenic bacteria from the uterus) or persistent inflammation that impairs rather than enhances reproductive function. The degree of mobilization of fat and how effectively it is used as a metabolic fuel is well recognized as a risk factor for metabolic and infectious disease. Release of non-esterified fatty acids has direct effects on liver and immune function but also produces pro-inflammatory cytokines (tumor necrosis factor α and interleukin-6), which contribute to systemic inflammation and to insulin resistance. Therefore, reproductive tract inflammatory disease may be a function of both local and systemic inflammatory stimuli and regulation as well as regulation of fat metabolism. Better understanding of variables associated with insulin resistance and inflammatory regulation in the liver and adipose tissue may lead to improvement of reproductive tract health. This paper reviews factors that may contribute to postpartum reproductive tract inflammatory diseases in dairy cows and their inter-relationships, impacts and treatment. PMID:24679404

  2. The potential impacts of formyl peptide receptor 1 in inflammatory diseases.

    PubMed

    Yang, Shun-Chin; Hwang, Tsong-Long

    2016-01-01

    Neutrophils play a critical role in acute and chronic inflammatory diseases. N-formyl peptides, which originate from bacterial peptides or mitochondrial proteins bind with a high binding affinity to formyl peptide receptor 1 (FPR1). N-formyl peptide-FPR1 is involved in the pathogenesis of sterile and infectious inflammatory processes and causes phagocytosis of pathogens or injured cells by neutrophils. Excessive activation of neutrophils by binding of N-formyl peptides is associated with tissue injury requiring drugs that block FPR1-dependent signaling. Here, we review the roles of FPR1 as a critical regulator of inflammatory processes and its involvement in pathological conditions. PMID:27100350

  3. Eosinophilic gastrointestinal disease and inflammatory bowel disease in children: is it a disease continuum?

    PubMed

    Mutalib, Mohamed; Blackstock, Sarah; Evans, Victoria; Huggett, Bonita; Chadokufa, Sibongile; Kiparissi, Fevronia; Elawad, Mamoun

    2015-01-01

    Eosinophilic gastrointestinal disease (EGID) and inflammatory bowel disease (IBD) are two distinct disorders that share some clinical manifestations but have different diagnostic criteria. In this article, we reviewed the clinical data of three children with EGID who later developed IBD. This study is a retrospective case note review that was conducted between 2007 and 2012. EGID seems to precede IBD in some subsets of children in whom the diagnosis of IBD may take a few years to fully develop. PMID:25358014

  4. Degradomics of matrix metalloproteinases in inflammatory diseases.

    PubMed

    Dufour, Antoine

    2015-01-01

    Organisms have evolved to react to stress, tissue damage and pathogen invasion to assure their survival. Leukocytes are the primary responders and they regulate repair, immune defense and inflammation with the aid of a wide variety of other cells (e.g. epithelial, fibroblasts). To assure proper responses, a plethora of proteins are involved including signaling molecules, chemokines and proteases to orchestrate a step-by-step reaction. Inflammation is an essential biological process, however, when it persists, it can lead to various diseases that are challenging to heal or cure. The technologies and techniques covered in this book chapter can be applied to study all proteases and their inhibitors although will be centered on the matrix metalloproteinases (MMPs). It will focus on the proteolysis performed by MMPs, their various beneficial and detrimental effects in inflammation and the novel methods to study their roles on human diseases. PMID:25961692

  5. Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications.

    PubMed

    McConnell, Ryan A; Mahadevan, Uma

    2016-06-01

    For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery. PMID:27261899

  6. Rare inflammatory and hereditary connective tissue diseases.

    PubMed

    Klipple, G L; Riordan, K K

    1989-05-01

    Polyarteritis nodosa developing during gestation has an extremely grave prognosis. To an uncertain extent, this results from a delay in recognition and therapy. The diagnosis of PAN is complicated by the expanded differential of common conditions associated with pregnancy such as pre-eclampsia and toxemia which can present with similar symptoms and signs. On the other hand, the pregnant woman with known, quiescent disease has a much better prognosis with only one of four women experiencing exacerbation. In women with Behcet's disease, convincing reports of both pregnancy-related flares and remissions involving primarily mucocutaneous manifestations are found in the literature. Gestational exacerbation of the more serious manifestations including chorioretinitis, vasculitis and CNS disease does not appear to be a problem. Also, a significant effect on fetal development or survival is not evident. The pregnant woman with the Marfan syndrome and pre-existing cardiovascular disease, particularly dilatation of the aortic root, has a substantially increased risk of developing a major complication during gestation most commonly aortic aneurysm, dissection, rupture or insufficiency. Echocardiographic determination of the aortic root diameter is prognostic with a decreased risk at a diameter of 40 mm or less. A diameter of greater than 40 to 45 mm constitutes a significant contraindication to pregnancy. All pregnancies in patients with the Marfan syndrome are considered high risk and frequent evaluations and echocardiograms are required. The EDS patient is subject to a wide range of gestational complications resulting from the basic connective tissue defect manifested clinically by hyperextensible skin, joint hypermobility, connective tissue and vascular fragility, and poor wound healing. The most serious complications occur in type I EDS (gravis) and type IV (ecchymotic) and include extensive perineal tears and hematoma after vaginal delivery, uterine prolapse and rupture

  7. Genomic responses in mouse models poorly mimic human inflammatory diseases

    PubMed Central

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  8. Immune reconstitution inflammatory syndrome during treatment of Whipple's disease.

    PubMed

    Vayssade, Marielle; Tournadre, Anne; D'Incan, Michel; Soubrier, Martin; Dubost, Jean-Jacques

    2015-03-01

    Immune reconstitution inflammatory syndrome is a rare complication of the treatment of Whipple's disease. Here, we report the case of a 65-year-old man treated for Whipple's disease affecting the joints, with positive Tropheryma whipplei PCR in CSF, who developed fever and nodular eruption on the trunk, arms and face in association with biological inflammatory syndrome 10 days after initiation of antimicrobial treatment. Skin manifestations and the patient's general condition improved on corticosteroids (0.5mg/kg prednisone), but as steroids were gradually tapered, new nodules appeared below a prednisone dose of 10-15mg. One year after starting treatment, lumbar puncture showed asymptomatic meningitis with negative T. whipplei PCR results which had regressed spontaneously. Two years after the diagnosis, on prednisone 5mg daily and antimicrobial treatment, the patient had only transient, episodic nodular rash without fever or inflammatory syndrome. PMID:25553832

  9. Fecal calprotectin use in inflammatory bowel disease and beyond: A mini-review.

    PubMed

    Alibrahim, Bashaar; Aljasser, Mohammed I; Salh, Baljinder

    2015-04-01

    Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders. PMID:25855880

  10. Fecal calprotectin use in inflammatory bowel disease and beyond: A mini-review

    PubMed Central

    Alibrahim, Bashaar; Aljasser, Mohammed I; Salh, Baljinder

    2015-01-01

    Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders. PMID:25855880

  11. Anti-inflammatory activity of mycelial extracts from medicinal mushrooms.

    PubMed

    Geng, Yan; Zhu, Shuiling; Lu, Zhenming; Xu, Hongyu; Shi, Jin-Song; Xu, Zheng-Hong

    2014-01-01

    Medicinal mushrooms have been essential components of traditional Chinese herbal medicines for thousands of years, and they protect against diverse health-related conditions. The components responsible for their anti-inflammatory activity have yet to be fully studied. This study investigates the anti-inflammatory activity of n-hexane, chloroform, ethyl acetate, and methanol extracts of mycelia in submerged culture from 5 commercially available medicinal mushrooms, namely Cephalosporium sinensis, Cordyceps mortierella, Hericium erinaceus, Ganoderma lucidum, and Armillaria mellea. MTT colorimetric assay was applied to measure the cytotoxic effects of different extracts. Their anti-inflammatory activities were evaluated via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) in murine macrophage-like cell line RAW264.7 cells. Of the 20 extracts, n-hexane, chloroform, ethyl acetate, and methanol extracts from C. sinensis, C. mortierella, and G. lucidum; chloroform extracts from H. erinaceus and A. mellea; and ethyl acetate extracts from A. mellea at nontoxic concentrations (<300 μg/mL) dose-dependently inhibited LPS-induced NO production. Among them, the chloroform extract from G. lucidum was the most effective inhibitor, with the lowest half maximal inhibitory concentration (64.09 ± 6.29 μg/mL) of the LPS-induced NO production. These results indicate that extracts from medicinal mushrooms exhibited anti-inflammatory activity that might be attributable to the inhibition of NO generation and can therefore be considered a useful therapeutic and preventive approach to various inflammation-related diseases. PMID:25271860

  12. Vitamin D and the Pathogenesis of Inflammatory Bowel Disease.

    PubMed

    Limketkai, Berkeley N; Bechtold, Matthew L; Nguyen, Douglas L

    2016-10-01

    Vitamin D has traditionally been known for its role in bone metabolism, but emerging evidence has suggested a broader role for vitamin D in immune regulation. Vitamin D deficiency has been associated with the pathogenesis of diverse autoimmune disorders and has similarly been implicated as a contributor to inflammatory bowel disease. In this review, we discuss animal, in vitro, genetic, and epidemiologic studies that have linked vitamin D deficiency with inflammatory bowel disease pathogenesis or severity. Nonetheless, we present the caveat in interpreting these studies in the context of reverse causation: Does vitamin D deficiency lead to gastrointestinal disease, or does gastrointestinal disease (with related changes in dietary choices, intestinal absorption, nutritional status, lifestyle) lead to vitamin D deficiency? PMID:27538982

  13. Nanoparticle-based imaging of inflammatory bowel disease.

    PubMed

    Wu, Yingwei; Briley, Karen; Tao, Xiaofeng

    2016-03-01

    Although inflammatory bowel disease (IBD) has been extensively studied, the pathogenesis is still not completely understood. As a result, the treatment options remain unsatisfactory and nonspecific. With the rapid advancement of diagnostic imaging techniques, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are playing a more important role in IBD diagnosis and evaluation. Recent developments in nanotechnology utilize an interdisciplinary approach to specifically target molecular or cellular IBD pathological process thereby generating nanoparticles (NPs) with high specificity and diagnostic and/or therapeutic efficacy. Nano-based imaging, which incorporates nanotechnology and imaging modalities, may allow for the early detection of IBD, the monitoring of disease activity, and may be used to monitor the therapeutic response at cellular and/or molecular level. In this review, we highlight issues related to nano-based imaging and its application in IBD field. WIREs Nanomed Nanobiotechnol 2016, 8:300-315. doi: 10.1002/wnan.1357 For further resources related to this article, please visit the WIREs website. PMID:26371464

  14. Antimicrobial Proteins in Intestine and Inflammatory Bowel Diseases

    PubMed Central

    2014-01-01

    Mucosal surface of the intestinal tract is continuously exposed to a large number of microorganisms. To manage the substantial microbial exposure, epithelial surfaces produce a diverse arsenal of antimicrobial proteins (AMPs) that directly kill or inhibit the growth of microorganisms. Thus, AMPs are important components of innate immunity in the gut mucosa. They are frequently expressed in response to colonic inflammation and infection. Expression of many AMPs, including human β-defensin 2-4 and cathelicidin, is induced in response to invasion of pathogens or enteric microbiota into the mucosal barrier. In contrast, some AMPs, including human α-defensin 5-6 and human β-defensin 1, are constitutively expressed without microbial contact or invasion. In addition, specific AMPs are reported to be associated with inflammatory bowel disease (IBD) due to altered expression of AMPs or development of autoantibodies against AMPs. The advanced knowledge for AMPs expression in IBD can lead to its potential use as biomarkers for disease activity. Although the administration of exogenous AMPs as therapeutic strategies against IBD is still at an early stage of development, augmented induction of endogenous AMPs may be another interesting future research direction for the protective and therapeutic purposes. This review discusses new advances in our understanding of how intestinal AMPs protect against pathogens and contribute to pathophysiology of IBD. PMID:25349560

  15. Endoscopic management of inflammatory bowel disease strictures

    PubMed Central

    Vrabie, Raluca; Irwin, Gerald L; Friedel, David

    2012-01-01

    Stricture formation is a common complication of Crohn’s disease, occurring in approximately one third of all patients with this condition. While the traditional management of such strictures has been largely surgical, there have been case series going back three decades highlighting the potential role of endoscopic balloon dilation in this clinical setting. This review article summarizes the stricture pathogenesis, focusing on known clinical and genetic risk factors. It then highlights the endoscopic balloon dilation research to date, with particular emphasis on three large recent case series. It concludes by describing the literature consensus regarding specific methodology and presenting avenues for future investigations. PMID:23189221

  16. Pathophysiology and treatment of inflammatory anorexia in chronic disease.

    PubMed

    Braun, Theodore P; Marks, Daniel L

    2010-12-01

    Decreased appetite and involuntary weight loss are common occurrences in chronic disease and have a negative impact on both quality of life and eventual mortality. Weight loss in chronic disease comes from both fat and lean mass, and is known as cachexia. Both alterations in appetite and body weight loss occur in a wide variety of diseases, including cancer, heart failure, renal failure, chronic obstructive pulmonary disease and HIV. An increase in circulating inflammatory cytokines has been implicated as a uniting pathogenic mechanism of cachexia and associated anorexia. One of the targets of inflammatory mediators is the central nervous system, and in particular feeding centers in the hypothalamus located in the ventral diencephalon. Current research has begun to elucidate the mechanisms by which inflammation reaches the hypothalamus, and the neural substrates underlying inflammatory anorexia. Research into these neural mechanisms has suggested new therapeutic possibilities, which have produced promising results in preclinical and clinical trials. This review will discuss inflammatory signaling in the hypothalamus that mediates anorexia, and the opportunities for therapeutic intervention that these mechanisms present. PMID:21475703

  17. Develop Anti-Inflammatory Nanotherapies to Treat Cardiovascular Disease

    NASA Astrophysics Data System (ADS)

    Tang, Jun

    Cardiovascular disease (CVD) is the leading cause of disease-related death in the world, accounting for 30 % global mortality. The majority of CVD is caused by atherosclerosis, a chronic inflammatory disease of major arteries featured by the deposition of lipids and cholesterol. Inflammation of atherosclerosis is mainly promoted by the pathological macrophages and monocytes, and modulating their functions has been proposed as a promising therapeutic target. This dissertation first presents the development of a novel simvastatin-loaded high-density lipoprotein (HDL) based nanoparticle ([S]-rHDL), which was able to deliver anti-inflammatory simvastatin preferentially to inflammatory monocytes in the blood and to macrophages in advanced atherosclerotic plaques, leading to the reduced inflammation in the tissue. Second, extensive in vivo characterization of [S]-rHDL in a mouse atherosclerosis model revealed that the anti-inflammatory capability of [S]-rHDL derived from its effects on blood monocytes, endothelial layer, monocyte recruitment, and plaque macrophage function. Third, a translational study that integrated the use of [S]-rHDL into oral statin treatment demonstrated a great potential for this nanomedicine as an attractive addition to the current high-dose oral statin standard-of-care for acute coronary syndrome. Finally, preliminary results suggested potential applications of the rHDL platform to other macrophage-implicated diseases.

  18. Increased matriptase zymogen activation in inflammatory skin disorders

    PubMed Central

    Chen, Cheng-Jueng; Wu, Bai-Yao; Tsao, Pai-In; Chen, Chi-Yung; Wu, Mei-Hsuan; Chan, Yee Lam E.; Lee, Herng-Sheng; Johnson, Michael D.; Eckert, Richard L.; Chen, Ya-Wen; Chou, Fengpai; Lin, Chen-Yong

    2011-01-01

    Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases. PMID:21123732

  19. BET Inhibition Attenuates Helicobacter pylori-Induced Inflammatory Response by Suppressing Inflammatory Gene Transcription and Enhancer Activation.

    PubMed

    Chen, Jinjing; Wang, Zhen; Hu, Xiangming; Chen, Ruichuan; Romero-Gallo, Judith; Peek, Richard M; Chen, Lin-Feng

    2016-05-15

    Helicobacter pylori infection causes chronic gastritis and peptic ulceration. H. pylori-initiated chronic gastritis is characterized by enhanced expression of many NF-κB-regulated inflammatory cytokines. Brd4 has emerged as an important NF-κB regulator and regulates the expression of many NF-κB-dependent inflammatory genes. In this study, we demonstrated that Brd4 was not only actively involved in H. pylori-induced inflammatory gene mRNA transcription but also H. pylori-induced inflammatory gene enhancer RNA (eRNA) synthesis. Suppression of H. pylori-induced eRNA synthesis impaired H. pylori-induced mRNA synthesis. Furthermore, H. pylori stimulated NF-κB-dependent recruitment of Brd4 to the promoters and enhancers of inflammatory genes to facilitate the RNA polymerase II-mediated eRNA and mRNA synthesis. Inhibition of Brd4 by JQ1 attenuated H. pylori-induced eRNA and mRNA synthesis for a subset of NF-κB-dependent inflammatory genes. JQ1 also inhibited H. pylori-induced interaction between Brd4 and RelA and the recruitment of Brd4 and RNA polymerase II to the promoters and enhancers of inflammatory genes. Finally, we demonstrated that JQ1 suppressed inflammatory gene expression, inflammation, and cell proliferation in H. pylori-infected mice. These studies highlight the importance of Brd4 in H. pylori-induced inflammatory gene expression and suggest that Brd4 could be a potential therapeutic target for the treatment of H. pylori-triggered inflammatory diseases and cancer. PMID:27084101

  20. Integrative Therapies and Pediatric Inflammatory Bowel Disease: The Current Evidence

    PubMed Central

    Misra, Sanghamitra M.

    2014-01-01

    Inflammatory bowel disease (IBD) primarily describes two distinct chronic conditions with unknown etiology, ulcerative colitis (UC) and Crohn’s disease (CD). UC is limited to the colon, while CD may involve any portion of the gastrointestinal tract from mouth to anus. These diseases exhibit a pattern of relapse and remission, and the disease processes are often painful and debilitating. Due to the chronic nature of IBD and the negative side effects of many of the conventional therapies, many patients and their families turn to complementary and alternative medicine (CAM) for symptom relief. This article focuses on the current available evidence behind CAM/integrative therapies for IBD. PMID:27417473

  1. Management of inflammatory bowel disease in the pregnant patient

    PubMed Central

    Habal, Flavio M; Ravindran, Nikila C

    2008-01-01

    Inflammatory bowel disease (IBD) is a chronic disorder affecting young adults in their reproductive years. Many young women with IBD express concern about the effect their disease will have on fertility, pregnancy course and fetal development. This article presents an approach to management of IBD in the pregnant patient, including counseling and investigation, and summarizes existing data on the safety of medications used to treat IBD in pregnancy and breastfeeding. PMID:18322943

  2. Koch's postulates, microbial dysbiosis and inflammatory bowel disease.

    PubMed

    Singh, V P; Proctor, S D; Willing, B P

    2016-07-01

    Over the past 20 years, a growing amount of evidence supports the role of microbes and an imbalanced microbiota in inflammatory bowel disease (IBD). While many reviews have been written on the microbiota in IBD, few have considered how they fulfil the Koch's postulates. In this review, we consider how the Koch's postulates might be modified so that they can be fulfilled for polymicrobial diseases, and we discuss the progress made to date in fulfilling them. PMID:27179648

  3. Protein kinases are potential targets to treat inflammatory bowel disease

    PubMed Central

    Yang, Lei; Yan, Yutao

    2014-01-01

    Protein kinases play a crucial role in the pathogenesis of inflammatory bowel disease (IBD), the two main forms of which are ulcerative colitis and Crohn’s disease. In this article, we will review the mechanisms of involvement of protein kinases in the pathogenesis of and intervention against IBD, in terms of their effects on genetics, microbiota, mucous layer and tight junction, and the potential of protein kinases as therapeutic targets against IBD. PMID:25374761

  4. Intestinal Behçet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis?

    PubMed Central

    Kim, Duk Hwan

    2016-01-01

    Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor α antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision. PMID:26632379

  5. Glucocorticoid analogues: potential therapeutic alternatives for treating inflammatory muscle diseases.

    PubMed

    Reeves, Erica K M; Rayavarapu, Sree; Damsker, Jesse M; Nagaraju, Kanneboyina

    2012-03-01

    Glucocorticoids (GCs) have been prescribed to treat a variety of diseases, including inflammatory myopathies and Duchenne muscular dystrophy for over 50 years. However, their prescription remains controversial due to the significant side effects associated with the chronic treatment. It is a common belief that the clinical efficacy of GCs is due to their transrepression of pro-inflammatory genes through inhibition of inflammatory transcription factors (i.e. NF-κB, AP-1) whereas the adverse side effects are attributed to the glucocorticoid receptor (GR)-mediated transcription of target genes (transactivation). The past decade has seen an increased interest in the development of GR modulators that maintain the effective anti-inflammatory properties but lack the GR-dependent transcriptional response as a safe alternative to traditional GCs. Many of these analogues or "dissociative" compounds show potential promise in in vitro studies but fail to reach human clinical trials. In this review, we discuss molecular effects of currently prescribed GCs on skeletal muscle and also discuss the current state of development of GC analogues as alternative therapeutics for inflammatory muscle diseases. PMID:22214335

  6. Hp: an inflammatory indicator in cardiovascular disease.

    PubMed

    Graves, Karen L; Vigerust, David J

    2016-07-01

    Over the past decade significant advancement has occurred in the biological and pathological role that Hp has in cardiovascular disease. Hp is an acute-phase protein with a role in the neutralization and clearance of free heme. Iron has tremendous potential for initiating vascular oxidation, inflammation and exacerbating coronary atherosclerosis. Hp genotype has been linked as a prognostic biomarker of acute myocardial infarction, heart failure, restenosis and cardiac transplant rejection. The increased understanding of Hp as a biomarker has provided new insights into the mechanisms of inflammation after cardiac injury and support the concept that Hp is not only an important antioxidant in vascular inflammation and atherosclerosis, but also an enhancer of inflammation in cardiac transplant. PMID:27203711

  7. Comparison of experimental mouse models of inflammatory bowel disease.

    PubMed

    Oh, Soo Youn; Cho, Kyung-Ah; Kang, Jihee Lee; Kim, Kwang Ho; Woo, So-Youn

    2014-02-01

    Inflammatory bowel disease (IBD) is multifactorial and involves immunological, environmental and genetic factors. Although there are no animal models that effectively mimic human IBD, experimental models allow us to analyze the mechanisms of chronic intestinal inflammation. IBD can be induced in mice by dextran sulfate sodium (DSS) or by a 2,4,6-trinitrobenzene sulfonic acid (TNBS)‑ethanol enema, which evoke immune responses and colitis. In this study, in order to compare the mechanisms of inflammatory response in mice, 3 distinct models of IBD were established: 2% TNBS-induced acute colitis, 4% DSS-induced acute colitis and 2% DSS-induced chronic colitis. In addition, to evaluate the effects of TNBS on inflammasome activation, we used caspase-1 knockout (KO) mice. Changes in both body weight and survival became prominent after day 1 in the 2% TNBS‑induced colitis model, and after day 5 in the 4% DSS-induced colitis model. The TNBS- and DSS-treated mice, but not the caspase-1 KO mice, showed a massive bowel edema and disruption of epithelial cells. The level of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) was increased in all tested tissues of the TNBS- and DSS-treated groups, apart from the basal membrane (BM) in the DSS-induced colitis groups and the lamina propria (LP) in the DSS-induced chronic colitis group. We further analyzed different subsets of CD4(+) T cells in LP and found that the levels of interferon (IFN)γ‑secreting (IFNγ(+)), IL-17‑secreting (IL-17(+)), but not those of IL-4-secreting (IL-4(+)) T cells increased upon treatment with TNBS or DSS. In addition, discrepancies between the histopathologies of wild-type and caspase-1 KO mice indicated that the pathogenesis of IBD may be associated with the inflammasome pathway responses mediated by caspase‑1 in TNBS‑induced colitis. PMID:24285285

  8. Anti-Inflammatory and Antinociceptive Activities of Bufalin in Rodents

    PubMed Central

    Huang, Yang; Yin, Junqiang; Lin, Wenqian

    2014-01-01

    The aims of this study were to evaluate the anti-inflammatory and analgesic effects of bufalin, a major component of “Chan-su.” We used a carrageenan-induced paw edema model to assess the anti-inflammatory activity of this compound, and Western blot analysis detected NF-κB signaling during this effect. The antinociceptive activities were evaluated by acetic acid-induced writhing, formalin, and hot-plate tests; open-field test investigated effects on the central nervous system. Our data showed that bufalin (0.3 and 0.6 mg/kg, i.p.) potently decreased carrageenan-induced paw edema. Bufalin down regulated the expression levels of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) during these treatments. Further studies demonstrated that bufalin significantly inhibited the activation of NF-κB signaling. Bufalin also reduced acetic acid-induced writhing and the licking time in the formalin test and increased hot-plate reaction latencies. Naloxone pretreatment (2 mg/kg, i.p.) in the early phases of the formalin test and hot-plate test significantly attenuated the bufalin-induced antinociception effects, which suggests the involvement of the opioid system. A reduction in locomotion was not observed in the open-field test after bufalin administration. Taken together, bufalin treatment resulted in in vivo anti-inflammatory and analgesic effects, and bufalin may be a novel, potential drug for the treatment of inflammatory diseases. PMID:24719521

  9. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines.

    PubMed

    Danese, Silvio; Grisham, Matthew; Hodge, Jennifer; Telliez, Jean-Baptiste

    2016-02-01

    The inflammatory diseases ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease (IBD). They are characterized by chronic, relapsing inflammation of the gastrointestinal tract, significantly impacting on patient quality of life and often requiring prolonged treatment. Existing therapies for IBD are not effective for all patients, and an unmet need exists for additional therapies to induce and maintain remission. Here we describe the mechanism of action of the Janus kinase (JAK) inhibitor, tofacitinib, for the treatment of IBD and the effect of JAK inhibition on the chronic cycle of inflammation that is characteristic of the disease. The pathogenesis of IBD involves a dysfunctional response from the innate and adaptive immune system, resulting in overexpression of multiple inflammatory cytokines, many of which signal through JAKs. Thus JAK inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in IBD, thereby interrupting the cycle of inflammation. Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated as a targeted immunomodulator for IBD. Clinical development of tofacitinib and other JAK inhibitors is ongoing, with the aspiration of providing new treatment options for IBD that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits. PMID:26608188

  10. The Search for Causative Environmental Factors in Inflammatory Bowel Disease.

    PubMed

    Rogler, Gerhard; Zeitz, Jonas; Biedermann, Luc

    2016-01-01

    Inflammatory bowel disease (IBD) has become a 'prototype disease' for chronic auto-inflammatory disorders with a polygenic background and important multifaceted environmental trigger components. The environmental factors contribute both to pathogenesis and disease flares. Thus, IBD is a disease par excellence to study the interactions between host genetics, environmental factors (such as infections or smoking) and 'in-vironmental' factors - for example, our intestinal microbiota. Longitudinal intercurrent events, including the impact of long-term medication on disease progression or stabilization, can exemplarily be studied in this disease group. Whilst alterations in the human genome coding relevant variant protein products have most likely not emerged significantly over the last 50 years, the incidence of Crohn's disease and ulcerative colitis has dramatically increased in Western countries and more recently in the Asia Pacific area. An interesting concept indicates that 'Western lifestyle factors' trigger chronic intestinal inflammation or disease flares in a genetically susceptible host. To understand the disease pathogenesis as well as triggers for flares or determinants of disease courses, we must further investigate potential en(in)vironmental factors. As environmental conditions, in contrast to genetic risk factors, can be influenced, knowledge on those risk factors becomes crucial to modulate disease incidence, disease course or clinical presentation. It is obvious that prevention of environmentally triggered disease flares would be a goal most relevant for IBD patients. An increased prevalence of IBD in urban environment has been documented in Switzerland by the Swiss IBD cohort study. Several studies have attempted to identify such factors; however, only a few have been validated. The best investigated environmental factor identified in IBD cohort analyses is smoking. Other environmental factors that have been associated with clinical presentation or

  11. Nutrition in adult patients with inflammatory bowel disease.

    PubMed

    Hebuterne, Xavier; Filippi, Jerome; Schneider, Stephane M

    2014-01-01

    Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesity. IBD patients have many vitamin and nutrient deficiencies, which can lead to important consequences such as hyperhomocysteinemia, which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as metabolic disturbances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases. PMID:25266810

  12. Concomitant Thyroid Disorders and Inflammatory Bowel Disease: A Literature Review

    PubMed Central

    2016-01-01

    The aim of this report was to review and summarize the literature on cases of concomitant inflammatory bowel disease (IBD) and thyroid diseases. We included the following previous case reports of concomitant IBD and thyroid diseases: 16 cases of ulcerative colitis (UC) and Graves' disease (GD), 3 cases of Crohn's disease (CD) and GD, 10 cases of CD and Hashimoto's thyroiditis (HT), 4 cases of IBD and subacute thyroiditis (SAT) or SAT-like symptoms, and 13 cases of IBD (12/13 cases were CD) and amyloid goiter. There might be no obvious differences of prevalence of thyroid dysfunction (hyper- or hypothyroidism), GD, and thyroid cancer between IBD patients and general populations. However, concomitant UC and HT might be relatively common in patients with multiple autoimmune disorders, and AG is one of the complications with CD patients. There might be no obvious differences of fatal prognoses between IBD patients with thyroid diseases and patients with thyroid diseases without IBD. PMID:27042663

  13. Concomitant Thyroid Disorders and Inflammatory Bowel Disease: A Literature Review.

    PubMed

    Shizuma, Toru

    2016-01-01

    The aim of this report was to review and summarize the literature on cases of concomitant inflammatory bowel disease (IBD) and thyroid diseases. We included the following previous case reports of concomitant IBD and thyroid diseases: 16 cases of ulcerative colitis (UC) and Graves' disease (GD), 3 cases of Crohn's disease (CD) and GD, 10 cases of CD and Hashimoto's thyroiditis (HT), 4 cases of IBD and subacute thyroiditis (SAT) or SAT-like symptoms, and 13 cases of IBD (12/13 cases were CD) and amyloid goiter. There might be no obvious differences of prevalence of thyroid dysfunction (hyper- or hypothyroidism), GD, and thyroid cancer between IBD patients and general populations. However, concomitant UC and HT might be relatively common in patients with multiple autoimmune disorders, and AG is one of the complications with CD patients. There might be no obvious differences of fatal prognoses between IBD patients with thyroid diseases and patients with thyroid diseases without IBD. PMID:27042663

  14. Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

    PubMed Central

    Hall, Christopher J.; Wicker, Sophie M.; Chien, An-Tzu; Tromp, Alisha; Lawrence, Lisa M.; Sun, Xueying; Krissansen, Geoffrey W.; Crosier, Kathryn E.; Crosier, Philip S.

    2014-01-01

    Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs. PMID:25038060

  15. Kynurenines in CNS disease: regulation by inflammatory cytokines.

    PubMed

    Campbell, Brian M; Charych, Erik; Lee, Anna W; Möller, Thomas

    2014-01-01

    The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the "neurotoxic" and "neuroprotective" arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders. PMID:24567701

  16. Cocoa polyphenols and inflammatory markers of cardiovascular disease.

    PubMed

    Khan, Nasiruddin; Khymenets, Olha; Urpí-Sardà, Mireia; Tulipani, Sara; Garcia-Aloy, Mar; Monagas, María; Mora-Cubillos, Ximena; Llorach, Rafael; Andres-Lacueva, Cristina

    2014-01-01

    Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review. PMID:24566441

  17. Cocoa Polyphenols and Inflammatory Markers of Cardiovascular Disease

    PubMed Central

    Khan, Nasiruddin; Khymenets, Olha; Urpí-Sardà, Mireia; Tulipani, Sara; Garcia-Aloy, Mar; Monagas, María; Mora-Cubillos, Ximena; Llorach, Rafael; Andres-Lacueva, Cristina

    2014-01-01

    Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review. PMID:24566441

  18. The role of latanoprost in an inflammatory bowel disease flare

    PubMed Central

    Paul, Sonali; Wand, Martin; Emerick, Geoffrey T.; Richter, James M.

    2014-01-01

    Ulcerative colitis and Crohn’s disease (CD) are characterized by inflammation of the intestinal mucosa and symptoms of abdominal pain and diarrhea. Many studies have shown an association between elevated levels of prostaglandins and mucosal damage in inflammatory bowel disease. We report a 50-year-old woman with a history of CD and open-angle glaucoma. Her glaucoma was treated with latanoprost, a prostaglandin analog, which was associated with an exacerbation of her CD. On discontinuation of latanoprost, her CD symptoms disappeared completely. This case suggests that in a patient with CD, topical administration of latanoprost may result in sufficient systemic absorption and circulation to promote a relapse of CD. This finding has important implications, not only for patients with inflammatory bowel disease and glaucoma, but also for both ophthalmologists and gastroenterologists. PMID:25064174

  19. The epidemiology and risk factors of inflammatory bowel disease

    PubMed Central

    Ye, Yulan; Pang, Zhi; Chen, Weichang; Ju, Songwen; Zhou, Chunli

    2015-01-01

    This review aimed to summarize the epidemiology (incidence, prevalence and morality) and risk factors of inflammatory bowel disease (IBD). IBD is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract and includes Crohn’s Disease (CD) and ulcerative colitis (UC). IBD has increasing incidence and prevalence in most of countries and becomes a global emerging disease. A westernized lifestyle or habits and some environmental factors have been found to contribute to the pathogenesis of IBD. The relevant risk factors include Smoking, hygiene hypothesis, microorganisms, appendectomy, medication, nutrition, and stress have all been found to be associated with the modality of IBD, but results are inconsistent on this issue in available studies. Therefore, more studies are required to identify and understand the environmental determinants of IBD. PMID:26885239

  20. Marijuana Use Patterns Among Patients with Inflammatory Bowel Disease

    PubMed Central

    Allegretti, Jessica Ravikoff; Courtwright, Andrew; Lucci, Matthew; Korzenik, Joshua R.; Levine, Jonathan

    2014-01-01

    Background The prevalence and perceived effectiveness of marijuana use has not been well studied in inflammatory bowel disease (IBD) despite increasing legal permission for its use in Crohn's disease. Health care providers have little guidance about the IBD symptoms that may improve with marijuana use. The aim of this study was to assess the prevalence, sociodemographic characteristics, and perceived benefits of marijuana use among patients with IBD. Methods Prospective cohort survey study of marijuana use patterns in patients with IBD at an academic medical center. Results A total of 292 patients completed the survey (response rate = 94%); 12.3% of patients were active marijuana users, 39.0% were past users, and 48.6% were never users. Among current and past users, 16.4% of patients used marijuana for disease symptoms, the majority of whom felt that marijuana was “very helpful” for relief of abdominal pain, nausea, and diarrhea. On multivariate analysis, age and chronic abdominal pain were associated with current marijuana use (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P < 0.001 and OR, 3.5; 95% CI, 1.24-9.82; P = 0.02). Age and chronic abdominal pain were also multivariate predictors of medicinal use of marijuana (OR, 0.93; 95% CI, 0.89–0.97; P < 0.001 and OR, 4.7; 95% CI, 1.8–12.2; P = 0.001). Half of the never users expressed an interest in using marijuana for abdominal pain, were it legally available. Conclusions A significant number of patients with IBD currently use marijuana. Most patients find it very helpful for symptom control, including patients with ulcerative colitis, who are currently excluded from medical marijuana laws. Clinical trials are needed to determine marijuana's potential as an IBD therapy and to guide prescribing decisions. PMID:24185313

  1. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    PubMed Central

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-01-01

    Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

  2. Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases

    PubMed Central

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Berry, Kayla N.; Brett, Tom J.

    2015-01-01

    Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases. PMID:26612971

  3. Cytomegalovirus in inflammatory bowel disease: A systematic review

    PubMed Central

    Römkens, Tessa EH; Bulte, Geert J; Nissen, Loes HC; Drenth, Joost PH

    2016-01-01

    AIM: To identify definitions of cytomegalovirus (CMV) infection and intestinal disease, in inflammatory bowel disease (IBD), to determine the prevalence associated with these definitions. METHODS: We conducted a systematic review and interrogated PubMed, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used “cytomegalovirus” OR “CMV” OR “cytomegalo virus” AND “inflammatory bowel disease” OR “IBD” OR “ulcerative colitis” OR “colitis ulcerosa” OR “Crohn’s disease”. Both MeSH-terms and free searches were performed. We included all types of English-language (clinical) trials concerning diagnostics and prevalence of CMV in IBD. RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR > 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia. CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials. PMID:26811669

  4. Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

    PubMed Central

    Wang, Hui; Liu, Jing-Shi; Peng, Shao-Hua; Deng, Xi-Yun; Zhu, De-Mao; Javidiparsijani, Sara; Wang, Gui-Rong; Li, Dai-Qiang; Li, Long-Xuan; Wang, Yi-Chun; Luo, Jun-Ming

    2013-01-01

    Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy. PMID:24187454

  5. Power Doppler ultrasonographic assessment of the ankle in patients with inflammatory rheumatic diseases

    PubMed Central

    Suzuki, Takeshi

    2014-01-01

    Ankle involvement is frequent in patients with inflammatory rheumatic diseases, but accurate evaluation by physical examination is often difficult because of the complex anatomical structures of the ankle. Over the last decade, ultrasound (US) has become a practical imaging tool for the assessment of articular and periarticular pathologies, including joint synovitis, tenosynovitis, and enthesitis in rheumatic diseases. Progress in power Doppler (PD) technology has enabled evaluation of the strength of ongoing inflammation. PDUS is very useful for identifying the location and kind of pathologies in rheumatic ankles as well as for distinguishing between inflammatory processes and degenerative changes or between active inflammation and residual damage. The aim of this paper is to illustrate the US assessment of ankle lesions in patients with inflammatory rheumatic diseases, including rheumatoid arthritis, spondyloarthritis, and systemic lupus erythematosus, focusing on the utility of PDUS. PMID:25405085

  6. Probiotics and prebiotics in inflammatory bowel disease: microflora ‘on the scope’

    PubMed Central

    Damaskos, Dimitrios; Kolios, George

    2008-01-01

    The intestinal microflora is a large bacterial community that colonizes the gut, with a metabolic activity equal to an organ and various functions that affect the physiology and pathology of the host's mucosal immune system. Intestinal bacteria are useful in promotion of human health, but certain components of microflora, in genetically susceptible individuals, contribute to various pathological disorders, including inflammatory bowel disease. Clinical and experimental observations indicate an imbalance in protective and harmful microflora components in these disorders. Manipulation of gut flora to enhance its protective and beneficial role represents a promising field of new therapeutic strategies of inflammatory bowel disease. In this review, we discuss the implication of gut flora in the intestinal inflammation that justifies the role of probiotics and prebiotics in the prevention and treatment of inflammatory bowel disease and we address the evidence for therapeutic benefits from their use in experimental models of colitis and clinical trials. PMID:18279467

  7. Fostering Inflammatory Bowel Disease: Sphingolipid Strategies to Join Forces

    PubMed Central

    Abdel Hadi, Loubna; Di Vito, Clara; Riboni, Laura

    2016-01-01

    Complex sphingolipids are essential structural components of intestinal membranes, providing protection and integrity to the intestinal mucosa and regulating intestinal absorption processes. The role of sphingolipid signaling has been established in numerous cellular events, including intestinal cell survival, growth, differentiation, and apoptosis. A significant body of knowledge demonstrates that intestinal sphingolipids play a crucial role, as such and through their signaling pathways, in immunity and inflammatory disorders. In this review, we report on and discuss the current knowledge on the metabolism, signaling, and functional implications of sphingolipids in inflammatory bowel disease (IBD), focusing on the different aspects of sphingolipid actions on inflammatory responses and on the potential of sphingolipid-targeted molecules as anti-IBD therapeutic agents. PMID:26880864

  8. Inflammatory bowel disease in rats: Bacterial and chemical interaction

    PubMed Central

    Hussein, Inaya Abdallah Hajj; Tohme, Rania; Barada, Kassem; Mostafa, Mostafa Hassan; Freund, Jean-Noel; Jurjus, Rosalyn A; Karam, Walid; Jurjus, Abdo

    2008-01-01

    AIM: To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 μL of 6% iodoacetamide (IA) in 1% MC, (c) 200 μL containing 4 × 108 colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-α gene expression. RESULTS: Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-α gene expression was upregulated compared to the control animals. CONCLUSION: The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity. PMID:18609687

  9. Biologic Therapy in Inflammatory and Immunomediated Skin Diseases: Safety Profile.

    PubMed

    Ganzetti, Giulia; Campanati, Anna; Molinelli, E; Offidani, A

    2016-01-01

    Biologic treatments have modified the therapeutic armamentarium in the treatment of many dermatological and non- dermatological diseases and data on literature have widely focused on the efficacy and safety of TNF-alpha inhibitors in psoriasis. Although the etiopathogenesis has not completely elucidated, inflammation appears the lait motif unifying the immune-pathogenesis of diverse skin disease, as atopic dermatitis, alopecia areata and hidradenitis suppurativa. Actually, data on the off-label use of biologics in cutaneous immune-mediated inflammatory diseases are scarce and restricted to anecdotal cases and case series. The present review aims to evidence the major off- label use of TNF-alpha inhibitors in dermatology. PMID:26463243

  10. Review article: thromboxanes in inflammatory bowel disease--pathogenic and therapeutic implications.

    PubMed

    Rampton, D S; Collins, C E

    1993-08-01

    Recent work suggests that thromboxanes may play a major pathogenic role in inflammatory bowel disease. Thromboxanes are produced in excess not only in inflamed mucosa but also in Crohn's disease, by uninflamed bowel and by isolated intestinal and peripheral blood mononuclear cells. Their cellular source is likely to include platelets, neutrophils, endothelial and epithelial cells as well as mononuclear cells, possible stimuli to their overproduction being chemotactic peptides, lipopolysaccharide, leukotrienes, platelet activating factor, interleukin-1, bradykinin and angiotensin II. The pro-inflammatory effects of thromboxanes are both direct (diapedesis and activation of neutrophils, mucosal ulceration, reduction of suppressor T-cell activity) and indirect (vasoconstriction, platelet activation). Although corticosteroids and aminosalicylates inhibit thromboxane synthesis, this action does not necessarily explain their therapeutic effect in inflammatory bowel disease. Selective thromboxane synthesis inhibitors and receptor antagonists, however, ameliorate experimental colitis in animals. Picotamide and ridogrel are dual thromboxane pathway blockers already used in man. Drugs of this type could prove useful not only for the prevention of systemic thrombo-embolism but also for suppressing intestinal mucosal inflammation in patients with inflammatory bowel disease. PMID:8218751

  11. Anti-inflammatory effects and antioxidant activity of dihydroasparagusic acid in lipopolysaccharide-activated microglial cells.

    PubMed

    Salemme, Adele; Togna, Anna Rita; Mastrofrancesco, Arianna; Cammisotto, Vittoria; Ottaviani, Monica; Bianco, Armandodoriano; Venditti, Alessandro

    2016-01-01

    The activation of microglia and subsequent release of toxic pro-inflammatory factors are crucially associated with neurodegenerative disease, characterized by increased oxidative stress and neuroinflammation, including Alzheimer and Parkinson diseases and multiple sclerosis. Dihydroasparagusic acid is the reduced form of asparagusic acid, a sulfur-containing flavor component produced by Asparagus plants. It has two thiolic functions able to coordinate the metal ions, and a carboxylic moiety, a polar function, which may enhance excretion of the complexes. Thiol functions are also present in several biomolecules with important physiological antioxidant role as glutathione. The aim of this study is to evaluate the anti-inflammatory and antioxidant potential effect of dihydroasparagusic acid on microglial activation in an in vitro model of neuroinflammation. We have used lipopolysaccharide to induce an inflammatory response in primary rat microglial cultures. Our results suggest that dihydroasparagusic acid significantly prevented lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators such as nitric oxide, tumor necrosis factor-α, prostaglandin E2, as well as inducible nitric oxide synthase and cyclooxygenase-2 protein expression and lipoxygenase activity in microglia cells. Moreover it effectively suppressed the level of reactive oxygen species and affected lipopolysaccharide-stimulated activation of mitogen activated protein kinase, including p38, and nuclear factor-kB pathway. These results suggest that dihydroasparagusic acid's neuroprotective properties may be due to its ability to dampen induction of microglial activation. It is a compound that can effectively inhibit inflammatory and oxidative processes that are important factors of the etiopathogenesis of neurodegenerative diseases. PMID:26592472

  12. The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease

    PubMed Central

    Azizi, Gholamreza; Navabi, Shadi S.; Al-Shukaili, Ahmed; Seyedzadeh, Mir H.; Yazdani, Reza; Mirshafiey, Abbas

    2015-01-01

    Alzheimer’s disease (AD), a neurodegenerative disorder associated with advanced age, is the most common cause of dementia globally. AD is characterised by cognitive dysfunction, deposition of amyloid plaques, neurofibrillary tangles and neuro-inflammation. Inflammation of the brain is a key pathological hallmark of AD. Thus, clinical and immunopathological evidence of AD could be potentially supported by inflammatory mediators, including cytokines, chemokines, the complement system, acute phase proteins and oxidative mediators. In particular, oxidative mediators may actively contribute to the progression of AD and on-going inflammation in the brain. This review provides an overview of the functions and activities of inflammatory mediators in AD. An improved understanding of inflammatory processes and their role in AD is needed to improve therapeutic research aims in the field of AD and similar diseases. PMID:26357550

  13. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review.

    PubMed

    Abreu, Cândida; Rocha-Pereira, Nuno; Sarmento, António; Magro, Fernando

    2015-06-01

    Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated. PMID:26074688

  14. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids. PMID:20450962

  15. Anti-inflammatory activity of extracts from Conyza canadensis.

    PubMed

    Lenfeld, J; Motl, O; Trka, A

    1986-04-01

    The petroleum ether and ethanolic extract from the epigean part of Conyza canadensis exhibits a significant anti-inflammatory effect on rats with a carrageenin and formalin oedema. Eight sesquiterpenic hydrocarbons with the highest anti-inflammatory activity were found in the petroleum ether fraction (beta-santalene, beta-himachalene, cuparene, alpha-curcumene, gamma-cadinene and three other unidentified hydrocarbons). Of these substances, beta-himachalene was further studied and its anti-inflammatory activity was demonstrated. PMID:3725873

  16. The Gut Microbiota in Immune-Mediated Inflammatory Diseases

    PubMed Central

    Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  17. The Gut Microbiota in Immune-Mediated Inflammatory Diseases.

    PubMed

    Forbes, Jessica D; Van Domselaar, Gary; Bernstein, Charles N

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  18. Antioxidant and anti-inflammatory effects of resveratrol in airway disease.

    PubMed

    Wood, Lisa G; Wark, Peter A B; Garg, Manohar L

    2010-11-15

    Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are a significant and increasing global health problem. These diseases are characterized by airway inflammation, which develops in response to various stimuli. In asthma, inflammation is driven by exposure to a variety of triggers, including allergens and viruses, which activate components of both the innate and acquired immune responses. In COPD, exposure to cigarette smoke is the primary stimulus of airway inflammation. Activation of airway inflammatory cells leads to the release of excessive quantities of reactive oxygen species (ROS), resulting in oxidative stress. Antioxidants provide protection against the damaging effects of oxidative stress and thus may be useful in the management of inflammatory airways disease. Resveratrol, a polyphenol that demonstrates both antioxidative and anti-inflammatory functions, has been shown to improve outcomes in a variety of diseases, in particular, in cancer. We review the evidence for a protective role of resveratrol in respiratory disease. Mechanisms of resveratrol action that may be relevant to respiratory disease are described. We conclude that resveratrol has potential as a therapeutic agent in respiratory disease, which should be further investigated. PMID:20214495

  19. High-Dose Intravenous Corticosteroids for Ocular Inflammatory Diseases

    PubMed Central

    Charkoudian, Leon D.; Ying, Gui-shuang; Pujari, Siddharth S.; Gangaputra, Sapna; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Kempen, John H.

    2011-01-01

    Purpose To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for non-infectious ocular inflammatory diseases. Methods Retrospective cohort study. One hundred four eyes of seventy patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within one month after treatment. Results Within ≤1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within one month. Complications of therapy were infrequent. PMID:22409561

  20. Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases.

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

    Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept. PMID:27455991

  1. Sleep and Inflammatory Bowel Disease: Exploring the Relationship Between Sleep Disturbances and Inflammation

    PubMed Central

    Kinnucan, Jami A.; Rubin, David T.

    2013-01-01

    Sleep disturbances are associated with a greater risk of serious adverse health events, economic consequences, and, most imp