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

Fibrosis is a common late effect of radiotherapy treatment for cancer patients. Current clinical assessment of radiation-induced fibrosis is generally limited to clinician-based rating scales, which are usually not sufficient for quantitative and objective evaluations. Ultrasonic propagation properties of tissues are widely reported to be sensitive to the alterations of tissue compositions and structures. Based on our previous feasibility study, we used four parameters including skin thickness and three ultrasonic parameters of dermal tissues (attenuation slope [beta], integrated attenuation [IA] and integrated backscatter [IBS]) in the frequency range of 10 to 25 MHz for the assessment of skin fibrosis. Experiments were conducted on the forearm and neck skin in patients with postirradiation fibrosis in the neck region. The palpation score and stiffness of the neck soft tissue were also measured as an indication of fibrotic severity. Comparisons of the results between 38 patients and 20 control subjects showed a significantly smaller beta (p = 0.005) and a significantly larger skin thickness (p < 0.004) and IA (p = 0.04) in the neck skins of the patients. However, age-matched comparisons showed there were neither significant differences among patient subgroups with different fibrotic levels assessed using manual palpation or significant correlations between the four parameters and the overall stiffness of the neck soft tissues (p > 0.05). In conclusion, ultrasound tissue characterization may provide additional information for the assessment of postirradiation skin fibrosis in the neck region. Further studies are necessary to investigate the feasibility of applying the current measurement for differentiating the severity of skin fibrosis.
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PMID:High frequency ultrasound assessment of skin fibrosis: clinical results. 1746 55

High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as a proinflammatory cytokine. We measured the HMGB1 concentration in the sera of mice with chemically induced colitis (DSS; dextran sulfate sodium salt) and found a marked increase. Inhibition of HMGB1 by neutralizing anti-HMGB1 antibody resulted in reduced inflammation in DSS-treated colons. In macrophages, HMGB1 induces several proinflammatory cytokines, such as IL-6, which are regulated by NF-kappaB activation. Two putative sources of HMGB1 were explored: in one, bacterial factors induce HMGB1 secretion from macrophages and in the other, necrotic epithelial cells directly release HMGB1. LPS induced a small amount of HMGB1 in macrophages, but macrophages incubated with supernatant prepared from necrotic cells and containing large amounts of HMGB1 activated NF-kappaB and induced IL-6. Using the colitis-associated cancer model, we demonstrated that neutralizing anti-HMGB1 antibody decreases tumor incidence and size. These observations suggest that HMGB1 is a potentially useful target for IBD treatment and the prevention of colitis-associated cancer.
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PMID:Essential roles of high-mobility group box 1 in the development of murine colitis and colitis-associated cancer. 1759 6

Whilst fruits and vegetables are an essential part of our dietary intake, the role of fiber in the prevention of colorectal diseases remains controversial. The main feature of a high-fiber diet is its poor digestibility. Soluble fiber like pectins, guar and ispaghula produce viscous solutions in the gastrointestinal tract delaying small bowel absorption and transit. Insoluble fiber, on the other hand, pass largely unaltered through the gut. The more fiber is ingested, the more stools will have to be passed. Fermentation in the intestines results in build up of large amounts of gases in the colon. This article reviews the physiology of ingestion of fiber and defecation. It also looks into the impact of dietary fiber on various colorectal diseases. A strong case cannot be made for a protective effect of dietary fiber against colorectal polyp or cancer. Neither has fiber been found to be useful in chronic constipation and irritable bowel syndrome. It is also not useful in the treatment of perianal conditions. The fiber deficit - diverticulosis theory should also be challenged. The authors urge clinicians to keep an open mind about fiber. One must be aware of the truths and myths about fiber before recommending it.
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PMID:Fiber and colorectal diseases: separating fact from fiction. 1769 43

Oral colon-specific drug-delivery systems have recently gained importance for delivering a variety of therapeutic agents. The major obstacles to delivering drugs to the colon are the absorption and degradation pathways in the upper gastrointestinal tract. However, a successfully designed colon-targeted system can overcome these obstacles. Targeting drugs to the colon has proven quite valuable in a variety of disorders, and the colon has proven to be a potential site for local as well as systemic administration of drugs. Colon targeting has proven beneficial for local action in a variety of disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, and colonic cancer. Aminosalicylates, corticosteroids, immunosuppressive agents, cationized antioxidant enzymes, genetically engineered bacteria to produce cytokines, nicotine, and other drugs have exhibited significantly enhanced efficacy when delivered to the colon. Targeting drugs to cancer cells through receptors and ligands have opened up new avenues in the treatment of colonic cancer. Colon targeting has also proven useful for systemic action of protein-peptide drugs such as insulin, calcitonin, and met-enkaphalin and even for other nonpeptide drugs such as cardiovascular and antiasthmatic agents. This review also presents various approaches for targeting orally administered dosage forms to the colon. The use of a prodrug approach, bioadhesive polymers, and coating with pH-sensitive and biodegradable polymers has been, to an extent, highly successful in delivering the targeted formulations to the site of action. Biodegrable hydrogels such as amylose, chondroitin sulphate, chitosan, inulin, guar gum, and pectin have also been successfully used to achieve oral colon-targeted delivery.
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PMID:Therapeutic opportunities in colon-specific drug-delivery systems. 1772 24

Colon specific drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Chron's disease, ulcerative colitis, irritable bowel syndrome, cancer or infections, but also for the potential it holds for the systemic delivery of proteins (e.g. insulin) and therapeutic peptides. These systems enable the protection of healthy tissues from the side effects of drugs and the drug intake of targeted cells, as well. The formulation of colon specific drug delivery systems is of great impact in the case of diseases having circadian rhythm (midnight gerd). Such circadian rhythm release drug delivery systems are designed to provide a plasma concentration--time profile, which varies according to physiological need at different times during the dosing period, i.e., mimicking the circadian rhythm and severity/manifestation of gastric acid secretion (and/or midnight gerd). In general four primary approaches have been proposed for colon targeted delivery namely pH-dependent systems, time dependent systems, colonic microflora activated systems and prodrugs.
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PMID:[Site-specific drug delivery systems. I. Colon targeted delivery]. 1801 84

The cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins. COX-1 is constitutively expressed and is a critical housekeeping gene, whereas COX-2 is rapidly upregulated by growth factors and cytokines and thus responsible for inflammation. COX-2 is frequently overexpressed in colonic adenoma and carcinoma. Specific inhibitors of COX-2 have been shown to induce apoptosis in tumor cells and to inhibit tumor growth in animal models and in humans. Long-standing IBD patients have increased risk of developing colorectal cancer compared to general population. IBD-associated colorectal carcinogenesis is probably promoted by chronic inflammation and closely related to COX-2. In a recent study, powerful chemopreventive ability of selective COX-2 inhibitor was observed in colitis-related colon carcinogenesis in mouse model. But it was reported that even selective COX inhibitors aggravated the DSS-induced colonic inflammation. It is assumed that endogenous PGs are involved in the mucosal defense against DSS-induced colonic ulcerations which are produced by COX-1 at early phase and by COX-2 at late phase. Long-term use of COX-2 inhibitors for the chemoprevention of colitic cancer is needed to define their mechanism of action, that reduce side effects and have specific tumor target.
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PMID:[COX-2 inhibitors in inflammatory bowel disease: friends or foes?]. 1815 71

Dairy foods (DFs) contain complex ingredients that could affect different diseases. The control of lactose digestion phenotypically divides populations into those who can [lactase persistent (LP)] and those who cannot [lactase nonpersistent (LNP)] assimilate lactose. LNP subjects, however, can adapt to lactose intolerance through intestinal bacteria. The DF/LNP status interactions may function as disease risk modifiers. We evaluated the relationship between DF and LNP with colorectal, breast, prostate, ovarian, lung, and stomach cancer and inflammatory bowel diseases (IBD; Crohn's disease and ulcerative colitis). Yearly per capita DF consumption, LNP national prevalence, cancer mortality, and incidence of IBD were obtained from several sources. A negative binomial regression model was used to derive incremental risks. There were statistically significant (P <or= 0.05) increases in risk for colorectal and prostate cancer and ulcerative colitis with DFs and a statistically significant decreased risk for stomach cancer. There were trends (P<0.1) for lung and ovarian cancers and Crohn's disease. As LNP prevalence increased, stomach cancer risk increased, whereas risks of all other conditions decreased (P<0.01). In 3 cancers (prostate, ovarian, and breast), meta-analyses of case-based studies support ecological data. In colorectal cancer, on the contrary, meta-analyses of case-based studies suggest protection. The possible importance of distinguishing LNP/LP status in studies is discussed.
Nutr Cancer 2008
PMID:Impact of lactose containing foods and the genetics of lactase on diseases: an analytical review of population data. 1844 63

According to the German definition, probiotics are defined viable microorganisms, sufficient amounts of which reach the intestine in an active state and thus exert positive health effects. Numerous probiotic microorganisms (e.g. Lactobacillus rhamnosus GG, L. reuteri, bifidobacteria and certain strains of L. casei or the L. acidophilus-group) are used in probiotic food, particularly fermented milk products, or have been investigated--as well as Escherichia coli strain Nissle 1917, certain enterococci (Enterococcus faecium SF68) and the probiotic yeast Saccharomyces boulardii--with regard to their medicinal use. Among the numerous purported health benefits attributed to probiotic bacteria, the (transient) modulation of the intestinal microflora of the host and the capacity to interact with the immune system directly or mediated by the autochthonous microflora, are basic mechanisms. They are supported by an increasing number of in vitro and in vivo experiments using conventional and molecular biologic methods. In addition to these, a limited number of randomized, well-controlled human intervention trials have been reported. Well-established probiotic effects are: 1. Prevention and/or reduction of duration and complaints of rotavirus-induced or antibiotic-associated diarrhea as well as alleviation of complaints due to lactose intolerance. 2. Reduction of the concentration of cancer-promoting enzymes and/or putrefactive (bacterial) metabolites in the gut. 3. Prevention and alleviation of unspecific and irregular complaints of the gastrointestinal tracts in healthy people. 4. Beneficial effects on microbial aberrancies, inflammation and other complaints in connection with: inflammatory diseases of the gastrointestinal tract, Helicobacter pylori infection or bacterial overgrowth. 5. Normalization of passing stool and stool consistency in subjects suffering from obstipation or an irritable colon. 6. Prevention or alleviation of allergies and atopic diseases in infants. 7. Prevention of respiratory tract infections (common cold, influenza) and other infectious diseases as well as treatment of urogenital infections. Insufficient or at most preliminary evidence exists with respect to cancer prevention, a so-called hypocholesterolemic effect, improvement of the mouth flora and caries prevention or prevention or therapy of ischemic heart diseases or amelioration of autoimmune diseases (e.g. arthritis). A prebiotic is "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well being and health", whereas synergistic combinations of pro- and prebiotics are called synbiotics. Today, only bifidogenic, non-digestible oligosaccharides (particularly inulin, its hydrolysis product oligofructose, and (trans)galactooligosaccharides), fulfill all the criteria for prebiotic classification. They are dietary fibers with a well-established positive impact on the intestinal microflora. Other health effects of prebiotics (prevention of diarrhoea or obstipation, modulation of the metabolism of the intestinal flora, cancer prevention, positive effects on lipid metabolism, stimulation of mineral adsorption and immunomodulatory properties) are indirect, i.e. mediated by the intestinal microflora, and therefore less-well proven. In the last years, successful attempts have been reported to make infant formula more breast milk-like by the addition of fructo- and (primarily) galactooligosaccharides.
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PMID:Probiotics, prebiotics, and synbiotics. 1846 Dec 93

The etiology of chronic pelvic pain in women is poorly understood. Although a specific diagnosis is not found in the majority of cases, some common diagnoses include endometriosis, adhesions, irritable bowel syndrome, and interstitial cystitis. The initial history and physical examination can narrow the diagnostic possibilities, guide any subsequent evaluation, and rule out malignancy or significant systemic disease. If the initial evaluation does not reveal a specific diagnosis, a limited laboratory and ultrasound evaluation can clarify the diagnosis, as well as rule out serious disease and reassure the patient. Few treatment modalities have demonstrated benefit for the symptoms of chronic pelvic pain. The evidence supports the use of oral medroxyprogesterone, goserelin, adhesiolysis for severe adhesions, and a multidisciplinary treatment approach for patients without a specific diagnosis. Less supporting evidence is available for oral analgesics, combined oral contraceptive pills, gonadotropin-releasing hormone agonists, intramuscular medroxyprogesterone, trigger point and botulinum A toxin injections, neuromodulative therapies, and hysterectomy.
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PMID:Chronic pelvic pain in women. 1858 34

Probiotics are live microbial feed supplement which beneficially affects the host animals by improving its microbial balance. Probiotics have been used in the treatment of bacterial or viral induced acute intestinal infection. In recent years, some clinical studies have shown the therapeutic effects of probiotics in the treatment of chronic inflammatory bowel disease (IBD) or prevention of allergic disease. Evidence exists for therapeutic use of probiotics in acute infectious diarrhea, Clostridium difficile colitis and antibiotic-associated diarrhea. Their exact role in IBD, irritable bowel syndrome and prevention of cancer has not to be determined. This review summarized the data about probiotics in gastrointestinal diseases and examine the mechanisms of action related to their therapeutic effects.
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PMID:[The efficacy of probiotics in gastrointestinal disease]. 1861 32


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