Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malnutrition is often a major clinical problem in patients affected by IBD. Assessment of nutritional status should be routinely carried out in these patients and, in case of severe malnutrition, artificial nutrition should be used. In ulcerative colitis and in Crohn disease localized to colonic segments both Parenteral Nutrition (PN) and Enteral Nutrition (EN) have similar results as support treatments but they have no primary therapeutic effects and then they are indicated only in case of severe malnutrition and/or when a surgical procedure is planned. Some theoretical advantages derived from supplementation of short chain fatty acids and omega3-series is still debated. More evident are the advantages of nutritional support in Crohn enteritis. Both PN and EN have a role as a primary therapy capable to induce remission although these results are not prolonged in time when nutrition is not associated with pharmacological treatments. Experiments of pharmaco-nutrition with glutamine and fish fatty acid have to be validated in the clinical practice. In case of integrity of the small bowel and tolerance of the patient, EN is preferable to PN for its lower costs and reduced related complications. PN is still indicated in more severe cases or in acute phase when the need of restoring rapidly the hydroelectrolitic and nitrogen/caloric balance prevails.
 ...
PMID:[Artificial nutrition in inflammatory bowel disease]. 1596 Mar 56

Chronic inflammation has long been recognized as a risk factor for human cancer at various sites. Examples include Helicobacter pylori-induced gastritis for gastric cancer, inflammatory bowel disease (ulcerative colitis and Crohn's disease) for colorectal cancer and chronic viral hepatitis for liver cancer. Here we review the role in carcinogenesis of nitrative damage to nucleic acids, DNA and RNA, which occurs during inflammation through the generation of reactive nitrogen species, such as peroxynitrite, nitroxyl, and nitrogen dioxide. Enhanced formation of 8-nitroguanine, representative of nitrative damage to nucleobases, has been detected in various inflammatory conditions. The biochemical nature of DNA damage mediated by reactive nitrogen species is discussed in relation to its possible involvement in mutations, genetic instability, and cell death. Better understanding of the mechanisms and role of such nitrative damage in chronic inflammation-associated human cancer is a necessary basis to develop new strategies for cancer prevention by modulating the process of inflammation.
 ...
PMID:Nitrative DNA damage in inflammation and its possible role in carcinogenesis. 1609 98

The p38 mitogen-activated protein (MAP) kinase has been implicated in the proinflammatory cytokine signal pathway, and its inhibitors are potentially useful for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease. To develop a new drug for RA, we synthesized a novel series of 4-phenyl-5-pyridyl-1,3-thiazoles and evaluated their inhibition of p38 MAP kinase, lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro, and LPS-induced TNF-alpha production in vivo in mice. During the course of the study, we found that these compounds risk the inhibition of cytochrome P450 (CYP) isoforms by coordination of the 4-pyridyl nitrogen with heme iron. We therefore investigated the effects of substitution at the 2-position of the pyridyl ring on the inhibitory activity of p38 MAP kinase and CYPs in more detail. As a result, N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (8h, TAK-715) exhibited potent inhibitory activity in these assays (inhibition of p38alpha, IC50 = 7.1 nM; LPS-stimulated release of TNF-alpha from THP-1, IC50 = 48 nM; LPS-induced TNF-alpha production in mice, 87.6% inhibition at 10 mg/kg, po) and no inhibitory activity for major CYPs, including CYP3A4. This compound also showed good bioavailability in mice and rats and significant efficacy in a rat adjuvant-induced arthritis model. Compound 8h was selected as a clinical candidate and is now under clinical investigation for the treatment of RA.
 ...
PMID:Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent. 1616

Infection and chronic inflammation are proposed to contribute to carcinogenesis through inflammation-related mechanisms. Infection with hepatitis C virus, Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are important risk factors for hepatocellular carcinoma (HCC), gastric cancer and cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with colon carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We performed a double immunofluorescence labeling study and found that nitrative and oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS) was expressed in epithelial cells and inflammatory cells at the site of carcinogenesis in humans and animal models. Antibacterial, antiviral and antiparasitic drugs dramatically diminished the formation of these DNA lesion markers and iNOS expression. These results suggest that oxidative and nitrative DNA damage occurs at the sites of carcinogenesis, regardless of etiology. Therefore, it is considered that excessive amounts of reactive nitrogen species produced via iNOS during chronic inflammation may play a key role in carcinogenesis by causing DNA damage. On the basis of our results, we propose that 8-nitroguanine is a promising biomarker to evaluate the potential risk of inflammation-mediated carcinogenesis.
 ...
PMID:Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. 1660 33

Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity and epithelial injury in inflammatory bowel disease (IBD). Current advances have defined the mechanisms by which neutrophils are activated or migrate across endothelial and mucosal epithelial cells. A better understanding of this process will likely provide new insights into novel treatment strategies for IBD. Especially, activated neutrophils produce reactive oxygen and nitrogen species and myeloperoxidase within intestinal mucosa, which induce oxidative stress. Posttranslational modification of proteins generated by these reactive species serves as a "molecular fingerprint" of protein modification by lipid peroxidation-, nitric oxide-, and myeloperoxidase-derived oxidants. Measurement of these modified proteins may serve both as a quantitative index of oxidative stress and an important new biological marker of clinical relevance to IBD. We have succeeded in the clinical development of a novel granulocyte adsorptive apheresis therapy for IBD. In this review, we discuss current advances in defining the role of neutrophil-dependent oxidative stress in IBD.
 ...
PMID:Molecular fingerprints of neutrophil-dependent oxidative stress in inflammatory bowel disease. 1794 Aug 31

Reactive oxygen metabolites (ROMs) and inducible nitric oxide synthase (iNOS) are involved in pathogenesis of inflammatory bowel disease. In this study, we examined the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), an active component extracted from Polygonum multiflorum Thunb, on acetic acid-induced acute colitis and mitomycin C-induced chronic colitis. The inflammatory degree was assessed by histology and myeloperoxidase (MPO) activity. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined with biochemical methods. In addition, inducible nitric oxide synthase (iNOS) expression was immunohistochemically studied. In acetic acid-induced acute model, THSG (60 and 120 mg/kg) significantly ameliorated colon damage, inhibited the increase of acetic acid-induced MPO activity, depressed MDA and NO level, and enhanced SOD activity. Moreover, the effects of 120 mg/kg THSG were better than that of positive control drug, 5-aminosalicylic acid (5-ASA). In mitomycin C-induced model, THSG (60 mg/kg) administered for 7 days and 24 days, significantly improved colon damage and inhibited MPO activity and MDA content while increased SOD activity only on the 7th day and debased NO level on the 24th day. Furthermore, on the 24th day, the effects of THSG were prior to that of 5-ASA. Additionally, THSG (60 mg/kg) could inhibit iNOS expression in both models. In conclusion, THSG exerts protective effects on experimental colitis through alleviating oxygen and nitrogen free radicals level and down-regulating iNOS expression.
 ...
PMID:Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside, an active component of Polygonum multiflorum Thunb, on experimental colitis in mice. 1796 44

Chronic inflammation increases cancer risk. While it is clear that cell signaling elicited by inflammatory cytokines promotes tumor development, the impact of DNA damage production resulting from inflammation-associated reactive oxygen and nitrogen species (RONS) on tumor development has not been directly tested. RONS induce DNA damage that can be recognized by alkyladenine DNA glycosylase (Aag) to initiate base excision repair. Using a mouse model of episodic inflammatory bowel disease by repeated administration of dextran sulfate sodium in the drinking water, we show that Aag-mediated DNA repair prevents colonic epithelial damage and reduces the severity of dextran sulfate sodium-induced colon tumorigenesis. Importantly, DNA base lesions expected to be induced by RONS and recognized by Aag accumulated to higher levels in Aag-deficient animals following stimulation of colonic inflammation. Finally, as a test of the generality of this effect we show that Aag-deficient animals display more severe gastric lesions that are precursors of gastric cancer after chronic infection with Helicobacter pylori. These data demonstrate that the repair of DNA lesions formed by RONS during chronic inflammation is important for protection against colon carcinogenesis.
 ...
PMID:DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. 1852 Nov 88

Chronic inflammation is a well-recognized risk factor for the development of human cancer. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a typical longstanding inflammatory disease of the colon with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic inflammatory process may contribute to multistage progression of human cancer development, including the overproduction of reactive oxygen and nitrogen species, overproduction/activation of key arachidonic acid metabolites and cytokines/growth factors, and immunity system dysfunction. Multiple animal models of IBD have been established, and in general, these models can be mainly categorized into chemically induced, genetically engineered (transgenic or gene knock-out), spontaneous, and adoptive transferring animal models. This chapter mainly focuses on (1) epidemiologic and molecular evidence on IBD and risk of colorectal cancer, (2) molecular pathogenesis of IBD-induced carcinogenesis, and (3) modeling of IBD-induced carcinogenesis in rodents and its application.
 ...
PMID:Inflammatory bowel disease: a model of chronic inflammation-induced cancer. 1934 99

Intestinal inflammation is accompanied by excessive production of reactive oxygen and nitrogen radical species because of the massive infiltration of polymorphonuclear and mononuclear leukocytes. Antioxidant compounds seem to protect against experimental colitis. Here we investigated the effects of the innovative non-peptidyl, low molecular weight radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate (IAC), which is highly reactive with most oxygen, nitrogen and carbon centred radicals and is easily distributed in cell membranes and intra-extra cellular compartments, in the DNBS model of colitis. Colitis was induced in male SD rats by intrarectal administration of DNBS (15 mg/rat). IAC (30 mg/kg b.w., hydrophilic or lipophilic form) was administered daily (orally or i.p.) starting from the day before the induction of colitis for 7 days (n=6-8 per group). Colonic damage was assessed by means of macroscopic and histological scores, myeloperoxidase activity (MPO) and TNF-alpha tissue levels. Colitis impaired body weight gain and markedly increased all inflammatory parameters. IAC significantly counteracted the reduction in body weight gain, decreased colonic damage and inflammation and TNF-alpha levels in DNBS-colitis. The antioxidant IAC significantly ameliorates experimental colitis in rats. This strengthens the notion that antioxidant compounds may have therapeutic potential in inflammatory bowel disease.
 ...
PMID:Effects of the non-peptidyl low molecular weight radical scavenger IAC in DNBS-induced colitis in rats. 1938 95

Patients with ulcerative colitis and Crohn's disease are at increased risk of developing intestinal cancers via mechanisms that remain incompletely understood. However, chronic inflammation and repeated events of inflammatory relapse in inflammatory bowel disease (IBD) expose these patients to a number of signals known to have tumorigenic effects including persistent activation of the nuclear factor-kappaB and cyclooxygenase-2/prostaglandin pathways, release of proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6, and enhanced local levels of reactive oxygen and nitrogen species. These inflammatory signals can contribute to carcinogenesis via 3 major processes: 1) by increasing oxidative stress, which promotes DNA mutagenesis thus contributing to tumor initiation; 2) by activating prosurvival and antiapoptotic pathways in epithelial cells, thereby contributing to tumor promotion; and 3) by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of tumor cells, thus supporting tumor progression and metastasis. The present review integrates clinical and basic research observations in an attempt to provide a comprehensive understanding of how inflammatory processes may contribute to intestinal cancer development in IBD patients.
 ...
PMID:Mechanisms by which inflammation may increase intestinal cancer risk in inflammatory bowel disease. 2015 48


<< Previous 1 2 3 4 5 6 7 8 9 Next >>