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

Malnutrition is frequently seen in patients with inflammatory bowel disease, and parenteral or enteral nutrition is considered essential in this patient group. However, many patients with Crohn's disease have difficulties in gaining weight in response to overfeeding, suggesting reduced energy retention. Substrate utilization and nutrient balances as well as changes in body composition were followed in 10 patients with Crohn's disease immediately in the course of remission on low-dose steroid treatment, during an eight-day period of continuous enteral nutrition at constant (protocol 1:1.5-fold basal energy expenditure) and increasing (protocol 2:0.5- to 2.0-fold basal energy expenditure) nutrient supply. Energy, substrate, and nitrogen balances all became positive in response to overfeeding. However, fat was predominantly oxidized at an infusion rate of 1.2 g/kg body wt/day, whereas carbohydrates and proteins were effectively stored. A positive energy balance was reached at an energy infusion rate exceeding 31 kcal/kg body wt/day and corresponding substrate supplies of 1.6, 1.7, and 1.1 g/kg body wt/day for carbohydrates, fat, and protein, respectively. Nitrogen balance normalized at a supply of 0.14 g/kg body wt/day, which also reduced myofibrillar protein breakdown. Considering the relative contributions made by these nutrients in the diets, an accumulation of carbohydrates and protein but a depletion in fat became evident from nutrient balances. In fact, body weight increased by 0.12 kg/day, which was explained by an increased extracellular (+0.18 kg/day) and body cell mass (+0.04 kg/day) at reduced fat mass (-0.10 kg/day). Concomitantly, plasma T3 and insulin secretion both increased, whereas sympathetic nervous system activity decreased with overfeeding. This is contrary to data observed in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced metabolic efficiency in patients with Crohn's disease. 822 73

Experimental approaches designed to define the role of reactive oxygen and nitrogen species generated by inflammatory cells in the tissue injury seen in inflammatory bowel disease rarely consider the chemical antioxidant defences against such increased oxidant stress in the mucosa. In this investigation, we have analysed components of the aqueous and lipid phase antioxidant mucosal defences by measuring the total peroxyl radical scavenging capacity and the levels of urate, glutathione, alpha-tocopherol, and ubiquinol-10 in paired noninflamed and inflamed mucosal biopsies from inflammatory bowel disease patients. Compared to paired noninflamed mucosa, decreases were observed in inflamed mucosa for total peroxyl radical scavenging capacity (55%, p = 0.0031), urate [Crohn's disease (CD), 62.2%, p = 0.066; ulcerative colitis (UC), 47.3%, p = 0.031], glutathione (UC, 59%, 7/8 patients, ns), total glutathione (UC 65.2%, 6/8 patients, ns), ubiquinol-10 (CD, 75.7%, p = 0.03; UC, 90.5%, p = 0.005). The mean alpha-tocopherol content was unchanged. These observations support our earlier findings of decreased reduced and total ascorbic acid in inflamed IBD mucosa and demonstrate that the loss of chemical antioxidant defences affects almost all the major components. The decreased antioxidant defences may severely compromise the inflamed mucosa, rendering it more susceptible to oxidative tissue damage, hindering recovery of the mucosa and return of epithelial cell layer integrity. The loss of chemical antioxidant components provides a strong rational for developing novel antioxidant therapies for the treatment of inflammatory bowel disease.
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PMID:Depleted mucosal antioxidant defences in inflammatory bowel disease. 858 68

Reactive metabolites are believed to be responsible for many types of toxicity, including idiosyncratic drug reactions. Bone marrow is a frequent target of idiosyncratic reactions, and, since these reactions have characteristics that suggest involvement of the immune system, the formation of reactive metabolites by leucocytes could also play a role in the aetiology of idiosyncratic drug reactions. The major oxidation system in neutrophils and monocytes is a combination of NADPH oxidase and myeloperoxidase. This system oxidizes primary arylamines, such as sulphonamides, to reactive metabolites and these drugs are also associated with a high incidence of agranulocytosis, generalized idiosyncratic reactions and/ or drug-induced lupus. Clozapine is oxidized by this system to a relatively stable nitrenium ion; clozapine is also associated with a high incidence of agranulocytosis. Arylamines that have an oxygen or nitrogen in the para position, such as amodiaquine, vesnarinone and 5-aminosalicylic acid, are oxidized to quinone-like reactive intermediates. Aminopyrine is oxidized to a very reactive dication. Such reactive metabolites could also inhibit neutrophil function and mediate some of the therapeutic effects of these drugs: for example, the use of dapsone for dermatitis herpetiformis and the use of 5-aminosalicylic acid for inflammatory bowel disease.
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PMID:Myeloperoxidase as a generator of drug free radicals. 866 Mar 93

A distinguishing feature of inflammatory bowel disease (IBD) is its apparently spontaneous, chronic relapsing course. Despite extensive research over several decades the etiology of IBD remains unknown, but evidence has accumulated to suggest that the mucosal inflammatory response may be caused by (i) a defective mucosal barrier function resulting in an abnormally increased exposure to luminal antigens and toxins, (ii) an appropriate immunologic response to an unusual infection, antigen or toxin, or (iii) an inappropriate immunological response to ubiquitous antigens or stimuli. In recent years, the identification of established and potential mediators of inflammation has expanded to include eicosanoids, platelet activating factor, biogenic amines, kinins, complement-derived peptides, chemotactic peptides, cytokines, neuropeptides, and reactive metabolites of oxygen and nitrogen. Thus, the study of the inflammatory process has become ever more complex. Until the predisposing and trigger factors have been identified the achievement of a more rational and effective approach to therapy in IBD relies on interruption of the mechanisms responsible for excess mediator formation. As summarized in this review on the role of soluble mediators of inflammation, several Danish gastroenterologists have been profoundly engaged in basic and clinical research in the past 25 years to place some pieces of the confusing puzzle of IBD.
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PMID:Mediators of inflammation in chronic inflammatory bowel disease. 872 87

The purpose of this study was to investigate the nutritional effect of perilla oil emulsion (POE) in a rat model with inflammatory bowel disease (IBD) induced by 2,4,6-trinitrobenzenesulfonic acid. POE and soybean oil emulsion (SOE) were infused at 20% of nonprotein energy during 7 days' total parenteral nutrition (TPN). After infusion of test solutions, body weight gain and cumulative nitrogen balance in the POE group were significantly higher than those in the fat-free TPN (FF) group after infusion of test solutions. Moreover, those in the POE group were higher than those in the SOE group, but no significant difference was observed between the POE and SOE groups. In the POE group, total cholesterol and phospholipid concentration in the plasma was significantly decreased compared with the FF and SOE groups. Triglyceride concentration in the plasma did not significantly differ between the POE, SOE and FF groups. Plasma lipid peroxide concentration in the POE group was significantly lower than that in the SOE group, but it was not different from the FF group. In fatty acid composition in the plasma total lipids, linoleic acid in the POE and SOE groups and alpha-linolenic acid in the POE group were significantly increased compared with those in the FF group. Arachidonic acid (AA) in the POE and FF groups were significantly decreased compared with that in the SOE group. Otherwise, eicosapentaenoic acid (EPA) in the POE group was significantly increased compared with that in the SOE and FF groups. EPA/AA ratio in the POE group was significantly increased compared with the SOE group. The thickness and damage score of the colon were significantly depressed in the POE group compared with the SOE group. These results suggest that POE has a superior nutritional effect and improves inflammation in the IBD.
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PMID:The nutritional effect of a-linolenic acid-rich emulsion with total parenteral nutrition in a rat model with inflammatory bowel disease. 888 51

Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.
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PMID:Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. 894 24

During the last few decades it has become increasingly evident that inflammatory bowel disease (IBD) is associated with abnormalities of systemic and mucosal immunity. This association has slowly moved from the phenomenological to the mechanistic level, and today there is solid evidence that the immune system mediates inflammation and tissue damage in the gut of patients suffering from IBD. However, the exact mechanisms of injury and what triggers such mechanisms are yet to be understood in spite of expanding knowledge of the cellular and molecular events underlying gut inflammation. Phenomena detected in the peripheral blood of IBD patients reflect some, but not all, of the events occurring in the gut and have limited meaning. On the contrary, the investigation of phenomena occurring in the inflamed mucosa has yielded valuable information on which progress in the understanding of IBD pathogenesis and the development of new therapies are currently based. It seems that all immune and non-immune components of the mucosa are involved in IBD, either directly or indirectly, as shown by abnormalities of humoral and cell-mediated immunity, cytokine and growth factor, eicosanoids, neuropeptides, reactive oxygen and nitrogen metabolises, cell adhesion molecules, apoptosis, and non-immune cells. Because of the multiplicity and complexity of the interactions of all these elements it is presently impossible to discern between primary and secondary, and pathogenic and non-pathogenic phenomena. In spite of these difficulties, an impressive amount of information is being gathered which is translated, at times in a preliminary or empirical fashion, into novel immunopathology-based forms of treatment.
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PMID:The immune system in inflammatory bowel disease. 926 Mar 27

Patients with active inflammatory bowel disease are often reported to be in negative nitrogen balance. Therefore, we examined basal and amino acid stimulated urea synthesis in 11 patients with active inflammatory bowel disease and in 10 patients with non-active disease. A primed continuous infusion of an amino acid mixture was given from t = 1 h to t = 5 h; during the first and the last two hours no amino acid infusion was given. Urea nitrogen synthesis rate was quantified independently of changes in blood amino acid concentration by means of the functional hepatic nitrogen clearance, i.e. the linear slope of the regression of urea nitrogen synthesis rate on blood amino acid concentration. Basal and amino acid stimulated urea nitrogen synthesis rate as well as functional hepatic nitrogen clearance were elevated twofold in the patients with active disease. No differences between the two groups were observed as regards basal or stimulated plasma glucagon, cortisol, catecholamines and serum levels of interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6. The results show that liver function related to conversion of amino-nitrogen to urea is increased and may contribute to the less efficient nitrogen economy in patients with active inflammatory bowel disease.
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PMID:[Increased urea synthesis in patients with active inflammatory bowel disease]. 941 71

During the past 20 years there has been growing interest in the importance of nutritional factors in the pathogenesis of inflammatory bowel disease. There are so far no definite links between ulcerative colitis and diet, but links with Crohn's disease have been studied by both epidemiologists and clinicians. Epidemiological studies, although retrospective, have suggested that patients with Crohn's disease eat more sugar and sweets that control individuals; however, when dietary sugar is restricted, there is little clinical benefit. The clinical approach to nutrition in Crohn's disease has been by the use of elemental diets, which will produce symptomatic and objective remission in up to 90% of compliant patients. Those who return to normal eating soon relapse but, in some studies, have enjoyed prolonged remission on exclusion diets. The foods excluded have been not sugar, but predominantly cereals, dairy products and yeast. Attention has now switched to the possible harmful role of fat in Crohn's disease. The efficacy of elemental feeds appears to depend not on the presentation of nitrogen but on the amount of long chain triglyceride present. Increases in recent years in the frequency of Crohn's disease in Japan have been correlated with increased dietary fat intake, and a recent study suggested that W-3 fatty acids, which are metabolized by immunomodulatory leukotrienes and prostaglandins, may have a beneficial role to play. The links between nutrition and Crohn's disease have now become strong and the role of fat may be the most exciting of all.
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PMID:Nutritional factors in inflammatory bowel disease. 958 29

Reactive oxygen and nitrogen species have been implicated as mediators of mucosal injury in inflammatory bowel disease. This study investigated hydroxyl radical (.OH) generation in the inflamed colon of dextran sulfate sodium (DSS)-induced colitis by measuring the .OH-specific product of salicylate hydroxylation, 2,3-dihydroxybenzoic acid (DHB). Colitis was induced in 6-7 week old CBA/H male mice by supplementing the drinking water with 5% DSS for 7 days. On the last day of dextran exposure, mice were injected with salicylate (SAL) (100 mg/kg i.p.) 60 min before sacrifice, and mucosal homogenates were assayed for SAL and 2,3-DHB by HPLC with fluorescence and electrochemical detection. Mucosal 2,3-DHB levels in mice exposed to 5% DSS were increased by 83% (p < .005); however, SAL levels were also elevated by 182% (p < .001). This translated to a 34% decrease in the ratio 2,3-DHB:SAL in inflamed mucosa, possibly indicating greater catabolism or decreased production of 2,3-DHB. In vitro investigation of the stability of DHBs and SAL in the presence of oxidants of inflammatory lesions revealed that 2,3-DHB and 2,5-DHB were rapidly degraded by hypochlorous acid (HOCl), with initial decomposition rates of 190 and 281 nmol/min, respectively (100microM DHB with 200microM HOCl). Methionine prevented decomposition of DHBs in vitro; however, in mice with 5% DSS-induced colitis, where mucosal myeloperoxidase activity was ten-fold control levels (p < .001), administration of methionine (up to 200 mg/kg i.p.) with SAL was ineffective at increasing the ratio 2,3-DHB:SAL. SAL was also degraded in vitro by HOCl (4.7 nmol/min) resulting in the formation of new fluorescent species which may be useful as indicators of HOCl-mediated injury. Salicylate hydroxylation was unable to provide conclusive evidence supporting a role for .OH in the tissue injury of DSS-induced colitis, as metabolic disturbances in the diseased animals other than changes in .OH generation may have altered 2,3-DHB levels. This problem is relevant to any study involving the in vivo use of trapping molecules. In particular, the susceptibility of 2,3-DHB to degradation by HOCl brings into question the usefulness of salicylate hydroxylation for measurement of .OH-generation in any neutrophilic inflammatory lesion.
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PMID:Salicylate hydroxylation as an indicator of hydroxyl radical generation in dextran sulfate-induced colitis. 968 Jan 76


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