Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced nitric oxide (NO) generation by stimulated NO synthase (NOS) activity may, through its oxidative metabolism contribute to tissue injury in experimental colitis. In this study the possible amelioration of experimental colitis by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS activity, was evaluated. Colitis was induced in rats by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol or by flushing the colon of capsaicin pretreated rats with 2 ml of 5% acetic acid. In several experiments, L-NAME 0.1 mg/ml was added to the drinking water at the time of colitis induction with TNB or seven days before acetic acid treatment. Rats were killed at various time intervals after induction of colitis. A 10 cm distal colonic segment was isolated, weighed, lesion area measured, and explants organ cultured for 24 hours for determination of NO generation by the Greiss reaction. The rest of the mucosa was scraped for determination of myeloperoxidase and NOS activities and leukotriene generation. In TNB treated rats mean arterial pressure was also determined up to 72 hours after damage induction, with or without cotreatment with nitroprusside. L-NAME significantly decreased the extent of tissue injury in TNB treated rats. Seven days after TNB treatment lesion area was reduced by 55%, colonic weight by 37%, and myeloperoxidase and NOS activity by 59% and 42%, respectively. Acetic acid induced colitis in capsaicin pretreated rats was also significantly decreased by L-NAME. Twenty four hours after acetic acid treatment lesion area was reduced by 61%, colonic weight by 21% and NOS activity by 39%. Mean (SEM) arterial blood pressure in TNB+L-NAME treated rats was 37.6 (8.1) mm Hg higher than in TNB treated rats, an effect that was only partially abolished by nitroprusside. These results show that inhibition of NO synthesis by an L-arginine analogue significantly ameliorates the extent of tissue injury in two models of experimental colitis, an effect that is not due only to its vasoconstrictor properties. Modulation of NO generation may be a novel therapeutic approach in inflammatory bowel disease.
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PMID:Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. 867 8

The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6-dependent immune processes observed in inflammatory bowel disease.
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PMID:Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6. 789 Feb 34

Leukotriene B4 (LTB4) is a potent neutrophil activator and chemotaxin that is present in increased concentrations in the colonic tissue and rectal dialysates of acute ulcerative colitis patients. Cotton-top tamarins (CTTs) with confirmed active colitis were treated with the second generation LTB4 receptor antagonist, SC-53228 ((+)-(S)-7-[3-(2-cyclopropyl-methyl)-3-methoxy-4-[(methylamino) carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2- propanoic acid), 20 mg/kg bodyweight by gavage, twice daily for 56 days. End points were body weights, stool consistency, colonic endoscopy, assay of inflammatory mediators, and haematology and clinical chemistry tests. LTB4 and prostaglandin E (PGE) values were measured in rectal dialysates at pretreatment, 28 day and 56 day time points. LTB4 concentrations were reduced from pretreatment mean (SEM) values of 37.3 (0.8) ng/ml to 3.7 (0.8) ng/ml (p < 0.001) and 2.3 (0.5) ng/ml (p < 0.01) at days 28 and 56, respectively. On the other hand, mucosal protective PGE values remained constant or slightly increased during SC-53228 treatment (pre: 6.9 (2.2) ng/ml; day 28: 6.7 (1.4) ng/ml; day 56: 9.9 (1.6) ng/ml). Furthermore, assessment of a panel of 35 clinical chemistry and haematology parameters throughout the treatment showed there were no significant untoward effects of drug treatment. Six CCTs finished the eight week treatment and five of six gained weight (ranging from 27-121 grams each) while one CTT lost weight (50 g). Stool condition improved in five of six animals while one of six remained unchanged. All CCTs showed dramatic improvement histologically, with no or only minimally active colitis after treatment. The histological changes plus significant weight gains and improvement of stool condition (quality of life parameters) after eight weeks of SC-53228 treatment were remarkable. Furthermore, in follow up biopsies seven months after treatment ceased, three of six CTTs had no active colitis. This is the first time afflicted CTTs have not had recurring colitic exacerbations after a treatment regimen was stopped. It is concluded that in colitic CTTs, SC-53228 has shown both an immediate and a long acting anticolitic activity. It is also concluded that reduced LTB4 concentrations during treatment inhibited neutrophil infiltration of the colonic tissue and this, coupled with the maintenance of mucosal protective prostaglandins, contributed to the dramatic anticolitic efficacy. The treatment was safe over eight weeks. A compound such as SC-53228 may be useful in the medical treatment of human inflammatory bowel disease.
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PMID:Oral efficacy of a leukotriene B4 receptor antagonist in colitic cotton-top tamarins. 854 49

A 69 year old woman developed chronic diarrhoea while being treated with ranitidine. Sigmoidoscopy was performed after six weeks and showed typical histological features of lymphocytic colitis. Ranitidine was withdrawn and the diarrhoea resolved. Eight months later, a 72 hour oral rechallenge period of ranitidine, was performed immediately preceded (period 1) and followed (period 2) by sigmoidoscopy and biopsy. Diarrhoea recurred during the rechallenge period and resolved again within one day after drug withdrawal. The mean (SEM) intraepithelial lymphocyte count was not significantly different between periods 1 and 2 (11.9 (0.6) and 13.1 (0.4) per 100, respectively). An immunopathological study of 30 serial sections of biopsy specimens was performed for both periods 1 and 2. The expression of HLA-DR by the rectal epithelium was mild or absent in all sections from period 1, and was considerable in 25 of 30 sections from period 2 (p < 10(-9)). It is suggested that the oral intake of ranitidine was responsible for the diarrhoea and induced the immunopathological signs of activation of the rectal mucosal immune system during the rechallenge period.
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PMID:Ranitidine, diarrhoea, and lymphocytic colitis. 854 50

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.
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PMID:Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study. 1276 45

To evaluate the role of estrogen treatment on the healing of acetic acid-induced gastric or colonic injury, rats were given 17beta estradiol benzoate (0.001, 0.1, and 10 mg/kg) or vehicle for 7 days (following the induction of ulcer) or 4 days (following the induction of colitis) until they were decapitated. Food intake and fecal output were decreased by estradiol treatment but gastric emptying rate was not changed. Estradiol (10 mg/kg) reduced gastric ulcer index and colonic damage score compared to vehicle-treated groups. SEM and light microscopy demonstrated a significant reduction in the severity of ulcers and colitis by estradiol treatment. Gastric microscopic score was not changed by estradiol treatment, whereas in the colonic tissue score was significantly reduced. Elevated gastric MPO levels were reduced in gastric but not in colonic tissues as compared with corresponding vehicle groups. In conclusion, exogenous estradiol treatment at pharmacological doses improves the healing of both gastric and colonic injury induced by acetic acid in rats.
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PMID:Estradiol treatment ameliorates acetic acid-induced gastric and colonic injuries in rats. 1476 Sep 43

The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans-pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague-Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t(1/2), urine t(1/2), Cl(total) and Vd(beta) were 17.5 +/- 6.6 microg/h/mL, 1.73 +/- 0.78 h, 17.3 +/- 5.6 h, 0.960 +/- 0.025 L/h/kg and 2.41 +/- 1.13 L/kg (mean +/- SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration-dependent anticancer activity in five cancer cell lines (1-100 microg/mL). An in vitro colitis model showed concentration-dependent suppression of PGE(2) production in the media of HT-29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene (1-100 microg/mL). The results showed decreased levels of MMP-3, sGAG and TNF-alpha compared with control levels. Pterostilbene exhibited concentration-dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail-flick and hot-plate analgesic tests.
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PMID:Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity. 1772 31

Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are representative agents for the chemoprevention of sporadic colorectal neoplasia. However, few reports have described the chemopreventive effects of such agents on colitis-associated tumorigenesis. To clarify whether treatment with the COX-2 inhibitor may reduce the risk of colitis-associated neoplasia, we investigated the effect of one such agent, etodolac, on tumorigenesis in the colitis-associated neoplasia model using p53-deficient mice treated with dextran sulfate sodium (DSS). The p53-/- mice were divided into four groups: i) treatment with DSS + etodolac, then after two cycles of DSS, the mice were given distilled water for 84 days. In addition, etodolac was administered three times a week at a dose of 10 mg/kg body weight throughout the experiment. ii) Treatment with two cycles of DSS only, followed by distilled water for 84 days. iii) Treatment with etodolac alone. iv) Distilled water alone was administered to the control group. The incidence of mice with neoplasia was 82.4% in the DSS + etodolac group and 100% in the DSS-alone group. No neoplasia was observed in the etodolac-alone and control groups. The mean (+/- SEM) number of total neoplasias per mouse was 1.29+/-0.2 in the DSS + etodolac group and 3.0+/-0.52 in the DSS-alone group, the inter-group difference being significant (p<0.01). There was no significant difference in the inflammation score between these two groups. These results showed that treatment with etodolac significantly reduced the occurrence of neoplasia, suggesting that this COX-2 inhibitor has chemopreventive activity against colitis-associated tumorigenesis.
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PMID:Inhibitory effects of the cyclooxygenase-2 inhibitor, etodolac, on colitis-associated tumorigenesis in p53-deficient mice treated with dextran sulfate sodium. 1820 86

Fish oils (FO) - rich in EPA and DHA - may protect against colitis development. Moreover, inflammatory bowel disease patients have elevated colonic arachidonic acid (AA) proportions. So far, effects of dietary AA v. FO on colitis have never been examined. We therefore designed three isoenergetic diets, which were fed to mice for 6 weeks preceding and during 7 d dextran sodium sulfate colitis induction. The control diet was rich in oleic acid (OA). For the other two diets, 1.0 % (w/w) OA was exchanged for EPA+DHA (FO group) or AA. At 7 d after colitis induction, the AA group had gained weight (0.46 (sem 0.54) g), whereas the FO and OA groups had lost weight (- 0.98 (SEM 0.81) g and - 0.79 (SEM 1.05) g, respectively; P < 0.01 v. AA). The AA group had less diarrhoea than the FO and OA groups (P < 0.05). Weight and length of the colon, histological scores and cytokine concentrations in colon homogenates showed no differences. Myeloperoxidase concentrations in plasma and polymorphonuclear cell infiltration in colon were decreased in the FO group as compared with the OA group. We conclude that in this mice model an AA-enriched diet increased colonic AA content, but did not result in more colonic inflammation as compared with FO- and OA-enriched diets. As we only examined effects after 7 d and because the time point for evaluating effects seems to be important, the present results should be regarded as preliminary. Future studies should further elucidate differential effects of fatty acids on colitis development in time.
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PMID:An arachidonic acid-enriched diet does not result in more colonic inflammation as compared with fish oil- or oleic acid-enriched diets in mice with experimental colitis. 1820 94

The surface ultrastructure (SEM) of adult worms and eggs of the equine caecal fluke, Gastodiscus aegyptiacus, together with some pathological observations of the caecum and colon of infected horses were studied. SEM showed that G. aegyptiacus had a disc-like body with anterior cone-like part. The oral sucker was surrounded by numerous dome-shaped papillae. The cone-like part possessed tubercle-like papillae at its anterior third. The large ventral sucker was subterminal with small papillae at its rim. The ventral surface was covered with large cauliflower-like papillae. Microvilli were densely arranged on the egg shell surface. The pathological changes were proved by severe haemorrhagic colitis.
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PMID:Ultrastructure and some pathological pictures of Gastrodicus aegyptiacus (Cobbold, 1876) in Egyptian horses. 1920 77


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