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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutagenicity testing can be used to assay faeces for genotoxic substances and the results are reported to correlate with population risk for colorectal cancer (Ehrich et al., 1979). It has been suggested that histidine in faeces may cause false positive results (Venitt and Bosworth, 1983). To determine the relationship between histidine and false positive mutagenicity assays aliquots of non-mutagenic faecal extract and saline were supplemented with histidine and subjected to the Ames Salmonella/mammalian microsome mutagenicity assay (Ames et al., 1975). Using high-pressure liquid chromatography the analytical recovery of histidine from water and faecal extract supplemented with histidine was equivalent (r = 0.998, p less than 0.001). Histidine was measured in faecal extracts (1 in 10 dilutions) from 35 volunteers, 10 patients with inflammatory bowel disease and 4 with rectal cancer. These extracts were also assayed for mutagens using the Salmonella/mammalian microsome mutagenicity assay. None of the faecal extracts gave mutagenicity ratios above 2. Faecal extracts from volunteers were free of detectable histidine. Although 9 of those from inflammatory bowel disease patients contained histidine (mean +/- SEM 255 +/- 34 mumoles l-1) as did 1 extract from a rectal cancer patient (50 mumoles l-1), none contained sufficient histidine to give a false positive Salmonella/mammalian microsome mutagenicity assay result (800 mumoles l-1 in test solution). Our results do not implicate histidine as a cause of error in faecal mutagenicity testing by the Salmonella/mammalian microsome mutagenicity assay.
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PMID:What is the role of histidine in studies of faecal mutagenicity? 351 71

The natural killer cell lymphocyte may represent an important element in immune defense. Since host defense may be abnormal in patients with inflammatory bowel disease, we assessed natural killer cell function in 34 patients with ulcerative colitis and Crohn's disease. Lymphocytes from 31 of 34 patients (91%) exhibited decreased natural killer cell activity (mean cytotoxicity +/- SEM was 25% +/- 7.5% of the mean normal values, p less than 0.01). Disease activity, type of disease, and steroid therapy had no influence on these values. None of the 10 age-matched disease controls with other intestinal inflammatory conditions had natural killer cell activity outside the normal range. The numbers of circulating killer cells present in patients with impaired activity were quantified using a cytofluorometric detection system. All patients tested had normal numbers of cells binding nonaggregated immunoglobulin G (Fc receptor positive) despite decreased natural killer cell activity. It appears that by using this cytofluorometric detection technique, decreased natural killer cell activity is not the consequence of diminished numbers of natural killer cells.
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PMID:Impaired natural killer cell activity in patients with inflammatory bowel disease: evidence for a qualitative defect. 688 9

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 hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.
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PMID:Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer. 761 74

1. Platelet-activating factor can be synthesized by two distinct biochemical pathways and is degraded by a number of enzymes, the first step of which is deacetylation by a specific acetyl hydrolase. 2. The biochemical pathway of platelet-activating factor synthesis de novo and the first step in platelet-activating factor degradation have been investigated for the first time in incubates of normal human colon mucosa and in inflamed mucosa from patients with inflammatory bowel disease. 3. In the presence of 100 mumol/l CDP-choline and 100 mumol/l hexadecyl acetyl glycerol, homogenates from inflamed mucosa synthesized significantly greater platelet-activating factor [851 +/- 574 pmol/mg of protein (mean +/- SEM) in 90 min incubation] than normal mucosa [105 +/- 61 pmol/mg of protein in 90 min incubation] (P < 0.05). 4. Under the same conditions of assay, the percentage turnover to inactive lyso-platelet-activating factor was similar in inflamed mucosa (35.5 +/- 9.4%) and normal mucosa (42.7 +/- 8.5%) in 90 min (P > 0.05). 5. The identity of platelet-activating factor was confirmed by HPLC, by its mobility on TLC and by the ability of WEB 2170, a selective platelet-activating factor receptor antagonist, to block its platelet-aggregatory action. 6. These findings confirm the presence of the pathway for the synthesis de novo of the potently proinflammatory platelet-activating factor in human colon mucosa in inflammatory bowel disease.
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PMID:Biosynthesis of platelet-activating factor in normal and inflamed human colon mucosa: evidence for the involvement of the pathway of platelet-activating factor synthesis de novo in inflammatory bowel disease. 763 57

Changes in substance P (SP) receptor concentration have been implicated in neuropsychiatric disorders, Parkinson's disease, arthritis, inflammatory bowel disease and asthma. Since, SP and peptide analogs are rapidly metabolized and do not penetrate into the CNS, they are not useful for PET. Recently, a non-peptide SP antagonist, (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994) was developed. As a prelude to PET studies, this compound was radiolabeled with 11C and biodistribution was determined in hamsters. CP-99,994 was radiolabeled by methylation of tert-Boc, desmethyl CP-99,994 with 11CH3I followed by deprotection and HPLC purification. The time required for the synthesis was 40 min from the end of bombardment. Radiochemical purity of the final product was > 95% and specific activity was routinely > 1000 mCi/mumol [EOS]. The biodistribution of 11C-CP-99,994 was determined in groups of six Syrian hamsters at 5 and 30 min after injection. The results of these studies demonstrated that significant concentrations (%ID/g +/- SEM) of CP-99,994 accumulate in most tissues of the hamster. The highest levels of drug were detected in the lung: 21.04 +/- 1.26 (5 min) and 13.49 +/- 1.71 (30 min). Brain accumulation was: 1.44 +/- 0.06 (5 min), 1.32 +/- 0.05 (30 min). These results indicate that 11C-CP-99,994 can be prepared in high purity and specific activity. This new radiopharmaceutical may be useful for studying both central and peripheral SP receptors by PET.
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PMID:Synthesis of a 11C-labeled NK1 receptor ligand for PET studies. 773 67

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.
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PMID:Microalbuminuria in inflammatory bowel disease. 782 80

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

Macrophage major histocompatibility complex (MHC) class II antigen expression is associated with defective antigen presentation to T lymphocytes in animals and is predictive of patient outcome after major trauma or sepsis. In this study, class II antigen (HLA-DR and DQ) expression on peripheral blood monocytes was investigated in patients with inflammatory bowel disease in relation to disease activity and outcome. The percentage positivity and fluorescent intensity of expression of HLA-DR and DQ antigens on monocytes were determined in whole blood samples using dual colour immunofluorescence labelling and flow cytometry. Disease activity was assessed using clinical and laboratory indices. There was no significant difference in percentage positivity or fluorescent intensity of class II antigen expression between patients with Crohn's disease, those with ulcerative colitis, and healthy volunteers. The percentage of monocytes displaying HLA-DR positivity was significantly decreased in patients with active ulcerative colitis (active %: 49.5 (5.6); inactive %: 78.9 (6.9); p = 0.01). Data expressed as mean (SEM). In patients requiring surgical resection of diseased bowel, the percentage of monocytes displaying HLA-DR positivity (51.9 (4.0) %) was significantly reduced compared with patients receiving medical treatment alone (81.1 (3.5) %; p < 0.001). Reduced monocyte HLA-DR expression is therefore associated with disease activity and seems to predict outcome in patients with inflammatory bowel disease.
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PMID:Class II major histocompatibility complex antigen expression on peripheral blood monocytes in patients with inflammatory bowel disease. 817 90

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


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