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Biomedical subjects

C Tagesson

Publications and source records attributed to C Tagesson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Role of phospholipase A2 and oxygenated free radicals in mucosal damage after small intestinal ischemia and reperfusion.

The influence of quinacrine, a phospholipase A2 inhibitor, and enzymatic scavengers of active oxygen metabolites (superoxide dismutase and catalase) on ischemic small intestinal mucosal damage has been investigated. In the absence of an inhibitor, ischemia and reperfusion caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content, and increased myeloperoxidase and phospholipase A2 (PLA2) activities in the mucosa. All these effects of ischemia were efficiently inhibited by the PLA2 inhibitor quinacrine. On the other hand, superoxide dismutase together with catalase, even if it totally prevented the increased formation of malondialdehyde, was only able to reduce 50 percent of the increases of the other parameters. These findings indicate that, in addition to free radicals, other factors are involved in the pathogenesis of small intestinal mucosal injury after ischemia and reperfusion. We suggest that one such factor is the activation of PLA2 and the generation of various PLA2-dependent compounds such as arachidonic acid metabolites, lysophosphatidyl choline, and platelet-activating factor.

Acetylglucosaminidase↗
PubMed1989

Hydroxyl radical mediated DNA base modification by manmade mineral fibres.

Manmade mineral fibres (MMMFs) were examined for their ability to hydroxylate 2-deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OH-dG), a reaction that is mediated by hydroxyl radicals. It appeared that (1) catalase and the hydroxyl radical scavengers, dimethylsulphoxide and sodium benzoate, inhibited the hydroxylation, whereas Fe2+ and H2O2 potentiated it; (2) pretreatment of MMMFs with the iron chelator, deferoxamine, or with extensive heat (200-400 degrees C), attenuated the hydroxylation; (3) the hydroxylation obtained by various MMMFs varied considerably; (4) there was no apparent correlation between the hydroxylation and the surface area of different MMMFs, although increasing the surface area of a fibre by crushing it increased its hydroxylating capacity; and (5) there was good correlation between the hydroxylation of dG residues in DNA and the hydroxylation of pure dG in solution for the 16 different MMMFs investigated. These findings indicate that MMMFs cause a hydroxyl radical mediated DNA base modification in vitro and that there is considerable variation in the reactivity of different fibre species. The DNA modifying ability seems to depend on physical or chemical characteristics, or both, of the fibre.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1989

Increase in permeability and phospholipase A2 activity of colonic mucosa in Crohn's colitis.

Patients with Crohn's colitis were investigated regarding the relationship between intestinal inflammation, mucosal activity of phospholipase A2 and intestinal permeability to different-sized polyethylene glycols (PEG). Mucosal specimens for phospholipase A2 were obtained at colonoscopy and PEG (590-942 daltons) were deposited in the descending colon. Colonic absorption was measured as urinary output of deposited PEG. Colonic absorption of PEG was higher in these patients, even when the colitis was in remission at colonoscopy, than in ileal Crohn's disease or control patients. Mucosal phospholipase A2 activity was increased in active colitis, but in the patients with endoscopic remission it was at the same level as in the controls or in the patients with ileal Crohn's disease. The observations suggest that increased intestinal permeability may be a primary factor in activation of mucosal phospholipase A2 activity and in intestinal inflammation.

Adolescent↗
PubMed1989

Does smoking tighten the gut?

There is a low prevalence of smoking in ulcerative colitis. The disease often starts or relapses after stopping smoking. Increased intestinal permeability for harmful substances has been proposed as one causal factor in ulcerative colitis. We therefore wanted to study the relationship between smoking and intestinal permeability in healthy subjects. In 25 smoking and 25 non-smoking healthy persons urine recoveries of two different oral probes, 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) and low-molecular-weight polymers of polyethylene glycol (PEG 400), were measured. The smokers had significantly lower 24-h urine recoveries of 51Cr-EDTA than the non-smokers (median, 1.6; range, 0.8-4.2, versus 2.1; range, 1.1-5.8; 2 p less than 0.001). In contrast, 6-h urine recoveries of PEG 400 were not significantly different in smokers and non-smokers. Thus, smoking appears to tighten the gut either by effects on the paracellular junctions in the intestinal epithelium or by decreasing the permeability in the distal small bowel and the colon.

Adult↗
PubMed1989

Phospholipase activation and arachidonic acid release in cultured intestinal epithelial cells (INT 407).

The release of free arachidonic acid (AA) in cultured intestinal epithelial cells (INT 407) was investigated. INT-407 cells were first incubated overnight with radiolabeled 14C-AA, and most of the incorporated 14C-AA esterified into phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol. Labeled cells were then exposed to different stimulating agents and the release of free 14C-AA determined. The calcium ionophore A23187 caused a dose-dependent AA release that was preceded by a rapid uptake and a subsequent efflux of 45Ca2+. By contrast, phospholipase C from Clostridium perfringens caused a great AA release that was accompanied by an apparent uptake and a sustained intracellular accumulation of 45Ca2+. The cells alos released AA when exposed to the protein kinase C activator, 4 beta-phorbol-12-myristate-13-acetate (PMA), and this agent, like the diacylglycerol 1-oleoyl-2-acetyl-rac-glycerol, significantly potentiated the AA release caused by A23187. Not only A23187-mediated but also phospholipase C- and PMA-mediated AA release was inhibited by 4-bromophenacyl bromide, a known phospholipase A2 inhibitor. These findings, taken together, indicate that AA release in intestinal epithelial cells can be caused by (i) Ca2+-mediated phospholipase activation, (ii) products of phospholipase C activity, and (iii) stimulation of protein kinase C. It is suggested, therefore, that AA release in intestinal epithelial cells is governed by intracellular Ca2+, protein kinase C-mediated protein phosphorylation, and activation of phospholipase A2.

Arachidonic Acid↗
PubMed1989

Abnormal intestinal permeability pattern in colonic Crohn's disease. Absorption of low molecular weight polyethylene glycols after oral or colonic load.

Intestinal permeability to different-sized polyethylene glycols in Crohn's disease of the colon was compared with that in ileal Crohn's disease and in controls without inflammatory bowel affection. The permeability was assessed both after ingestion of the marker (oral load) and after deposition in the colon during colonoscopy (colonic load). After oral load the absorption was least in the patients with colonic Crohn's disease, intermediate in ileal disease, and greatest in the controls. After colonic load, however, the values were highest in colonic Crohn's disease. The study indicated that in Crohn's disease of the colon there is abnormal permeability in apparently uninvolved proximal small intestine as well as in the colon. Since oral load tests preferentially reflect the absorptive properties of the proximal small bowel, regional tests of absorption are important when the aim is to assess the permeability of the distal small intestine or the colon.

Administration, Oral↗
PubMed1989

Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia.

We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.

Acetylglucosaminidase↗
PubMed1989

Decrease in intestinal permeability to polyethylene glycol 1000 during development in the pig.

Changes in intestinal permeability during postnatal development in the pig were investigated by using different-sized polyethylene glycols in the Mr 766-1338 range (polyethylene glycol 1000) as permeability probes. Pigs of varying age, newborn (Oh), 36-45 h old and 22-28 days old, were gavage fed polyethylene glycol 1000 together with the macromolecular markers bovine serum albumin, ovalbumin or FITC-labelled dextran 70,000. The 4-h blood serum concentrations of the different markers were determined and taken as an estimate of their intestinal transmission. In the newborn pigs, high serum levels of polyethylene glycols were obtained, concomitant with high serum levels of bovine serum albumin and FITC-dextran. After intestinal macromolecular closure in the 36-45 h-old pigs, lower serum polyethylene glycol levels were found, especially of those with a Mr greater than 1100 Da. In the 22-28 days-old pigs, polyethylene glycol levels were reduced to one-tenth or less of those in the 36-45 h-old pigs, with the levels decreasing markedly with increasing molecular size. These results show that there is a correlation between the intestinal permeability of polyethylene glycols, especially those larger than 1100, and macromolecules in the newborn pig around intestinal closure, suggesting that such polyethylene glycols traverse the gut by the macromolecular route. During later development, further intestinal maturation results in a markedly reduced permeability to polyethylene glycol 1000.

Aging↗
PubMed1988

Characterization of size-dependent exchange of PEG molecules between the blood and extravascular space in the pig.

Different sized polyethylene glycols (PEGs) have been used as probe molecules in studies of size-dependent permeation through the intestinal wall and the glomerular membranes. We have curve-fitted a three-compartment model to the urinary recovery data following intravenous injection of different sized PEG molecules in the pig. The rate constants to and from the extravascular space demonstrate a strong size-dependent selectivity for PEG molecules less than 502 Da, but the rate constants to the urine are almost the same for all PEG molecules. This is discussed in relation to the selectivity in the glomerular filtration, distribution volume, and the use of PEG molecules as tracers in the permeability studies.

Animals↗
PubMed1988

Selenium and vitamin E treatment of Duchenne muscular dystrophy: no effect on muscle function.

16 boys with Duchenne muscular dystrophy (DMD) were treated with sodium selenite and vitamin E for one year. One group of patients (10 boys) was examined using a battery of tests to assess muscular strength and function and cardiopulmonary function, and by CT scanning of 2 muscle groups over the 4 years prior to treatment. Six boys with DMD entered the study when the treatment was begun. Tests of muscular force and function, cardiopulmonary tests and CT-scanning were performed at the onset of treatment, and after 6 and 12 months. No beneficial effect on either muscular force or function was found during the treatment period. It is concluded that selenium and vitamin E in high doses do not improve muscle function in DMD.

Adolescent↗
PubMed1988

Effects of prostaglandin E2 on disease activity, gastric secretion and intestinal permeability, and morphology in patients with rheumatoid arthritis.

The effects of oral natural prostaglandin E2 (PGE2) on symptoms, disease activity, and gastrointestinal functions in rheumatoid arthritis (RA) were studied in an open pilot trial. Twelve patients, six taking and six not taking non-steroidal anti-inflammatory drugs (NSAIDs), received 1 mg natural PGE2 three times a day for six weeks. The treatment was tolerated well and the only side effect noted was slightly looser stools in three patients. Half of the patients reported subjective improvement and none had aggravation of symptoms. The Ritchie articular index and several biochemical inflammation markers decreased and were significantly reduced at the end of the treatment period. The thickness of the small intestinal mucosa increased during the PGE2 treatment. The intestinal permeability pattern, measured by urinary excretion of polyethylene glycols (PEG 400), differed between the patients taking and not taking NSAIDs. The initially high urinary PEG 400 excretion values in the patients taking NSAIDs decreased and the initially low excretion values in patients not taking NSAIDs increased during the PGE2 treatment. The jejunal contents became sterile in 5/6 patients not taking NSAIDs and remained sterile in 1/6 patients taking NSAIDs at the end of the treatment. The treatment period was associated with a reduction of lactobacilli in patients not treated with NSAIDs. Thus the treatment appeared to decrease disease activity and to improve small intestinal functions in patients with RA, findings that need confirmation in a controlled trial.

Adult↗
PubMed1988

Intestinal permeability to polyethyleneglycol 600 in Crohn's disease. Peroperative determination in a defined segment of the small intestine.

Ileal permeability to different sized polyethyleneglycols (590-942 dalton PEG) was investigated peroperatively in 11 patients with Crohn's disease and seven with colonic carcinoma. A 15 cm ileal segment was converted into a tied loop, in which the PEG's were deposited. Absorption from the ileal segment was then measured as six-hour urinary recovery of the PEg dose. Polyethyleneglycol absorption in Crohn's disease was greater than in cancer patients and similar throughout the weight range, but in the cancer patients it was inversely proportional to molecular weight. Thus there was significantly greater absorption of the higher weights (greater than or equal to 678 dalton) in the Crohn's, than in the cancer patients. The apparently increased permeability of the small intestine in Crohn's disease may be an important factor in its pathogenesis.

Adolescent↗
PubMed1988

Phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia in rats.

The influence of various inflammatory inhibitors on the damaging effects of ischaemia in the small intestinal mucosa has been investigated. A rat experimental model was used, in which a ligated loop of the distal ileum was subjected to ischaemia and revascularisation and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. The mucosal content of malondialdehyde - a lipid peroxidation product - and its activity of myeloperoxidase - a neutrophil granulocyte marker was also determined. In the absence of inhibitor, ischaemia and revascularisation caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa and increased myeloperoxidase activity in the mucosa. All these effects were inhibited by the phospholipase A2 inhibitors, quinacrine and nordihydroguaiaretic acid (NDGA), while the lipoxygenase inhibitor, BW755C, had no influence and the cyclooxygenase inhibitor, indomethacin, potentiated the increases in mucosal permeability and N-acetyl-glucosaminidase release. BN 52021, a specific platelet activating factor antagonist, did not influence the myeloperoxidase activity, but it decreased the formation of malondialdehyde and the increases in mucosal permeability and N-acetyl-beta-glucosaminidase release, although not to the same extent as quinacrine and NDGA. These findings indicate that phospholipase A2 inhibition prevents mucosal damage associated with small intestinal ischaemia and suggest that at least part of the ischaemic damage is mediated by products of phospholipase A2 activity that are not arachidonic acid metabolites.

Acetylglucosaminidase↗
PubMed1988

Formation of 8-hydroxydeoxyguanosine by asbestos and man made mineral fibres.

Samples of rockwool and glass fibre were compared with chrysotile fibres for their capacity to hydroxylate 2-deoxyguanosine to 8-hydroxydeoxyguanosine, a reaction that is mediated by formation of hydroxyl radicals. All three fibres produced 8-hydroxydeoxyguanosine in the absence of H2O2. The chrysotile fibres were most potent and produced about ten times more of the modified nucleoside than rockwool and glass fibre. This investigation shows that not only asbestos but also man made mineral fibres are able to modify nucleosides.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1988

Increased phospholipase A2 activity of Ileal mucosa in Crohn's disease.

The activity of phospholipase A2 (EC 3.1.1.4) in endoscopic biopsy specimens of intestinal mucosa was compared in patients with Crohn's disease and controls without inflammatory bowel disease. In postresection Crohn patients there was significantly enhanced phospholipase A2 activity proximal to the anastomosis in the neoterminal ileum, whether or not the mucosa was inflamed at the time of biopsy. Highly elevated ileal phospholipase A2 activity had a predictive value for symptomatic relapse within 1 year after resection. Patients with concomitant Crohn's colitis, in whom the risk of ileal recurrence is particularly high, had greater ileal phospholipase A2 activity than noncolitis Crohn patients. Association thus was demonstrated between activity of phospholipase A2 in ileal mucosa and proneness to ileal inflammation in Crohn's disease.

Adult↗
PubMed1988

Lysophosphatidylcholine and the inflammatory action of neutrophils.

Lysophosphatidylcholine (lysoPC) is a polar lipid formed in cells and tissues under normal conditions and is known to cause tissue damage in a variety of experimental systems. We have therefore examined the possibility that increased amounts of lysoPC are formed in activated inflammatory cells and are involved in their tissue-damaging action. Human neutrophil leucocytes were labelled with [14C]arachidonic acid (AA), activated with the calcium ionophore A23187, and the degradation of phospholipids, with subsequent release of AA and AA metabolites, was studied. We also studied neutrophil metabolism of [14C]lysoPC in the presence of different concentrations of cold lysoPC, and the relation between phospholipid degradation and release of N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme. We found that the release of both AA and NAG was coupled to a degradation of phosphatidylcholine (PC), and that the neutrophils were able to metabolise lower, but not higher, concentrations of lysoPC. Moreover, the phospholipase A2 inhibitor, nordihydroguaiaretic acid significantly inhibited PC degradation, lysoPC formation, and NAG release, whereas the lipoxygenase inhibitor, BW 755C had little effect on these parameters. These findings demonstrate that the AA mobilization in activated neutrophils is associated with PC degradation, and point to be possibility that the ensuing lysoPC formation might mediate lysosomal enzyme release.

Acetylglucosaminidase↗
PubMed1988

Phospholipase activation and arachidonic acid release in isolated intestinal epithelial cells.

A novel method for studying the mobilization of free arachidonic acid (AA) in isolated intestinal epithelial cells is described. The method is based on labeling the cellular phospholipids with 14C-AA and studying the release of this 14C-AA on subsequent phospholipase activation. Cells of high viability were isolated from the small intestine of guinea pigs and incubated with 14C-AA for 2 h; most of the incorporated 14C-AA was then esterified into phosphatidylethanolamine and phosphatidylcholine. When the labeled cells were stimulated with the calcium ionophore A23187 in the presence of external calcium, they released significant amounts of AA. In contrast, the cells released no AA when stimulated with A23187 in the absence of external calcium or in the presence of chlorpromazine or 4-bromophenacyl bromide, both of which are known to inhibit phospholipase A2 activity. On the other hand, the cells released significant AA in response to exogenous phospholipase C from Clostridium perfringens. These findings indicate that AA release in intestinal cells may be caused by calcium-mediated phospholipase A2 activation or by products of microbial phospholipase C activity. They also suggest the further use of 14C-AA-labeled cells for studying agents and mechanisms that may influence the release of AA in the gastrointestinal tract.

Animals↗