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Biomedical subjects

I Bjarnason

Publications and source records attributed to I Bjarnason.

At least 145 records · Page 8Linked to original sources
PubMed1986

The subcellular distribution and levels of calmodulin in jejunal biopsies from control subjects and patients with coeliac disease.

A radioimmunoassay has been established and validated for the estimation of calmodulin levels in human peroral jejunal biopsy samples. Total levels were similar in biopsies from control subjects and patients with coeliac disease, both in relapse and remission. The subcellular distribution of calmodulin was determined in biopsy samples from control subjects and a patient with coeliac disease in relapse by rapid single-step analytical subcellular fractionation and immunoassay. In both situations most (greater than 70%) of the calmodulin was recovered in the cytosolic fractions with no selective enrichment in any single organelle.

Adult↗
PubMed1986

Lactulose, 51Cr-labelled ethylenediaminetetra-acetate, L-rhamnose and polyethyleneglycol 400 [corrected] as probe markers for assessment in vivo of human intestinal permeability.

The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), L-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for L-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of L-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress. The 5 h permeation of lactulose, but not of L-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P less than 0.001). These findings are compatible with three distinct pathways of unmediated mucosal permeation, L-rhamnose (radius less than 0.4 nm) passing mainly through small aqueous 'pores' of high incidence, lactulose and 51Cr-EDTA (radius greater than 0.5 nm) through larger aqueous 'channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous 'pores'.

Cell Membrane Permeability↗
PubMed1986

Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.

Intestinal permeability was estimated in healthy subjects after ingestion of aspirin (1.2+1.2 g), ibuprofen (400+400 mg) and indomethacin (75+50 mg) at midnight and an hour before starting a 51chromium labelled ethylenediaminetetraacetate absorption test. Intestinal permeability increased significantly from control levels following each drug and the effect was related to drug potency to inhibit cyclooxygenase. Intestinal permeability increased to a similar extent after oral and rectal administration of indomethacin showing that the effect is systemically mediated. Prostaglandin E2 decreased intestinal permeability significantly but failed to prevent the indomethacin induced increased intestinal permeability. These studies show that non-steroidal anti-inflammatory drugs disrupt the intestinal barrier function in man and suggest that the morphological correlates of the damage may reside at the level of the intercellular junctions.

Adult↗
PubMed1986

Effect of non-steroidal anti-inflammatory drugs on the human small intestine.

The suggestion that the intestinal mucosa may be abnormally permeable and thus a site of antigen absorption in rheumatoid arthritis was tested by a 51Cr EDTA intestinal permeability test. Twelve patients with rheumatoid arthritis untreated by non-steroidal anti-inflammatory drugs (NSAIDs) had normal test results, while 12 NSAID-treated patients had increased intestinal permeability. Ten volunteers ingested aspirin, ibuprofen and indomethacin 8 and 1 hours before the study. The increased intestinal permeability was proportional to drug potency to inhibit cyclo-oxygenase. Intestinal permeability also increased following an indomethacin suppository, which suggests that the effect is systemically mediated. 111Indium leucocyte scintigrams and faecal collection showed no evidence of intestinal inflammation in 9 patients untreated by NSAIDs. Twenty-nine of 53 NSAID-treated patients showed abnormal localisation of 111indium in the right iliac fossa at 20 hours, and 32 of 49 patients had increased faecal excretion of 111indium. A 99mTc-porphyrin scan suggested that the main site of NSAID-induced intestinal inflammation was the small bowel. NSAIDs are thus shown to disrupt intestinal integrity and long term treatment leads to inflammation of the small intestine.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Rat gastrointestinal transglutaminase: demonstration of enzyme activity and cell and tissue distributions.

The properties, tissue and cellular distribution of intestinal transglutaminase have been investigated. Transglutaminase was assayed with dimethylcasein and [14C]putrescine as substrates. The enzyme has maximum activity at pH 10, although more reliable assays are made at pH 9. Transglutaminase showed an absolute requirement for Ca2+ and exhibited linear assay kinetics. The Km for putrescine was approx. 0.15 mmol/l. Tissue distribution studies suggest transglutaminase is more active in the more muscular segments of the gut. The cellular localization in jejunum was investigated by sequential cell release techniques. Approximately 2 per cent of the total activity was found in the enterocytes and crypt cells. Most of the activity was in the submucosa and serosa suggesting an interstitial cell localization. Acute hypoplastic enteropathy induced by methotrexate was accompanied by a striking decrease in mucosal transglutaminase but the activity returned to control values by 72 h. There was no significant increase in activity during the period of intense crypt cell hyperplasia and it is concluded that intestinal transglutaminase is not implicated in crypt cell proliferation.

Animals↗
PubMed1985

Human jejunal transglutaminase: demonstration of activity, enzyme kinetics and substrate specificity with special relation to gliadin and coeliac disease.

By use of a radiometric assay transglutaminase activity was demonstrated for the first time in human jejunal mucosa. The activity is similar to that in other tissues, with a pH optimum of 9.0, an absolute requirement for Ca2+ and an apparent Km for putrescine of 0.15 mmol/l. Assay of jejunal transglutaminase activity with a variety of dietary proteins as acceptors showed high activity with gliadin, comparable with that of the standard substrate, dimethylcasein. Deamidation of the gliadin markedly reduced its acceptor activity. Collagen, ovalbumin, elastin and zein exhibited very low acceptor activities. Increased transglutaminase activity was demonstrated in jejunal biopsies from four patients with untreated coeliac disease compared with 14 control subjects and eight patients with inflammatory bowel disease. Eight patients with coeliac disease in remission, with normal levels of brush border alpha-glucosidase, showed elevated transglutaminase activities compared with those of controls. It is postulated that intestinal transglutaminase activity may be important in gliadin binding to tissues and thus in the pathogenesis of coeliac disease.

Acyltransferases↗
PubMed1985

Intestinal permeability in patients with atopic eczema.

Intestinal permeability was investigated in adult patients with atopic eczema by in vivo and in vitro techniques. Patients with symptoms of 'immediate' food allergy were specifically excluded. A 51Cr-labelled ethylenediaminetetraacetate absorption test was carried out in eighteen patients. Their mean (+/- s.d.) 24-hour urine excretion following oral administration of the test substance (2.1 +/- 0.9%) did not differ significantly from that of thirty-four normal controls (1.9 +/- 0.5%). Small bowel permeability was estimated directly in jejunal mucosal samples in ten patients with three permeability probes of differing molecular weight. Mucosal permeability did not differ significantly from that of fifteen control patients for any of the test substances. Two patients had abnormal results by both tests and in one this was due to coeliac disease. These results suggest that altered intestinal permeability is not important in the pathogenesis of eczema. Patients demonstrating increased intestinal permeability should undergo jejunal biopsy to exclude significant small bowel disease.

Adolescent↗
PubMed1985

Intestinal permeability in patients with coeliac disease and dermatitis herpetiformis.

Intestinal permeability was investigated in patients with coeliac disease and dermatitis herpetiformis by a 51Chromium-labelled ethylenediaminetetraacetate (51Cr-EDTA) absorption test and the results correlated with histomorphometric analysis and intraepithelial lymphocyte counts of jejunal biopsies. The mean (+/- SD) 24 hour urine excretion of 51Cr-EDTA in 34 healthy volunteers was 1.9 +/- 0.5% of the orally administered test dose. Patients with untreated coeliac disease (19) or untreated dermatitis herpetiformis (five) excreted significantly more 51Cr-EDTA than controls (5.9 +/- 2.7% and 4.6 +/- 2.1%, respectively, p less than 0.001) and all were outside the normal range of 1.0-2.6%. Patients with coeliac disease (42) treated for 6 months-23 years (mean 5 years) and patients with dermatitis herpetiformis (11) treated for 6 months-8 years (mean 3 years) excreted significantly more 51Cr-EDTA than controls, 4.2 +/- 2.4% p less than 0.0001 and 3.0 +/- 0.9% p less than 0.003 respectively. Eleven of 14 (79%) treated patients with coeliac disease with an entirely normal jejunal mucosae demonstrated abnormal intestinal permeability. Intestinal permeability did not correlate significantly with either the mucosal height/crypt depth ratio or intraepithelial lymphocyte counts in jejunal biopsies from patients with untreated or treated coeliac disease. The demonstration of a persistent increase in intestinal permeability in patients with both coeliac disease and dermatitis herpetiformis may suggest a common pathogenetic mechanism in both disorders. It is postulated that altered permeability may facilitate the entry of gluten or a fraction thereof into the lamina propria where it causes a cascade of immunological events.

Adolescent↗
PubMed1985

Intestinal permeability to 51Cr-EDTA in rats with experimentally induced enteropathy.

Intestinal permeability has been investigated in the normal rat by measuring the five hour urine excretion of 51Cr-EDTA after intragastric administration. Twelve control animals excreted 2.06% +/- 0.22 (mean +/- SE) of the administered dose. Prolonged intestinal transit times with atropine had no significant effect on the apparent permeability with a urine excretion 2.31% +/- 0.36. The concomitant administration of a hypertonic, but rapidly absorbed glycerol solution, was accompanied by increased urinary excretion (3.05% +/- 0.33) while the administration of a poorly absorbed sugar, lactulose, significantly decreased the apparent permeability (urine excretion 0.61% +/- 0.14) showing that passive intestinal permeability estimations are affected by test dose composition. Enteropathy was induced by ethanol, cetrimide, or methotrexate and each was associated with increased permeability, with urine excretions of 4.19% +/- 0.47, 4.20% +/- 0.66 and 3.97% +/- 0.49 respectively. It is thus suggested that the normal rat mucosa is maximally resistant to the absorption of foreign compounds such as 51Cr-EDTA and intestinal damage will disrupt this barrier.

Animals↗
PubMed1984

Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal anti-inflammatory drugs.

The suggestion that the intestinal mucosa may be abnormally permeable and a site of absorption of antigens in rheumatoid arthritis was tested by the use of a 51Cr-EDTA (edetic acid) absorption test. 24 patients with rheumatoid arthritis excreted significantly more 51Cr-EDTA than did 34 controls. Intestinal permeability was normal in untreated patients but almost invariably abnormal in patients treated with non-steroidal anti-inflammatory drugs. Studies in patients with osteoarthritis showed that the permeability abnormalities were due to an effect of NSAIDs on both the proximal and the distal intestine and that the effect was systemically mediated. Indium-111-labelled leucocyte scans showed ileocaecal inflammation in 6 of 9 patients on or recently on NSAIDs. Although increased intestinal permeability does not seem to be important in the pathogenesis of rheumatoid arthritis, the administration of NSAIDs may lead to loss of intestinal integrity, thus facilitating antigenic absorption and perhaps contributing to persistence of the disease.

Anti-Inflammatory Agents↗
PubMed1984

The leaky gut of alcoholism: possible route of entry for toxic compounds.

Intestinal permeability was investigated with a chromium-51-EDTA (edetic acid) absorption test in 36 non-intoxicated alcoholic patients without liver cirrhosis or overt clinical evidence of malabsorption or malnutrition. Patients abstaining from alcohol for less than 4 days almost invariably had higher intestinal permeability than controls, and in many the abnormality persisted for up to 2 weeks after cessation of drinking. The presence of gastritis did not correlate with the presence of increased permeability. The site of altered intestinal permeability was shown by an in-vitro permeability test to be the small bowel. The increased intestinal permeability to toxic "non-absorbable" compounds of less than 5000 molecular weight may account for some of the extraintestinal tissue damage common in alcoholic patients.

Alcoholism↗
PubMed1984

In vitro determination of small intestinal permeability: demonstration of a persistent defect in patients with coeliac disease.

Previous methods for measuring intestinal permeability involve the urinary measurements of various poorly digested sugar or inert poly(ethylene glycol) polymers after their oral administration. The results reflect a variety of gastrointestinal parameters including transit time, mucosal surface area and transfer, mesenteric blood and/or lymphatic flow and renal function, as well as mucosal permeability. A new in vitro method for direct measurements of mucosal permeability to three probes is described and permeability is shown to be inversely related to the molecular weight of the probe molecule. Using this technique, a persistent increase in mucosal permeability to certain probes (molecular weight less than 1500 daltons) has been shown in patients with coeliac disease in whom treatment by strict gluten withdrawal has been accompanied by restoration of intestinal histological normality. It is suggested that this finding represents a primary defect in this syndrome.

Adolescent↗
PubMed1984

Giant lymph node hyperplasia (Castleman's disease) of the mesentery. Observations on the associated anemia.

A mesenteric mass, histologically characterized as giant lymph node hyperplasia was found in an 18-yr-old man with at least 11 yr of growth retardation and anemia. The anemia was characterized by iron deficiency from selective malabsorption of iron, and by features of the anemia of chronic disorders. In contrast with a previous report, no inhibitor of erythropoietin was found and there was no abnormality of erythropoietin secretion. Resection of the mass was followed by rapid correction of the anemia and catch-up growth. The mass had histologic features of the hyaline vascular and plasma cell types of Castleman's disease with multinucleate giant cells probably of macrophage origin. Immunologic studies of the mass showed that the B lymphocytes were polyclonal and the T lymphocyte helper/suppressor cell ratio was normal, suggesting that giant lymph node hyperplasia is a local inflammatory reaction.

Adolescent↗