PubMed Health⌕ Search

Biomedical subjects

C Tagesson

Publications and source records attributed to C Tagesson.

At least 109 records · Page 6Linked to original sources

Intestinal transmission of macromolecules (BSA and FITC-dextran) in the neonatal pig: enhancing effect of colostrum, proteins and proteinase inhibitors.

The effects of colostrum and constituents/factors in colostrum which may influence intestinal macromolecular transmission in the newborn preclosure pig were investigated. Unsuckled piglets were given, by use of a stomach tube, bovine serum albumin (BSA) and fluorescein-isothiocyanate (FITC)-labelled dextran 70,000 (FITC-D) as markers together with colostrum or the factors under study. The serum levels of BSA and FITC-D 4 h after feeding were then determined as a measure of the transfer. It was found that the two colostrums tested, bovine and especially porcine, markedly enhanced the transmission of both BSA and FITC-D. Furthermore, increasing amounts of the model proteins, BSA and bovine IgG (50-200 mg/ml), significantly increased the transfer of FITC-D, whereas unlabelled dextran 70,000 given in similar amounts did not. Proteinase inhibitors obtained from sow colostrum or soy bean also enhanced the transmission of both BSA and FITC-D while the inactive inhibitors, given as trypsin-inhibitor complexes, had no effect. On the other hand, addition of a proteinase, porcine trypsin, significantly decreased the transmission of FITC-D. These findings indicate that the intestinal transmission of macromolecules in the preclosure piglet is governed by the amount of protein available in the intestine. Therefore, feeding colostrum with a high protein content and proteinase inhibitors is likely to favour efficient intestinal transmission, although other colostrum factors may also be of importance.

Animals↗

Studies of the phospholipase A2 activity of rat ileal mucosa.

A rapid and simple procedure has been used to determine phospholipase A2 activity (EC 3.1.1.4) in rat ileal mucosa. We used 14C-oleate-labeled Escherichia coli as substrate for the phospholipase activity and a 0.45-micron Millipore filter to separate the product of hydrolysis--the 14C-oleic acid--from the unhydrolyzed substrate. The phospholipase A2 activity was optimal at pH 9.8 and at 2 mM Ca2+, but another peak of activity appeared at pH 7.2. In addition, cell fractionation revealed yet another phospholipase A2 activity at pH 5.0 in the absence of Ca2+. These findings suggest the presence of more than one phospholipase A2 in the ileal mucosa and points to the possible use of a simple procedure for studying their distribution and properties.

Animals↗

Ineffectiveness of vitamin A therapy in severe Crohn's disease.

In Crohn's disease there are changes in the ultrastructure of the intestinal epithelium, not only in the inflammatory tissue but also in non-ulcerated areas and in non-involved resection margins. Vitamin A is known to influence the metabolism and differentiation of epithelial tissue and has also been reported to normalize the number of stools after ileocaecal resection for Crohn's disease. We gave vitamin A (150 000 U daily) for 2 weeks to 8 patients with severe but not acute Crohn's disease. Various clinical parameters and the mucosal permeability to different-sized polyethyleneglycols were investigated before and after the administration of vitamin A. Disappointingly, no patient derived any benefit from the vitamin A ingestion as regards subjective manifestations, clinical signs, or mucosal permeability. However, some patients with Crohn's disease have low plasma concentrations of vitamin A and should be offered replacement therapy.

Administration, Oral↗

Influence of surface-active food additives on the integrity and permeability of rat intestinal mucosa.

The influence of two surface-active food additives on the integrity and permeability of rat ileal mucosa has been studied. We determined the activity of N-acetyl-beta-glucosaminidase, a lysosomal enzyme, in the rat intestinal lumen after deposition of polyoxyethylene (20) sorbitan monostearate (polysorbate 60; Tween 60) or polyoxyethylene (20) sorbitan monooleate (polysorbate 80; Tween 80) in a section of ligated, cannulated gut. We also determined the activities of N-acetyl-beta-glucosaminidase, alkaline phosphatase, 5'-nucleotidase and phospholipase A2 in mixtures of isolated mucosal cells and polysorbate 60 or polysorbate 80. The activity of N-acetyl-beta-glucosaminidase was increased in the luminal contents of the cannulated gut 15 min after deposition of either polysorbate 60 or polysorbate 80 (10 mg/ml fluid instilled into gut). It was also increased in mixtures of mucosal cells and polysorbate 60 or polysorbate 80 (0.1-10 mg/ml). In contrast, the activities of alkaline phosphatase and 5'-nucleotidase were unaffected and that of phospholipase A2 was decreased by the presence of either polysorbate. These findings indicated that polysorbate 60 and polysorbate 80 released lysosomal enzymes from the intestinal mucosal cells and that these agents might damage the intestinal mucosa and increase its permeability. We therefore determined the intestinal permeability to sodium fluorescein in the absence and presence of polysorbate 60 or 80 and found that the permeability was slightly increased in the presence of either of the compounds at concentrations of 10 mg/ml fluid instilled into gut. It is possible therefore that surface-active food additives might impair the function of the mucosal barrier and increase the permeability of the gut to potentially toxic and pathogenic molecules.

5'-Nucleotidase↗

Intestinal permeability to polyethyleneglycol 600 in relation to macromolecular 'closure' in the neonatal pig.

The intestinal permeability of different sized molecules in the neonatal pig was investigated. Piglets of varying age (0-168 h) were given a mixture of different sized polyethyleneglycols (414-942 dalton polyethyleneglycols) together with ovalbumin and bovine serum albumin by stomach tube, and the serum concentrations were determined two hours after feeding. Considerable amounts of ovalbumin and bovine serum albumin were found in the serum of animals up to 24 hours of age, whereas very little or none at all was found in sera from older animals. By contrast, an intestinal permeability barrier to polyethyleneglycols in the 414-942 dalton range was found not only in the older animals but in all pigs investigated, including the newborn, unsuckled. In addition, the permeability barrier to polyethyleneglycols was found in a pig which was starved to prevent macromolecular closure and, therefore, absorbed considerable amounts of bovine serum albumin and ovalbumin. These findings indicate that 414-942 dalton polyethyleneglycols cross the intestinal mucosa at different rates due to size regardless of age of the animals and regardless of whether the mucosa is permeable to protein or not. This suggests that low molecular weight molecules like 414-942 dalton polyethyleneglycols and macromolecules (proteins) cross the neonatal gut wall through different routes.

Animals↗

Raised serum bile acid concentrations after occupational exposure to styrene: a possible sign of hepatotoxicity?

Fasting serum concentrations of conjugated bile acids were investigated in 23 men who had been exposed to styrene and compared with the concentrations in 60 non-exposed individuals. Eleven of the exposed subjects had raised concentrations of either cholic acid or chenodeoxycholic acid or both. There were no indications of alcohol abuse, drug intake, or undiagnosed liver disease. It is possible, therefore, that the raised bile acid concentrations were due to exposure to styrene. This would support the concept that occupational exposure to styrene may affect the liver and point to the possibility that raised serum bile acid concentrations might be a sensitive and early indicator of hepatic injury in individuals exposed to organic solvents.

Adult↗

Passage of molecules through the wall of the gastrointestinal tract. Intestinal permeability to polyethylene glycols in the 414- to 1,074-dalton range.

We describe the application of a simple and reliable experimental model for studying intestinal permeability. Swedish Landrace pigs were anesthetized and catheters put in the carotid artery, the external jugular vein, the proximal part of the duodenum, and the urinary bladder. A mixture of polyethylene glycols (PEGs) with molecular weights ranging from 414 to 1,074 daltons was then instilled into the duodenum and the urinary recovery of different-sized PEGs determined at time intervals using reversed-phase high-performance liquid chromatography. The recovery was inversely related to molecular size; after 4 h, 13.7% of the instilled amount of PEG 414 was recovered in the urine, whereas the corresponding value for PEG 1,074 was 0.34%. The presence of bile in the duodenum increased the recoveries of all PEGs: corresponding values for PEG 414 and 1,074 were then 28.3 and 0.79%, respectively. These data indicate that (i) intestinal permeability to PEGs in the 414- to 1,074-dalton range can be studied in a quantitative, yet simple way using a pig experimental model, and (ii) the presence of bile in the duodenum considerably increases the intestinal absorption of 414- to 1,074-dalton PEGs. The possibility that bile interacts with PEGs much the same as with hydrophobic and amphiphilic compounds is discussed.

Animals↗

Decreased lysophospholipase and increased phospholipase A2 activity in ileal mucosa from patients with Crohn's disease.

Lysophospholipase (EC 3.1.1.5) and phospholipase A2 (EC 3.1.1.4) were determined in ileal mucosa from patients with Crohn's disease (CD) and non-inflammatory bowel diseases ( NIBD ). In addition, the activities of alkaline phosphatase, sucrase, maltase, and lactase were determined. The lysophospholipase activity, like that of alkaline phosphatase, sucrase and maltase, was decreased in affected areas of CD, whereas the phospholipase A2 activity was rather increased. Lysophospholipase and phospholipase A2 activities in apparently unaffected mucosa from CD patients were in between those in healthy mucosa from NIBD patients and those in affected mucosa from CD patients. These findings point to the possibility that the mucosal activity of lysophospholipase, like that of other brush border enzymes, is decreased in CD. This may render the mucosa less capable to handle lysolecithin, a potentially harmful agent formed in the intestine and known to induce inflammation in a number of experimental systems.

Crohn Disease↗

Intestinal transmission of macromolecules (BSA and FITC-labelled dextrans) in the neonatal pig. Influence of age of piglet and molecular weight of markers.

The intestinal transmission of two macromolecular markers, of similar molecular weight but different susceptibility to proteolytic digestion, was investigated in the neonatal pig. Piglets of varying age (0 h-7 days old) were given a mixture of bovine serum albumin (BSA) and fluorescein-isothiocyanate labelled dextran 70,000 (FITC-D 70) by stomach tube, and the serum concentrations were determined 2 h after feeding. A high correlation between the patterns of transmission were obtained for the two marker substances (r=0.91, n=39). Furthermore, a rapid decrease in the transmission of the markers was observed during the first day of life in suckled piglets, and intestinal macromolecular closure was well developed in the piglets after 18-36 h of life. These findings indicate that 'closure' is unrelated to changes in intestinal proteolytic activity. After closure, only small amounts of the markers were transmitted to the serum. During the first day of life, great individual differences in the transmission were found between piglets. As shown by feeding different-sized FITC-D (MW = 3,000-70,000 dalton) and unconjugated FITC (MW = 389 dalton), molecules having a molecular weight greater than 3,000 daltons were excluded upon macromolecular closure. On the other hand, smaller molecules like FITC were transmitted across the intestinal barriers independent of closure.

Aging↗

Rapid and sensitive assay of human plasma phospholipase A2 activity.

Phospholipase A2 (EC 3.1.1.4) can be determined with 14C-oleate labeled E. coli as substrate and with the use of a Millipore filter to separate the product of hydrolysis, i.e. the 14C-oleic acid, from the unhydrolyzed substrate. After incubation, the enzyme-substrate mixture is simply passed through a Millipore filter; the radioactivity in the filtrate then provides a sensitive and accurate measure of phospholipase A2 activity. The procedure is rapid and simple and can be used to determine the increased plasma levels of phospholipase A2 activity that may occur in human disease states.

Adult↗

Reduced intestinal permeability to low-molecular-weight polyethyleneglycols (PEG 400) in patients with jejunoileal bypass.

The intestinal permeation and 6-hour urinary recovery of small, multisized tracers, polyethyleneglycol 400 (PEG 400), was used to characterize gut permeability in nine patients after bypass surgery for morbid obesity and in ten healthy volunteers. In the patients, who also had hyperoxaluria, the urinary recovery of ingested PEG 400 was lower than in the healthy persons (10.9 and 24.7%). The patients also showed stronger intestinal exclusion of the larger polymers within the PEG 400.

Adult↗

Passage of molecules through the wall of the gastrointestinal tract. Urinary recovery of different-sized polyethylene glycols after intravenous and intestinal deposition.

The urinary recovery of different-sized (282-1206 dalton) polyethylene glycols (PEGs) after intravenous administration was determined. Mixtures of different-sized PEGs were injected intravenously in anesthetized pigs, and the urinary recovery at different times was determined by means of reversed-phase high-performance liquid chromatography. PEGs in the 722-1206-dalton range were all recovered to the same extent, whereas the recovery of PEGs in the 282-678-dalton range was related to molecular size; that is, the smaller the molecule, the less the urinary recovery. Moreover, less was found of the 370-414-dalton PEGs than of the 678-722-dalton PEGs in the blood after intravenous injection. These findings have a bearing on the measurements of intestinal permeability to different-sized PEGs, in which absorption-molecular weight profiles are assessed by urinary recovery after oral load. Thus, if PEGs in the 282-678-dalton range are used for such measurements, the absorption-molecular weight profile should be corrected for non-intestinal, size-dependent filtration.

Animals↗

Decreased absorption of ingested unconjugated chenodeoxycholic acid in patients with Crohn's disease.

The intestinal absorption of unconjugated chenodeoxycholic acid (CDA) was studied in 27 healthy individuals and 28 patients with Crohn's disease who had undergone ileal resection. After they had taken 1 g CDA orally serum levels of bile acids were significantly lower in the patients than in the healthy individuals; the difference was apparent already 30 min after ingestion. There was no correlation between CDA absorption and recurrent disease, length of ileal resection, or number of defecations. These findings indicate that the intestinal absorption of ingested CDA in patients with Crohn's disease is decreased. Since CDA is absorbed mainly in proximal areas of the gut, these observations may indicate that proximal areas are involved in ileocolic Crohn's disease.

Adult↗

Intestinal permeability to different-sized polyethyleneglycols in patients with rheumatoid arthritis.

The intestinal permeability to polyethyleneglycols (PEGs) of varying size in patients with rheumatoid arthritis has been investigated. Permeability was determined by measuring the 6-hour urinary recovery of different-sized PEGs after oral intake of PEG 400, PEG 1000, or PEG 3000. Patients with rheumatoid arthritis excreted significantly less PEG 400 and PEG 1000 than healthy individuals, whereas the excretion of PEG 3000 was the same or even greater than in healthy individuals. These findings point to the possibility that intestinal permeability is altered in rheumatoid arthritis.

Absorption↗