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Biomedical subjects

P Leandersson

Publications and source records attributed to P Leandersson.

5 recordsLinked to original sources

Biliary excretion of different sized polyethylene glycols in the cat.

Polyethylene glycol (PEG) 900 is excreted more extensively into bile than mannitol and erythritol. In this study, the biliary recovery of intravenously injected marker molecules was analysed in anaesthetised cats with ligated renal pedicles. It was demonstrated that among polyethylene glycols sized 292-1250 Da, the species sized 1074 Da was maximally excreted in the bile. After 5 h, about 12% of the injected amount of this molecular species was recovered in bile. Both larger and smaller polyethylene glycol molecules had a lower biliary excretion. The distribution of different sized PEGs in the range 766-1250 Da in serum was fairly constant and cannot explain the recovery profile in bile. 14C-Labelled mannitol was recovered in bile to the extent of 0.7% of the amount given i.v. after 5 h, a figure that corresponds to that obtained for polyethylene glycol with a size of 370 Da. Bile/plasma ratios during steady state conditions of labelled PEG 450, PEG 900, PEG 2500 and PEG 4000 were 10, 36, 3 and 4, respectively. The results may be tentatively explained by restricted passage of the larger PEG molecules into the canaliculi, and leakage of the smaller molecules from bile back to plasma.

Animals

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

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

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

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