| 1. |
- Berggren, S, et al.
(författare)
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Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine
- 2003
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Ingår i: Journal of Pharmacy and Pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 55:7, s. 963-972
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Tidskriftsartikel (refereegranskat)abstract
- The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum
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| 2. |
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| 3. |
- Evilevitch, Lena, et al.
(författare)
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CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs
- 2004
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 39:9, s. 886-890
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate the mechanisms by which cholecystokinin (CCK) regulates the exocrine pancreas, the role and location of CCK receptors in the pig were investigated using the CCK-B receptor antagonist YF476 and different administration routes of CCK. Methods: In 11 anaesthetized pigs, catheters were surgically implanted in the pancreatic duct for juice collection, and in the gastric arteries and jugular vein, so that infusions of CCK-33 could be directed to the duodenal/gastric, duodenal/ pancreatic or general circulations, respectively. Experiments were performed under control conditions, and after pretreatment by gavage feeding with YF476, using either a single, low dose of 0.3 mumol kg(-1), which would block the CCK-B receptors, or a 1000 times higher dose (300 mumol kg(-1)), which would also block the CCK-A receptors. Results: The increase in the pancreatic output of protein and the enzymes trypsin and amylase observed after the infusion of CCK-33 at 13 pmol kg(-1) to the duodenum/stomach or duodenum/pancreas was inhibited by pretreatment with YF476 at both dosages. In contrast, the increase in protein and enzyme output after the infusion of a supraphysiological dose of CCK-33 (130 pmol kg(-1)) to the general circulation was not affected by pretreatment with low dosage YF476, whereas high dosage YF476 completely inhibited the stimulated secretion. Conclusions: These data indicate that CCK-33 given locally to the duodenum in doses raising CCK to physiological plasma levels stimulates the pancreatic enzyme secretion via duodenal CCK-B receptors. Supra-physiological doses of CCK-33 to the general circulation appeared to affect the pancreatic enzyme secretion via CCK-A receptors located elsewhere than in the pancreatic and duodenal tissue.
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| 4. |
- Evilevitch, Lena, et al.
(författare)
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CCK regulates pancreatic enzyme secretion via short duodenal-pancreatic reflexes in pigs
- 2003
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 38:2, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different routes of administration of CCK-33 and blockage of CCK-A and muscarinic (m(3)) receptors are used in this study to evaluate the mechanisms by which cholecystokinin can stimulate the exocrine pancreas. Methods: The experiment was performed on eight anaesthetized pigs during control conditions and after administration of the CCK-A and m(3) receptor antagonists, Tarazepide and 4-DAMP, respectively. Catheters were surgically implanted in the pancreatic duct for juice collection and in the gastric and right gastro-epipoic arteries and in the jugular vein, so that infusions of CCK-33 could be made exclusively to the duodenum/stomach, duodenum/pancreas or general circulation, respectively. Results: Infusion of a low dose of CCK-33 (13 pmol kg(-1)) to the general circulation did not affect pancreatic protein or trypsin output. When the same dose was given directly to the duodenum/stomach or the duodenum/pancreas, pancreatic output increased during both control conditions and after Tarazepide and/or 4-DAMP treatment, though the increase in trypsin Output was lower after Tarazepide and/or 4-DAMP blockade. A high dose of CCK-33 (130 pmol kg(-1)) given peripherally stimulated the pancreatic secretion, but this response was totally abolished in Tarazepide and 4-Damp treated animals. Conclusions: Pancreatic enzyme secretion due to CCK-33 stimulation depends on the presence of short duodenal-pancreatic peptidergic reflexes evoked mainly via low sensitive, probably CCK-B, receptors located in the duodenum/stomach. Pancreatic secretion evoked by peripheral CCK-33 in pharmacological doses was independent Of m(3) receptors blockade but depended on CCK-A receptors located elsewhere than in the duodenum/pancreas.
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| 5. |
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| 6. |
- Kruszewska, Danuta, et al.
(författare)
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Enteral crude red kidney bean (Phaseolus vulgaris) lectin--phytohemagglutinin--induces maturational changes in the enterocyte membrane proteins of suckling rats.
- 2003
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Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 84:2, s. 152-158
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the effect of enterally administered crude red kidney bean (Phaseolus vulgaris) lectin, PHA, on the expression of brush-border membrane vesicle (BBMV) proteins, in particular Na+/H+ exchangers (NHEs), in the small intestine of suckling rats. Gavage of PHA to 14-day-old rats for 3 days resulted in altered protein/glycoprotein patterns as analyzed by SDS-PAGE. Immunoblots demonstrated the appearance of two 71- and 27-kD protein bands indicative for NHE3 - one of the NHE isoforms - and PHA, respectively. PHA treatment also resulted in an augmented uptake of 22Na+ by the BBMV indicating an increase in NHE activity. Overall, the data suggests that enteral PHA exposure may induce maturational changes in enterocyte membrane proteins in young rats. In view of these findings, an investigation into the addition of PHA to infant formulas and weaning diets is warranted.
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| 7. |
- Mangell, Peter, et al.
(författare)
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Lactobacillus plantarum 299v inhibits Escherichia coli-induced intestinal permeability.
- 2002
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Ingår i: Digestive Diseases and Sciences. - 1573-2568. ; 47:3, s. 511-516
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work was to investigate whether a probiotic bacterium, Lactobacillus plantarum 299v, could affect Escherichia coli-induced passage of mannitol across the intestinal wall. Sprague-Dawley rats were pretreated for one week by either tube feeding with L. plantarum 299v twice daily, free access to L. plantarum 299v by adding the bacterium in the drinking water, or negative control receiving regular feeding. Intestinal segments were mounted in Ussing chambers and the mucosa was exposed to control medium, E. coli, and L. plantarum 299v (alone or together). [14C]Mannitol was added as a marker of intestinal permeability and samples were taken from the serosal side. E. coli exposure induced a 53% increase in mannitol passage across the intestinal wall (P < 0.05). One week of pretreatment with L. plantarum 299v in the drinking water abolished the E. coli-induced increase in permeability. Tube feeding for one week or short-term addition of L. plantarum 299v in the Ussing chambers had no effect on the permeability provoked by E. coli challenge. Notably, L. plantanum 299v itself did not change the intestinal passage of mannitol. These data demonstrate that pretreatment with L. plantarum 299v, which is a probiotic bacterium, protects against E. coli-induced increase in intestinal permeability, and that L. plantarum 299v alone has no influence on the intestinal permeability. Thus, this study supports the concept that probiotics may exert beneficial effects in the gastrointestinal tract.
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| 8. |
- Nejdfors, P, et al.
(författare)
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Intestinal permeability in humans is increased after radiation therapy
- 2000
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706. ; 43:11, s. 1582-1587
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Irradiation inflicts acute injuries to the intestinal mucosa with rapid apoptosis induction and subsequent reduction in epithelial surface area. It may therefore be assumed that the intestinal barrier function is affected. The aim of this study was to compare the mucosal permeability in irradiated rectum and nonirradiated sigmoid colon from patients subjected to radiation therapy before surgical treatment for rectal cancer. METHODS: Segments from sigmoid colon and rectum obtained from irradiated and nonirradiated patients were stripped from the serosa-muscle layer and mounted in Ussing diffusion chambers. The mucosa-to-serosa passage of the marker molecules 14C-mannitol, fluorescein isothiocyanate-dextran 4,400, and ovalbumin was followed for 120 minutes. RESULTS: The permeability to the markers was size-dependent and increased linearly across time in all specimens. The passage of all markers was increased in irradiated rectum compared with nonirradiated sigmoid colon, whereas in specimens from nonirradiated patients there were no differences between rectum and sigmoid colon. Histologic signs of crypt and mucosal atrophy were found in the irradiated rectal specimens. CONCLUSIONS: Early gastrointestinal complications after radiation therapy may be the result of mucosal atrophy in addition to mucosal damage, with a loss of barrier integrity.
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| 9. |
- Nejdfors, P, et al.
(författare)
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Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man: species- and region-related differences
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 35:5, s. 501-507
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The barrier properties of the gastrointestinal mucosa may be studied by measuring its permeability to different-sized marker molecules. Owing to difficulties in obtaining human tissue it is, however, often necessary to extrapolate findings from experimental animals to man. The aim of the present study was to compare regional intestinal mucosal permeability in man, the rat, and the pig, using the same marker molecules and in vitro technique. METHODS: Segments from jejunum, ileum, colon, and rectum were mounted in Ussing diffusion chambers, and the mucosa-to-serosa passage of 14C-mannitol, fluorescein isothiocyanate (FITC)-dextran 4,400, alpha-lactalbumin, ovalbumin, and FITC-dextran 70,000 was studied. RESULTS: Irrespective of species or intestinal region an inverse relationship between the molecular weight of the markers and the permeability was seen. The mannitol permeability was higher in the small intestine than in the colon in man, whereas the rat showed a higher permeability in the ileum than in the jejunum and colon. The FITC-dextran 4,400 permeability was higher in all intestinal regions in the rat than in man and the pig. The macromolecules showed low permeability with no regional differences. CONCLUSIONS: The results showed differences between intestinal regions and between species. Permeability data from the pig correlated fairly well with those of man, whereas the rat differed, making it difficult to extrapolate from the rat to man.
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| 10. |
- Pluske, JR, et al.
(författare)
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Age, sex, and weight at weaning influence organ weight and gastrointestinal development of weanling pigs
- 2003
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Ingår i: Australian Journal of Agricultural Research. - 0004-9409. ; 54:5, s. 515-527
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Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to determine the interrelationships between sex, weaning age, and weaning weight on aspects of physiological and gastrointestinal development in pigs. Forty-eight Large White x Landrace pigs were used in a factorial arrangement with the respective factors being: age at weaning ( 14 or 28 days), weight at weaning ( heavy or light), sex ( boar or gilt), and time after weaning ( 1, 7, and 14 days). At weaning, 48 pigs were removed from the sow; 16 pigs were then fasted for 24 h before euthanasia for determination of organ weights, gut histology, and enzymology, and 32 pigs were offered a high quality pelleted weaner diet ad libitum for subsequent assessment of organ weights, histology, and enzymology at 7 and 14 days after weaning. On Day 6 and 13 after weaning, 2 pigs from each group had their feed removed, and 24 h later were euthanased and similar measurements were taken. In general, the data highlighted the overall gastrointestinal underdevelopment of pigs weaned at 2 weeks of age and of pigs weaned light-for-age at either 2 or 4 weeks. Heavier body organs, gastrointestinal organs, and accessory digestive organs observed after weaning, except for the spleen, presumably reflected the increase in substrates available for cellular growth as feed intake increased after weaning, and the development of organs required to process this feed. Interestingly, the relative weights (% of liveweight) of the stomach and small intestine and, to a lesser extent, the caecum and colon, were greater in the light, 14-day-old weaned pigs, but these differences diminished with increasing time after weaning. Consistent effects due to age, weight, and sex were not observed for villous height and crypt depth, or for the specific activities of the brush-border and pancreatic enzymes measured. However, increases (P < 0.001) in the activities of maltase (P < 0.001), glucoamylase ( P < 0.001), and sucrase (P = 0.020) ( all expressed per gram of mucosa), and that of trypsin ( per gram of pancreas), occurred by 14 days after weaning. This most likely reflected the inducible nature of these enzymes in response to the increasing intake of substrates provided in the diet. In contrast, the specific activity of lactase declined (P = 0.012) in the first 14 days after weaning. These data suggest that pigs weaned at 2 weeks of age and pigs weaned light-for-age at either 2 or 4 weeks have a less developed gastrointestinal tract, and that its development after weaning might proceed differently to that of pigs weaned older and heavier.
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