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Sökning: WFRF:(Weström Björn)

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  • Arévalo Sureda, Ester, et al. (författare)
  • Early effects on the intestinal barrier and pancreatic function after enteral stimulation with protease or kidney bean lectin in neonatal rats
  • 2018
  • Ingår i: British Journal of Nutrition. - Cambridge University Press. - 1475-2662. ; 119:9, s. 992-1002
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut maturation naturally accelerates at weaning in altricial mammalian species, such as the rat. Mimicking this, gut development can also be induced precociously, 3–4 d earlier than it would occur naturally, by enteral exposure to phytohaemagglutinin (PHA), or various proteases. We investigated the early effects of gut provocation on intestinal barrier and pancreatic functions, to get a better understanding of the mechanisms that initiate gut maturation. The effects of oral administration of protease (trypsin) or PHA to 14-d-old suckling rats were studied during 24 h in comparison with water-fed controls. Intestinal in vivo permeability was assessed by oral administration of different-sized marker molecules and measuring their passage into the blood or urine 3 h later. A period of 24 h following oral administration, both PHA and protease provocation stimulated small intestinal (SI) growth and pancreatic secretion, as indicated by decreased pancreatic trypsin and increased luminal enzyme content. Within 1 h of oral administration, both treatments prevented the absorption of macromolecules to blood that was observed in controls. PHA treatment hindered the passage of fluorescein isothiocyanate-dextran (FD) 4 to blood, whereas protease treatment temporarily increased plasma levels of FD4, and the urine lactulose:mannitol ratio, indicating increased intestinal leakiness. Following protease treatment, fluorescence microscopy showed decreased vesicular uptake of FD70 in the proximal SI and increased epithelial fluorescence in the distal SI. In conclusion, PHA and protease differed in their early effects on the intestinal barrier; both exerted a blocking effect on epithelial endocytosis, whereas protease treatment alone temporarily increased epithelial leakiness, which seemed to be confined to the distal SI.
  • Arévalo Sureda, Ester, et al. (författare)
  • Maturation of the intestinal epithelial barrier in neonatal rats coincides with decreased FcRn expression, replacement of vacuolated enterocytes and changed Blimp-1 expression
  • 2016
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The intestinal barrier is immature in newborn mammals allowing for transfer of bioactive macromolecules, e.g. protecting antibodies, from mother's milk to the blood circulation and in neonatal rodents lasts until weaning. This passage involves the neonatal-Fc-receptor (FcRn) binding IgG in the proximal and highly endocytic vacuolated enterocytes in the distal immature small intestine (SI). Recent studies have suggested an involvement of the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) in the regulation of SI maturation in mice. Hence, the objective of the present study was to monitor the development of the intestinal barrier function, in relation to Blimp-1 expression during both natural and precociously induced intestinal maturation in rats. Results: During the suckling period IgG plasma levels increased, while after gut closure it temporarily decreased. This corresponded to a high expression of FcRn in the proximal SI epithelium and the presence of vacuolated enterocytes in the distal SI. The immature foetal-type epithelium was replaced after weaning or induced precocious maturation, by an adult-type epithelium with FcRnneg cells in the proximal and by non-vacuolated enterocytes in the distal SI. In parallel to this epithelial shift, Blimp-1 expression decreased in the distal SI. Conclusion: The switch from foetal- to adult-type epithelium, with decreased proximal expression of FcRn and distal replacement of vacuolated enterocytes, was concurrent in the two SI regions and could be used for monitoring SI maturation in the rat. The changes in expression of Blimp-1 in the distal SI epithelium followed the maturation pattern.
  • Axelsson, Jakob B, et al. (författare)
  • Initiation of acute pancreatitis by heparan sulphate in the rat.
  • 2008
  • Ingår i: Scandinavian Journal of Gastroenterology. - Taylor & Francis. - 1502-7708. ; 43:4, s. 480-489
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The initiating events in the onset of pancreatitis are poorly understood. Possible candidates may be endogenous ligands, acting on receptors within ductal, acinar or stellate cells, which have previously been shown to cause a systemic inflammatory response syndrome. The aim of this study was to investigate whether acute pancreatitis could be induced by heparan sulphate (HS)infused into the pancreatic ducts in the rat. MATERIAL AND METHODS: Retrograde biliary-pancreatic infusion of heparan sulphate of different structures, taurodeoxycholate (TDC) or phosphate buffered saline (PBS) was performed. Local pancreatic inflammation was evaluated after 6 h by means of morphological evaluation, neutrophil and macrophage infiltration and levels of plasma amylase. Systemic inflammation was evaluated by measuring plasma IL-6, MCP-1 and CINC-1 concentrations. RESULTS: Heparan sulphate induced a local inflammatory response visualized as a rapid infiltration of neutrophils and macrophages into the pancreas. Heparan sulphate induced inflammation and oedema without causing damage to acinar cells, as measured by morphological changes and plasma amylase concentrations. Furthermore, an increase in serum concentrations of CINC-1 and IL-6 was seen. The positive control (TDC) had increased levels of all variables analysed and the negative control (heparan sulphate administered intraperitoneally) was without effects. CONCLUSIONS: Our findings suggest a receptor-mediated innate immune response of the pancreatic cells induced by heparan sulphate. This finding may be helpful in elucidating some of the mechanisms involved during the initiation of pancreatitis, as well as in the search for a potential future therapeutic application.
  • Axelsson, Jakob B, et al. (författare)
  • Intestinal bacteria and permeability during experimental acute pancreatitis in rats
  • 2006
  • Ingår i: Annals of Gastroenterology. - Hellenic Society of Gastroenterology. - 1108-7471. ; 19:3, s. 276-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An increase in intestinal permeability and subsequent bacterial translocation has been demonstrated in critical illness. Cellulose derivatives have in the past been shown to reduce gut leakage following liver resection. Aims: The aim of the present study was to evaluate changes in microbial counts in experimental acute pancreatitis and the effect of pre-treatment with cellulose derivatives and N-acetyl cysteine. Subjects: 92 male Sprague Dawley rats. Methods: Acute pancreatitis was induced by intraductal taurodeoxycholic acid infusion. Animals received oral pretreatment and were randomized to either sham operation or the pancreatitis groups, with or without pre-treatment with cellulose derivatives, the antioxidant or their combinations. Intestinal bacterial populations and permeability were evaluated using bacterial counts and Ussing chamber, respectively. Results: The number of E. coli increased in the luminal content and ileal and colonic mucosa, but levels were restored to almost those seen in controls in all pre-treatment groups except for N-acetyl cysteine. When intestinal permeability was measured, none of the treatment groups showed significant differences compared to challenge, except for Nacetyl cysteine, which significantly increased permeability. Conclusion: Pre-treatment with cellulose derivatives was more efficient against disturbances in intestinal permeability and microbial populations than the antioxidant Nacetyl cysteine.
  • Berggren, S, et al. (författare)
  • Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine
  • 2003
  • Ingår i: Journal of Pharmacy and Pharmacology. - Pharmaceutical Press. - 0022-3573. ; 55:7, s. 963-972
  • 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 <ileum<colon. Ropivacaine was not found to be subjected to any carrier-mediated intestinal efflux. However, the CYP3A4 metabolite left the human enterocyte in a polarized manner and both the extent of CYP3A4 metabolism of ropivacaine and the extrusion of its metabolite to the mucosal chamber were more efficient in jejunum than in ileum. P-glycoprotein was probably not involved in the metabolite extrusion. No other metabolite than PPX was found. This in-vitro study with human intestinal tissues provides new mechanistic insights into regional transport and metabolism of drugs.
  • Carlsson, Anders, 1980- (författare)
  • Role of mast cells and probiotics in the regulation of intestinal barrier function
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicles. The epithelium covering the Peyer’s patches is called follicle-associated epithelium and is specialized in antigen sampling and uptake. The special epithelium enables presentation of luminal antigen to immune cells in the underlying follicle.</p><p>Persistent life stress and stressful life events affect the course of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) through largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immune-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis and Crohns disease. Vasoactive intestinal polypeptide (VIP) and corticotropin-releasing factor have been implicated as important mediators of stress-induced abnormalities in intestinal mucosal functions in animal models. Both of these mediators have been reported to regulate bowel ion secretion in humans during stress and uptake of horseradish peroxidase in rodents. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated.</p><p>The aim of this thesis was to elucidate whether mast cells play an important role in intestinal barrier function during stress and inflammation. Moreover, we wanted to determine whether probiotics can ameliorate the mucosal barrier integrity during stress and inflammation.</p><p>To study the function of mast cells we conducted in vitro experiments on cell lines and ex vivo experiments in Ussing chambers on mouse, rat and human intestinal tissue. The Ussing chamber technique measures electrophysiological properties of the tissue and also gives the possibility to study transcellular and paracellular passage of markers and bacteria. Immunohistology and confocal microscopy have been used to identify mast cells and receptors of interest.</p><p>Our results show that stress affects the follicle-associated epithelium barrier by mechanisms involving VIP and mast cells. These findings were corroborated by the localization of VIP receptors on mucosal mast cells. Furthermore, pretreatment with probiotics was effective in protecting the gut against stress-induced intestinal barrier dysfunction and mucosal inflammation. This protection appeared to involve a mast cell and peroxisome proliferatoractivated receptor-γ dependent mechanism.</p>
  • Donaldson, J, et al. (författare)
  • The effectiveness of enzymatic replacement therapy measured by turbidimetry and the lipaemic index in exocrine pancreatic insufficient young, growing pigs, fed a high-fat diet.
  • 2009
  • Ingår i: Advances in Medical Sciences. - Versita. - 1898-4402. ; 54:1, s. 7-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Conventionally, the management of exocrine pancreatic insufficiency (EPI) involves the consumption of a specific diet as well as the replacement of pancreatic enzymes, the effectiveness of which is usually measured by a classical method of blood analyses of non-esterified fatty acids (NEFA) and triglycerides (TG). Dietary supplementation with a pancreatic enzyme preparation (PEP), in conjunction with a high-fat diet, on growth performance, digestibility and absorption (analysed using turbidimetry) of dietary fat in pigs with EPI was investigated.Materials/Methods: EPI was developed by surgical ligation of the pancreatic duct of six male pigs, 6 weeks of age. The pigs were fed a high fat diet (twice daily). A PEP containing 1800 mg entero-coated pancreatin was included in the high fat meals. Blood, urine and faecal samples were collected. The urine and faeces were analysed for dry matter, crude protein and fat content. The lipaemic index and plasma lipid profiles were assessed.Results: EPI completely stopped growth of the pigs. Treatment with PEP significantly increased (P<0.05) growth and body mass as well as the digestibility of dry matter and crude protein. PEP significantly improved the co-efficient of fat absorption, the lipaemic index (measured by turbidimetry methods) and caused significant changes in plasma nonesterified fatty acids and triglyceride concentrations.Conclusions: The short term enzymatic replacement therapy together with a high fat meal has immediate beneficial effects on diet digestibility and on the growth retardation observed in EPI pigs. The turbidimetry method used to measure lipaemic index is a reliable, quick and efficient technique in measuring plasma lipid profiles and thus a good tool for assessing fat absorption.
  • Edwards, M. V., et al. (författare)
  • Spray-dried porcine plasma and yeast derived protein meal influence the adaption to weaning of primiparous and multiparous sow progeny in different ways
  • 2013
  • Ingår i: Animal Production Science. - CSIRO Publishing. - 1836-5787. ; 53:1, s. 75-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Pigs from 154 litters (n = 1132, 19 +/- 3 days of age, 4.9 +/- 1.1 kg of bodyweight) were used in a 3 x 2 factorial design to evaluate two raw materials with nutraceutical properties being used in feeds, spray-dried porcine plasma (SDPP) and a yeast protein meal, and their effects on growth performance, immune parameters and gastrointestinal adaption of piglets to weaning. Factors included dietary treatments being (1) 5% SDPP (PLA), (2) 3.5% yeast protein meal (NUP) and (3) medicated control (TMC) and parity (primiparous versus multiparous). The treatment groups were imposed from Day 19 through to weaning at Day 27. Selected pigs (n = 720, 28 +/- 3 days of age, 7.4 +/- 1.0 kg of bodyweight) were weaned and remained on their respective diets from Day 28 to Day 34. From Day 35 to Day 48 all group-housed pigs were offered a commercial weaner 1 diet, and from Day 49 to Day 68 pigs were offered a commercial weaner 2 diet. Growth performance, survival, and serum immunoglobulinGwere monitored throughout the nursery phase (Day 28 to Day 68). Adaptation of the gastrointestinal tract in the acute post-weaning phase (Day 28 to Day 34) was assessed in 36 individually housed male weaners, with the effects of feed on structural, digestive, microbial and immune parameters along the gastrointestinal tract determined atDay 34. Pre-weaning feed disappearance was greater (P< 0.01) in multiparous litters independent of diet. In the commercial nursery, total removals (mortality and morbidity) were highest (P<0.01) in primiparous sow progeny, with pigs offered NUP having greater (P <= 0.05) total removals. Pigs offered PLA had superior average daily gain, average daily feed intake and feed conversion ratio from Day 28 to Day 34 (P<0.05). Pigs offered NUP tended to (P=0.07) have superior average daily gain from Day 35 to Day 49. Pigs offered NUP had higher (P<0.05) serum immunoglobulinGconcentrations at Day 68 compared with pigs offered TMC, with the effect most pronounced in primiparous sow progeny. Individually housed weaners offered PLA consumed more (P<0.05) feed on Day 30 to Day 31, had shorter relative intestine length (P<0.05), greater villous height in the medial jejunum (P<0.10) and lower immuno-pathology scores along the intestine. Pigs offered PLA also tended (P<0.10) to have increased pancreatic-specific lipase and amylase activity compared with pigs offered NUP. Pigs offered NUP had a higher ratio of E. coli : coliforms in the colon (P<0.01) and more counts of beta-haemolytic bacteria in the medial jejunum (P<0.05) and colon (P<0.10). Diets containing either SDPP or NUP offered pigs benefits beyond nutrition relative to the medicated control diet. The benefits of SDPPwere highly effective but transient, while the yeast derived protein had a successive or accumulative effect which was more pronounced in primiparous sow progeny. Received 3 May 2012, accepted 17 October 2012, published online 29 November 2012
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