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| 2. |
- Wierup, Nils, et al.
(författare)
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Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3573-3581
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Tidskriftsartikel (refereegranskat)abstract
- Context: Ghrelin is a novel hormone produced mainly in the gastric body. Hitherto, mapping studies of ghrelin cells covering the entire gastrointestinal (GI) tract in humans have been lacking. Furthermore, the phenotype of extragastric ghrelin cells is not known. Objective: The objective of the study was to perform a detailed mapping with specimens from all parts of the GI tract, and colocalization studies to phenotype ghrelin cells along the tract. In addition, mapping of ghrelin cells was performed in porcine GI tract, and the plasma profiles of ghrelin and motilin in blood from the porcine intestine were measured. Design: Biopsies from patients were obtained during gastroscopy or surgery. Ghrelin cell density and phenotyping was assessed with immunocytochemistry, in situ hybridization, and immunogold electron microscopy. Plasma ghrelin and motilin levels were measured in pigs, fitted with cannulas in the mesenteric vein. Results: The upper small intestine is unexpectedly rich in ghrelin cells, and these cells contribute to circulating ghrelin. Ghrelin and motilin are coproduced in the same cells in the duodenum and jejunum of both species, and ghrelin and motilin are stored in all secretory granules of such cells in humans, indicating cosecretion. The plasma profiles of ghrelin and motilin in pig were parallel, and a correlation between ghrelin and motilin ( r(2) = 0.22; P < 0.001) was evident in intestinal blood. Conclusions: The upper small intestine is an important source of ghrelin. The likely cosecretion of intestinal ghrelin and motilin suggests concerted actions of the two hormones. These data may have implications for understanding gut motility and clinical implications for dysmotility and bariatric surgery.
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| 3. |
- Evilevitch, L., et al.
(författare)
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Three-Day Enteral Exposure to a Red Kidney Bean Lectin Preparation Enhances the Pancreatic Response to CCK Stimulation in Suckling Pigs.
- 2005
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Ingår i: Biology of the Neonate. - : S. Karger AG. - 1421-9727. ; 87:1, s. 20-25
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Tidskriftsartikel (refereegranskat)abstract
- Background: A reason for the digestive problems that often occur around early weaning in piglets could be that the pancreas is not yet fully developed and the enzymes required for degradation of the solid food are not secreted in enough amounts. Objectives: The aim of the study was to investigate the possibility of inducing pancreas maturation with enhanced enzyme secretion. Methods: 10-day-old suckling pigs were gavage fed with a red kidney bean lectin preparation for 3 days, and the pancreatic response to intravenous infusion of CCK-33 was measured in the anaesthetized animals fitted with pancreatic duct catheters. Results: The pancreatic fluid secretion, protein output, and the trypsin and amylase outputs were significantly increased in response to CCK stimulation after the lectin treatment, as compared to those of the control littermates (p le 0.05). In addition, the plasma insulin basal levels and those observed during CCK-33 stimulation were lower in the lectin-treated piglets. Conclusion: The results suggested that the lectin treatment led to an increase in the capacity for pancreatic enzyme secretion in the suckling piglets. An enhanced pancreatic function might help to ameliorate the problems that may appear in modern pig production which are associated with weaning.
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| 4. |
- Fåk, Frida, et al.
(författare)
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Effects of a high-fat diet during pregnancy and lactation are modulated by E. coli in rat offspring
- 2012
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 36:5, s. 744-751
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied. Methods: Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water. Results: Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin. Conclusions: The present study demonstrates for the first time how bacterial administration to the maternal diet during the neonatal period can affect body weight and fat deposition in the offspring. The results point to a mechanistic link between the gut microbiota, increased intestinal permeability and metabolic endotoxemia, which appear to have led to increased adiposity in the young rats. International Journal of Obesity (2012) 36, 744-751; doi:10.1038/ijo.2011.118; published online 5 July 2011
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| 6. |
- Nouri, Mehrnaz, et al.
(författare)
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Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers). These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms) and at 14 days (i.e., at the stage of paralysis) after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.
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| 7. |
- Axelsson, Jakob B, et al.
(författare)
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Intestinal bacteria and permeability during experimental acute pancreatitis in rats
- 2006
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Ingår i: Annals of Gastroenterology. - 1108-7471. ; 19:3, s. 276-284
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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.
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| 8. |
- Arévalo Sureda, Ester, et al.
(författare)
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Early effects on the intestinal barrier and pancreatic function after enteral stimulation with protease or kidney bean lectin in neonatal rats
- 2018
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 119:9, s. 992-1002
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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.
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| 9. |
- Axelsson, Jakob B, et al.
(författare)
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Initiation of acute pancreatitis by heparan sulphate in the rat.
- 2008
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 43:4, s. 480-489
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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.
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| 10. |
- 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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